Datasets:

findzebra
/

corpus

Dataset card Data Studio Files Files and versions Community

Split (1)

train · 30.7k rows

text stringlengths 297 230k	title stringlengths 4 145	cui stringlengths 4 10	idx int64 0 30.7k	source stringclasses 6 values	source_url stringlengths 33 155	retrieved_date timestamp[s]	classification_map stringlengths 2 1.45k
Xanthomatous biliary cirrhosis Other namesObstructive liver disease, Xanthomatous biliary cirrhosis, is a condition in which there is hyperlipoproteinemia due to liver disease resulting in plane xanthomas.[1]:534 ## See also[edit] * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Xanthomatous biliary cirrhosis	None	26,600	wikipedia	https://en.wikipedia.org/wiki/Xanthomatous_biliary_cirrhosis	2021-01-18T18:31:44	{"wikidata": ["Q8043043"]}
At risk mental state is the clinical presentation of those considered at risk of developing psychosis or schizophrenia.[1] Such states were formerly considered treated as prodromes, emerging symptoms of psychosis, but this view is no longer prevalent as a prodromal period can not be confirmed unless the emergence of the condition has occurred. The original specialist service for those with subclinical symptoms of psychosis was The Pace Clinic[2] in Melbourne, Australia.[3] Other clinics have since developed around the world.[4][5][6][7] There has been some considerable development of how the concept can be applied clinically.[8][9][10][11] Assessed during the structured interview developed by PACE[clarification needed].[12] ## See also[edit] * Early psychosis * Schizophreniform disorder * Schizothymia * Schizotypal personality disorder ## References[edit] 1. ^ Yung AR, McGorry PD, McFarlane CA, Jackson HJ, Patton GC, Rakkar A (1996). "Monitoring and care of young people at incipient risk of psychosis". Schizophr Bull. 22 (2): 283–303. doi:10.1093/schbul/22.2.283. PMID 8782287. 2. ^ "Archived copy". Archived from the original on 2009-10-24. Retrieved 2011-08-04.CS1 maint: archived copy as title (link) 3. ^ Yung AR, McGorry PD, McFarlane CA, Jackson HJ, Patton GC, Rakkar A (1996). "Monitoring and care of young people at incipient risk of psychosis". Schizophr Bull. 22 (2): 283–303. doi:10.1093/schbul/22.2.283. PMID 8782287. 4. ^ Broome MR, Woolley JB, Johns LC, et al. (August 2005). "Outreach and support in south London (OASIS): implementation of a clinical service for prodromal psychosis and the at risk mental state". Eur. Psychiatry. 20 (5–6): 372–8. doi:10.1016/j.eurpsy.2005.03.001. PMID 16171652. 5. ^ PRIME 6. ^ (COPE) 7. ^ "Emory University". Archived from the original on 2011-07-22. Retrieved 2011-08-04. 8. ^ Yung AR, Phillips LJ, Yuen HP, et al. (March 2003). "Psychosis prediction: 12-month follow up of a high-risk ("prodromal") group". Schizophr. Res. 60 (1): 21–32. doi:10.1016/S0920-9964(02)00167-6. PMID 12505135. 9. ^ McGorry PD, Yung AR, Phillips LJ, et al. (October 2002). "Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms". Arch. Gen. Psychiatry. 59 (10): 921–8. doi:10.1001/archpsyc.59.10.921. PMID 12365879. 10. ^ Morrison AP, French P, Parker S, et al. (May 2007). "Three-year follow-up of a randomized controlled trial of cognitive therapy for the prevention of psychosis in people at ultrahigh risk". Schizophr Bull. 33 (3): 682–7. doi:10.1093/schbul/sbl042. PMC 2526150. PMID 16973786. 11. ^ Schäfer Amminger; Papageorgiou Harrigan; Cotton McGorry, Berger (2008). "Indicated Prevention of Psychotic Disorders with Long-Chainomega-3 Fatty Acids: A Randomized, Placebo-Controlled Trial". Schizophrenia Research. 102 (1–3): 252. doi:10.1016/s0920-9964(08)70758-8. 12. ^ Yung AR, Yuen HP, McGorry PD, et al. (2005). "Mapping the onset of psychosis: the Comprehensive Assessment of At-Risk Mental States". Aust N Z J Psychiatry. 39 (11–12): 964–71. doi:10.1080/j.1440-1614.2005.01714.x. PMID 16343296. This medical symptom article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	At risk mental state	None	26,601	wikipedia	https://en.wikipedia.org/wiki/At_risk_mental_state	2021-01-18T19:08:55	{"wikidata": ["Q4812457"]}
A number sign (#) is used with this entry because susceptibility to Stevens-Johnson syndrome, allopurinol-induced severe cutaneous adverse reaction, and carbamazepine-induced hypersensitivity syndrome have been associated with HLA-class I alleles (see HLA-A, 142800 and HLA-B, 142830). Clinical Features Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare severe blistering mucocutaneous diseases that share clinical and histopathologic features but vary in the extent of epidermal detachment (Roujeau et al., 1995). Both disorders are characterized by high fever, malaise, and a rapidly developing blistering exanthema of macules and target-like lesions accompanied by mucosal involvement (Rzany et al., 1999). When there is very extensive skin detachment and poor prognosis (death rates of 30 to 40%) the condition is usually called toxic epidermal necrolysis; milder forms are known as Stevens-Johnson syndrome or overlapping Stevens-Johnson syndrome and toxic epidermal necrolysis (Bastuji-Garin et al., 1993). The carbamazepine-induced hypersensitivity syndrome includes symptoms such as rash, fever, eosinophilia, hepatitis, and nephritis. This phenotype is associated with a mortality of up to 10% (summary by McCormack et al., 2011). Pathogenesis Drugs are an important cause of Stevens-Johnson syndrome, but infections or a combination of infections and drugs has also been implicated (Yetiv et al., 1980; Roujeau et al., 1995). It is associated with short-term therapy with the antiepileptic drugs phenytoin, phenobarbital, and carbamazepine (Rzany et al., 1999). Lamotrigine also has the potential for severe skin reactions. Viard et al. (1998) detected high levels of soluble FASL (134638) in the sera of patients with TEN. Keratinocytes of TEN patients produced FASL, which induced keratinic apoptosis. Incubating keratinocytes with intravenous immunoglobulin (IVIG) completely inhibited FAS-mediated keratinocyte apoptosis. A naturally occurring anti-FAS immunoglobulin present in IVIG blocks the FAS receptor and mediates this response. Ten patients with TEN were treated with IVIG, and all showed a rapid reversion in the progression of skin disease. Chung et al. (2008) showed that fresh blister cells from skin lesions of patients with SJS/TEN primarily consisted of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and that both blister fluids and cells were cytotoxic. Gene expression profiling identified granulysin (GNLY; 188855) as the most highly expressed cytotoxic molecule, confirmed by quantitative PCR and immunohistochemistry. Granulysin concentrations in the blister fluids were 2- to 4-orders of magnitude higher than other candidate molecules, including perforin (PRF1; 170280), granzyme B (GZMB; 123910), or soluble Fas ligand. Depletion of granulysin reduced cytotoxicity. In blister fluids, granulysin was in a 15-kD secretory form, and injection of this form into mouse skin resulted in features mimicking SJS/TEN. Chung et al. (2008) concluded that secretory granulysin is a key molecule responsible for the disseminated keratinocyte death in SJS/TEN. The findings also implicated a CTL- or NK cell-mediated cytotoxicity that does not require direct cellular contact, as is the case with FAS/FASL. Molecular Genetics Chung et al. (2004) studied 44 patients with carbamazepine-induced Stevens-Johnson syndrome, including 5 with overlapping toxic epidermal necrolysis, in whom the clinical morphology fulfilled Roujeau's diagnostic criteria (Roujeau, 1994). Controls included 101 patients who had been treated with carbamazepine for at least 3 months without adverse reaction and 93 normal individuals. All participants were Han Chinese residing in Taiwan. Chung et al. (2004) found that 100% of the patients who developed Stevens-Johnson syndrome carried the HLA-B1502 allele (142830.0002), while only 3% of the carbamazepine-tolerant group and 8.6% of normal controls carried that allele. When the carbamazepine-tolerant group was used as the control, the presence of the HLA-B1502 allele had a 93.6% positive predictive value for carbamazepine-induced Stevens-Johnson syndrome, whereas its absence had a negative predictive value of 100%. In a test for carbamazepine-induced Stevens-Johnson syndrome, the HLA-B1502 allele should therefore have 100% sensitivity and 97% specificity. In an expanded study of 60 Chinese patients with carbamazepine-induced Stevens-Johnson syndrome or toxic epidermal necrolysis, including the 44 patients reported by Chung et al. (2004), Hung et al. (2006) confirmed the association between these adverse drug reactions and the HLA-B1502 allele (p = 1.6 x 10(-41), odds ratio of 1.357). Fifty-nine of the 60 patients had the susceptibility allele, compared to 6 (4.2%) of 144 tolerant controls. There was no association between HLA-B1502 and 31 patients with nonbullous adverse drug reactions, suggesting that HLA-B1502 is specific for bullous phenotypes. In addition, fine mapping in the HLA region showed significant linkage of SJS and/or TEN to the T allele of a T/G SNP (rs3130690) near HLA-B. Hung et al. (2005) genotyped 51 patients with allopurinol-induced severe cutaneous adverse reaction and 228 controls (135 allopurinol-tolerant patients and 93 healthy individuals). The HLA-B5801 allele (142830.0004) was present in all 51 of the patients with allopurinol-SCAR, but in only 15% of allopurinol-tolerant controls and 20% of healthy controls (p = 4.7 x 10(-24) and p = 8.1 x 10(-18), respectively). Hung et al. (2005) concluded that the HLA-B5801 allele is an important genetic risk factor for severe cutaneous adverse reactions to allopurinol in the Han Chinese population. Ueta et al. (2007) examined the histocompatibility class I antigen genes HLA-A, -B, and -C of 40 Japanese SJS/TEN patients with ocular complications and 113 healthy Japanese volunteers. They found that HLA-A0206 was strongly associated with SJS/TEN with ocular complications (Pc less than .0005, OR = 5.1), whereas HLA-B, HLA-C, and other HLA-A alleles were not. Because this finding was completely different from data reported on Taiwanese Han Chinese patients (Lonjou et al., 2006) and Caucasian patients (Roujeau et al., 1987), which showed strong association with HLA-Bw44 and HLA-B1502, respectively, Ueta et al. (2007) suggested that there are strong ethnic differences in the HLA-SJS association. Chen et al. (2011) recruited 4,877 candidate subjects from 23 hospitals in Taiwan who had not taken carbamazepine. All were genotyped to determine whether they carried the HLA-B1502 allele. Those testing positive (7.7% of the total) were advised not to take carbamazepine. None of the 92.3% who were advised to take carbamazepine developed SJS-TEN. Chen et al. (2011) concluded that the identification of subjects carrying the HLA-B1502 allele and the avoidance of carbamazepine therapy in these subjects was strongly associated with a decrease in the incidence of carbamazepine-induced SJS-TEN. The estimated historical incidence of carbamazepine-induced SJS-TEN (0.23%) would translate into approximately 10 cases among study subjects (P less than 0.001). McCormack et al. (2011) performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine-induced maculopapular exanthema, and 3,987 control subjects, all of European descent. They replicated the associations in samples from 145 subjects with carbamazepine-induced hypersensitivity reactions. The HLA-A3101 allele, which has a prevalence of 2 to 5% in northern European populations, was significantly associated with the hypersensitivity syndrome (P = 3.5 x 10(-8)). An independent genomewide association study of samples from subjects with maculopapular exanthema also showed an association with the HLA-A3101 allele (P = 1.1 x 10(-6)). Follow-up genotyping confirmed the variant as a risk factor for the hypersensitivity syndrome (odds ratio, 12.41; 95 CI, 1.27-121.03), maculopapular exanthema (odds ratio, 8.33; 95% CI, 3.59-19.36), and SJS-TEN (odds ratio, 25.93; 95% CI, 4.93-116.18). The presence of the HLA-A3101 allele was associated with carbamazepine-induced hypersensitivity reactions among subjects of northern European ancestry. The presence of the allele increased the risk from 5.0% to 26.0%, whereas its absence reduced the risk from 5.0% to 3.8%. Amstutz et al. (2013) studied HLA-A3101 and HLA-B1502 in 42 Canadian children of diverse ancestries who experienced carbamazepine (CBZ)-induced hypersensitivity reactions. Twenty-six children had maculopapular exanthema (MPE), 9 had SJS/TEN, 6 had hypersensitivity syndrome (HSS), and 1 had acute generalized exanthema pustulosis (AGEP). Compared to 91 CBZ-tolerant control children, HLA-A3101 was significantly associated with CBZ-HSS (odds ratio (OR), 26.4; p = 0.0025) and MPE (OR, 8.6; p = 0.0037) but not with CBZ-SJS. Conversely, HLA-B1502 was associated with CBZ-SJS (OR, 38.6; p = 0.002) but not with HSS or MPE. Population Genetics Chung et al. (2004) stated that the incidence of Stevens-Johnson syndrome in Han Chinese is higher than that in Caucasians (8 cases per million person-years in Han Chinese compared with 2 to 3 cases in Caucasians). Carbamazepine is the drug most commonly associated with the syndrome in Asians, accounting for 25 to 33% of cases, whereas only 5 to 6% of Caucasian Stevens-Johnson syndrome cases are caused by it. The HLA-B1502 allele is present in 8% of Han Chinese but in only 1 to 2% of Caucasians; Chung et al. (2004) postulated that this may explain the lower incidence of carbamazepine-induced Stevens-Johnson syndrome in Caucasians. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SEVERE CUTANEOUS ADVERSE REACTION, SUSCEPTIBILITY TO	c0038325	26,602	omim	https://www.omim.org/entry/608579	2019-09-22T16:07:36	{"mesh": ["D013262"], "omim": ["608579"], "orphanet": ["36426", "95455"]}
Trichobacteriosis axillaris An armpit with variably encrusted hairs SpecialtyDermatology Trichobacteriosis axillaris is a superficial bacterial colonization of the hair shafts in sweat gland–bearing areas, such as the armpits and the groin. It is a trivial disease of worldwide occurrence that is believed to be caused by the genus Corynebacteria.[1] The condition has been called extensively trichomycosis axillaris in the literature, but because it is a bacterial infection and not a fungal infection, it should be called trichobacteriosis.[2] ## Contents * 1 Presentation * 2 Cause * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Presentation[edit] It is characterized by the presence of concretions along the hair shafts, clinically observed as yellow, and rarely as red or black nodules. These concretions derive from bacterial colonization along the hair shaft containing dried apocrine sweat with a cementing substance generated by the bacteria.[2] ## Cause[edit] It is caused by several species of Corynebacterium.[2] Obesity, hyperhidrosis, poor local hygiene, and warm, moist environments are common predisposing factors.[3] ## Diagnosis[edit] The infection is diagnosed by close examination of the hair shafts where brown to yellow material called concretions are seen. There is usually an associated rancid odour. A microscopic examination can confirm the diagnosis, but this is rarely needed.[4] Some patients with excessive sweating present the so-called corynebacterial triad, that is, the simultaneous presence of trichobacteriosis axillaris, erythrasma, and pitted keratolysis.[5] ## Treatment[edit] No specific therapeutic studies on trichobacteriosis are available.[6] Many authors consider that the most effective treatment consist in shaving of the affected area for a period of 2-3 weeks.[4][7] The use of a concomitant treatment, such as sulfur soaps or benzoyl peroxide[8] is also recommended.[2] Rubbing whilst washing may help to disrupt the biofilm, hence increasing the accessibility of antiseptics to the bacteria.[6] Patients who shave the affected area only once will generally experience a recurrence of the infection, since, the bacteria begin to develop the concretions once again as the hair grows back.[2] Corynebacterium infections are related to excessive sweating; for this reason, deodorants containing an aluminum chloride solution may be used for treatment and prevention.[7] Maintaining good local hygiene is recommended.[4] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1089. ISBN 978-1-4160-2999-1. 2. ^ a b c d e Bonifaz A, Váquez-González D, Fierro L, Araiza J, Ponce RM (January 2013). "Trichomycosis (trichobacteriosis): clinical and microbiological experience with 56 cases". International Journal of Trichology. 5 (1): 12–6. doi:10.4103/0974-7753.114704. PMC 3746219. PMID 23960390. 3. ^ Ma DL, Vano-Galvan S (October 2013). "Images in clinical medicine. Trichomycosis axillaris". The New England Journal of Medicine. 369 (18): 1735. doi:10.1056/nejmicm1300241. PMID 24171519. 4. ^ a b c Huang C, Liaw F, Liu Y, Wang W (2013). "Answer: Can you identify this condition?". Canadian Family Physician. 59 (6): 648. PMC 3681455. 5. ^ Rho NK, Kim BJ (February 2008). "A corynebacterial triad: Prevalence of erythrasma and trichomycosis axillaris in soldiers with pitted keratolysis". Journal of the American Academy of Dermatology. 58 (2 Suppl): S57–8. doi:10.1016/j.jaad.2006.05.054. PMID 18191714. 6. ^ a b Blaise G, Nikkels AF, Hermanns-Lê T, Nikkels-Tassoudji N, Piérard GE (September 2008). "Corynebacterium-associated skin infections". International Journal of Dermatology. 47 (9): 884–90. doi:10.1111/j.1365-4632.2008.03773.x. PMID 18937649. 7. ^ a b Barboza-Guadagnini L, Fernández-Figueras MT, Bassas-Vila J (September 2015). "Creamy Yellow Concretions in Axillary Hair". JAMA Dermatology. 151 (9): 1023–4. doi:10.1001/jamadermatol.2015.0989. PMID 25970422. 8. ^ Swart MN, Weinberg AN. Bacterial diseases with cutaneous involvement. In: Fitzpatrick’s Dermatology in General Medicine, 6th edn. New York: McGraw-Hill, 2003: 1843–1878. ## External links[edit] Classification D * ICD-10: A48.8, L08.8 (ILDS L08.88) * ICD-9-CM: 039.0 * DiseasesDB: 32451 External resources * eMedicine: derm/601 * v * t * e Bacterial skin disease Gram +ve Firmicutes * Staphylococcus * Staphylococcal scalded skin syndrome * Impetigo * Toxic shock syndrome * Streptococcus * Impetigo * Cutaneous group B streptococcal infection * Streptococcal intertrigo * Cutaneous Streptococcus iniae infection * Erysipelas / Chronic recurrent erysipelas * Scarlet fever * Corynebacterium * Erythrasma * Listeriosis * Clostridium * Gas gangrene * Dermatitis gangrenosa * Mycoplasma * Erysipeloid of Rosenbach Actinobacteria * Mycobacterium-related: Aquarium granuloma * Borderline lepromatous leprosy * Borderline leprosy * Borderline tuberculoid leprosy * Buruli ulcer * Erythema induratum * Histoid leprosy * Lepromatous leprosy * Leprosy * Lichen scrofulosorum * Lupus vulgaris * Miliary tuberculosis * Mycobacterium avium-intracellulare complex infection * Mycobacterium haemophilum infection * Mycobacterium kansasii infection * Papulonecrotic tuberculid * Primary inoculation tuberculosis * Rapid growing mycobacterium infection * Scrofuloderma * Tuberculosis cutis orificialis * Tuberculosis verrucosa cutis * Tuberculous cellulitis * Tuberculous gumma * Tuberculoid leprosy * Cutaneous actinomycosis * Nocardiosis * Cutaneous diphtheria infection * Arcanobacterium haemolyticum infection * Group JK corynebacterium sepsis Gram -ve Proteobacteria * α: Endemic typhus * Epidemic typhus * Scrub typhus * North Asian tick typhus * Queensland tick typhus * Flying squirrel typhus * Trench fever * Bacillary angiomatosis * African tick bite fever * American tick bite fever * Rickettsia aeschlimannii infection * Rickettsialpox * Rocky Mountain spotted fever * Human granulocytotropic anaplasmosis * Human monocytotropic ehrlichiosis * Flea-borne spotted fever * Japanese spotted fever * Mediterranean spotted fever * Flinders Island spotted fever * Verruga peruana * Brill–Zinsser disease * Brucellosis * Cat-scratch disease * Oroya fever * Ehrlichiosis ewingii infection * β: Gonococcemia/Gonorrhea/Primary gonococcal dermatitis * Melioidosis * Cutaneous Pasteurella hemolytica infection * Meningococcemia * Glanders * Chromobacteriosis infection * γ: Pasteurellosis * Tularemia * Vibrio vulnificus * Rhinoscleroma * Haemophilus influenzae cellulitis * Pseudomonal pyoderma / Pseudomonas hot-foot syndrome / Hot tub folliculitis / Ecthyma gangrenosum / Green nail syndrome * Q fever * Salmonellosis * Shigellosis * Plague * Granuloma inguinale * Chancroid * Aeromonas infection * ε: Helicobacter cellulitis Other * Syphilid * Syphilis * Chancre * Yaws * Pinta * Bejel * Chlamydia infection * Leptospirosis * Rat-bite fever * Lyme disease * Lymphogranuloma venereum Unspecified pathogen * Abscess * Periapical abscess * Boil/furuncle * Hospital furunculosis * Carbuncle * Cellulitis * Paronychia / Pyogenic paronychia * Perianal cellulitis * Acute lymphadenitis * Pilonidal cyst * Pyoderma * Folliculitis * Superficial pustular folliculitis * Sycosis vulgaris * Pimple * Ecthyma * Pitted keratolysis * Trichomycosis axillaris * Necrotizing fascitis * Gangrene * Chronic undermining burrowing ulcers * Fournier gangrene * Elephantiasis nostras * Blistering distal dactylitis * Botryomycosis * Malakoplakia * Gram-negative folliculitis * Gram-negative toe web infection * Pyomyositis * Blastomycosis-like pyoderma * Bullous impetigo * Chronic lymphangitis * Recurrent toxin-mediated perineal erythema * Tick-borne lymphadenopathy * Tropical ulcer [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Trichobacteriosis axillaris	c0040930	26,603	wikipedia	https://en.wikipedia.org/wiki/Trichobacteriosis_axillaris	2021-01-18T18:49:45	{"umls": ["C0040930"], "icd-9": ["039.0"], "icd-10": ["L08.8", "A48.8"], "wikidata": ["Q4116442"]}
Neuronal ceroid lipofuscinosis 10 (CLN10 disease) is a type of neuronal ceroid lipofuscinosis (NCL), a group of severe diseases that affect the nervous system. Signs and symptoms of CLN10 usually appear soon after birth. They may include muscle stiffness, respiratory failure, and seizures that last several minutes (status epilepticus). Infants with CLN10 disease have a small brain and small head (microcephaly). They also have problems controlling their movements. The areas of the brain involved in thinking and emotions are also severely affected. Sadly, infants with CLN10 disease often do not survive longer than hours or weeks after birth. In some cases, people with CLN10 disease do not develop symptoms until later in infancy, childhood, or adulthood. Symptoms in these cases may be more gradual and include ataxia, loss of speech and vision, and problems with memory and thinking (cognitive impairment). The lifespan of people diagnosed after early infancy is also shortened, but varies based on when their symptoms began. CLN10 disease is caused by changes (mutations) in the CTSD gene and inheritance is autosomal recessive. If the disease-causing genetic change completely prevents the CLN10 protein (cathepsin D) from being made, the infant will be born with the severe type. If however, some working CLN2 protein is made, the person will develop either the late infantile, juvenile, or adult type. At this time, there are no effective treatment options for CLN10 disease. Therefore, therapy is aimed at easing symptoms and improving quality of life (palliative care). Please note: Batten disease originally referred specifically to the juvenile and most common form of NCL, now known as CLN3. However, the term Batten disease is increasingly used to describe all forms of NCL. All types of NCL also belong to a larger group of diseases known as lysosomal storage disorders. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Neuronal ceroid lipofuscinosis 10	c1864669	26,604	gard	https://rarediseases.info.nih.gov/diseases/1218/neuronal-ceroid-lipofuscinosis-10	2021-01-18T17:58:43	{"mesh": ["C566438"], "omim": ["610127"], "umls": ["C1864669"], "orphanet": ["228337"], "synonyms": ["CLN10", "Ceroid lipofuscinosis neuronal Cathepsin D-deficient", "Neuronal ceroid lipofuscinosis due to Cathepsin D deficiency", "Neuronal ceroid lipofuscinosis 10", "CLN10 disease, congenital (subtype)", "CLN10 disease, late infantile (subtype)", "CLN10 disease, juvenile (subtype)", "CLN10 disease, adult (subtype)", "Cathepsin D deficiency"]}
Miller syndrome Other namesMandibulfacial dysostosis with postaxial limb anomalies This condition is inherited in an autosomal recessive manner. Miller syndrome, also known as Genée–Wiedemann syndrome, Wildervanck–Smith syndrome or postaxial acrofacial dystosis, is an extremely rare genetic condition that manifests as craniofacial, limb and eye deformities. It is caused by a mutation in the DHODH gene. The incidence of the condition is not known, and nothing is known of its pathogenesis. ## Contents * 1 Presentation * 2 Cause * 3 Genetics * 4 Diagnosis * 4.1 Differential diagnosis * 5 Treatment * 6 History * 7 Eponym * 8 References * 9 External links ## Presentation[edit] The syndrome consists of severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the postaxial elements of the limbs, coloboma of the eyelids and supernumerary nipples. Additional features of the syndrome include downward-slanting palpebral fissures, malar hypoplasia, malformed ears, and a broad nasal ridge. Other features include supernumerary vertebrae and other vertebral segmentation and rib defects, heart defects (patent ductus arteriosus, ventricular septal defect and ostium primum atrial septal defect), lung disease from chronic infection, single umbilical artery, absence of the hemidiaphragm, hypoplasia of the femora, ossification defects of the ischium and pubis, bilobed tongue, lung hypoplasia, and renal reflux.[citation needed] ## Cause[edit] The gene responsible for this disorder is DHODH[1][2] located at chromosome 16q22. This gene encodes an enzyme – dihydroorotate dehydrogenase – which catalyses the ubiquinone-mediated oxidation of dihydroorotate to orotate, the fourth enzymatic step in de novo pyrimidine biosynthesis. The protein is normally located on the outer surface of the inner mitochondrial membrane.[citation needed] ## Genetics[edit] A mutation in this gene was reported by Morgan in 1910 in the fruit fly Drosophila melanogaster. In the fly this mutation is characterized by wing anomalies, defective oogenesis, and malformed posterior legs.[3] In humans Miller syndrome is due to recessive mutation in the DHODH gene.[1] ## Diagnosis[edit] ### Differential diagnosis[edit] The differential diagnosis includes Treacher Collins syndrome, Nager acrofacial dysostosis (preaxial cranial dysostosis). Other types of axial cranial dysostosis included the Kelly, Reynolds, Arens (Tel Aviv), Rodríguez (Madrid), Richieri-Costa and Patterson-Stevenson-Fontaine forms.[citation needed] ## Treatment[edit] This section is empty. You can help by adding to it. (November 2017) ## History[edit] This condition was first described in 1969 by Genée, who assumed the condition to be an extreme form of Treacher Collins syndrome (dysostosis mandibulofacialis).[4] Wiedemann in 1975 described it as a separate entity.[5] Further cases were reported by Wildervanck in 1975[6] and by Miller et al in 1979[7] The syndrome was named the Genée-Wiedemann syndrome in 1987.[8] A family harboring Miller syndrome was the first human family to be ever sequenced with whole genome sequencing.[9] ## Eponym[edit] Genée–Wiedemann syndrome is named after two German physicians: Ekkart Genée (1936–), and his mentor Hans-Rudolf Wiedemann (1915–2006).[citation needed] ## References[edit] 1. ^ a b Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ (January 2010). "Exome sequencing identifies the cause of a mendelian disorder". Nature Genetics. 42 (1): 30–5. doi:10.1038/ng.499. PMC 2847889. PMID 19915526. 2. ^ Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, Rowen L, Pant KP, Goodman N, Bamshad M, Shendure J, Drmanac R, Jorde LB, Hood L, Galas DJ (April 2010). "Analysis of genetic inheritance in a family quartet by whole-genome sequencing". Science. 328 (5978): 636–9. Bibcode:2010Sci...328..636R. doi:10.1126/science.1186802. PMC 3037280. PMID 20220176. 3. ^ Morgan TH (July 1910). "Sex limited inheritance in drosophila". Science. 32 (812): 120–2. Bibcode:1910Sci....32..120M. doi:10.1126/science.32.812.120. PMID 17759620. 4. ^ Genée E (1969). "Une forme de dysostose mandibulo-faciale" [A form of mandibulo-facial dysostosis]. J. De Génét. Humaine (in French). 17: 45–52. 5. ^ Wiedemann HR (1973). "Missbildungs-Retardierungs-Syndrom mit Fehlen des 5. Strahls an Händen und Füssen, Gaumenspalte, dysplastischen Ohren und Augenlidern und radioulnarer Synostose" [Malformation retardation syndrome with absence of 5th ray on hands and feet, cleft palate, dysplastic ears and eyelids, and radioactive synostosis]. Klin Padiatr (in German). 185 (3): 181–6. PMID 4795571. 6. ^ Wildervanck LS (1975). "Case report 28". Syndrome Identification. 3 (1): 1–13. 7. ^ Miller M, Fineman R, Smith DW (December 1979). "Postaxial acrofacial dysostosis syndrome". The Journal of Pediatrics. 95 (6): 970–5. doi:10.1016/S0022-3476(79)80285-1. PMID 501501. 8. ^ Opitz JM, Stickler GB (August 1987). "The Genée-Wiedemann syndrome, an acrofacial dysostosis--further observation". American Journal of Medical Genetics. 27 (4): 971–5. doi:10.1002/ajmg.1320270427. PMID 3425606. 9. ^ McAuliffe, Kathleen (April 27, 2011). "#5: Family Genomics Links DNA to Disease". Discover. January/February 2011. ## External links[edit] Classification D * ICD-10: Q75.4 * OMIM: 263750 * MeSH: C537680 External resources * Orphanet: 246 * v * t * e Inborn error of purine–pyrimidine metabolism Purine metabolism Anabolism * Adenylosuccinate lyase deficiency * Adenosine Monophosphate Deaminase Deficiency type 1 Nucleotide salvage * Lesch–Nyhan syndrome/Hyperuricemia * Adenine phosphoribosyltransferase deficiency Catabolism * Adenosine deaminase deficiency * Purine nucleoside phosphorylase deficiency * Xanthinuria * Gout * Mitochondrial neurogastrointestinal encephalopathy syndrome Pyrimidine metabolism Anabolism * Orotic aciduria * Miller syndrome Catabolism * Dihydropyrimidine dehydrogenase deficiency [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Miller syndrome	c0265257	26,605	wikipedia	https://en.wikipedia.org/wiki/Miller_syndrome	2021-01-18T18:46:23	{"gard": ["8410"], "mesh": ["C537680"], "umls": ["C0265257"], "orphanet": ["246"], "wikidata": ["Q2691713"]}
A rare, complex chromosomal duplication/inversion in the region 15q11.2-q13.1 characterized by early central hypotonia, global developmental delay and intellectual deficit, autistic behavior, and seizures. ## Epidemiology Prevalence at birth is estimated at 1 in 30,000 but may be an underestimate. In patients with developmental concerns (developmental delay, intellectual disability, or autism spectrum disorder) or multiple congenital anomalies, the prevalence of partial tetrasomy of chromosome 15 is estimated to range between 1/253-584. There is an observed male predilection of 2:1. ## Clinical description Presentation is typically with neonatal hypotonia, feeding difficulties and gross motor delay. Global developmental delay is typical in early childhood with speech and language particularly affected. Expressive language is absent or very poor and often echolalic. Comprehension is very limited and contextual. Intention to communicate is absent or very limited. Most children and adults have moderate to severe intellectual disability. The distinct behavioral disorder manifesting in children and adolescents has been widely described as autistic or autistic-like. Seizures occur in over half of affected individuals, with onset typically between 6 months and 9 years, and may include infantile spasms and myoclonic, tonic-clonic, tonic, atonic, atypical absences, and focal seizures. Various EEG (electroencephalography) abnormalities have been described. Muscle hypotonia is observed in almost all individuals, associated, in most cases, with joint hyperextensibility and drooling. Facial dysmorphism is absent or subtle, and major malformations are rare. ## Etiology Chromosome region 15q11q13, known for its instability, is highly susceptible to clinically relevant genomic rearrangements, such as supernumerary marker chromosomes formed by the inverted duplication of proximal chromosome 15 (Inv dup(15)). It results in tetrasomy 15p and partial tetrasomy 15q. Large rearrangements, containing the Prader-Willi/Angelman syndrome critical region (PWS/ASCR), are responsible for the inv dup(15)/isodicentric 15 (idic(15)) phenotype. ## Diagnostic methods Diagnosis is established by standard cytogenetic and FISH (fluorescence in situ hybridization) analysis, using probes both from proximal chromosome 15 and from the PWS/ASCR. Microsatellite analysis on parental DNA or methylation analysis on the proband DNA are also needed to detect the parent-of-origin of the inv dup(15) chromosome. Array CGH (comparative genomic hybridization) has been shown to be a powerful approach for identifying and detecting both the increases in copy number of the 15q11.2q13.1 region and its extent, as well as atypical forms of idic(15). ## Differential diagnosis The possible occurrence of double supernumerary isodicentric chromosomes derived from chromosome 15, resulting in partial hexasomy of the maternally inherited PWS/ASCR, should be considered in the differential diagnosis. Mitochondrial encephalomyopathy, Rett and Angelman syndromes, and CDKL5 mutations should also be considered in the differential diagnosis. ## Antenatal diagnosis Due to possible maternal germline mosaicism, antenatal diagnosis maybe considered where there is an affected sibling. ## Genetic counseling Genetic counseling may be proposed due to possible maternal germline mosaicism but large rearrangements involving the PWS/ASCR and idic(15) are nearly always sporadic. ## Management and treatment Management of inv dup(15)/idic(15) includes a comprehensive neurophysiologic and developmental evaluation. ## Prognosis Life expectancy is not significantly reduced. Many adults have a severe intellectual disability with poor social interaction, and are unable to manage full self-care. Most live at home with their original family and a minority in a sheltered environment. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Inverted duplicated chromosome 15 syndrome	c3711376	26,606	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3306	2021-01-23T18:25:23	{"gard": ["5153"], "mesh": ["C580205"], "umls": ["C3711376"], "icd-10": ["Q99.8"], "synonyms": ["Duplication/inversion 15q11", "Inv dup (15) syndrome", "Isodicentric chromosome 15 syndrome", "Non-distal tetrasomy 15q", "Non-telomeric tetrasomy 15q", "idic (15) syndrome"]}
Bolivian hemorrhagic fever (BHF), caused by the Machupo virus (MACV), is a severe acute viral hemorrhagic fever characterized by fever, myalgia, and arthralgia followed by hemorrhagic and neurological manifestations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Bolivian hemorrhagic fever	c0282192	26,607	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=319229	2021-01-23T18:44:00	{"mesh": ["D006478"], "umls": ["C0282192"], "icd-10": ["A96.1"], "synonyms": ["Machupo hemorrhagic fever"]}
"LCDD" redirects here. For other uses, see LCDD (disambiguation). Light chain deposition disease Other namesLCDD SpecialtyOncology Light chain deposition disease (LCDD) is a rare blood cell disease which is characterized by deposition of fragments of infection-fighting immunoglobulins, called light chains (LCs), in the body. LCs are normally cleared by the kidneys, but in LCDD, these light chain deposits damage organs and cause disease. The kidneys are almost always affected and this often leads to kidney failure. About half of people with light chain deposition disease also have a plasma cell dyscrasia, a spectrum of diseases that includes multiple myeloma, Waldenström's macroglobulinemia, and the monoclonal gammopathy of undetermined significance premalignant stages of these two diseases.[1][2] Unlike in AL amyloidosis, in which light chains are laid down in characteristic amyloid deposits, in LCDD, light chains are deposited in non-amyloid granules.[3] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 Prognosis * 5 References * 6 External links ## Signs and symptoms[edit] The kidney is the organ most frequently affected. Proteinuria, the presence of protein in the urine, is characteristic. More than 90% of people with LCDD develop kidney failure, often with rapid progression of disease.[3] Light chains may be deposited in many other organs and may or may not result in any symptoms. Other than the kidneys, liver and heart are the most commonly involved organs. Deposition of light chains in the liver may lead to hepatomegaly, an enlarged liver, or rarely portal hypertension or liver failure. The heart is affected in up to 80% of patients with LCDD, and may cause arrhythmias and congestive heart failure.[3] ## Diagnosis[edit] A number of laboratory tests are required in order to assist in diagnosing LCDD. Blood and urine samples are collected for evaluation of kidney and liver function and determination of the presence of a monoclonal protein. Imaging studies such as echocardiography and an ultrasound of the abdomen will be performed. A CT scan, magnetic resonance imaging (MRI) or positron emission tomography (PET) may also be indicated.[4]In patients with LCDD, a biopsy of the affected organ will show deposited light chains. A bone marrow biopsy will be done in order to rule out multiple myeloma.[4] ## Treatment[edit] Decreasing production of the organ-damaging light chains is the treatment goal. Options include chemotherapy using bortezomib, autologous stem cell transplantation, immunomodulatory drugs, and kidney transplant.[5] There is no standard treatment for LCDD. High-dose melphalan in conjunction with autologous stem cell transplantation has been used in some patients. A regimen of bortezomib and dexamethasone has also been examined.[1] ## Prognosis[edit] The median time to progression to end stage renal disease is 2.7 years. After 5 years, about 37% of patients with LCDD are alive and do not have end stage renal disease.[1] ## References[edit] 1. ^ a b c Kastritis (February 2009). "Treatment of light chain deposition disease with bortezomib and dexamethasone". Haematologica. 94 (2): 300–302. doi:10.3324/haematol.13548. PMC 2635400. PMID 19066331. 2. ^ UNC Kidney Center. "Light Chain Deposition Disease". UNC. Archived from the original on 22 December 2011. Retrieved 29 November 2011. 3. ^ a b c Ronco (July 2001). "Light Chain Deposition Disease: A Model of Glomerulosclerosis Defined at the Molecular Level". J Am Soc Nephrol. 12 (7): 1558–1565. PMID 11423587. 4. ^ a b "Light-Chain Deposition Disease Workup: Laboratory Studies, Imaging Studies, Procedures". emedicine.medscape.com. Retrieved 2018-04-17. 5. ^ "Light chain deposition disease \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-18. ## External links[edit] * National Institutes of Health Genetic and Rare Diseases Information Center * Emedicine Classification D * ICD-10: D89.8 * ICD-9-CM: 203.8 External resources * Orphanet: 93558 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Light chain deposition disease	c0238239	26,608	wikipedia	https://en.wikipedia.org/wiki/Light_chain_deposition_disease	2021-01-18T18:48:03	{"gard": ["6906"], "umls": ["C0238239"], "orphanet": ["93558"], "wikidata": ["Q17142640"]}
Membranoproliferative glomerulonephritis (MPGN) is a chronic progressive kidney disorder characterized by glomerular capillary wall structural changes and mesangial cell proliferation leading to nephrotic syndrome, hypocomplementemia, hypertension, proteinuria and end-stage kidney disease. MPGN can be due to either idiopathic (type 1, 2 and 3 MPGN; see these terms) or secondary (associated with infectious and immune complex diseases) causes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Primary membranoproliferative glomerulonephritis	c0017662	26,609	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=54370	2021-01-23T17:40:06	{"gard": ["11982"], "mesh": ["D015432"], "omim": ["305800", "609814", "614809", "615008"], "umls": ["C0017662"], "icd-10": ["N00.5"], "synonyms": ["Mesangiocapillary glomerulonephritis", "Primary MPGN"]}
A rare epilepsy syndrome characterized by absence seizures with perioral myoclonia as the main seizure type, accompanied by generalized tonic-clonic seizures, appearing before or together with absences. Consciousness is usually impaired, although to variable degree. Commonly observed absence status epilepticus, poor response to antiepileptic drugs and persistence of seizures into adulthood, in the presence of normal neurological status and intelligence, are additional clinical features of this syndrome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Perioral myoclonia with absences	c4707846	26,610	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=139426	2021-01-23T17:15:38	{"synonyms": ["POMA"]}
For a discussion of autoimmunity, see 109100. See also vitiligo (606579). Mapping Generalized vitiligo is a common acquired autoimmune disorder of the skin and hair that results from selective destruction of melanocytes and is often associated with other autoimmune manifestations. In a genomewide linkage analysis of 57 multiplex Chinese families, each with at least 2 affected sibs, and in a further analysis of 49 additional families from a Chinese population, Chen et al. (2005) obtained highly significant evidence for linkage of vitiligo to chromosome 4q13-q21: multipoint linkage analysis yielded a maximum nonparametric lod score of 4.62 for the interval between markers D4S392 and D4S3042 and a maximum heterogeneity lod (hlod) score of 4.01 at the adjacent interval between D4S3042 and D4S2947 under a recessive model of inheritance. There was a minimal overlap between the linkage results of this genomewide analysis in the Chinese population and the results of previous analyses in white populations. Chen et al. (2005) hypothesized that, as a polygenic disorder, vitiligo may be associated with great genetic heterogeneity and a substantial difference in its genetic basis between ethnic populations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	AUTOIMMUNE DISEASE, SUSCEPTIBILITY TO, 4	c1836258	26,611	omim	https://www.omim.org/entry/609400	2019-09-22T16:06:07	{"omim": ["609400"], "synonyms": ["Alternative titles", "VITILIGO-ASSOCIATED MULTIPLE AUTOIMMUNE DISEASE SUSCEPTIBILITY 5", "AUTOIMMUNE DISEASE SUSCEPTIBILITY LOCUS, CHROMOSOME 4-RELATED"]}
Cervical stenosis SpecialtyGynecology Not to be confused with cervical spinal stenosis. Cervical stenosis means that the opening in the cervix (the endocervical canal) is more narrow than is typical. In some cases, the endocervical canal may be completely closed. A stenosis is any passage in the body that is more narrow than it should typically be. ## Contents * 1 Signs and symptoms * 1.1 Fertility * 2 Causes * 3 Treatment * 4 References * 5 External links ## Signs and symptoms[edit] Symptoms depend on whether the cervical canal is partially or completely obstructed and on the patient's menopausal status. Pre-menopausal patients may have a build up of blood inside the uterus which may cause infection, sporadic bleeding, or pelvic pain. Patients also have an increased risk of infertility and endometriosis.[1] ### Fertility[edit] Cervical stenosis may impact natural fertility by impeding the passage of sperm into the uterus. In the context of infertility treatments, cervical stenosis may complicate or prevent the use of intrauterine insemination (IUI) or in vitro fertilization (IVF) procedures.[2] ## Causes[edit] Cervical stenosis may be present from birth or may be caused by other factors: * Surgical procedures performed on the cervix such as colposcopy, cone biopsy, or a cryosurgery procedure[3] * Trauma to the cervix[3] * Repeated vaginal infections[3] * Atrophy of the cervix after menopause[3] * Cervical cancer[1] * Radiation[1] * Cervical nabothian cysts ## Treatment[edit] Treatment of cervical stenosis involves opening or widening the cervical canal. The condition may improve on its own following the vaginal delivery of a baby.[4] Cervical canal widening can be temporarily achieved by the insertion of dilators into the cervix. If the stenosis is caused by scar tissue, a laser treatment can be used to vaporize the scarring.[5] Finally, the surgical enlargement of the cervical canal can be performed by hysteroscopic shaving of the cervical tissue.[6] ## References[edit] 1. ^ a b c The Merck Manual Home Edition. Last full review/revision December 2008 by S. Gene McNeeley. Cervical Stenosis 2. ^ Pabuccu R; Ceyhan ST; Onalan G; Goktolga U; Ercan CM; Selam B (Sep–Oct 2005). "Successful treatment of cervical stenosis with hysteroscopic canalization before embryo transfer in patients undergoing IVF: a case series". Journal of Minimally Invasive Gynecology. 12 (5): 436–8. doi:10.1016/j.jmig.2005.06.003. PMID 16213431. 3. ^ a b c d "Cervical Stenosis". Health Science Report. Alotek Supplement Company. Retrieved 2007-02-10. 4. ^ "Dysmenorrhoea". Health24. Media24 (Naspers) Group. Retrieved 2007-02-10. 5. ^ Baggish MS; Baltoyannis P (July 1987). "Carbon dioxide laser treatment of cervical stenosis". Fertility and Sterility. 48 (1): 24–8. PMID 3595913. 6. ^ Noyes, N (May 1999). "Hysteroscopic cervical canal shaving: a new therapy for cervical stenosis before embryo transfer in patients undergoing in vitro fertilization". Fertility and Sterility. 71 (5): 965–6. doi:10.1016/S0015-0282(99)00097-7. PMID 10231067. ## External links[edit] Classification D * ICD-10: N88.2 * DiseasesDB: 2335 * v * t * e Female diseases of the pelvis and genitals Internal Adnexa Ovary * Endometriosis of ovary * Female infertility * Anovulation * Poor ovarian reserve * Mittelschmerz * Oophoritis * Ovarian apoplexy * Ovarian cyst * Corpus luteum cyst * Follicular cyst of ovary * Theca lutein cyst * Ovarian hyperstimulation syndrome * Ovarian torsion Fallopian tube * Female infertility * Fallopian tube obstruction * Hematosalpinx * Hydrosalpinx * Salpingitis Uterus Endometrium * Asherman's syndrome * Dysfunctional uterine bleeding * Endometrial hyperplasia * Endometrial polyp * Endometriosis * Endometritis Menstruation * Flow * Amenorrhoea * Hypomenorrhea * Oligomenorrhea * Pain * Dysmenorrhea * PMS * Timing * Menometrorrhagia * Menorrhagia * Metrorrhagia * Female infertility * Recurrent miscarriage Myometrium * Adenomyosis Parametrium * Parametritis Cervix * Cervical dysplasia * Cervical incompetence * Cervical polyp * Cervicitis * Female infertility * Cervical stenosis * Nabothian cyst General * Hematometra / Pyometra * Retroverted uterus Vagina * Hematocolpos / Hydrocolpos * Leukorrhea / Vaginal discharge * Vaginitis * Atrophic vaginitis * Bacterial vaginosis * Candidal vulvovaginitis * Hydrocolpos Sexual dysfunction * Dyspareunia * Hypoactive sexual desire disorder * Sexual arousal disorder * Vaginismus * Urogenital fistulas * Ureterovaginal * Vesicovaginal * Obstetric fistula * Rectovaginal fistula * Prolapse * Cystocele * Enterocele * Rectocele * Sigmoidocele * Urethrocele * Vaginal bleeding * Postcoital bleeding Other / general * Pelvic congestion syndrome * Pelvic inflammatory disease External Vulva * Bartholin's cyst * Kraurosis vulvae * Vestibular papillomatosis * Vulvitis * Vulvodynia Clitoral hood or clitoris * Persistent genital arousal disorder [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Stenosis of uterine cervix	None	26,612	wikipedia	https://en.wikipedia.org/wiki/Stenosis_of_uterine_cervix	2021-01-18T18:32:43	{"icd-10": ["N88.2"], "wikidata": ["Q7607894"]}
Aufderheide (1972) described a large kindred with cytopenia (involving red cells, white cells, platelets or any combination of these elements) and occlusive vascular disease. Cytopenia varied widely in degree. It was first identified in the second decade of life. Symptoms became overt by the third decade. Death occurred in the fifth and sixth decades. Vascular occlusive disease occurred in 9 of 13 adults. Both males and females were affected and male-to-male transmission was observed. Vascular \- Occlusive vascular disease Misc \- Onset in second decade Inheritance \- Autosomal dominant Heme \- Anemia \- Leukopenia \- Thrombocytopenia \- Pancytopenia ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PANCYTOPENIA AND OCCLUSIVE VASCULAR DISEASE	c1868652	26,613	omim	https://www.omim.org/entry/167850	2019-09-22T16:36:40	{"mesh": ["C566836"], "omim": ["167850"]}
A robovirus is a zoonotic virus that is transmitted by a rodent vector (i.e., rodent borne).[1][2] Roboviruses mainly belong to the virus families Arenaviridae and Hantaviridae.[3][4] Like arbovirus (arthropod borne) and tibovirus (tick borne) the name refers to its method of transmission, known as its vector. This is distinguished from a clade, which groups around a common ancestor. Some scientists now refer to arbovirus and robovirus together with the term ArboRobo-virus.[5] ## Contents * 1 Methods of transmission * 1.1 Viral diseases transmitted by rodents * 1.2 Viral diseases indirectly transmitted by rats * 1.3 Factors affecting roboviruses * 2 References ## Methods of transmission[edit] Rodent borne disease can be transmitted through different forms of contact such as rodent bites, scratches, urine, saliva, etc.[6] Potential sites of contact with rodents include habitats such as barns, outbuildings, sheds, and dense urban areas. Transmission of disease through rodents can be spread to humans through direct handling and contact, or indirectly through rodents carrying the disease spread to ticks, mites, fleas (arboborne). ### Viral diseases transmitted by rodents[edit] One example of a robovirus is hantavirus, which causes hantavirus pulmonary syndrome. Humans can be infected with Hantavirus Pulmonary Syndrome through direct contact with rodent droppings, saliva, or urine infected with strains of the virus. These components mix into the air and get transmitted when inhaled through airborne transmission.[7] Lassa virus from the Arenaviridae family causes Lassa hemorrhagic fever and is also a robovirus transmitted by the rodent genus Mastomys natalensis.[8][9] The multimammate rat is able to excrete the virus in its urine and droppings. These rat are often found in the savannas and forests of Africa. When these rats scavenge and enter households this provides an outlet for direct contact transmission with humans. It has also been found that airborne transmission can occur by engaging in cleaning activities such as sweeping. In some areas of Africa, the Mastomys rodent is caught and used as a source of food. This process can also lead to transmission and infection.[10] ### Viral diseases indirectly transmitted by rats[edit] Colorado tick fever virus causes high fevers, chills, headache, fatigue and sometimes vomiting, skin rash, and abdominal pain. The virus is caused by a Rocky Mountain wood tick (Dermacentor andersoni). It is an arbovirus, but rodents serve as the reservoir. The tick is carried by five species of rodents: the least chipmunk (Eutamias minimus), Richardson's ground squirrel (Urocitellus richardsonii), deer mice (Peromyscus maniculatus), the golden-mantled ground squirrel (Callospermophilus lateraliss), and the Uinta chipmunk (Neotamias umbrinus).[11] The infected tick will be carried by its rodent host and infect another host (animal or human) as it feeds.[12] ### Factors affecting roboviruses[edit] Rodent populations are affected by a number of diverse factors, including climatic conditions. Warmer winters and increased rainfall will make it more likely for rodent populations to survive, therefore increasing the number of rodent reservoirs for disease. Increased rainfall accompanied by flooding can also increase human to rodent contact[13] Global climate change will affect the distribution and prevalence of roboviruses. Inadequate hygiene and sanitation, as seen in some European countries, also contribute to increase rodent populations and higher risks of rodent borne disease transmission.[14] ## References[edit] 1. ^ Spicer, W. John (2008). Clinical Microbiology and Infectious Diseases. Edinburgh: Churchill Livingstone. p. 117. ISBN 978-0-443-10303-2. 2. ^ Sandra I Kim; Swanson, Todd; Flomin, Olga E. (2008). Microbiology. Philadelphia: Wolters Kluwer Heath. p. 88. ISBN 978-0-7817-6470-4. 3. ^ Briese, Thomas et al. (2016) Create a new order, Bunyavirales, to accommodate nine families (eight new, one renamed) comprising thirteen genera. ICTV 11th report 4. ^ Hjelle, Brian; Torres-Perez, Fernando (2009). "Ch. 34. Rodent-Borne Viruses". In Steven Specter; Richard L. Hodinka; Stephen A. Young; Danny L. Wiedbrauk (eds.). Clinical Virology Manual (4th ed.). American Society for Microbiology. pp. 641–657. doi:10.1128/9781555815974.ch34. ISBN 9781555815974. 5. ^ Kurolt; Ivan-Christian; et al. (14 November 2014). Molecular epidemiology of human pathogenic "ArboRobo-viruses" in Croatia (PDF). CroViWo-1st Croatian Virus Workshop. Rijeka. pp. 15–16. Retrieved 25 November 2015. 6. ^ "Rodents", U.S. Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, and Division of High- Consequence Pathogens and Pathology. 7. ^ "Transmission \| Hantavirus". Centers for Disease Control and Prevention. 29 August 2012. 8. ^ Lecompte, Emilie; Fichet-Calvet, Elisabeth; Daffis, Stephane; Koulemou, Kekoura; Sylla, Oumar; Kourouma, Fode; Dore, Amadou; Soropogui, Barre; Aniskin, Vladimir; Allali, Bernard; Kouassi Ka, Stephane; Lalis, Aude; Koivogui, Lamine; Gunthe, Stephan; Denys, Christiane; ter Meulen, January (2006). "Mastomys natalensis and Lassa Fever, West Africa". Emerging Infectious Diseases. 12 (12): 1971–1974. doi:10.3201/eid1212.060812. PMC 3291371. PMID 17326956. 9. ^ McCormick, Joseph B.; King, Isabel J.; Webb, Patricia A.; Scribner, Curtis L.; Craven, Robert B.; Johnson, Karl M.; Elliott, Luanne H.; Belmont-Williams, Rose (2 January 1986). "Lassa Fever". New England Journal of Medicine. 314 (1): 20–26. doi:10.1056/nejm198601023140104. PMID 3940312. 10. ^ "Transmission of Lassa fever". Centers for Disease control and Prevention. 6 March 2019. 11. ^ Bowen, G. S.; Kirk, L. J.; Shriner, R. B.; McLean, R. G.; Pokorny, K. S. (1980). "Experimental Colorado Tick Fever virus Infection in Colorado Mammals". The American Journal of Tropical Medicine and Hygiene. 30 (1): 224–229. doi:10.4269/ajtmh.1981.30.224. PMID 6259958. 12. ^ Colorado Tick fever - "Transmission", U.S. Centers for Disease Control and Prevention. 13. ^ Charron, Dominique F., Fleury, Manon, Lindsay, Leslie Robbin, Ogden, Nicholas and Schuster-Wallace, Corinne J. (2008) "The Impacts of Climate Change on Water-, Food-, Vector- and Rodent-Borne Diseases" in Human Health in a Changing Climate. ed. Séguin, Jacinthe. Health Canada, Ch. 5, p. 188 14. ^ "Rodent-borne diseases" (website). European Centre for Disease Prevention and Control. 2009. Retrieved 30 October 2017. * v * t * e Zoonotic viral diseases (A80–B34, 042–079) Arthropod -borne Mosquito -borne Bunyavirales * Arbovirus encephalitides: La Crosse encephalitis * LACV * Batai virus * BATV * Bwamba Fever * BWAV * California encephalitis * CEV * Jamestown Canyon encephalitis * Tete virus * Tahyna virus * TAHV * Viral hemorrhagic fevers: Rift Valley fever * RVFV * Bunyamwera fever * BUNV * Ngari virus * NRIV Flaviviridae * Arbovirus encephalitides: Japanese encephalitis * JEV * Australian encephalitis * MVEV * KUNV * Saint Louis encephalitis * SLEV * Usutu virus * West Nile fever * WNV * Viral hemorrhagic fevers: Dengue fever * DENV-1-4 * Yellow fever * YFV * Zika fever * Zika virus Togaviridae * Arbovirus encephalitides: Eastern equine encephalomyelitis * EEEV * Western equine encephalomyelitis * WEEV * Venezuelan equine encephalomyelitis * VEEV * Chikungunya * CHIKV * O'nyong'nyong fever * ONNV * Pogosta disease * Sindbis virus * Ross River fever * RRV * Semliki Forest virus Reoviridae * Banna virus encephalitis Tick -borne Bunyavirales * Viral hemorrhagic fevers: Bhanja virus * Crimean–Congo hemorrhagic fever (CCHFV) * Heartland virus * Severe fever with thrombocytopenia syndrome (Huaiyangshan banyangvirus) * Tete virus Flaviviridae * Arbovirus encephalitides: Tick-borne encephalitis * TBEV * Powassan encephalitis * POWV * Viral hemorrhagic fevers: Omsk hemorrhagic fever * OHFV * Kyasanur Forest disease * KFDV * AHFV * Langat virus * LGTV Orthomyxoviridae * Bourbon virus Reoviridae * Colorado tick fever * CTFV * Kemerovo tickborne viral fever Sandfly -borne Bunyavirales * Adria virus (ADRV) * Oropouche fever * Oropouche virus * Pappataci fever * Toscana virus * Sandfly fever Naples virus Rhabdoviridae * Chandipura virus Mammal -borne Rodent -borne Arenaviridae * Viral hemorrhagic fevers: Lassa fever * LASV * Venezuelan hemorrhagic fever * GTOV * Argentine hemorrhagic fever * JUNV * Brazilian hemorrhagic fever * SABV * Bolivian hemorrhagic fever * MACV * LUJV * CHPV Bunyavirales * Hemorrhagic fever with renal syndrome * DOBV * HTNV * PUUV * SEOV * AMRV * THAIV * Hantavirus pulmonary syndrome * ANDV * SNV Herpesviridae * Murid gammaherpesvirus 4 Bat -borne Filoviridae * BDBV * SUDV * TAFV * Marburg virus disease * MARV * RAVV Rhabdoviridae * Rabies * ABLV * MOKV * DUVV * LBV * CHPV Paramyxoviridae * Henipavirus encephalitis * HeV * NiV Coronaviridae * SARS-related coronavirus * SARS-CoV * MERS-CoV * SARS-CoV-2 Primate -borne Herpesviridae * Macacine alphaherpesvirus 1 Retroviridae * Simian foamy virus * HTLV-1 * HTLV-2 Poxviridae * Tanapox * Yaba monkey tumor virus Multiple vectors Rhabdoviridae * Rabies * RABV * Mokola virus Poxviridae * Monkeypox [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Robovirus	None	26,614	wikipedia	https://en.wikipedia.org/wiki/Robovirus	2021-01-18T18:39:18	{"wikidata": ["Q7353480"]}
Brachydactyly - long thumb syndrome is a very rare autosomal dominant heart-hand syndrome (see this term) that is characterized by bisymmetric brachydactyly accompanied by long thumbs, joint anomalies (restriction of motion at the shoulder and metacarpophalangeal joints) and cardiac conduction defects. Additional features include small hands and feet, clinodactyly, narrow shoulders with short clavicles, pectus excavatum and mild shortness of the limbs, cardiomegaly and murmur of pulmonic stenosis.It has been described in four family members from three generations, with no new cases having been reported since 1981. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Brachydactyly-long thumb syndrome	c1862169	26,615	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2946	2021-01-23T18:40:10	{"gard": ["968"], "mesh": ["C566204"], "omim": ["112430"], "umls": ["C1862169"], "icd-10": ["Q87.2"], "synonyms": ["Brachydactyly, long thumb type"]}
Group of lung diseases affecting the tissue and space around the air sacs of the lungs Interstitial lung disease Other namesDiffuse parenchymal lung disease (DPLD) End-stage pulmonary fibrosis of unknown origin, taken from an autopsy SpecialtyPulmonology Frequency1.9 million (2015)[1] Deaths122,000 (2015)[2] Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD),[3] is a group of respiratory diseases affecting the interstitium (the tissue and space around the alveoli (air sacs) of the lungs.[4] It concerns alveolar epithelium, pulmonary capillary endothelium, basement membrane, and perivascular and perilymphatic tissues. It may occur when an injury to the lungs triggers an abnormal healing response. Ordinarily, the body generates just the right amount of tissue to repair damage, but in interstitial lung disease, the repair process is disrupted, and the tissue around the air sacs (alveoli) becomes scarred and thickened. This makes it more difficult for oxygen to pass into the bloodstream. The disease presents itself with the following symptoms: shortness of breath, nonproductive coughing, fatigue, and weight loss, which tend to develop slowly, over several months. The average rate of survival for someone with this disease is between three and five years.[5] The term ILD is used to distinguish these diseases from obstructive airways diseases. There are specific types in children, known as children's interstitial lung diseases. The acronym ChILD is sometimes used for this group of diseases.[6] Prolonged ILD may result in pulmonary fibrosis, but this is not always the case. Idiopathic pulmonary fibrosis is interstitial lung disease for which no obvious cause can be identified (idiopathic) and is associated with typical findings both radiographic (basal and pleural-based fibrosis with honeycombing) and pathologic (temporally and spatially heterogeneous fibrosis, histopathologic honeycombing, and fibroblastic foci). In 2015, interstitial lung disease, together with pulmonary sarcoidosis, affected 1.9 million people.[1] They resulted in 122,000 deaths.[2] ## Contents * 1 Causes * 1.1 Idiopathic * 1.2 Secondary * 2 Diagnosis * 2.1 X-rays * 2.1.1 Pattern of opacities * 2.1.2 Distribution * 2.1.3 Associated findings * 2.2 Genetic testing * 2.2.1 ILDs related to alveolar surfactant region * 2.2.2 Diffuse developmental disorder * 2.2.3 Idiopathic pulmonary fibrosis * 3 Treatment * 4 References * 5 External links ## Causes[edit] Interstitial lung disease affects gas flow in the alveoli The alveoli Micrograph of usual interstitial pneumonia (UIP). UIP is the most common pattern of idiopathic interstitial pneumonia (a type of interstitial lung disease) and usually represents idiopathic pulmonary fibrosis. H&E stain. Autopsy specimen. An ILD may be classified as to whether its cause is not known (idiopathic) or known (secondary).[7] ### Idiopathic[edit] Idiopathic interstitial pneumonia is the term given to ILDs with an unknown cause. They represent the majority of cases of interstitial lung diseases (up to two-thirds of cases).[8] They were subclassified by the American Thoracic Society in 2002 into 7 subgroups:[citation needed] * Idiopathic pulmonary fibrosis (IPF): the most common subgroup * Desquamative interstitial pneumonia (DIP) * Acute interstitial pneumonia (AIP): also known as Hamman-Rich syndrome * Nonspecific interstitial pneumonia (NSIP) * Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) * Cryptogenic organizing pneumonia (COP): also known as Bronchiolitis Obliterans Organizing Pneumonia (BOOP) * Lymphoid interstitial pneumonia (LIP) ### Secondary[edit] Secondary ILDs are those diseases with a known etiology, including: * Connective tissue and Autoimmune diseases * Sarcoidosis * Rheumatoid arthritis * Systemic lupus erythematosus * Systemic sclerosis * Polymyositis * Dermatomyositis * Antisynthetase syndrome * Inhaled substances * Inorganic * Silicosis * Asbestosis * Berylliosis * Industrial printing chemicals (e.g. carbon black, ink mist) * Organic * Hypersensitivity pneumonitis (Extrinisic allergic alveolitis) * Drug-induced * Antibiotics * Chemotherapeutic drugs * Antiarrhythmic agents * Infection * Coronavirus disease 2019[9] * Atypical pneumonia * Pneumocystis pneumonia (PCP) * Tuberculosis * Chlamydia trachomatis * Respiratory Syncytial Virus * Malignancy * Lymphangitic carcinomatosis * Predominately in children * Diffuse developmental disorders * Growth abnormalities deficient alveolarisation * Infant conditions of undefined cause * ILD related to alveolar surfactant region ## Diagnosis[edit] Pneumocystis pneumonia can present with interstitial lung disease, as seen in the reticular markings on this AP chest x-ray. A chest X-ray demonstrating pulmonary fibrosis due to amiodarone Investigation is tailored towards the symptoms and signs. A proper and detailed history looking for the occupational exposures, and for signs of conditions listed above is the first and probably the most important part of the workup in patients with interstitial lung disease. Pulmonary function tests usually show a restrictive defect with decreased diffusion capacity (DLCO).[citation needed] A lung biopsy is required if the clinical history and imaging are not clearly suggestive of a specific diagnosis or malignancy cannot otherwise be ruled out. In cases where a lung biopsy is indicated, a trans-bronchial biopsy is usually unhelpful, and a surgical lung biopsy is often required.[citation needed] ### X-rays[edit] Chest radiography is usually the first test to detect interstitial lung diseases, but the chest radiograph can be normal in up to 10% of patients, especially early on the disease process.[10][11] High resolution CT of the chest is the preferred modality, and differs from routine CT of the chest. Conventional (regular) CT chest examines 7–10 mm slices obtained at 10 mm intervals; high resolution CT examines 1–1.5 mm slices at 10 mm intervals using a high spatial frequency reconstruction algorithm. The HRCT therefore provides approximately 10 times more resolution than the conventional CT chest, allowing the HRCT to elicit details that cannot otherwise be visualized.[10][12] Radiologic appearance alone however is not adequate and should be interpreted in the clinical context, keeping in mind the temporal profile of the disease process.[10] Interstitial lung diseases can be classified according to radiologic patterns.[10] #### Pattern of opacities[edit] Consolidation Acute: Alveolar hemorrhage syndromes, acute eosinophilic pneumonia, acute interstitial pneumonia, cryptogenic organizing pneumonia Chronic: Chronic eosinophilic pneumonia, cryptogenic organizing pneumonia, lymphoproliferative disorders, pulmonary alveolar proteinosis, sarcoidosis Linear or reticular opacities Acute: Pulmonary edema Chronic: Idiopathic pulmonary fibrosis, connective tissue associated interstitial lung diseases, asbestosis, sarcoidosis, hypersensitivity pneumonitis, drug-induced lung disease Small nodules Acute: Hypersensitivity pneumonitis Chronic: Hypersensitivity pneumonitis, sarcoidosis, silicosis, coal workers pneumoconiosis, respiratory bronchiolitis, alveolar microlithiasis Cystic airspaces Chronic: Pulmonary langerhans cell histiocytosis, pulmonary lymphangioleiomyomatosis, honeycomb lung caused by IPF or other diseases Ground glass opacities Acute: Alveolar hemorrhage syndromes, pulmonary edema, hypersensitivity pneumonitis, acute inhalational exposures, drug-induced lung diseases, acute interstitial pneumonia Chronic: Nonspecific interstitial pneumonia, respiratory bronchiolitis associated interstitial lung disease, desquamative interstitial pneumonia, drug-induced lung diseases, pulmonary alveolar proteinosis Thickened alveolar septa Acute: Pulmonary edema Chronic: Lymphangitic carcinomatosis, pulmonary alveolar proteinosis, sarcoidosis, pulmonary veno occlusive disease[10] #### Distribution[edit] Upper lung predominance Pulmonary Langerhans cell histiocytosis, silicosis, coal workers pneumoconiosis, carmustine related pulmonary fibrosis, respiratory broncholitis associated with interstitial lung disease. Lower lung predominance Idiopathic pulmonary fibrosis, pulmonary fibrosis associated with connective tissue diseases, asbestosis, chronic aspiration Central predominance (perihilar) Sarcoidosis, berylliosis Peripheral predominance Idiopathic pulmonary fibrosis, chronic eosinophilic pneumonia, cryptogenic organizing pneumonia[10] #### Associated findings[edit] Pleural effusion or thickening Pulmonary edema, connective tissue diseases, asbestosis, lymphangitic carcinomatosis, lymphoma, lymphangioleiomyomatosis, drug-induced lung diseases Lymphadenopathy Sarcoidosis, silicosis, berylliosis, lymphangitic carcinomatosis, lymphoma, lymphocytic interstitial pneumonia[10] ### Genetic testing[edit] For some types of paediatric ILDs and few forms adult ILDs, genetic causes have been identified. These may be identified by blood tests. For a limited number of cases this is a definite advantage, as a precise molecular diagnosis can be done; frequently then there is no need for a lung biopsy. Testing is available for #### ILDs related to alveolar surfactant region[edit] Surfactant-Protein-B Deficiency (Mutations in SFTPB) Surfactant-Protein-C Deficiency (Mutations in SFTPC) ABCA3-Deficiency (Mutations in ABCA3) Brain Lung Thyroid Syndrome (Mutations in TTF1) Congenital Pulmonary Alveolar Proteinosis (Mutations in CSFR2A, CSFR2B) #### Diffuse developmental disorder[edit] Alveolar Capillary Dysplasia (Mutations in FoxF1) #### Idiopathic pulmonary fibrosis[edit] Mutations in telomerase reverse transcriptase (TERT) Mutations in telomerase RNA component (TERC) Mutations in the regulator of telomere elongation helicase 1 (RTEL1) Mutations in poly(A)-specific ribonuclease (PARN) ## Treatment[edit] ILD is not a single disease, but encompasses many different pathological processes. Hence treatment is different for each disease.If a specific occupational exposure cause is found, the person should avoid that environment. If a drug cause is suspected, that drug should be discontinued. Many cases due to unknown or connective tissue-based causes are treated with corticosteroids,[13] such as prednisolone. Some people respond to immunosuppressant treatment. Oxygen therapy at home is recommended in those with significantly low oxygen levels.[14] Pulmonary rehabilitation appears to be useful.[15] Lung transplantation is an option if the ILD progresses despite therapy in appropriately selected patients with no other contraindications.[16][17] On October 16, 2014, the Food and Drug Administration approved a new drug for the treatment of Idiopathic Pulmonary Fibrosis (IPF). This drug, Ofev (nintedanib), is marketed by Boehringer Ingelheim Pharmaceuticals, Inc. This drug has been shown to slow the decline of lung function although the drug has not been shown to reduce mortality or improve lung function. The estimated cost of the drug per year is approximately $94,000.[18] ## References[edit] 1. ^ a b GBD 2015 Disease and Injury Incidence and Prevalence, Collaborators. (8 October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282. 2. ^ a b GBD 2015 Mortality and Causes of Death, Collaborators. (8 October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/S0140-6736(16)31012-1. PMC 5388903. PMID 27733281. 3. ^ King TE (August 2005). "Clinical advances in the diagnosis and therapy of the interstitial lung diseases". American Journal of Respiratory and Critical Care Medicine. 172 (3): 268–79. doi:10.1164/rccm.200503-483OE. PMID 15879420. 4. ^ "Frequently Asked Questions About Interstitial Lung Disease". University of Chicago Medical Center. 5. ^ Meyer, Keith C; Decker, Catherine A (2017-04-03). "Role of pirfenidone in the management of pulmonary fibrosis". Therapeutics and Clinical Risk Management. 13: 427–437. doi:10.2147/TCRM.S81141. ISSN 1176-6336. PMC 5388201. PMID 28435277. 6. ^ Bush A, Cunningham S, de Blic J, Barbato A, Clement A, Epaud R, Hengst M, Kiper N, Nicholson AG, Wetzke M, Snijders D, Schwerk N, Griese M (November 2015). "European protocols for the diagnosis and initial treatment of interstitial lung disease in children". review. Thorax. 70 (11): 1078–84. doi:10.1136/thoraxjnl-2015-207349. PMID 26135832. 7. ^ Bourke SJ (August 2006). "Interstitial lung disease: progress and problems". Postgraduate Medical Journal. 82 (970): 494–9. doi:10.1136/pgmj.2006.046417. PMC 2585700. PMID 16891438. 8. ^ Kreuter, Michael; Herth, Felix J. F.; Wacker, Margarethe; Leidl, Reiner; Hellmann, Andreas; Pfeifer, Michael; Behr, Jürgen; Witt, Sabine; Kauschka, Dagmar (2015). "Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases: Rationale, Aims, and Design of a Nationwide Prospective Registry—The EXCITING-ILD Registry". BioMed Research International. 2015: 123876. doi:10.1155/2015/123876. PMC 4657073. PMID 26640781. 9. ^ "Dr. Daniele Macchini, Treating COVID-19 Patients in Bergamo, Italy, Describes Horrible Situation". 11 March 2020. 10. ^ a b c d e f g Ryu JH, Olson EJ, Midthun DE, Swensen SJ (November 2002). "Diagnostic approach to the patient with diffuse lung disease". Mayo Clinic Proceedings. 77 (11): 1221–7, quiz 1227. doi:10.4065/77.11.1221. PMID 12440558. 11. ^ "What Is Pulmonary Fibrosis?". Northwestern Medicine. Archived from the original on 2014-02-26. Retrieved 2014-02-22. 12. ^ Zare Mehrjardi M, Kahkouee S, Pourabdollah M (March 2017). "Radio-pathological correlation of organizing pneumonia (OP): a pictorial review". The British Journal of Radiology. 90 (1071): 20160723. doi:10.1259/bjr.20160723. PMC 5601538. PMID 28106480. 13. ^ "Interstitial lung disease: Treatments and drugs". MayoClinic.com. 14. ^ Hayes D, Jr; Wilson, KC; Krivchenia, K; Hawkins, SMM; Balfour-Lynn, IM; Gozal, D; Panitch, HB; Splaingard, ML; Rhein, LM; Kurland, G; Abman, SH; Hoffman, TM; Carroll, CL; Cataletto, ME; Tumin, D; Oren, E; Martin, RJ; Baker, J; Porta, GR; Kaley, D; Gettys, A; Deterding, RR (1 February 2019). "Home Oxygen Therapy for Children. An Official American Thoracic Society Clinical Practice Guideline". American Journal of Respiratory and Critical Care Medicine. 199 (3): e5–e23. doi:10.1164/rccm.201812-2276ST. PMC 6802853. PMID 30707039. 15. ^ Dowman L, Hill CJ, Holland AE (October 2014). "Pulmonary rehabilitation for interstitial lung disease". The Cochrane Database of Systematic Reviews. 10 (10): CD006322. doi:10.1002/14651858.CD006322.pub3. PMID 25284270. 16. ^ Kotloff RM, Thabut G (July 2011). "Lung transplantation". American Journal of Respiratory and Critical Care Medicine. 184 (2): 159–71. doi:10.1164/rccm.201101-0134CI. PMID 21471083. 17. ^ Whelan TP (March 2012). "Lung transplantation for interstitial lung disease". Clinics in Chest Medicine. 33 (1): 179–89. doi:10.1016/j.ccm.2011.12.003. PMID 22365254. 18. ^ "FDA approves Ofev to treat idiopathic pulmonary fibrosis". U.S. Food and Drug Administration. Archived from the original on 17 October 2014. 19\. ^Health, St Vincent’s Heart. “Home.” St Vincent's Lung Health, St Vincent's Heart Health, www.svhlunghealth.com.au/conditions/ild-interstitial-lung-disease. 20\. ^“Interstitial Lung Disease: Symptoms, Causes, Tests and Treatment.” Cleveland Clinic, my.clevelandclinic.org/health/diseases/17809-interstitial-lung-disease. ## External links[edit] Classification D * ICD-10: J84.9 * ICD-9-CM: 518.89, 508.1, 515, 516.3, 714.81, 770.7 * MeSH: D017563 External resources * Orphanet: 182095 * 00736 at CHORUS * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Interstitial lung disease	c0206062	26,616	wikipedia	https://en.wikipedia.org/wiki/Interstitial_lung_disease	2021-01-18T18:40:38	{"gard": ["13336"], "mesh": ["D017563"], "umls": ["C0206062"], "icd-9": ["506.4", "508.1", "516.3", "515", "714.81", "770.7"], "orphanet": ["182095"], "wikidata": ["Q1153419"]}
Mycetoma is a chronic subcutaneous infection caused by aerobic actinomycetic bacteria (actinomycetoma) or fungi eumycetoma.[1] While most cases of mycetoma occur in Sudan, Venezuela, Mexico, and India, its true prevalence and incidence are not well-known.[1][2] It appears most frequently in people living in rural areas, particularly farmers and shepherds.[3] It is listed by the World Health Organization (WHO) as a neglected tropical disease.[2] ## Contents * 1 Risk * 2 Pathogenesis * 3 Diagnosis * 4 Treatment * 5 Research * 6 References * 7 External links ## Risk[edit] Frequent exposure to penetrating wounds by thorns or splinters is a risk factor.[3] This risk can be reduced by disinfecting wounds and wearing shoes.[4] ## Pathogenesis[edit] Mycetoma is caused by common saprotrophs found in the soil and on thorny shrubs in semi-desert climates.[4] The most common causative agents are: * Madurella mycetomatis (fungus) * Nocardia brasiliensis (bacteria) * Actinomadure madura (bacteria) * Streptomyces somaliensis (bacteria) * Actinomadura pelletieri (bacteria)[2] Infection is caused as a result of localized skin trauma, such as stepping on a needle or wood splinter, or through a pre-existing wound.[4] The first visible symptom of mycetoma is a typically painless swelling beneath the skin; over several years, this will grow to a nodule (lump).[3] Affected people will experience massive swelling and hardening of the area, in addition to skin rupture and the formation of sinus tracts that discharge pus and grains filled with organisms.[3] In many instances, the underlying bone is affected.[5][4] Some people with mycetoma will not experience pain or discomfort, while others will report itching and/or pain.[3] ## Diagnosis[edit] There are currently no rapid diagnostic tools for mycetoma.[2] Mycetoma is diagnosed through microscopic examination of the grains in the nodule and by analysis of cultures.[4] Since the bacterial form and the fungal form of mycetoma infection of the foot share similar clinical and radiological features, diagnosis can be a challenge.[1] Magnetic resonance imaging is a very valuable diagnostic tool. However, its results should be closely correlated with the clinical, laboratory and pathological findings.[5][6] ## Treatment[edit] While treatment will vary depending on the cause of the condition, it may include antibiotics or antifungal medication.[3] Actinomycetoma, the bacterial form, can be cured with antibiotics.[1] Eumycetoma, the fungal form, is treated with antifungals.[6] Surgery in the form of bone resection may be necessary in late presenting cases or to enhance the effects of medical treatment.[5] In the more extensive cases amputation is another surgical treatment option.[7][4] For both forms, extended treatment is necessary.[1] In cats, mycetoma can be treated with complete surgical removal. Antifungal drugs are rarely effective.[8] ## Research[edit] For a list of trials that are related to mycetoma, go to this ClinicalTrials.gov link: https://www.clinicaltrials.gov/ct2/results?cond=%22Mycetoma%22 ## References[edit] 1. ^ a b c d e Welsh O, Al-Abdely HM, Salinas-Carmona MC, Fahal AH (October 2014). "Mycetoma medical therapy". PLOS Neglected Tropical Diseases. 8 (10): e3218. doi:10.1371/journal.pntd.0003218. PMC 4199551. PMID 25330342. 2. ^ a b c d van de Sande WW, Maghoub El S, Fahal AH, Goodfellow M, Welsh O, Zijlstra E (March 2014). "The mycetoma knowledge gap: identification of research priorities". PLOS Neglected Tropical Diseases. 8 (3): e2667. doi:10.1371/journal.pntd.0002667. PMC 3967943. PMID 24675533. 3. ^ a b c d e f "Mycetoma". Genetic and Rare Diseases Information Center (GARD). National Institutes of Health. Retrieved 2018-04-17. 4. ^ a b c d e f RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Mycetoma". www.orpha.net. Retrieved 2018-04-17. 5. ^ a b c El-Sobky, TA; Haleem, JF; Samir, S (2015). "Eumycetoma Osteomyelitis of the Calcaneus in a Child: A Radiologic-Pathologic Correlation following Total Calcanectomy". Case Reports in Pathology. 2015: 129020. doi:10.1155/2015/129020. PMC 4592886. PMID 26483983. 6. ^ a b Karrakchou, B; Boubnane, I; Senouci, K; Hassam, B (10 January 2020). "Madurella mycetomatis infection of the foot: a case report of a neglected tropical disease in a non-endemic region". BMC Dermatology. 20 (1): 1. doi:10.1186/s12895-019-0097-1. PMC 6953183. PMID 31918687. 7. ^ Efared, Boubacar; Tahiri, Layla; Boubacar, Marou Soumana; Atsam-Ebang, Gabrielle; Hammas, Nawal; Hinde, El Fatemi; Chbani, Laila (December 2017). "Mycetoma in a non-endemic area: a diagnostic challenge". BMC Clinical Pathology. 17 (1): 1. doi:10.1186/s12907-017-0040-5. ISSN 1472-6890. PMC 5288886. PMID 28167862. 8. ^ Eldredge, Debra M.; Carlson, Delbert G.; Carlson, Liisa D.; Giffin, James M. (2008). Cat Owner's Home Veterinary Handbook. Howell Book House. p. 160. ## External links[edit] * DermNet NZ: an online resource about skin diseases from the New Zealand Dermatological Society Incorporated. * Orphanet: a reference portal from Europe that provides information on rare diseases and orphan drugs. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mycetoma	c0024449	26,617	wikipedia	https://en.wikipedia.org/wiki/Mycetoma	2021-01-18T19:05:50	{"mesh": ["D008271"], "umls": ["C0024449"], "icd-10": ["B47"], "orphanet": ["2583"], "wikidata": ["Q16877704"]}
Congenital diaphragmatic hernia Other namesCDH Morgagni hernia seen on a chest radiograph. SpecialtyMedical genetics, pediatrics Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm. The most common type of CDH is a Bochdalek hernia; other types include Morgagni hernia, diaphragm eventration and central tendon defects of the diaphragm. Malformation of the diaphragm allows the abdominal organs to push into the chest cavity, hindering proper lung formation.[citation needed] CDH is a life-threatening pathology in infants and a major cause of death due to two complications: pulmonary hypoplasia and pulmonary hypertension.[1] Experts disagree on the relative importance of these two conditions, with some focusing on hypoplasia, others on hypertension.[2] Newborns with CDH often have severe respiratory distress which can be life-threatening unless treated appropriately. ## Contents * 1 Classification * 1.1 Bochdalek hernia * 1.2 Morgagni hernia * 1.3 Diaphragm eventration * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 See also * 7 References * 8 External links ## Classification[edit] ### Bochdalek hernia[edit] Main article: Bochdalek hernia The Bochdalek hernia, also known as a postero-lateral diaphragmatic hernia, is the most common manifestation of CDH, accounting for more than 95% of cases. In this instance the diaphragm abnormality is characterized by a hole in the postero-lateral corner of the diaphragm which allows passage of the abdominal viscera into the chest cavity. The majority of Bochdalek hernias (80–85%) occur on the left side of the diaphragm, a large proportion of the remaining cases occur on the right side. To date, it carries a high mortality and is an active area of clinical research.[citation needed] ### Morgagni hernia[edit] CT of the chest demonstrates a Morgagni hernia (red arrow) This rare anterior defect of the diaphragm is variably referred to as a Morgagni, retrosternal, or parasternal hernia. Accounting for approximately 2% of all CDH cases, it is characterized by herniation through the foramina of Morgagni which are located immediately adjacent and posterior to the xiphoid process of the sternum.[3] ### Diaphragm eventration[edit] The diagnosis of congenital diaphragmatic eventration is used when there is abnormal displacement (i.e. elevation) of part or all of an otherwise intact diaphragm into the chest cavity. This rare type of CDH occurs because in the region of eventration the diaphragm is thinner, allowing the abdominal viscera to protrude upwards.[citation needed] ## Pathophysiology[edit] It involves three major defects:[citation needed] * A failure of the diaphragm to completely close during development * Herniation of the abdominal contents into the chest * Pulmonary hypoplasia ## Diagnosis[edit] Congenital diaphragmatic hernia: coronal obstetric ultrasound (head to right of image, thorax centre, abdomen left) shows the stomach and heart both within the thorax. This condition can often be diagnosed before birth and fetal intervention can sometimes help, depending on the severity of the condition.[4] Infants born with diaphragmatic hernia experience respiratory failure due to both pulmonary hypertension and pulmonary hypoplasia. The first condition is a restriction of blood flow through the lungs thought to be caused by defects in the lung. Pulmonary hypoplasia or decreased lung volume is directly related to the abdominal organs presence in the chest cavity which causes the lungs to be severely undersized, especially on the side of the hernia.[citation needed] Survival rates for infants with this condition vary, but have generally been increasing through advances in neonatal medicine. Work has been done to correlate survival rates to ultrasound measurements of the lung volume as compared to the baby's head circumference. This figure known as the lung to head ratio (LHR). Still, LHR remains an inconsistent measure of survival. Outcomes of CDH are largely dependent on the severity of the defect and the appropriate timing of treatment. A small percentage of cases go unrecognized into adulthood.[5] ## Treatment[edit] The first step in management is orogastric tube placement and securing the airway (intubation). Ideally, the baby will never take a breath, to avoid air going into the intestines and compressing the lungs and heart. The baby will then be immediately placed on a ventilator. Extracorporeal membrane oxygenation (ECMO) has been used as part of the treatment strategy at some hospitals.[6][7] ECMO acts as a heart-lung bypass. Diaphragm eventration is typically repaired thoracoscopically, by a technique called plication of the diaphragm.[8] Plication basically involves a folding of the eventrated diaphragm which is then sutured in order to “take up the slack” of the excess diaphragm tissue.[citation needed] ## Prognosis[edit] Congenital diaphragmatic hernia has a mortality rate of 40–62%,[9] with outcomes being more favorable in the absence of other congenital abnormalities. Individual rates vary greatly dependent upon multiple factors: size of hernia, organs involved, additional birth defects, and/or genetic problems, amount of lung growth, age and size at birth, type of treatments, timing of treatments, complications (such as infections) and lack of lung function.[citation needed] ## See also[edit] * CHERUBS * Diaphragmatic rupture ## References[edit] 1. ^ Gaxiola A, Varon J, Valladolid G (April 2009). "Congenital diaphragmatic hernia: an overview of the etiology and current management". Acta Paediatrica. 98 (4): 621–7. doi:10.1111/j.1651-2227.2008.01212.x. PMID 19154527. 2. ^ Migliazza L, Bellan C, Alberti D, Auriemma A, Burgio G, Locatelli G, Colombo A (September 2007). "Retrospective study of 111 cases of congenital diaphragmatic hernia treated with early high-frequency oscillatory ventilation and presurgical stabilization". Journal of Pediatric Surgery. 42 (9): 1526–32. doi:10.1016/j.jpedsurg.2007.04.015. PMID 17848243. 3. ^ Arráez-Aybar LA, González-Gómez CC, Torres-García AJ (2009). "Morgagni-Larrey parasternal diaphragmatic hernia in the adult". Rev Esp Enferm Dig. 101 (5): 357–66. doi:10.4321/S1130-01082009000500009. PMID 19527083. 4. ^ "Deadly hernia corrected in womb – Surgeons have developed an operation to repair a potentially fatal abnormality in babies before they are born". BBC news. 2004-07-26. Retrieved 2006-07-14. – report of new operation, pioneered at London's King's College Hospital which reduced death rates in the most at risk by 50% 5. ^ Swain F, Klaus A, Achem S, Hinder R (2001). "Congenital Diaphragmatic Hernia in Adults". Surgical Innovation. 8 (4): 246–255. doi:10.1177/155335060100800404. 6. ^ Tiruvoipati R, Vinogradova Y, Faulkner G, Sosnowski AW, Firmin RK, Peek GJ (2007). "Predictors of outcome in patients with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation". J. Pediatr. Surg. 42 (8): 1345–50. doi:10.1016/j.jpedsurg.2007.03.031. PMID 17706494. 7. ^ Logan JW, Rice HE, Goldberg RN, Cotten CM (2007). "Congenital diaphragmatic hernia: a systematic review and summary of best-evidence practice strategies". Journal of Perinatology. 27 (9): 535–49. doi:10.1038/sj.jp.7211794. PMID 17637787. 8. ^ Becmeur F, Talon I, Schaarschmidt K, et al. (2005). "Thoracoscopic diaphragmatic eventration repair in children: about 10 cases". J. Pediatr. Surg. 40 (11): 1712–5. doi:10.1016/j.jpedsurg.2005.07.008. PMID 16291157. 9. ^ Pediatric Congenital Diaphragmatic Hernia at eMedicine ## External links[edit] Classification D * ICD-10: Q79.0 * ICD-9-CM: 756.6 * OMIM: 142340 222400 * MeSH: D006548 * DiseasesDB: 32489 External resources * MedlinePlus: 001135 * eMedicine: ped/2603 * Patient UK: Congenital diaphragmatic hernia * GeneReviews: Congenital Diaphragmatic Hernia * Orphanet: 2140 Wikimedia Commons has media related to Congenital diaphragmatic hernia. * v * t * e Congenital diaphragm and abdominal wall defects, abdominopelvic cavity Thoracic diaphragm * Hernia * Congenital diaphragmatic hernia * Bochdalek hernia Abdominal wall * Omphalocele * Gastroschisis * Prune belly syndrome * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Congenital diaphragmatic hernia	c1857284	26,618	wikipedia	https://en.wikipedia.org/wiki/Congenital_diaphragmatic_hernia	2021-01-18T18:43:02	{"gard": ["1481"], "mesh": ["D065630", "C565629"], "umls": ["C1857284"], "orphanet": ["2140"], "wikidata": ["Q2163245"]}
## Description Regular exposure to continuous noise or an exposure to a single acoustic overstimulation can lead to noise-induced hearing loss (NIHL). Millions of people worldwide are exposed daily to harmful levels of noise, making NIHL a likely widespread occupational health hazard. NIHL is a complex disease resulting from an interaction between genetic and environmental factors and is highly variable between individuals (Konings et al., 2009). Mapping ### Associations Pending Confirmation In a study of 218 Swedish noise-exposed male workers, Van Laer et al. (2006) identified the asp85-to-asn variant in the KCNE1 gene (rs1805128; 176261.0005) on chromosome 21q22 as the possible cause of susceptibility to NIHL (p = 0.023). However, the authors suggested that further studies were necessary before KCNE1 D85N could be designated as a causative SNP. Heat-shock proteins (HSPs) are induced after exposure to severe noise. When first induced by exposure to moderate sound levels, they can protect the ear from damage from excessive noise exposure. Konings et al. (2009) analyzed SNPs in 3 HSP genes in 206 Swedish and 238 Polish DNA samples of individuals exposed to occupational noise. In the Swedish sample set, there was a significant association between all 3 SNPs and hearing loss: rs1043618 in the HSPA1A gene (140550) on chromosome 6p21 (p = 0.037, odds ratio of 0.61 for the GG genotype), rs1061581 in the HSPA2 gene (140560) on chromosome 14q24 (p = 0.033, odds ratio of 1.63 for the GG genotype), and rs2227956 in the HSPA1L gene (140559) on chromosome 6p21 (p = 0.010, odds ratio of 2.09 for the TT genotype). In the Polish sample set, only rs2227956 in the HSPA1L gene showed a significant genotype effect (p = 0.048, odds ratio of 1.75 for the TT genotype). The findings suggested an association between variation in HSP genes with NIHL. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HEARING LOSS, NOISE-INDUCED, SUSCEPTIBILITY TO	c2751629	26,619	omim	https://www.omim.org/entry/613035	2019-09-22T15:59:56	{"omim": ["613035"]}
## Mapping Prior to the report by Copeman et al. (1995), 2 chromosomal regions had been shown by replicated, independent studies to be both associated with, and linked to, the autoimmune disease type I diabetes mellitus (insulin-dependent diabetes mellitus, or IDDM): the HLA region on 6p21 (IDDM1; 222100), and the insulin gene region on chromosome 11p15 (IDDM2; 125852). IDDM4 (600319) is the symbol for a possible susceptibility locus on 11q13, and IDDM5 (600320) for a susceptibility locus possibly on 6q24-q27. IDDM3 (600318) is the symbol for a susceptibility locus that has been linked to 15q26. One of the 18 chromosome regions for which linkage to diabetes was detected previously (Davies et al., 1994) was on chromosome 2q near marker locus D2S326. Part of this region is homologous to the region of mouse chromosome 1 that contains the murine type I diabetes susceptibility gene Idd5. To investigate the role of human chromosome 2 in type I diabetes, Copeman et al. (1995) analyzed linkage and linkage disequilibrium at 21 microsatellite marker loci, using 348 affected sib-pair families and 107 simplex families. The microsatellite D2S152 was found to be linked to, and associated with, disease in families from 3 different populations. Thus, the evidence localized a new diabetes susceptibility gene, symbolized IDDM7, to a region within 2 cM of D2S152. This is a region of 2q that shows conserved synteny with the region of mouse chromosome 1 containing the Idd5 gene. Luo et al. (1995) confirmed linkage evidence for IDDM7 on 2q. The NEUROD gene (601724) maps within the same region of chromosome 2q as IDDM7. Tamimi et al. (1996) found that NEUROD is identical to the hamster beta-2 gene, which was cloned as a regulator of insulin (176730) gene expression. Since NEUROD may regulate insulin gene expression, it is a potential candidate gene for IDDM7. The pancreatic beta cell-specific homolog of glucose-6-phosphatase (613742), namely, islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP; 608058), has emerged as a major target of cell-mediated autoimmunity in diabetes (Hutton and Eisenbarth, 2003). The human IGRP gene (Martin et al., 2001) and IDDM7 map to the same region of chromosome 2 (Pociot and McDermott, 2002). Martinez et al. (2008) genotyped 311 Spanish patients with type 1 diabetes and 723 ethnically matched controls for a SNP in the STAT4 gene (rs7574865) on chromosome 2q32 and found an association with type 1 diabetes (p = 0.008; odds ratio 1.36). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DIABETES MELLITUS, INSULIN-DEPENDENT, 7	c1838259	26,620	omim	https://www.omim.org/entry/600321	2019-09-22T16:16:18	{"mesh": ["C563957"], "omim": ["600321"], "synonyms": ["Alternative titles", "INSULIN-DEPENDENT DIABETES MELLITUS 7"]}
For a phenotypic description and a discussion of genetic heterogeneity of malignant hyperthermia, see MHS1 (145600). Mapping In a single German pedigree with classic malignant hyperthermia, Sudbrak et al. (1995) found a maximum multipoint lod score of 3.22 for linkage to markers defining a 1-cM interval on 3q13.1. The malignant hyperthermia phenotype was determined by the in vitro contracture test (IVCT) performed on a sample of freshly obtained muscle. Muscle \- Masseter or generalized muscle contracture \- Rhabdomyolysis Misc \- Triggered by certain anesthetics, such as halothane or succinylcholine \- Rapid body temperature rise Inheritance \- Autosomal dominant (3q13.1) Metabolic \- Malignant hyperthermia \- Acidosis \- Hypoxia ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 4	c0024591	26,621	omim	https://www.omim.org/entry/600467	2019-09-22T16:16:09	{"mesh": ["D008305"], "omim": ["600467"], "orphanet": ["423"], "synonyms": ["Alternative titles", "MHS4"], "genereviews": ["NBK1146"]}
A rare genetic vascular disease characterized by early onset (between in utero to infancy) of extensive calcification and stenosis of the large and medium sized arteries. Presentation is typically with respiratory distress, congestive heart failure and systemic hypertension. ## Epidemiology Approximately 300 cases have been reported worldwide in the medical literature. The prevalence is unknown; however, based on carrier frequency of the recognized pathogenic variants, the frequency of 1/566,000 has been suggested. ## Clinical description Disease onset is either early (in utero to within the first week of life) or late (median age three months). Early-onset disease presents variably with fetal distress, heart failure, polyhydramnios, hypertension, respiratory distress, hydrops fetalis, edema, visceral effusions, cyanosis, cardiomegaly, and ascites. Presentation of late-onset disease variably includes respiratory distress, cyanosis, feeding difficulties, congestive heart failure, vomiting, irritability, failure to thrive, fever, hypertension, and edema. Additional findings can include extravascular calcifications (particularly periarticular), typical skin and retinal manifestations of pseudoxanthoma elasticum, hearing loss, and development of rickets after infancy. Pathologically, the condition is characterized by deposition of calcium along the internal elastic membrane of arteries, accompanied by fibrous thickening of the intima, which causes luminal narrowing. ## Etiology Causal mutations have been identified in the genes ENPP1 (chromosome 6q23.2) and ABCC6 (chromosome 16p13.11) respectively encoding ectonucleotide pyrophosphatase/ phosphodiesterase 1 and multidrug resistance-associated protein 6, a transmembrane protein belonging to the family of ATP-binding cassette (ABC) transport proteins. Pathological variants lead to aberrant tissue mineralization, and the subsequent luminal narrowing invariably leads to coronary arterial occlusion and myocardial ischemia or stenoses of different arteries leading to end-organ damage. ENPP1 mutations also cause autosomal recessive hypophosphatemic rickets, which is associated with longer survival. ## Diagnostic methods Diagnosis of is made by the combination of clinical, imaging or histopathological findings, together with genetic results. The preferred imaging modality to assess calcifications extension is whole-body computed tomography combined with CT angiography. ## Differential diagnosis Differential diagnosis includes endocardial fibroelastosis, myocardititis, storage disorders, infarction, anomalous insertion of the coronary arteries, cardiac anomalies, metastatic calcification due to renal disease, hypervitaminosis D, infections, and non-immune fetal hydrops, Takayasu arteriitis. ## Antenatal diagnosis Antenatal diagnosis has been reported, with findings of arterial calcifications, hydrops, abnormal cardiac contractility, and hyperechoic kidneys. The diagnosis is essential for genetic counseling, and for screening of siblings at risk for developing the disease. ## Genetic counseling The pattern of inheritance is autosomal recessive. The sibling-recurrence risk is 25%. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if the pathogenic variants in the family are known. ## Management and treatment Use of bisphosphonates appears to significantly increase survival. Aspirin therapy is warranted in those with severe coronary stenosis who are at increased risk for coronary thrombosis. Anti-hypertensive therapy is warranted for hypertension. Treatment of hypophosphatemic rickets involves calcitriol and oral phosphate supplements. It seems prudent to avoid the use of warfarin if possible. Where endotracheal intubation is required, lateral cervical spine x-ray is recommended to evaluate for cervical spine fusion, and thereby avoid secondary complications. ## Prognosis Prognosis is poor; most infants die from myocardial infarction within the first year of life, with the greatest number of deaths occurring within the first six months. Nevertheless, long-term survival into the second and third decade has been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Generalized arterial calcification of infancy	c1859727	26,622	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=51608	2021-01-23T18:54:51	{"gard": ["8380"], "mesh": ["C537440"], "omim": ["208000", "614473"], "umls": ["C0264955", "C1859727"], "icd-10": ["Q28.8"], "synonyms": ["Idiopathic infantile arterial calcification", "Idiopathic obliterative arteriopathy", "Infantile arteriosclerosis", "Occlusive infantile arteriopathy"]}
## Clinical Features Jakkula et al. (2005) identified a novel form of multiple epiphyseal dysplasia in 2 patients characterized by strikingly small ossification centers ('mini-epiphyses'), which resulted in severe dysplasia of the proximal femoral heads. The spine was normal in both patients. Inheritance One of the patients reported by Jakkula et al. (2005) was the child of consanguineous parents, suggesting autosomal recessive inheritance. Molecular Genetics ### Exclusion Studies In the patients reported by Jakkula et al. (2005), no mutations were identified in the COMP (600310), DTDST (606718), or MATN3 (602109) genes. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature (<3rd percentile) SKELETAL \- Generalized joint laxity Spine \- Increased lumbar lordosis \- Normal vertebrae Pelvis \- Abnormal proximal femur with miniepiphyses \- Wide, deformed femoral neck Limbs \- Genua vara \- Small, secondary ossification centers (miniepiphyses) \- Small, irregular patellae ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	EPIPHYSEAL DYSPLASIA, MULTIPLE, WITH MINIEPIPHYSES	c1836307	26,623	omim	https://www.omim.org/entry/609325	2019-09-22T16:06:16	{"mesh": ["C563735"], "omim": ["609325"], "orphanet": ["166032"]}
Kobayashi et al. (1995) described a family in which a grandmother, 1 of her sons, and 1 of her grandsons through an unaffected daughter showed various manifestations of infundibulopelvic dysgenesis. The proband was a 4-year-old male with multicystic kidney on the right and a normal left kidney which was hypertrophied. A maternal uncle had presented at age 18 years with abdominal pain and microscopic hematuria. Renal ultrasonography showed 'cysts' in both kidneys. A diagnosis of adult polycystic kidney disease was made. Renal dialysis and subsequently kidney transplantation was performed. The correct diagnosis in this individual was bilateral infundibulopelvic stenosis. (Another brother of the proband's mother had suffered a ruptured cerebral aneurysm at age 24 years but had a normal renal ultrasound at age 35 years.) The maternal grandmother of the proband had shown, on intravenous urogram at age 36 years, a normal left kidney and widening of the infundibula with blunting of the calyces of the right kidney without evidence of obstruction. INHERITANCE \- Autosomal dominant ABDOMEN Gastrointestinal \- Abdominal pain GENITOURINARY Kidneys \- Infundibulopelvic dysgenesis \- Cystic kidneys LABORATORY ABNORMALITIES \- Hematuria ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	INFUNDIBULOPELVIC DYSGENESIS	c1832949	26,624	omim	https://www.omim.org/entry/600989	2019-09-22T16:15:31	{"mesh": ["C535528"], "omim": ["600989"]}
A number sign (#) is used with this entry because of evidence that X-linked epilepsy with variable learning disabilities and behavior disorders is caused by mutation in the SYN1 gene (313440) on chromosome Xp11. Clinical Features Garcia et al. (2004) reported a novel X-linked recessive syndrome in a 4-generation kindred in which some males of normal intelligence had epilepsy and others had various combinations of epilepsy, learning difficulties, macrocephaly, and aggressive behavior. One patient had a diagnosis of autism. The natural history of seizures was variable, occurring only during childhood in some, developing at age 27 in 1, and appearing only in association with specific stimuli in others. Fassio et al. (2011) reported a large French Canadian family in which 7 males had X-linked partial epilepsy with variable learning disabilities and behavioral disorders. Two patients also had autism. Inheritance The transmission pattern of partial seizures and learning disabilities in the family reported by Fassio et al. (2011) was consistent with X-linked recessive inheritance. Mapping By genetic linkage analysis, Garcia et al. (2004) mapped an X-linked epilepsy disorder in a 4-generation kindred to Xp11.3-q12, between the MAOB gene and marker DXS1275. A maximum 2-point lod score of 4.06 at theta = 0.0 was found with DXS1039. Molecular Genetics By direct sequencing of the SYN1 gene, Garcia et al. (2004) identified a trp356-to-ter mutation (W356X; 313440.0001) in all 10 affected males and in obligate carrier females. In 6 males from a large French Canadian family with X-linked partial epilepsy and learning disabilities, Fassio et al. (2011) identified a truncating mutation in the SYN1 gene (Q555X; 313440.0002). Investigation of this gene in several large cohorts of patients with epilepsy and/or autism identified 3 additional variants in the SYN1 gene (see, e.g., 313440.0003 and 313440.0004) in 1% of patients with autism spectrum disorders and 3.5% of patients with epilepsy. Three of the 4 mutations affected the D-domain, which is important for protein function. When expressed in Syn1-null neurons, these 3 mutant proteins were unable to rescue impairments in the size and trafficking of synaptic vesicle pools. The findings demonstrated that SYN1 is a predisposing gene to epilepsy and autism spectrum disorders and strengthened the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both disorders. INHERITANCE \- X-linked recessive \- X-linked dominant HEAD & NECK Head \- Macrocephaly (in some patients) NEUROLOGIC Central Nervous System \- Seizures \- Partial epilepsy Behavioral Psychiatric Manifestations \- Autism spectrum disorders \- Learning difficulties \- Aggressive behavior MISCELLANEOUS \- Affected patients have various combinations of the main clinical features \- Carrier females may be affected MOLECULAR BASIS \- Caused by mutation in the synapsin-1 gene (SYN1, 313440.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	EPILEPSY, X-LINKED, WITH VARIABLE LEARNING DISABILITIES AND BEHAVIOR DISORDERS	c1845343	26,625	omim	https://www.omim.org/entry/300491	2019-09-22T16:20:21	{"mesh": ["C564505"], "omim": ["300491"], "orphanet": ["85294"]}
A rare bacterial infectious disease characterized by severe coughing paroxysms with inspiratory whooping and posttussive vomiting, caused by infection with Bordetella pertussis. After a variable incubation time, the clinical course progresses through a catarrhal stage with sore throat, nasal congestion, rhinorrhea, and mild progressive dry cough, a paroxysmal stage with the typical paroxysmal coughing, and finally convalescence. Disease duration is usually 2-3 months, often with milder presentation in adolescents and adults than in infants and children. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Whooping cough	c0043167	26,626	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1489	2021-01-23T17:13:07	{"gard": ["8692"], "mesh": ["D014917"], "umls": ["C0043167", "C0043168"], "icd-10": ["A37.0", "A37.1", "A37.8", "A37.9"], "synonyms": ["Pertussis"]}
For a phenotypic description and a discussion of genetic heterogeneity of specific language impairment, see SLI1 (602081). Description Vernes et al. (2008) identified polymorphisms and a haplotype within the CNTNAP2 gene (604569) on chromosome 7q35-q36 implicated in the endophenotype of nonsense word repetition as a marker of specific language impairment. Mapping Because mutations in the FOXP2 (605317) gene cause a monogenic speech and language disorder (602081), O'Brien et al. (2003) used samples from children with specific language impairment and their family members to study linkage and association of SLI to markers within and around the FOXP2 gene and samples from 96 probands with SLI were directly sequenced for the mutation in exon 14 of the FOXP2 gene (R553H). No mutations were found in exon 14 of FOXP2, but strong association was found to a marker within the cystic fibrosis gene, CFTR (602421), and another marker on 7q31, D7S3052, both adjacent to FOXP2, suggesting that genetic factors for regulation of common language impairment reside in the vicinity of FOXP2. Using chromatin immunoprecipitation, Vernes et al. (2008) performed genomic screening for regions bound by FOXP2 and discovered a FOXP2-bound fragment located within intron 1 of CNTNAP2. They then tested for association between single-nucleotide polymorphisms (SNPs) in CNTNAP2 in 184 families enrolled in the Specific Language Impairment Consortium (SLI Consortium (2002, 2004)), recruited from 4 sites in the United Kingdom. Using the Children's Test of Nonword Repetition, which had been established as a robust endophenotype of specific language impairment, Vernes et al. (2008) found that the SNP rs17236239 generated a P value of 5.0 x 10(-5) for association with this phenotype. After an 'overly conservative' Bonferroni correction the P value remained significant at P = 0.002. This SNP is located in the region between exons 13 and 15 of CNTNAP2, polymorphisms in which had shown an association with age at first spoken word in a study of children with autism (see 612100). Vernes et al. (2008) constructed multimarker haplotypes with the 9 SNPs implicated in the ability to repeat nonsense words and observed 11 different combinations. Four haplotypes represented 94% of subjects. The most common haplotype, ht1, negatively influenced the ability to repeat nonsense words; it was more often present in family members with poor scores (a frequency of 40% among those with scores of greater than 2 standard deviations below the population mean) than in those with good scores (a frequency of 29% among those with scores of greater than 0.5 standard deviations above the population mean). Family-based quantitative association analyses of the 9-marker haplotypes and scores on nonsense-word repetition yielded a P value of 6.0 x 10(-4) for ht1, again indicating that this haplotype is significantly associated with impaired language performance. Vernes et al. (2008) also showed that CNTNAP2 is a direct target of FOXP2. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SPECIFIC LANGUAGE IMPAIRMENT 4	c2675874	26,627	omim	https://www.omim.org/entry/612514	2019-09-22T16:01:24	{"mesh": ["C567288"], "omim": ["612514"]}
Ongoing COVID-19 viral pandemic in Africa COVID-19 pandemic in Africa Map of the 2020 COVID-19 pandemic in Africa as of 24 December 2020 100,000+ Confirmed cases 10,000–99,999 Confirmed cases 1,000–9,999 Confirmed cases 100–999 Confirmed cases 10–99 Confirmed cases DiseaseCOVID-19 Virus strainSARS-CoV-2 LocationAfrica First outbreakWuhan, Hubei, China Index caseCairo, Egypt Arrival date14 February 2020 (11 months and 4 days ago) Confirmed cases3,251,235 (as of 16 January)[1] Active cases511,357 (as of 16 January)[1] Recovered2,661,465 (as of 16 January)[1] Deaths 78,413 (as of 16 January)[1] Territories 57[1] Part of a series on the COVID-19 pandemic * SARS-CoV-2 (virus) * COVID-19 (disease) Timeline 2019 2020 * January * February * responses * March * responses * April * responses * May * responses * June * responses * July * responses * August * responses * September * responses * October * responses * November * responses * December * responses 2021 * January * responses Locations * By continent * Africa * Antarctica * Asia * Europe * North America * Oceania * South America * By conveyance * Cruise ships * Naval ships * Cases * Deaths International response * United Nations * National responses * India * New Zealand * Philippines * Russia * Sweden * U.K. * U.S. * European Union response * Protests * U.S. * Lockdowns * Evacuations * Travel restrictions * International aid * Face masks Medical response * Disease testing * COVID-19 vaccines * * Gamaleya * Moderna * Oxford–AstraZeneca * Pfizer-BioNTech * Sinopharm * Sinovac * Drug development * Drug repurposing * Variants of SARS-CoV-2 Impact * Socio-economic * Crime * Ireland * Death rates by country * Disability * Domestic violence * Economic * Canada * India * Ireland * U.K. * U.S. * Recession * Emergency evacuations * Environment * Fake treatments * Financial markets * Food security * Hospitals * Language * Long-term care * Migration * Misinformation * Military * Other health issues * Politics * Ireland * Pregnancy * Prisons * Religion * Catholic Church * Hajj * Science and technology * Social * Ireland * U.K. * U.S. * Strikes * Xenophobia and racism * Notable deaths * By industry * Arts and culture * Aviation * Cannabis * Cinema * films * Education * Ireland * United Kingdom * Event cancellations * Fashion * Food * Canada meat * U.S. meat * Journalism * Music * Performing arts * Retail * Sports * Ireland * Television * U.S. * Tourism * Video games COVID-19 Portal * v * t * e The COVID-19 pandemic was confirmed to have spread to Africa on 14 February 2020, with the first confirmed case announced in Egypt.[2][3] The first confirmed case in sub-Saharan Africa was announced in Nigeria at the end of February.[4] Within three months, the virus had spread throughout the continent, as Lesotho, the last African sovereign state to have remained free of the virus, reported a case on 13 May.[5][6] By 26 May, it appeared that most African countries were experiencing community transmission, although testing capacity was limited.[7] Most of the identified imported cases arrived from Europe and the United States rather than from China where the virus originated.[8] It is believed that there is widespread under-reporting in many African countries with less developed healthcare systems.[9] Experts have worried about COVID-19 spreading to Africa, because many of the healthcare systems on the continent are inadequate, having problems such as lack of equipment, lack of funding, insufficient training of healthcare workers, and inefficient data transmission. It was feared that the pandemic could be difficult to keep under control in Africa, and could cause huge economic problems if it spread widely.[10][8] As of 18 April 2020, the supply of ventilators was low in much of Africa: 41 countries had only 2,000 ventilators between them, and ten countries had no ventilators at all. Even basic supplies like soap and water are subject to shortages in parts of the continent.[11] Matshidiso Moeti of the World Health Organization said that hand washing and physical distancing could be challenging in some places in Africa. Lockdown may not be possible, and challenges may be exacerbated by the prevalence of diseases such as malaria, AIDS, tuberculosis, and cholera.[10] Advisers say that a strategy based on testing could allow African countries to minimise lockdowns that inflict enormous hardship on those who depend on income earned per day to be able to feed themselves and their families. Despite this, there is an increased risk of famine in several African nations.[12] Even in the best scenario, the United Nations says 74 million test kits and 30,000 ventilators will be needed by the continent's 1.3 billion people in 2020.[13] The World Health Organization helped many countries on the continent set up laboratories for COVID-19 testing.[10] Matshidiso Moeti of the WHO said: "We need to test, trace, isolate and treat".[14] Many preventive measures have been implemented in different countries in Africa, including travel restrictions, flight cancellations, event cancellations,[15] school closures, and border closures.[16] Experts say that experience battling Ebola helped some countries prepare for COVID-19.[10][15][17] By the second week of June, Africa had surpassed 200,000 cases in total.[18] The number of confirmed new cases is accelerating, with the continent having taken 98 days to record the first 100,000 cases, and 18 days for the second 100,000. The pace of acceleration has continued, with cases passing both the 300,000 and 400,000 marks on 6 July. On 8 July 2020, cases had exceeded half a million. Half of the 500,000 cases reported in the continent are from South Africa or Egypt.[19] Ten countries account for 80% of the reported cases.[19] The World Health Organization voiced alarm at the spread in Africa on 20 July 2020, stating that South Africa's surging numbers could be a precursor for further outbreaks across the continent.[20] The number exceeded a million by 6 August, with five countries making up over 75% of the total confirmed cases: South Africa, Egypt, Morocco, Ethiopia and Nigeria.[21] The true case numbers are believed to be significantly higher than the confirmed counts, due to low testing rates in many African countries.[22] The mortality rates of African countries, however, are relatively low compared to Europe due to the younger age of their populations.[21] On 21 August the Africa Centres for Disease Control and Prevention (Africa CDC) expressed "cautious optimism" as the number of new cases took a downturn, while warning against complacency.[23] In some countries, the number of cases began to rise. On 29 October, John Nkengasong, the head of Africa CDC, said: "The time to prepare for a second wave is truly now."[24] The pandemic has had a serious economic impact in African countries, damaging the continent's growing middle class and threatening to increase the rates of poverty and extreme poverty.[25] There are also lessons such as early travel bans, well-organised contact tracers, etc. that need training, as they are critical for containment of the pandemic.[26] As of September 9, Morocco and Ethiopia have increasing cases in the continent. On November 12, the Africa Centres for Disease Control and Prevention (CDC) and the World Health Organization (WHO) reported that confirmed cases have been increasing since July, particularly in North Africa (Tunisia, Morocco and Libya). The curve has flattened in South Africa and Kenya, while Senegal and Equatorial Guinea have seen a steady decline.[27] New strains of the virus were found in December 2020 in South Africa and Nigeria, in addition to the Variant of Concern 202012/01 reported in the United Kingdom in September.[28] The African Union has secured close to 300 million COVID-19 vaccine doses in the largest such agreement yet for Africa, it was announced on January 13, 2021. This is independent of the global Access to COVID-19 Tools Accelerator (COVAX) effort aimed at distributing COVID-19 vaccines to lower-income countries.[29] ## Contents * 1 Statistics * 1.1 Total confirmed cases by country * 2 Confirmed cases by country and territory * 2.1 Algeria * 2.2 Angola * 2.3 Benin * 2.4 Botswana * 2.5 Burkina Faso * 2.6 Burundi * 2.7 Cameroon * 2.8 Cape Verde * 2.9 Central African Republic * 2.10 Chad * 2.11 Comoros * 2.12 Democratic Republic of the Congo * 2.13 Republic of the Congo * 2.14 Djibouti * 2.15 Egypt * 2.16 Equatorial Guinea * 2.17 Eritrea * 2.18 Eswatini * 2.19 Ethiopia * 2.20 Territories of France * 2.20.1 Mayotte * 2.20.2 Réunion * 2.21 Gabon * 2.22 The Gambia * 2.23 Ghana * 2.24 Guinea * 2.25 Guinea-Bissau * 2.26 Territories of Italy * 2.27 Ivory Coast * 2.28 Kenya * 2.29 Lesotho * 2.30 Liberia * 2.31 Libya * 2.32 Madagascar * 2.33 Malawi * 2.34 Mali * 2.35 Mauritania * 2.36 Mauritius * 2.37 Morocco * 2.38 Mozambique * 2.39 Namibia * 2.40 Niger * 2.41 Nigeria * 2.41.1 Lock-down measures * 2.41.2 High-profile individuals with COVID-19 * 2.42 Territories of Portugal * 2.42.1 Madeira * 2.43 Rwanda * 2.44 São Tomé and Príncipe * 2.45 Senegal * 2.46 Seychelles * 2.47 Sierra Leone * 2.48 Somalia * 2.48.1 Somaliland * 2.49 South Africa * 2.50 South Sudan * 2.51 Territories of Spain * 2.51.1 Canary Islands * 2.51.2 Ceuta * 2.51.3 Melilla * 2.52 Sudan * 2.53 Tanzania * 2.54 Togo * 2.55 Tunisia * 2.56 Uganda * 2.57 Western Sahara * 2.58 Zambia * 2.59 Zimbabwe * 3 Suspected cases * 3.1 Saint Helena, Ascension and Tristan da Cunha * 4 Responses * 5 Prevention in other territories * 5.1 British Indian Ocean Territory * 6 See also * 7 Notes * 8 External links * 9 References ## Statistics[edit] ### Total confirmed cases by country[edit] Daily cases for the most infected African countries: Total confirmed cases since Day 1 of Outbreak The number of active cases by country.[30][31][32][33][34][35][36][37][38][39][40][41] ## Confirmed cases by country and territory[edit] Summary table of confirmed cases in Africa (as of 16 January 2021) Country Confirmed cases Active confirmed cases Recoveries Deaths Ref. South Africa 1,325,659 204,830 1,083,978 36,851 [1] Morocco 458,865 17,017 433,937 7,911 [1] Tunisia 177,231 43,761 127,854 5,616 [1] Egypt 155,507 24,689 122,291 8,527 [1] Ethiopia 130,772 12,698 116,045 2,029 [1] Nigeria 108,943 22,156 85,367 1,420 [1] Libya 108,017 21,298 85,068 1,651 [1] Algeria 103,611 30,407 70,373 2,831 [1] Kenya 99,082 14,030 83,324 1,728 [1] Ghana 56,981 1,404 55,236 341 [1] Uganda 38,085 24,698 13,083 304 [1] Zambia 36,074 10,431 25,106 537 [1] Namibia 30,198 3,450 26,468 280 [1] Cameroon 28,010 694 26,861 455 [1] Zimbabwe 26,881 10,326 15,872 683 [1] Mozambique 25,862 7,113 18,515 234 [1] Sudan 25,730 8,914 15,240 1,576 [1] Ivory Coast 24,856 1,611 23,104 141 [1] Senegal 22,738 3,177 19,052 509 [1] Democratic Republic of the Congo 20,692 5,259 14,804 630 [1] Angola 18,765 2,109 16,225 431 [1] Madagascar 18,001 287 17,447 267 [1] Botswana 17,365 3,775 13,519 71 [1] Mauritania 15,999 1,167 14,431 401 [1] Guinea 14,098 697 13,320 81 [1] Cape Verde 12,901 648 12,134 119 [1] Eswatini 12,736 4,300 8,076 360 [1] Malawi 11,785 5,493 5,992 300 [1] Rwanda 10,850 3,517 7,193 140 [1] Gabon 9,899 175 9,658 66 [1] Réunion 9,446 348 9,053 45 [1] Burkina Faso 9,000 1,797 7,102 101 [1] Mali 7,823 1,984 5,531 308 [1] Republic of the Congo 7,709 1,749 5,846 114 [1] Mayotte 6,611 3,589 2,964 58 [1] Lesotho 6,371 4,643 1,635 93 [1] Djibouti 5,903 26 5,816 61 [1] Equatorial Guinea 5,356 81 5,189 86 [1] Central African Republic 4,973 25 4,885 63 [1] Somalia 4,744 948 3,666 130 [1] Togo 4,272 436 3,763 73 [1] Niger 4,132 1,043 2,951 138 [1] Gambia 3,897 81 3,689 127 [1] South Sudan 3,670 426 3,181 63 [1] Benin 3,413 122 3,245 46 [1] Sierra Leone 2,970 868 2,025 77 [1] Chad 2,855 637 2,107 111 [1] Guinea-Bissau 2,478 33 2,400 45 [1] Liberia 1,887 102 1,701 84 [1] Eritrea 1,877 798 1,073 6 [1] Comoros 1,577 467 1,069 41 [1] Burundi 1,185 410 773 2 [1] São Tomé and Príncipe 1,130 120 993 17 [1] Seychelles 696 169 525 2 [1] Mauritius 547 21 516 10 [1] Tanzania 509 305 183 21 [1] Western Sahara 10 1 8 1 [1] Totals 3,251,235 511,357 2,661,465 78,413 ### Algeria[edit] Main article: COVID-19 pandemic in Algeria The first case in the country was confirmed on 25 February. On the morning of 2 March, Algeria confirmed two new cases of the coronavirus, a woman and her daughter.[42] On 3 March, Algeria reported another two new cases of the coronavirus. The two new cases were from the same family, a father and daughter, and were living in France.[43] On 4 March, the Ministry of Health recorded 4 new confirmed cases of the coronavirus, all from the same family, bringing the total number to 12 confirmed cases.[44][43] According to WHO prediction modelling estimates Algeria faces a relatively high risk for a spread of COVID-19 if containment measures such as contact tracing are not prioritized.[14] ### Angola[edit] Main article: COVID-19 pandemic in Angola On 21 March, the first two cases in the country were confirmed.[45] Effective 20 March, all Angolan borders have been closed for 15 days.[46] As of 18 April 2020, there was a total of 19 confirmed cases, 2 deaths and 6 recovered cases.[47] ### Benin[edit] Main article: COVID-19 pandemic in Benin On 16 March, the first case in the country was confirmed.[48] As of 18 April 2020, there was a total of 35 confirmed cases, 1 death and 18 recovered cases.[49] ### Botswana[edit] Main article: COVID-19 pandemic in Botswana On 30 March, the first three cases in Botswana were confirmed.[50] ### Burkina Faso[edit] Main article: COVID-19 pandemic in Burkina Faso On 9 March, the first two cases in the country were reported in Burkina Faso.[51] On 13 March, the third case was also confirmed, a person who had had direct contact with the first two cases.[52] As of March 14, 2020, a total of 7 cases have been confirmed in the country. 5 of the new confirmed cases had had direct contact with the first two cases. 1 is an English national employed at a gold mine in the country who vacationed in Liverpool and came back on March 10, transiting through Vancouver and Paris.[53] As of 18 April 2020 there was a total of 557 confirmed cases, 35 deaths and 294 recovered cases.[54] ### Burundi[edit] Main article: COVID-19 pandemic in Burundi On 31 March, the first two cases in the country were confirmed.[55] The President of Burundi, Pierre Nkurunziza, died during the pandemic; officially he died of a heart attack, but it is speculated that he may have died from COVID-19 with members of his family also reported to have contracted the disease.[56] ### Cameroon[edit] Main article: COVID-19 pandemic in Cameroon On 6 March the first case was confirmed in Cameroon.[57] According to WHO prediction modelling estimates Cameroon faces a relatively high risk for a spread of COVID-19 if containment measures such as contact tracing are not prioritized.[14] Cameroon reported 27,336 total cases, 1,993 active cases, and 451 total deaths on 13 January 2021. This is 17 deaths per one million population.[58] ### Cape Verde[edit] Main article: COVID-19 pandemic in Cape Verde On 20 March, the first case in the country was confirmed, a 62 year old from the United Kingdom.[59][60] ### Central African Republic[edit] Main article: COVID-19 pandemic in the Central African Republic On 14 March, the first case in the country was confirmed.[61] ### Chad[edit] Main article: COVID-19 pandemic in Chad On 19 March, the first case in the country was confirmed.[62] ### Comoros[edit] Main article: COVID-19 pandemic in the Comoros As a preventive measure, arriving travellers were to be quarantined for 14 days upon arrival. In order to prevent the spread of the virus, the government has cancelled all incoming flights and banned large gatherings.[63] On 15 April 2020, a person arriving in Mayotte from the Comoros tested positive for COVID-19.[64] On 30 April, the first case was confirmed in the Comoros.[65] On 4 May, the first death was announced.[66] 54 people had been tested, and 53 contacts had been traced.[67] ### Democratic Republic of the Congo[edit] In the DRC, the MONUSCO Force Intervention Brigade has taken measures to boost hygiene to help slow the spread of the virus. Main article: COVID-19 pandemic in the Democratic Republic of the Congo On 10 March, the first case was reported in the country.[68] ### Republic of the Congo[edit] Main article: COVID-19 pandemic in the Republic of the Congo The country's first case was announced on 14 March, a 50-year-old man who had returned to the Republic of the Congo from Paris, France.[69] ### Djibouti[edit] Main article: COVID-19 pandemic in Djibouti On 18 March, the first case in Djibouti was confirmed.[1] ### Egypt[edit] Main article: COVID-19 pandemic in Egypt Egypt's health ministry announced the first case in the country at Cairo International Airport involving a Chinese national on 14 February.[70][71] On 6 March, the Egyptian Health Ministry and WHO confirmed 12 new cases of coronavirus infection.[72] The infected persons were among the Egyptian staff aboard the Nile cruise ship MS River Anuket, which was travelling from Aswan to Luxor. On 7 March 2020, health authorities announced that 45 people on board had tested positive, and that the ship had been placed in quarantine at a dock in Luxor.[73] Egypt reported 152,719 total cases, 24,045 active cases, and 8,362 total deaths on 13 January 2021. This is 81 deaths per one million population.[58] In January 2021, the relative of a 62-year-old Covid-19 patient who died in Egypt’s El Husseineya Central Hospital due to the shortage of oxygen posted a video of the hospital on Facebook. The video that showed the medical staff in distress, resuscitating a man with the help of a manual ventilator went viral on the Internet, inviting global attention concerning the government’s shortcomings in handling the pandemic. Four patients had died that day and the official statement issued by the hospital concluded that the patients suffered “complications”, denying “any connection” of their deaths with the shortage of oxygen. An investigation led by the New York Times found otherwise in which statements given during interviews by both, the patients’ relatives, as well as the medical staff, confirmed the cause of death as deprivation of oxygen.[74] ### Equatorial Guinea[edit] Main article: COVID-19 pandemic in Equatorial Guinea On 14 March, the first case in the country was confirmed.[75] ### Eritrea[edit] Main article: COVID-19 pandemic in Eritrea On 20 March, the first case in Eritrea was confirmed.[76] ### Eswatini[edit] Main article: COVID-19 pandemic in Eswatini On 14 March, the first case in the country was confirmed.[77] ### Ethiopia[edit] Main article: COVID-19 pandemic in Ethiopia The country's first case was announced on 13 March, a Japanese man who had arrived in the country on 4 March from Burkina Faso.[78] Three additional cases of the virus were reported on March 15. The three individuals had close contact with the person who was reported to be infected by the virus on 13 March . Since then eight more confirmed cases were reported by the health ministry to the public, bringing the total to twelve. Among the infected individuals an elderly Ethiopian in her eighties has been said to have some escalating symptoms while other eight have been on a recovery route and showing fewer symptoms of the disease. On March 27, another statement was issued by the health minister stating that four additional cases have been identified while one case being in the Adama city of the Oromia regional state and the other three being in Addis Ababa. Moreover, three more cases were confirmed by the Health Minister on March 31, 2020. Similarly, the following day another three cases were added. On the previous press release the government authorities had noted that one case was retested and confirmed negative and two of the confirmed cases have been sent to their country (Japan). In aggregate, twenty-nine cases are confirmed so far as of 1 April 2020. On April 3, 2020 due to further tests made, six additional cases have been discovered moving up the tally to thirty-five. Measures are being taken by the government and the community together strictly to suppress the further spreading of this deadly virus. Among the six cases identified there were individuals with no traveling history recently, that has made it alarming to the public.[1] On 4 April, three additional cases of the virus were reported. All of the cases were from Addis Ababa. Two of the patients, a 29-year-old and a 34-year-old male Ethiopians, had travel histories to Dubai on different dates. The third case is of a 35-year-old female Ethiopian who had arrived from Sweden on 3 April.[31] On the same date, one additional recovery was reported, increasing the total number of recoveries to 4. On 5 April, five more positive cases of the virus were reported. Three of them are Ethiopians. The other two are Libyan and Eritrean nationals.[33]. There are 43 total cases as of April 5, 2020. On April 7 more individuals detected and totally 54. Among 200+ tests conducted on April 8, 2020, one additional case has been added to the tally making it 55. With the current situation indicating the spread of the virus Ethiopia has declared a state of emergency. As of April 17, the total cases reported were 92 of which three patients have died and fifteen have recovered. Ethiopia has tested more than 5,000 citizens since the first case was reported.[citation needed] Tilahun Woldemichael, an Ethiopian Orthodox monk who is said to be 114 years old, was released from the hospital on 25 June after being treated with oxygen and dexamethasone for coronavirus. Ethiopia has 5,200 confirmed cases.[79] Ethiopia reported 129,455 total cases, 12,882 active cases, and 2,006 total deaths on 13 January 2021. This equals 17 deaths per one million population.[58] ### Territories of France[edit] Further information: COVID-19 pandemic in France § Overseas territories #### Mayotte[edit] Main article: COVID-19 pandemic in Mayotte The first case of the COVID-19 pandemic in the French overseas department and region of Mayotte was reported on 13 March 2020.[80] On 31 March the first person died of COVID-19.[81] #### Réunion[edit] Main article: COVID-19 pandemic in Réunion The COVID-19 pandemic was confirmed to have reached the French overseas department and region of Réunion on 11 March 2020.[82] ### Gabon[edit] Main article: COVID-19 pandemic in Gabon The country's first case was announced on 12 March, a 27 year old Gabonese man who returned to Gabon from France 4 days prior to confirmation of the coronavirus.[83] ### The Gambia[edit] Main article: COVID-19 pandemic in the Gambia The Gambia reported its first case of coronavirus from a 20-year-old woman who returned from the United Kingdom on 17 March.[84] ### Ghana[edit] Main article: COVID-19 pandemic in Ghana Ghana reported its first two cases on 12 March. The two cases were people who came back to the country from Norway and Turkey, with the contact tracing process beginning.[85][86] On 11 March, the Minister of Finance, Ken Ofori-Atta, made the cedi equivalent of $100 million available to enhance Ghana's coronavirus preparedness and response plan. The Ghana Health Service reported on August 6 that over 2,000 health workers had been infected and six have died.[87] Ghana reported 56,981 total cases, 1,404 active cases, and 341 total deaths on 13 January 2021. This is 11 deaths per one million population.[58] ### Guinea[edit] Main article: COVID-19 pandemic in Guinea On 13 March, Guinea confirmed its first case, an employee of the European Union delegation in Guinea.[88] A mosque was forcefully opened by faithful in Dubréka in May.[89] ### Guinea-Bissau[edit] Main article: COVID-19 pandemic in Guinea-Bissau On 25 March, Guinea-Bissau confirmed its first two COVID-19 cases, a Congolese U.N. employee and an Indian citizen.[90] ### Territories of Italy[edit] Further information: COVID-19 pandemic in Italy ### Ivory Coast[edit] Main article: COVID-19 pandemic in Ivory Coast On 11 March, the first case in the country was confirmed.[91] Ivory Coast reported 24,369 total cases, 1,373 active cases, and 140 total deaths on 13 January 2021. This is five deaths per one million population.[58] ### Kenya[edit] Main article: COVID-19 pandemic in Kenya On 12 March 2020, the first case was confirmed in Kenya by President Uhuru Muigai Kenyatta.[92] On 13 March, the first case in Kenya was confirmed, a woman who came from the US via London.[93] On 15 March 2020, further restrictions were ordered, including closing of schools, banning of all social gatherings including religious gatherings, and banning of all flights banned effective 25 March.[citation needed] Kenya reported 98,555 total cases, 15,168 active cases, and 1,720 total deaths on 13 January 2021. This is 32 deaths per one million population.[58] ### Lesotho[edit] Main article: COVID-19 pandemic in Lesotho On 13 May, the first case in Lesotho was confirmed.[6][94] The country recorded its first death on 9 July.[95] ### Liberia[edit] Main article: COVID-19 pandemic in Liberia On 16 March, the first case in Liberia was confirmed.[96][97] Churches and mosques were allowed to reopen as of May 17.[89] ### Libya[edit] Main article: COVID-19 pandemic in Libya On 17 March, in order to prevent the spread of the virus, the UN-recognised Government of National Accord closed the country's borders, suspended flights for three weeks and banned foreign nationals from entering the country; schools, cafes, mosques and public gatherings have also been closed.[98] On 24 March, the first case in Libya was confirmed.[99] Libya reported 106,670 total cases, 21,730 active cases, and 1,629 total deaths on 13 January 2021. This is 235 deaths per one million population.[58] ### Madagascar[edit] Main article: COVID-19 pandemic in Madagascar On 20 March, the three first cases were confirmed in Madagascar. All were women.[100] Madagascar had a total 225 confirmed coronavirus cases, 98 recoveries, and no deaths as of 8 May 2020.[101] Madagascar's plant-based "cure" called COVID-19 Organics is being pushed despite warnings from the World Health Organization that its efficacy is unproven. Tanzania, Equatorial Guinea, Central African Republic, the Republic of Congo, the Democratic Republic of Congo, Liberia, and Guinea Bissau have all already received thousands of doses of COVID-19 Organics free of charge.[101] ### Malawi[edit] Main article: COVID-19 pandemic in Malawi On 2 April, the three first cases were confirmed in Malawi.[102] In April 2020 the High Court of Malawi issued an order temporarily blocking the lockdown measures imposed by the government of Malawi.[103][104] In August 2020 the government of Malawi instituted additional measures including mandatory mask wearing in public areas to stem the spread of the virus [105] ### Mali[edit] Main article: COVID-19 pandemic in Mali On 25 March, the two first cases were confirmed in Mali.[106] ### Mauritania[edit] Main article: COVID-19 pandemic in Mauritania On 13 March, the first case in the country was confirmed.[107] By 18 April 2020, there had been 7 confirmed cases in the country, 6 of whom recovered, and one died making Mauritania at the time the only affected country in Africa and in the world to become free of COVID-19.[108] A further case was confirmed on the 29th of April.[109] ### Mauritius[edit] Main article: COVID-19 pandemic in Mauritius Since the first three cases of COVID-19 were confirmed on 18 March 2020, the Mauritian authorities have been conducting 'Contact tracing': people who have been in contact with infected patients have been placed under quarantine, including doctors, nurses and police officers.[110][111][112] No cases have been reported in Rodrigues, Agaléga and St. Brandon.[113][114] On 1 May 2020, the Prime Minister announced that the ongoing COVID-19 curfew will be extended to 1 June 2020 and schools will remain closed till 1 August 2020. As of 15 May 2020, more businesses were allowed to operate, namely bakeries, hardware stores and fish markets and the opening hours of supermarkets will be extended to 20 00 hrs. Banks will continue to operate under strict hygiene protocol.[115][116][117] On 13 May 2020, the government elaborated strict guidelines and regulations that both commuters and public transport operators will have to adhere to. These guidelines and regulations were in line with Government's strategy to ensure that there is no risk of the propagation of COVID-19 as the country gradually prepares itself to allow certain economic activities to resume as from 15 May 2020.[118][119] On 15 May 2020, Mauritius embarks on the first phase of easing its lockdown protocol.[120] ### Morocco[edit] Main article: COVID-19 pandemic in Morocco On 2 March, Morocco recorded its first case of COVID-19. It was a Moroccan national residing in Italy who had returned to Morocco.[121] ### Mozambique[edit] Main article: COVID-19 pandemic in Mozambique The country's first case was announced on 22 March, a 75-year-old man who returned from the United Kingdom.[122] Mozambique reported 23,726 total cases, 5,239 active cases, and 205 total deaths on 13 January 2021. This is 39 deaths per one million population.[58] ### Namibia[edit] Main article: COVID-19 pandemic in Namibia On 14 March, the first two cases in the country were confirmed.[123] In a first reaction by government air travel to and from Qatar, Ethiopia and Germany was suspended for 30 days. All public and private schools were closed for a month, and gatherings were restricted to fewer than 50 people. This included celebrations for the 30th anniversary of Namibian independence that took place on 21 March.[124] Libraries, museums, and art galleries were also closed.[125] On 17 March, President Hage Geingob declared a state of emergency as a legal basis to restrict fundamental rights, e.g. to freely move and assemble, guaranteed by the Constitution.[126] By 25 March 2020 the total number of cases reached seven, of which one is thought to be a local transmission. A 21-day lockdown of the regions of Erongo and Khomas was announced for 27 March with inter-regional travel forbidden, excluding the commuter towns of Okahandja and Rehoboth. Parliament sessions were suspended for the same period, and bars and markets were closed.[127] On 14 April this lockdown was extended for another 2 weeks ending 4 May, now encompassing all regions, although the stay-at-home order was already enforced countrywide.[128] After 5 April 2020, when 16 cases were identified, no new infections occurred until the end of April. Government subsequently eased the restrictions as from 5 May.[129] The country recorded its first death on 10 July.[130] Namibia reported 29,183 total cases, 3,504 active cases, and 271 total deaths on 13 January 2021 in Libya\2021. This is 106 deaths per one million population.[58] ### Niger[edit] Main article: COVID-19 pandemic in Niger Niger confirmed its first case on 19 March 2020.[131] ### Nigeria[edit] Main article: COVID-19 pandemic in Nigeria On 27 February, Nigeria confirmed its first case, the first case of coronavirus in sub-Saharan Africa.[132][133] An Italian citizen who works in Nigeria had returned on 25 February from Milan, Italy through the Murtala Muhammed International Airport, fell ill on 26 February and was transferred to Lagos State Biosecurity Facilities for isolation and testing.[134][135][136] The test was confirmed positive by the Virology Laboratory of the Lagos University Teaching Hospital, part of the Nigeria Centre for Disease Control.[137] He was transferred to the Infectious Disease Hospital in Yaba, Lagos.[136] On 28 February, the Lagos State Commissioner for Health announced that the Italian man had travelled on Turkish Airlines with a brief transit at Istanbul.[138] As of 6 March, a total of 219 primary and secondary contacts of the index case had been identified and were being actively monitored.[139] #### Lock-down measures[edit] The Federal government of Nigeria has instructed institutions to shut down for 30 days as a lockdown measure to limit the spread of COVID-19. It has also banned public gatherings. The state government of Lagos has asked schools to close and banned public gatherings of more than 50 people, particularly religious gatherings.[140][141] There was no order from government to shutdown markets and club halls.[citation needed] Several schools in Nigeria have shut down, following the directives of the federal government at Abuja. This led the Management of one of the most populated schools in Nigeria, the Federal Polytechnic Nekede, Owerri to declare an emergency holidays a precaution against COVID-19, stating that the emergency holiday will last for 30 days. The institution had already fixed the dates for the 2019/2020 academic year examinations.[142] There is widespread tension and anxiety in cities across Nigeria as students return to their various homes for fear of contracting COVID-19.[citation needed] #### High-profile individuals with COVID-19[edit] Reports have shown that some high-profile individuals in Nigeria have tested positive for coronavirus. The Nigeria's high profiled persons that have tested positive for COVID-19 are: Buhari's chief of staff, Abba Kyari, Governor of Bauchi state Bala Mohammed, Governor of Oyo state, Seyi Makinde, Governor of Kaduna state Nasir el-Rufai, Governor of Ekiti state, Kayode Fayemi, Governor of Delta state Ifeanyi Okowa, Governor of Ebonyi state, Dave Umahi, Governor of Ondo state Rotimi Akeredolu. In June, 2020 the former governor of Oyo state Abiola Ajimobi also announced he tested positive, he later succumbed to the disease on 25 June 2020. On the 19th of July, 2020, the Minister of Foreign Affairs, Geoffrey Onyeama, a member of the presidential task force on COVID-19, also announced he had tested positive.[143][144][145] As Muhammadu Buhari's closest staff, Nigerians suspected that the president would have the virus as his chief of staff tested positive. Meanwhile, Nigeria Centre for Disease Control (NCDC) reported that president Buhari tested negative after the test was carried out on him.[146] In Nigeria, there were fears everywhere that the chief of staff, Abba Kyari who had tested positive for the coronavirus may have transmitted it to more people including governor Yahaya Bello of Kogi, minister of information, Lai Mohammed, special assistant to the president on media, Garba Shehu; minister of special duties, George Akume; minister of state for FCT, Ramatu Tijani; Geoffrey Onyeama, and other dignitaries and visitors at the prayers held on March 17, 2020, for the deceased mother of the Kogi State governor.[144] The governor of Kogi State, Yahaya Bello was tested for coronavirus, but tested negative. Others from the list who met with Abba Kyari also tested negative, for the disease.[147] ### Territories of Portugal[edit] Further information: COVID-19 pandemic in Portugal #### Madeira[edit] Main article: COVID-19 pandemic in Madeira ### Rwanda[edit] Main article: COVID-19 pandemic in Rwanda On 14 March, the first case in the country was confirmed.[148] In an interview with the Financial Times on 20 April, President Paul Kagame said he believes it will cost $100 billion (£80 billion) and an entire generation for Africa to recuperate from the pandemic.[149] ### São Tomé and Príncipe[edit] Main article: COVID-19 pandemic in São Tomé and Príncipe On 6 April, the first four cases in the country were confirmed. The first death was recorded on 30 April.[150] ### Senegal[edit] Main article: COVID-19 pandemic in Senegal On 2 March, the first case in the country was confirmed.[151] Mosques are allowed to reopen for Ramadan despite 2,000 confirmed cases of the virus.[89] Police used tear gas to break up a demonstration in Ngor, Dakar after President Macky Sall declared a 9 p.m.–5 a.m. curfew in Dakar and Thiès Region on January 13, 2021.[152] Senegal reported 21,883 total cases, 2,773 active cases, and 489 total deaths on 13 January 2021. This is 29 deaths per one million population.[58] ### Seychelles[edit] Main article: COVID-19 pandemic in Seychelles Seychelles reported its first two cases on 14 March. The two cases were people who were in contact with someone in Italy who tested positive.[153] As of January 2021, there has been one death in Seychelles [154] ### Sierra Leone[edit] Main article: COVID-19 pandemic in Sierra Leone On 16 March, the government banned public officials from travelling abroad, and urged citizens to avoid foreign travel.[155][156] Quarantine measures were put in place for all visitors arriving from countries with more than 50 cases.[155] Public gatherings of more than 100 people were also banned.[155] On 24 March, President Julius Maada Bio announced a year-long 'state of emergency' in order to deal with a potential outbreak.[157] The president of Sierra Leone confirmed the country's first case of coronavirus on 31 March, a person who traveled from France on 16 March and had been in isolation since.[158] ### Somalia[edit] Main article: COVID-19 pandemic in Somalia On 16 March, the first case in Somalia was confirmed.[97] Somalia's Health Ministry reported that this was a Somali citizen returning home from China.[159] #### Somaliland[edit] Main article: COVID-19 pandemic in Somaliland On 31 March, the first two cases in Somaliland were confirmed. The two cases were a Somaliland citizen and a Chinese national.[160] ### South Africa[edit] Main article: COVID-19 pandemic in South Africa On 5 March 2020 the first confirmed case was announced, a South African returning from Italy.[161] On 15 March, President Cyril Ramaphosa declared a national state of disaster[97] and a national lockdown started on 26 March.[162] From 1 May, a gradual and phased easing of the lockdown restrictions started, lowering the national alert level to 4,[163] to be lowered to level 3 from 1 June.[164] According to WHO prediction modelling estimates South Africa faces a relatively high risk for a spread of COVID-19 if containment measures, including contact tracing, are not prioritized.[14] The country is projected to have 40000 to 48000 COVID-19 deaths by November 2020.[165] South Africa's infections doubled to 250,000 in the first two weeks of July as public hospitals report shortages of medical oxygen. Treatment of coronavirus patients in South Africa is seen the most unequal in the world.[166] So far South Africa has been able to conduct almost 6.4 million tests with South Africa Surpassing 1 million people testing positive on 27 December 2020 [167] On 18 December, Minister of Health Zweli Mkhize said scientists had discovered a new variant of virus, called 501.V2 Variant.[168] It has so far suspected to have spread to the UK ### South Sudan[edit] Main article: COVID-19 pandemic in South Sudan On 5 April, the first case was confirmed.[169] Two cases COVID-19 were confirmed on 13 May in a crowded civilian protection camp in Juba. The camp houses 30,000 people.[170] ### Territories of Spain[edit] Further information: COVID-19 pandemic in Spain #### Canary Islands[edit] Main article: COVID-19 pandemic in the Canary Islands The COVID-19 pandemic was confirmed to have reached the Canary Islands on 31 January 2020.[171][172] #### Ceuta[edit] Main article: COVID-19 pandemic in Ceuta The COVID-19 pandemic was confirmed to have reached in Ceuta on 13 March 2020.[173] #### Melilla[edit] Main article: COVID-19 pandemic in Melilla The COVID-19 pandemic was confirmed to have reached in Melilla on 10 March 2020.[173] ### Sudan[edit] Main article: COVID-19 pandemic in Sudan The country's first case was announced on 13 March, a man who had died in Khartoum the previous day. He had visited the United Arab Emirates in the first week of March.[174] By 29 May, a surge of reported deaths in North Darfur raised fears of a serious outbreak in the region, although testing remains poor.[175] Sudan reported 25,730 total cases, 8,914 active cases, and 1,576 total deaths on 13 January 2021. This is 36 deaths per one million population.[58] ### Tanzania[edit] Main article: COVID-19 pandemic in Tanzania On 16 March, the first case was confirmed.[97] Tanzanian authorities stopped reporting case numbers in May.[176][177] ### Togo[edit] Main article: COVID-19 pandemic in Togo On 6 March, the first case in the country was confirmed.[178] ### Tunisia[edit] Main article: COVID-19 pandemic in Tunisia On 2 March, the first case in the country was confirmed.[179][180] 168,568 total cases, 40,378 active cases, and 5,415 total deaths were reported on January 13, 2021 in Tunisia. This is a death rate of 456 per one million population.[58] ### Uganda[edit] Main article: COVID-19 pandemic in Uganda On 20 March, the first case in Uganda was confirmed.[76][181] The first confirmed death was on 24 July.[182] Uganda reported 38,085 total cases, 24,698 active cases, and 304 total deaths on 13 January 2021. This is seven deaths per one million population.[58] ### Western Sahara[edit] Main articles: COVID-19 pandemic in Western Sahara and Sahrawi Arab Democratic Republic On 4 April, the first four cases in Moroccan-controlled part of Western Sahara were confirmed.[183] Sahrawi Arab Democratic Republic reported its first cases on 25 July 2020.[184] ### Zambia[edit] Main article: COVID-19 pandemic in Zambia Zambia reported its first 2 cases of COVID-19 on 18 March. The patients were a couple that had travelled to France on holiday.[185] A third case was recorded on 22 March. The patient was a man who had travelled to Pakistan.[186] On March 25, President Edgar Lungu confirmed a total of 12 cases. He also announced measures which includes suspension of international flights Simon Mwansa Kapwepwe, Harry Mwaanga Nkumbula and Mfuwe International Airports and re-routing of all international flights to Kenneth Kaunda International Airport to facilitate screening of incoming passengers and mandatory quarantine where necessary, closure of all bars, nightclubs, casinos, cinemas and gyms and restriction of all public gatherings to 50 people or less.[187] By 17 March, the government had shut all educational institutions and put in place some restrictions on foreign travel.[188] On 19 August, the Vice President of Zambia, Inonge Wina tested positive for COVID-19.[189] Zambia reported 31,100 total cases, 9,023 active cases, and 509 total deaths on 13 January 2021. This is 27 deaths per one million population.[58] ### Zimbabwe[edit] Main article: COVID-19 pandemic in Zimbabwe Before there were any confirmed cases in the country, President Emmerson Mnangagwa had declared a national emergency, putting in place travel restrictions and banning large gatherings.[190][191] The country's defence minister Oppah Muchinguri caused controversy by stating the coronavirus could be a divine punishment on Western nations for imposing sanctions on Zimbabwe.[192] Its first case was reported on 21 March: it was a male resident of Victoria Falls who travelled from the United Kingdom via South Africa on 15 March.[193] Police report that 105,000 have been arrested for violating health measures between March and July, including 1,000 arrests for not wearing facemasks on July 18 and 19.[194] Zimbabwe reported 24,256 total cases, 10,009 active cases, and 589 total deaths on 13 January 2021. This is 39 deaths per one million population.[58] ## Suspected cases[edit] ### Saint Helena, Ascension and Tristan da Cunha[edit] On 16 March three people who arrived by air to Ascension Island showed symptoms of COVID-19.[195] However, on 23 March it was announced that they had tested negative on 22 March [196] On 17 March all travel by air to the Saint Helena island was banned, except for island citizens or residents and similar cases.[197] There were no known cases on Saint Helena at this time.[198] On 16 March as a precaution the Tristan da Cunha Island Council on Tristan da Cunha made the decision to ban visitors to the island to prevent the potential transmission of the disease to islanders.[199] ## Responses[edit] Further information: National responses to the COVID-19 pandemic in Africa Many preventive measures have been implemented in different countries in Africa, including travel restrictions, flight cancellations, event cancellations,[15] school closures, and border closures.[16] Other measures to contain and limit the spread of the virus has included curfews, lockdowns, and enforcing the wearing of face masks.[200] The Integrated Disease Surveillance Programme has been leveraged for surveillance and case-finding.[200] Molecular testing has been scaled up across the continent utilising existing disease surveillance programs such as those for HIV, drug-resistant tuberculosis and Lassa fever.[200] Pooled testing to expedite processing times has been pioneered in countries such as Ghana.[200][201] Key leadership has been provided at country and regional level by public health institutes such as the Nigeria Centre for Disease Control, the five regional Centres for Disease Control, and the Africa Centres for Disease Control and Prevention. The Africa Centres for Disease Control and Prevention has worked to support the response across the continent and distributed tests donated by the Jack Ma Foundation.[202] The Africa Centres for Disease Control and Prevention, World Health Organization and COVID-19 Africa Open Data Project[203] have collected and reported continent-wide data on the number of cases, recoveries and deaths. The COVID-19 Africa Open Data Project provides additional data on healthcare workers infected, health services, urgent needs and local laboratories.[204] Innovative uses of technology in health and other sectors such as drone delivery of test kits to isolated areas have been piloted.[200] Local businesses have financially supported response efforts and initiated the manufacture of masks and hand sanitizers.[200] There have been significant efforts to combat COVID-19 disinformation and provide accurate information to support the response to COVID-19.[200][205] Social influencers and celebrities have joined voices with public health experts urging people to practice social distancing.[200] The “Verified” social media initiative of the United Nations utilised “information volunteers” to help debunk false claims about vaccine trials and fake cures.[205] UNESCO #DontGoViral initiative crowdsourced culturally relevant, open-sourced information in local languages.[205] The Communications agency 35-North partnered with the COVID-19 Africa Open Data Project to combat misinformation through Telegaram and WhatsApp.[206] Africa Centres for Disease Control and Prevention director John Nkengasong warned on December 10 that Africa might not see vaccines until after the second quarter of 2021. Separately, Richard Mihigo of the World Health Organization (WHO) warned against inequality in access to COVID-19 vaccines.[207] ## Prevention in other territories[edit] ### British Indian Ocean Territory[edit] As of 5 May there have been no cases in the British territory. Access to the islands, already heavily restricted due to the presence of a military base on Diego Garcia, have been further curtailed, with licenses for visiting vessels suspended.[208] All people arriving into the territory are subject to a 14-day quarantine; social distancing measures have also been enacted.[209] ## See also[edit] * 1899–1923 cholera pandemic * 1918 Spanish flu pandemic * 2008 Zimbabwean cholera outbreak * 2009–2010 West African meningitis outbreak * 2012 yellow fever outbreak in Darfur, Sudan * 2013-16 Western African Ebola virus epidemic * 2014 & 2017 Madagascar plague outbreaks * 2016 Angola and DR Congo yellow fever outbreak * 2018 Kivu Ebola epidemic * 2019–2020 measles outbreak in the Democratic Republic of the Congo * Black Death * HIV/AIDS in Africa ## Notes[edit] ## External links[edit] * Africa Centres for Disease Control and Prevention (CDC) Dashboard on Covid-19 * COVID-19 Africa Open Data Project Dashboard * West African Health Organization COVID-19 Dashboard * WHO COVID-19 Dashboard ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl "Coronavirus update (live)". Retrieved 7 January 2020. 2. ^ "Beijing orders 14-day quarantine for all returnees". BBC News. 15 February 2020. Archived from the original on 14 February 2020. Retrieved 24 March 2020. 3. ^ "Egypt announces first Coronavirus infection". Egypt Today. Archived from the original on 15 February 2020. Retrieved 24 March 2020. 4. ^ "Nigeria confirms first coronavirus case". BBC News. 28 February 2020. Archived from the original on 2 March 2020. Retrieved 24 March 2020. 5. ^ "Remote Lesotho becomes last country in Africa to record COVID-19 case". Reuters. 13 May 2020. Archived from the original on 14 May 2020. Retrieved 13 May 2020. 6. ^ a b "Coronavirus live updates: Lesotho becomes last African nation to report a coronavirus case". Los Angeles Times. Archived from the original on 13 May 2020. Retrieved 13 May 2020. 7. ^ Akinwotu, Emmanuel (26 May 2020). "Experts sound alarm over lack of Covid-19 test kits in Africa". The Guardian. Archived from the original on 29 May 2020. Retrieved 29 May 2020. 8. ^ a b Maclean, Ruth (17 March 2020). "Africa Braces for Coronavirus, but Slowly". The New York Times. Archived from the original on 25 March 2020. Retrieved 25 March 2020. 9. ^ Jason Burke; Abdalle Ahmed Mumin (2 May 2020). "Somali medics report rapid rise in deaths as Covid-19 fears grow". The Guardian. Archived from the original on 19 May 2020. Retrieved 2 May 2020. 10. ^ a b c d "African Countries Respond Quickly To Spread Of COVID-19". NPR.org. Archived from the original on 26 March 2020. Retrieved 23 March 2020. 11. ^ Maclean, Ruth; Marks, Simon (18 April 2020). "10 African Countries Have No Ventilators. That's Only Part of the Problem". The New York Times. Archived from the original on 18 April 2020. Retrieved 20 April 2020. 12. ^ Picheta, Rob. "Coronavirus pandemic will cause global famines of 'biblical proportions,' UN warns". CNN. Retrieved 13 July 2020. 13. ^ Burke, Jason (26 April 2020). "'It's just beginning here': Africa turns to testing as pandemic grips the continent". The Observer. ISSN 0029-7712. Archived from the original on 26 April 2020. Retrieved 26 April 2020. 14. ^ a b c d "New WHO estimates: Up to 190 000 people could die of COVID-19 in Africa if not controlled". WHO \| Regional Office for Africa. 7 May 2020. Retrieved 9 May 2020. 15. ^ a b c "Here are the African countries with confirmed coronavirus cases". CNN. Archived from the original on 22 March 2020. Retrieved 24 March 2020. 16. ^ a b "UN Sees Africa Sliding Into Recession Without Debt-Service Help". Bloomberg.com. 24 March 2020. Archived from the original on 27 March 2020. Retrieved 25 March 2020. 17. ^ Moore, Jina (15 May 2020). "What African Nations Are Teaching the West About Fighting the Coronavirus". The New Yorker. Archived from the original on 21 May 2020. 18. ^ "Global report: WHO warns of accelerating Covid-19 infections in Africa". the Guardian. 12 June 2020. Archived from the original on 12 June 2020. Retrieved 12 June 2020. 19. ^ a b "Coronavirus: How fast is it spreading in Africa?". news.yahoo.com. Archived from the original on 7 July 2020. Retrieved 8 July 2020. 20. ^ "Covid-19: Situation in SA 'a warning' for the rest of the continent - WHO". News24. Retrieved 21 July 2020. 21. ^ a b Burke, Jason (6 August 2020). "Total confirmed coronavirus cases in Africa pass 1 million". The Guardian. 22. ^ "Africa reaches one million confirmed cases, although the true toll may be higher". The New York Times. 7 August 2020. Retrieved 14 August 2020. 23. ^ "Coronavirus in Africa: 'Signs of hope' as cases level off". news.yahoo.com. BBC. Retrieved 22 August 2020. 24. ^ McSweeney, Eoin (30 October 2020). "Africa must prepare for second COVID wave, disease control group says". CNN. Retrieved 30 October 2020. 25. ^ Dahir, Abdi Latif (29 June 2020). "Coronavirus Is Battering Africa's Growing Middle Class". The New York Times. Retrieved 14 August 2020. 26. ^ Etteh, Chinedu Casmir; Adoga, Moses P; Ogbaga, Chukwuma C (August 2020). "COVID-19 Response in Nigeria: Health System Preparedness and Lessons for Future Epidemics in Africa". Ethics, Medicine and Public Health: 100580. doi:10.1016/j.jemep.2020.100580. PMC 7440033. 27. ^ Mwai, Peter (12 November 2020). "Coronavirus: What's happening to the numbers in Africa?". BBC Reality Check ,BBC. Retrieved 19 November 2020. 28. ^ "Another new COVID strain found in Nigeria, says Africa CDC". aljazeera.com. Al Jazeera English. 24 December 2020. Retrieved 24 December 2020. 29. ^ "Africa secures 300 million COVID-19 vaccine doses in deal with manufacturers". Africanews. 13 January 2021. Retrieved 13 January 2021. 30. ^ "Active Cases in South Africa". Worldometers. 1 May 2020. Retrieved 1 May 2020. 31. ^ "Active Cases in Egypt". Worldometers. 1 May 2020. Retrieved 1 May 2020. 32. ^ "Active Cases in Morocco". Worldometers. 1 May 2020. Retrieved 1 May 2020. 33. ^ "Active Cases in Algeria". Worldometers. 1 May 2020. Retrieved 1 May 2020. 34. ^ "Active Cases in Ghana". Worldometers. 1 May 2020. Retrieved 1 May 2020. 35. ^ "Active Cases in Cameroon". Worldometers. 1 May 2020. Retrieved 1 May 2020. 36. ^ "Active Cases in Nigeria". Worldometers. 1 May 2020. Retrieved 1 May 2020. 37. ^ "Active Cases in Guinea". Worldometers. 1 May 2020. Retrieved 1 May 2020. 38. ^ "Active Cases in Djibouti". Worldometers. 1 May 2020. Retrieved 1 May 2020. 39. ^ "Active Cases in Cote d'Ivoire". Worldometers. 1 May 2020. Retrieved 1 May 2020. 40. ^ "Active Cases in Tunisia". Worldometers. 1 May 2020. Retrieved 1 May 2020. 41. ^ "Mauritius Statistics". Besafemoris. 1 May 2020. Retrieved 1 May 2020. 42. ^ "Algeria confirms two more coronavirus cases". 2 March 2020. Archived from the original on 2 March 2020. Retrieved 2 March 2020. 43. ^ a b "Algeria reports two new coronavirus cases, bringing the total to five". Reuters. 2 March 2020. Archived from the original on 30 May 2020. Retrieved 2 March 2020. 44. ^ "ارتفاع عدد الإصابات المؤكدة بفيروس كورونا إلى 12 حالة". النهار أونلاين (in Arabic). 4 March 2020. Archived from the original on 5 March 2020. Retrieved 4 March 2020. 45. ^ "Angola registered its first coronavirus case". Informanté. 19 March 2020. Archived from the original on 2 April 2020. Retrieved 20 March 2020. 46. ^ Oliveira, Yokani (19 March 2020). "Angola closes borders for 15 days". The Namibian. Archived from the original on 2 April 2020. Retrieved 20 March 2020. 47. ^ "Coronavirus: African Union Member States (52) reporting COVID-19 cases, 18th April 2020". CNBC Africa. 18 April 2020. Archived from the original on 2 May 2020. Retrieved 27 May 2020. 48. ^ "Somalia, Liberia, Benin and Tanzania confirm first coronavirus cases". news.trust.org. 16 March 2020. Archived from the original on 23 March 2020. Retrieved 27 April 2020. 49. ^ "Coronavirus - Africa: African Union Member States reporting COVID-19 cases, 18 April 2020 6pm EAT". CNBC Africa. 18 April 2020. Archived from the original on 2 May 2020. Retrieved 27 May 2020. 50. ^ "Botswana registers first Covid-19 cases as three people test positive". iol.co.za. 31 March 2020. Archived from the original on 31 March 2020. Retrieved 31 March 2020. 51. ^ "Burkina Faso Confirms First Cases of Coronavirus". 9 March 2020. Retrieved 9 March 2020. 52. ^ "Coronavirus: un troisième cas confirmé au Burkina Faso". VOA (in French). Archived from the original on 19 March 2020. Retrieved 15 March 2020. 53. ^ B24, Rédaction (14 March 2020). "Coronavirus (COVID-19) : 7 cas confirmés au Burkina". L'Actualité du Burkina Faso 24h/24 (in French). Archived from the original on 16 March 2020. Retrieved 14 March 2020. 54. ^ "Coronavirus - Africa: African Union Member States reporting COVID-19 cases, 18 April 2020 6pm EAT". CNBC Africa. 18 April 2020. Archived from the original on 2 May 2020. Retrieved 28 May 2020. 55. ^ "East African nation of Burundi confirms first coronavirus cases - Health Ministry". Reuters. 31 March 2020. Archived from the original on 4 April 2020. Retrieved 31 March 2020. 56. ^ Pilling, David; Schipani, Andres (15 June 2020). "Coronavirus stalks Burundi's political elite after president's death". Financial Times. Archived from the original on 30 June 2020. Retrieved 28 June 2020. 57. ^ Reuters (6 March 2020). "Cameroon Confirms First Case of Coronavirus". The New York Times. ISSN 0362-4331. Archived from the original on 8 March 2020. Retrieved 6 March 2020 – via NYTimes.com. 58. ^ a b c d e f g h i j k l m n o "Coronavirus Update (Live): 92,727,735 Cases and 1,985,084 Deaths from COVID-19 Virus Pandemic - Worldometer". worldometers.info. Retrieved 13 January 2021. 59. ^ "Cape Verde registers an Adverse Analytical Finding of First COVID-19". insp.gov.cv. 20 March 2020. Archived from the original on 24 March 2020. Retrieved 24 March 2020. 60. ^ "Coronavírus: Inglês de 62 anos é o primeiro caso confirmado em Cabo Verde". publico.pt (in Portuguese). 20 March 2020. Archived from the original on 4 April 2020. Retrieved 20 March 2020. 61. ^ "Central African Republic confirms first coronavirus case -WHO". Reuters. 14 March 2020. Archived from the original on 15 March 2020. Retrieved 15 March 2020. 62. ^ Reuters (19 March 2020). "Chad confirms first case of coronavirus: government statement". Archived from the original on 20 March 2020. Retrieved 19 March 2020. 63. ^ "Coronavirus - Comoros travel advice". GOV.UK. Archived from the original on 3 April 2020. Retrieved 3 April 2020. 64. ^ "Un cas de Coronavirus a été importé des Comores". Mayotte la 1ère (in French). Archived from the original on 23 April 2020. Retrieved 15 April 2020. 65. ^ "Comoros reports 1st COVID-19 case". China.org.cn. Archived from the original on 1 May 2020. Retrieved 30 April 2020. 66. ^ "Stop Covid-19 Comores". Stop Coronavirus.km (in French). Archived from the original on 4 May 2020. Retrieved 6 May 2020. 67. ^ "Bulletin quotidien sur le Covid-19". Stop Coronavirus.km. Archived from the original on 16 May 2020. Retrieved 7 May 2020. 68. ^ Health, P. M. N. (10 March 2020). "Democratic Republic of Congo confirms first coronavirus case \| National Post". Archived from the original on 30 May 2020. Retrieved 10 March 2020. 69. ^ "Congo Republic confirms first coronavirus case -government". 15 March 2020. Archived from the original on 16 March 2020. Retrieved 17 March 2020. 70. ^ "Egypt announces first Coronavirus infection". Egypt Today. 14 February 2020. Archived from the original on 15 February 2020. Retrieved 14 February 2020. 71. ^ "Beijing orders 14-day quarantine for all returnees". BBC News. 14 February 2020. Archived from the original on 14 February 2020. Retrieved 14 February 2020. 72. ^ "Twelve asymptomatic coronavirus cases registered on Nile cruise ship". Reuters. 6 March 2020. Archived from the original on 7 March 2020. Retrieved 7 March 2020. 73. ^ Michael, Maggie; Magdy, Samy. "Egypt says cruise ship quarantined over new virus cluster". The Washington Post. AP. Archived from the original on 8 March 2020. Retrieved 8 March 2020. 74. ^ "Egypt Denied an Oxygen Failure Killed Covid Patients. We Found That It Did". The New York Times. Retrieved 18 January 2021. 75. ^ "Equatorial Guinea announces first coronavirus case". Deccan Herald. 14 March 2020. Archived from the original on 15 March 2020. Retrieved 15 March 2020. 76. ^ a b Health, P. M. N. (21 March 2020). "Angola, Eritrea, Uganda confirm first cases as coronavirus spreads in Africa \| National Post". Archived from the original on 30 May 2020. Retrieved 26 March 2020. 77. ^ "Eswatini in Southern Africa reports first coronavirus case". Archived from the original on 14 March 2020. Retrieved 14 March 2020. 78. ^ "Ethiopia confirms first coronavirus case: Live updates". aljazeera.com. Archived from the original on 13 March 2020. Retrieved 13 March 2020. 79. ^ "Ethiopian monk said to be 114 years old survives coronavirus". ABC News. Archived from the original on 28 June 2020. Retrieved 27 June 2020. 80. ^ Andjilani, Toufaili (14 March 2020). "Mayotte enregistre un premier cas de Coronavirus". Mayotte 1ère (in French). Archived from the original on 15 March 2020. Retrieved 21 April 2020. 81. ^ "Coronavirus COVID-19 : 12 nouveaux cas confirmés à Mayotte : 94 au total". Mayotte la 1ère (in French). Archived from the original on 7 April 2020. Retrieved 31 March 2020. 82. ^ Philippon, Laura (11 March 2020). "Un premier cas de coronavirus confirmé à La Réunion". La1ere.francetvinfo.fr (in French). Archived from the original on 5 April 2020. Retrieved 21 April 2020. 83. ^ Health, P. M. N. (13 March 2020). "Ghana, Gabon confirm first cases of coronavirus \| National Post". Archived from the original on 30 May 2020. Retrieved 13 March 2020. 84. ^ Health, P. M. N. (17 March 2020). "Gambia reports first case of coronavirus -health minister\| National Post". Archived from the original on 30 May 2020. Retrieved 18 March 2020. 85. ^ "Ghana, Gabon confirm first cases of coronavirus". Reuters. 13 March 2020. Archived from the original on 13 March 2020. Retrieved 13 March 2020. 86. ^ Acheampong, Kwame. "Ghana confirms two Coronavirus cases". Starr Fm. Archived from the original on 24 March 2020. Retrieved 13 March 2020. 87. ^ Adamu, Zaina. "Over 2,000 health care workers in Ghana have been infected with coronavirus". CNN. Retrieved 6 August 2020. 88. ^ "EU Employee Tests Positive for Coronavirus in Guinea's First Case". Archived from the original on 24 March 2020. Retrieved 14 March 2020. 89. ^ a b c "As mosques reopen in West Africa, COVID-19 fears grow". ABC News. Archived from the original on 17 May 2020. Retrieved 17 May 2020. 90. ^ "Guinea-Bissau confirms first two cases of coronavirus". Reuters. 25 March 2020. Archived from the original on 25 March 2020. Retrieved 25 March 2020. 91. ^ "Ivory Coast confirms first case of coronavirus". Daily Sabah. 11 March 2020. Archived from the original on 18 March 2020. Retrieved 11 March 2020. 92. ^ "Kenya coronavirus cases rise to four, CS health – MINISTRY OF HEALTH". Archived from the original on 25 March 2020. Retrieved 25 March 2020. 93. ^ By ELIZABETH MERAB More by this Author. "Kenya confirms first coronavirus case - VIDEO - Daily Nation". Nation.co.ke. Archived from the original on 14 March 2020. Retrieved 14 March 2020. 94. ^ "All 54 African Countries Now Report Coronavirus Cases". Time. Archived from the original on 13 May 2020. Retrieved 13 May 2020. 95. ^ "Lesotho Coronavirus: 134 Cases and 1 Deaths - Worldometer". worldometers.info. Archived from the original on 14 May 2020. Retrieved 10 July 2020. 96. ^ "Liberia Records First Case of Coronavirus; Health Authorities Hold Emergency Meeting". FrontPage Africa. 16 March 2020. Archived from the original on 16 March 2020. Retrieved 16 March 2020. 97. ^ a b c d Burke, Jason (16 March 2020). "African nations impose stricter measures as coronavirus spreads". The Guardian. ISSN 0261-3077. Archived from the original on 16 March 2020. Retrieved 16 March 2020. 98. ^ "Libyan gov't suspends flights in wake of COVID-19". Anadolu Agency. 16 March 2020. Archived from the original on 17 March 2020. Retrieved 17 March 2020. 99. ^ "Libya confirms first coronavirus case amid fear over readiness". Reuters. 24 March 2020. Archived from the original on 28 May 2020. Retrieved 24 March 2020. 100. ^ "Officiel trois premiers cas de Coronavirus à Madagascar". Orange Madagascar. 20 March 2020. Archived from the original on 20 March 2020. Retrieved 20 March 2020. 101. ^ a b "Madagascar coronavirus herbal mix draws demand from across Africa despite WHO misgivings". news.yahoo.com. Archived from the original on 13 May 2020. Retrieved 8 May 2020. 102. ^ "Malawi confirms three cases of coronavirus:Predident Mutharika calls for calm". Nyasa Times. 2 April 2020. Archived from the original on 4 April 2020. Retrieved 2 April 2020. 103. ^ "Malawi high court blocks coronavirus lockdown". Retrieved 18 November 2020. 104. ^ "S v President of Malawi and Others; Ex Parte: Kathumba and Others (Judicial Review Cause No. 22 of 2020) [2020] MWHC 7 (17 April 2020)". High Court of Malawi. 17 April 2020. Retrieved 18 November 2020. 105. ^ "Malawi Makes Masks Mandatory in COVID-19 Fight". 8 August 2020. Retrieved 18 November 2020. 106. ^ "Mali: Authorities confirm first COVID-19 cases March 25 /update 2". garda.com. 25 March 2020. Archived from the original on 25 March 2020. Retrieved 25 March 2020. 107. ^ "Mauritania confirms first coronavirus case". Archived from the original on 14 March 2020. Retrieved 14 March 2020. 108. ^ "La Mauritanie ne compte plus de cas positifs suivis (Ministère de la Santé)". Cridem.org. Archived from the original on 22 April 2020. Retrieved 21 April 2020. 109. ^ "وكالة الأخبار المستقلة". facebook.com. Retrieved 29 April 2020. 110. ^ "Covid-19 : Le patient zéro est la deuxième victime du coronavirus". ION NEWS (in French). 23 March 2020. Archived from the original on 23 March 2020. Retrieved 23 March 2020. 111. ^ "Covid-19 : un policier, proche de la patiente de 20 ans, en quarantaine". Le Défi Media Group (in French). 28 March 2020. Archived from the original on 28 March 2020. Retrieved 4 April 2020. 112. ^ "Covid-19 : 40 membres du personnel soignant en quarantaine". Le Défi Media Group (in French). 27 March 2020. Archived from the original on 28 March 2020. Retrieved 4 April 2020. 113. ^ "COVID-19 - Rodrigues : Aucun cas positif, 157 personnes en quarantaine". Le Défi Media Group (in French). 2 April 2020. Archived from the original on 4 April 2020. Retrieved 4 April 2020. 114. ^ "[Vidéo] Jugnauth : On est passé de 48 à 81 cas à Maurice en un jour". ION News (in French). 26 March 2020. Archived from the original on 27 March 2020. Retrieved 27 March 2020. 115. ^ "Covid-19: Curfew extended to 1st June and schools to remain closed till 1st August". Government Portal of Mauritius. 1 May 2020. Archived from the original on 21 May 2020. Retrieved 24 May 2020. 116. ^ "Covid-19 : le couvre-feu sanitaire étendu jusqu'au 1er juin ; les écoles fermées jusqu'au 1er août". Le Défi Media Group (in French). 1 June 2020. Archived from the original on 17 May 2020. Retrieved 24 May 2020. 117. ^ "Covid-19/Couvre-feu sanitaire : un plus grand nombre d'activités seront autorisées à partir du 15 mai". Le Défi Media Group (in French). 1 June 2020. Archived from the original on 17 May 2020. Retrieved 24 May 2020. 118. ^ "Covid-19: Strict measures on public transport for safer travel". Government Portal of Mauritius. 13 May 2020. Archived from the original on 28 May 2020. Retrieved 24 May 2020. 119. ^ "Déconfinement partiel : Transports en commun : ce qui change". Le Défi Media Group (in French). 15 May 2020. Archived from the original on 21 May 2020. Retrieved 24 May 2020. 120. ^ "Covid-19: Mauritius embarks on first phase of easing its lockdown protocol". Government Portal of Mauritius. 15 May 2020. Archived from the original on 22 May 2020. Retrieved 24 May 2020. 121. ^ Kasraoui, Safaa (2 March 2020). "Morocco Records First Case of Coronavirus". Archived from the original on 3 March 2020. Retrieved 6 March 2020. 122. ^ "Mozambique confirms first coronavirus case". National Post. 22 March 2020. Retrieved 22 March 2020. 123. ^ "Namibia Says Couple Visiting From Spain Test Positive for Virus". Bloomberg. 14 March 2020. Archived from the original on 15 March 2020. Retrieved 14 March 2020. 124. ^ Shikongo, Arlana (16 March 2020). "Namibia battles coronavirus". The Namibian. p. 1. Archived from the original on 21 March 2020. Retrieved 16 March 2020. 125. ^ Nakale, Albertina (16 March 2020). "Corona mayhem". New Era. p. 1. Archived from the original on 4 April 2020. Retrieved 16 March 2020. 126. ^ Ngatjiheue, Charmaine (18 March 2020). "Govt raises Covid-19 surveillance". The Namibian. p. 1. Archived from the original on 3 April 2020. Retrieved 19 March 2020. 127. ^ Shikongo, Arlana (25 March 2020). "Partial lockdown in effect from Friday". The Namibian. p. 1. Archived from the original on 25 March 2020. Retrieved 25 March 2020. 128. ^ Ngutjinazo, Okeri (15 April 2020). "Informal sector gets lifeline". The Namibian. p. 1. Archived from the original on 16 April 2020. Retrieved 15 April 2020. 129. ^ Ngatjiheue, Charmaine (30 April 2020). "Namibia to reopen economy ... moves to 'stage two', post-lockdown". The Namibian. p. 1. Archived from the original on 21 June 2020. Retrieved 12 July 2020. 130. ^ "Namibia has recorded its first death due to COVID-19". Twitter. Archived from the original on 10 July 2020. Retrieved 10 July 2020. 131. ^ "Niger announces first coronavirus case". medicalxpress.com. Archived from the original on 20 March 2020. Retrieved 20 March 2020. 132. ^ "Nigeria confirms first coronavirus case". BBC News. 28 February 2020. Archived from the original on 2 March 2020. Retrieved 6 March 2020 – via bbc.co.uk. 133. ^ correspondent, Jason Burke Africa; Rourke, Alison (28 February 2020). "Nigeria confirms first coronavirus case in sub-Saharan Africa". The Guardian. ISSN 0261-3077. Archived from the original on 6 March 2020. Retrieved 6 March 2020 – via theguardian.com. 134. ^ "Nigeria Centre for Disease Control". ncdc.gov.ng. Archived from the original on 2 March 2020. Retrieved 8 March 2020. 135. ^ "Nigeria confirms first coronavirus case". BBC News. 28 February 2020. Archived from the original on 2 March 2020. Retrieved 8 March 2020. 136. ^ a b "Breaking: Deadly Coronavirus confirmed in Lagos, Nigeria at last". 25 February 2020. Archived from the original on 28 February 2020. Retrieved 28 February 2020. 137. ^ Mustapha JO, Adedokun KA, Abdullahi IN (2020). "Public health preparedness towards COVID-19 outbreak in Nigeria". Asian Pacific Journal of Tropical Medicine. 13 (5): 197–198. doi:10.4103/1995-7645.279650. S2CID 218632316. 138. ^ "Nigeria's first coronavirus case came on flight via Istanbul, went to Ogun state: Lagos health commission". Reuters. 28 February 2020. Archived from the original on 29 February 2020. Retrieved 29 February 2020. 139. ^ "NCDC Situation Report 6 March 2019" (PDF). Archived (PDF) from the original on 17 March 2020. Retrieved 26 March 2020. 140. ^ "Nigerian Government Places Lock-down Measures Against COVID-19". Archived from the original on 20 March 2020. Retrieved 19 March 2020. 141. ^ "COVID-19: Federal Government Orders Immediate Shutdown of Schools". Archived from the original on 22 March 2020. Retrieved 20 March 2020. 142. ^ "Federal Polytechnic Nekede Dismissed Students Over COVID-19". Archived from the original on 22 March 2020. Retrieved 21 March 2020. 143. ^ "Buhari's Chief of Staff, Abba Kyari tests Positive for Coronavirus". Archived from the original on 24 March 2020. Retrieved 24 March 2020. 144. ^ a b "President Tests Negative, Chief of Staff Infected". Archived from the original on 24 March 2020. Retrieved 24 March 2020. 145. ^ "Bala Mohammed, Bauchi Governor, Pests Positive for Coronavirus". Archived from the original on 25 March 2020. Retrieved 24 March 2020. 146. ^ "COVID-19: Buhari Tests Negative". Archived from the original on 24 March 2020. Retrieved 24 March 2020. 147. ^ "Yahaya Bello Tests Positive for Coronavirus". Archived from the original on 25 May 2020. Retrieved 25 March 2020. 148. ^ "Rwanda confirms first case of coronavirus - health ministry". Reuters. 14 March 2020. Archived from the original on 14 March 2020. Retrieved 14 March 2020. 149. ^ "World News - BBC News". BBC News. Archived from the original on 20 April 2020. Retrieved 20 April 2020. 150. ^ "BOLETIM COVID-19 ATUALIZAÇÃO 30 de abril de 2020". Facebook (in Portuguese). Government of Sao Tome and Principe. Retrieved 1 May 2020. 151. ^ "Coronavirus : Le Sénégal enregistre son premier cas \| Lequotidien Journal d'informations Générales". Archived from the original on 13 March 2020. Retrieved 26 March 2020. 152. ^ "Protests erupt in Senegal over new Covid-19 measures". Africanews. Retrieved 13 January 2021. 153. ^ Bonnelame, Betyme (14 March 2020). "2 Seychellois test positive for COVID-19 as globe-sweeping virus reaches island nation". Seychelles News Agency. Archived from the original on 17 March 2020. Retrieved 14 March 2020. 154. ^ http://www.seychellesnewsagency.com/articles/14129/Seychellois+man+dies+of+COVID-%2C+first+pandemic+fatality+recorded+in+island+nation 155. ^ a b c "Sierra Leone institutes additional measures in preparedness to prevent and respond to COVID-19". Relief Web. 18 March 2020. Archived from the original on 18 March 2020. Retrieved 18 March 2020. 156. ^ "Sierra Leone introduces a raft of measures to keep coronavirus out". Politico SL. 18 March 2020. Archived from the original on 18 March 2020. Retrieved 18 March 2020. 157. ^ "Sierra Leone announces year-long state of emergency despite no confirmed coronavirus". RFI. 25 March 2020. Archived from the original on 25 March 2020. Retrieved 26 March 2020. 158. ^ "Sierra Leone has confirmed its first case of coronavirus, president says". Reuters. 31 March 2020. Archived from the original on 5 April 2020. Retrieved 31 March 2020 – via www.reuters.com. 159. ^ "Somalia, Tanzania confirm first coronavirus cases". Anadolu Agency. 16 March 2020. Archived from the original on 17 March 2020. Retrieved 17 March 2020. 160. ^ "Somaliland Reports First COVID-19 Cases". Voice of America. 31 March 2020. Archived from the original on 1 April 2020. Retrieved 1 April 2020. 161. ^ "Minister Zweli Mkhize reports first case of Covid-19 Coronavirus". South African Ministry of Health. 5 March 2020. Archived from the original on 9 March 2020. Retrieved 6 March 2020. 162. ^ Burke, Jason (25 March 2020). "Coronavirus cases in Africa pass 2,400 amid fears for health services". The Guardian. ISSN 0261-3077. Archived from the original on 25 March 2020. Retrieved 25 March 2020. 163. ^ "Statement by president Cyril Ramaphosa on South Africa's response to the coronavirus pandemic, Union buildings, Tshwane". SA Corona Virus Online Portal. 23 April 2020. Archived from the original on 3 May 2020. Retrieved 23 April 2020. 164. ^ "President Cyril Ramaphosa: Developments in South Africa's risk-adjusted strategy to manage the spread of Coronavirus COVID-19". Department of Health. 24 May 2020. Archived from the original on 5 June 2020. Retrieved 24 May 2020. 165. ^ "New coronavirus projections from Mkhize and top scientists". BusinessTech. 20 May 2020. Archived from the original on 26 May 2020. Retrieved 25 May 2020. 166. ^ "Coronavirus Cases Spike in South Africa and India, Exposing Inequalities in Virus Treatment". Time. Retrieved 12 July 2020. 167. ^ "COVID-19 South African coronavirus news and information portal". SA Corona Virus Online Portal. Retrieved 31 October 2020. 168. ^ "South Africa identifies new coronavirus strain causing surge in cases". news.yahoo.com. Yahoo News. Reuters. Retrieved 18 December 2020. 169. ^ "South Sudan confirms second Covid-19 case". Reuters. 5 April 2020. Archived from the original on 7 April 2020. Retrieved 7 April 2020. 170. ^ "COVID-19 confirmed in crowded UN-run camp in South Sudan". ABC News. Archived from the original on 13 May 2020. Retrieved 13 May 2020. 171. ^ "Sanidad confirma en La Gomera el primer caso de coronavirus en España". El Pais (in Spanish). 31 January 2020. Archived from the original on 31 January 2020. Retrieved 31 January 2020. 172. ^ "First confirmed coronavirus case in Spain in La Gomera, Canary Islands". Outbreak News Today. 3 February 2020. Archived from the original on 28 February 2020. Retrieved 28 February 2020. 173. ^ a b "Ministerio de Sanidad, Consumo y Bienestar Social - Profesionales - Teléfonos de información - Coronavirus". mscbs.gob.es. Archived from the original on 4 April 2020. Retrieved 7 April 2020. 174. ^ Reuters (13 March 2020). "Sudan Reports First Coronavirus Case". The New York Times. ISSN 0362-4331. Archived from the original on 13 March 2020. Retrieved 13 March 2020 – via NYTimes.com. 175. ^ "Surge in deaths in North Darfur raises fears of disastrous Covid-19 outbreak". the Guardian. 29 May 2020. Archived from the original on 29 May 2020. Retrieved 29 May 2020. 176. ^ "Tanzanian doctors sound alarm over hidden coronavirus cases". The New Humanitarian. 14 May 2020. Archived from the original on 21 May 2020. 177. ^ "Tanzania opposition angry over no coronavirus update in two weeks". aljazeera.com. 13 May 2020. Archived from the original on 21 May 2020. 178. ^ "Togo confirms first case of coronavirus". Reuters. 6 March 2020. Archived from the original on 6 March 2020. Retrieved 6 March 2020. 179. ^ "Italian returnee confirmed Tunisia's first coronavirus case". Archived from the original on 3 March 2020. Retrieved 6 March 2020. 180. ^ "Gafsa-COVID-19: legal action taken after two cases fail to comply with home-confinement measures". TAP. Archived from the original on 22 March 2020. Retrieved 15 March 2020. 181. ^ "Twitter". mobile.twitter.com. Archived from the original on 22 March 2020. Retrieved 26 March 2020. 182. ^ "Results of COVID-19 tests done on 23 July 2020 \| 10 new confirmed cases. Cumulative confirmed cases of Ugandans to-date: 1,089 \| COVID-19 Ugandan recoveries to-date: 975 \| COVID-19 deaths to-date: 01 #STAYSAFEUG". Twitter. Retrieved 25 July 2020. 183. ^ "Regular Updates by MINURSO on Covid-19". United Nations Mission for the Referendum in Western Sahara. 9 April 2020. Archived from the original on 6 April 2020. Retrieved 9 April 2020. 184. ^ "Coronavirus - African Union Member States (55) reporting COVID-19 cases (811,260) deaths (17,105), and recoveries (463,156)". Africa Newsroom. 25 July 2020. Retrieved 22 September 2020. 185. ^ "Zambia Confirms 2 Covid-19 cases". News Diggers. 18 March 2020. Archived from the original on 19 March 2020. Retrieved 18 March 2020. 186. ^ "Zambia confirms third coronavirus case". News Diggers. 22 March 2020. Archived from the original on 22 March 2020. Retrieved 22 March 2020. 187. ^ "Lungu's full address: Zambia confirms 12 COVID-19 cases as lock down looms". News Diggers. 25 March 2020. Archived from the original on 25 March 2020. Retrieved 25 March 2020. 188. ^ "Government shuts all schools to prevent COVID-19 outbreak". News Diggers. 17 March 2020. Archived from the original on 19 March 2020. Retrieved 17 March 2020. 189. ^ "Zambia's vice president tests positive for COVID-19". 19 August 2020 – via uk.reuters.com. 190. ^ "Zimbabwe, Namibia Declare National Emergencies Over Virus". Bloomberg. 17 March 2020. Archived from the original on 17 March 2020. Retrieved 17 March 2020. 191. ^ "Zimbabwe's President declares COVID-19 a national disaster". Xinhua. 17 March 2020. Archived from the original on 17 March 2020. Retrieved 17 March 2020. 192. ^ "Zimbabwe, Namibia Declare National Emergencies Over Virus". GulfNews. 15 March 2020. Archived from the original on 20 March 2020. Retrieved 17 March 2020. 193. ^ Marsh, Kevin Rawlinson (now); Sarah; Quinn, Ben; Perraudin, Frances; Farrer (earlier), Martin; Greenfield, Patrick; Cowie, Sam; Wintour, Patrick; Wintour, Patrick; Willsher, Kim (20 March 2020). "Coronavirus live updates: global cases top quarter of a million, as Italy sees biggest daily rise in deaths". The Guardian. Archived from the original on 8 June 2020. Retrieved 20 March 2020. 194. ^ "Zimbabwe arrests 100,000 for Covid-19 'breaches'". BBC News. 19 July 2020. Retrieved 19 July 2020. 195. ^ "Three Possible COVID-19 Cases Identified – Ascension Island Government". Archived from the original on 22 March 2020. Retrieved 26 March 2020. 196. ^ "COVID-19 Results Negative". Ascension Island Government. Archived from the original on 25 March 2020. Retrieved 16 April 2020. 197. ^ "Travel Restrictions in response to the COVID -19 virus" (PDF). Archived (PDF) from the original on 18 March 2020. Retrieved 26 March 2020. 198. ^ "Coronavirus (Covid-19): Live Q&A". Archived from the original on 26 March 2020. Retrieved 26 March 2020. 199. ^ Grundy, Richard (16 March 2020). "Tristan da Cunha Government News: Island Council takes steps to protect island from coronavirus". tristandc.com. Archived from the original on 25 March 2020. Retrieved 25 March 2020. 200. ^ a b c d e f g h Ihekweazu C, Agogo E (May 2020). "Africa's response to COVID-19". BMC Med. 151 (18). doi:10.1186/s12916-020-01622-w. 201. ^ "Should African countries embrace Ghana's Covid-19 'pooled testing'?". Myjoyonline. 202. ^ Rashid, Zaheena; Gadzo, Mersiha; Stepansky, Joseph (7 May 2020). "Coronavirus could kill 190,000 in Africa, WHO warns: Live updates". Al Jazeera. Archived from the original on 8 May 2020. Retrieved 7 May 2020. 203. ^ "COVID-19 Africa Open Data". Retrieved 16 November 2020. 204. ^ "Cédric Moro, Administrator of CoViD19-F-CIC: "As a Senegalese, I must participate in African resilience in the face of Coronavirus". Dakaractu. Retrieved 16 November 2020. 205. ^ a b c "UN, news organizations and artists fight against COVID-19 fake news". Africa Renewal Magazine. United Nations. 206. ^ "Philippe Perdrix et Romain Grandjean : face à la crise, "une information fiable permet de prendre les mesures adéquates et efficaces"". 207. ^ Anna, Cara (10 December 2020). "African health official blasts 'terrible' vaccine inequality". AP NEWS. AP. Retrieved 11 December 2020. 208. ^ "Visiting \| British Indian Ocean Territory". Biot.gov.io. Archived from the original on 1 August 2019. Retrieved 30 March 2020. 209. ^ "Coronavirus - British Indian Ocean Territory travel advice". GOV.UK. Archived from the original on 29 March 2020. Retrieved 30 March 2020. * v * t * e COVID-19 pandemic * SARS-CoV-2 (virus) * COVID-19 (disease) Timeline * Pre-pandemic * Crimson Contagion * Disease X * Event 201 * Exercise Cygnus * 2019 * 2020 * January * February * responses * March * responses * April * responses * May * responses * June * responses * July * responses * August * responses * September * responses * October * responses * November * responses * December * responses * 2021 * January Locations Africa Northern * Algeria * Canary Islands * Ceuta * Egypt * Libya * Mauritania * Melilla * Morocco * Sudan * Tunisia * Western Sahara * Sahrawi Arab Democratic Republic Eastern * Burundi * Comoros * Djibouti * Eritrea * Ethiopia * Kenya * Madagascar * Mauritius * Mayotte * Réunion * Rwanda * Seychelles * Somalia * Puntland * Somaliland * South Sudan * Tanzania * Uganda Southern * Angola * Botswana * Eswatini * Lesotho * Malawi * Mozambique * Namibia * South Africa * Zambia * Zimbabwe Central * Cameroon * Central African Republic * Chad * Democratic Republic of the Congo * Republic of the Congo * Gabon * São Tomé and Príncipe Western * Benin * Burkina Faso * Cape Verde * Equatorial Guinea * Gambia * Ghana * timeline * Guinea * Guinea-Bissau * Ivory Coast * Liberia * Mali * Niger * Nigeria * Senegal * Sierra Leone * Togo Asia Central / North * Kazakhstan * Kyrgyzstan * Russia * timeline * Tajikistan * Turkmenistan * Uzbekistan East * Hong Kong * Japan * timeline * North Korea * South Korea * Macau * Mongolia * Taiwan China * Beijing * Heilongjiang * Henan * Hubei * lockdown * Inner Mongolia * Liaoning * Shanghai * Sichuan * Tibet * Xinjiang South * Afghanistan * timeline * Bangladesh * Bhutan * Maldives * Nepal * timeline * Pakistan * timeline * Sri Lanka India * timeline * January–May 2020 * June–December 2020 * economic impact * evacuations * lockdown * migrant workers' crisis * union government response * Operation Namaste * state government responses) * Andaman and Nicobar Islands * Andhra Pradesh * Arunachal Pradesh * Assam * Bihar * Chandigarh * Chhattisgarh * Dadra and Nagar Haveli and Daman and Diu * Delhi * Tablighi Jamaat hotspot * Goa * Gujarat * Haryana * Himachal Pradesh * Jammu and Kashmir * Jharkhand * Karnataka * Kerala * Ladakh * Madhya Pradesh * Maharashtra * Manipur * Meghalaya * Mizoram * Nagaland * Odisha * Puducherry * Punjab * Rajasthan * Sikkim * Tamil Nadu * Telangana * Tripura * Uttar Pradesh * Uttarakhand * West Bengal Southeast * Brunei * Cambodia * East Timor * Indonesia * timeline * social restrictions * Laos * Malaysia * timeline * movement control order * Johor * Kuala Lumpur * Sabah * Sarawak * Selangor * Myanmar * Singapore * timeline * circuit breaker response * Thailand * timeline * Vietnam * timeline Philippines * (timeline * government response * community quarantines * Luzon * evacuations * testing controversy) * Bangsamoro * Bicol Region * Cagayan Valley * Calabarzon * Caraga * Central Luzon * Central Visayas * Cordillera * Davao Region * Eastern Visayas * Ilocos Region * Metro Manila * Mimaropa * Northern Mindanao * Soccsksargen * Western Visayas * Zamboanga Peninsula * Overseas Filipinos West * Armenia * Azerbaijan * Artsakh * Bahrain * Georgia * Abkhazia * South Ossetia * Iran * Iraq * Kurdistan * Israel * Jordan * Kuwait * Lebanon * Oman * Palestine * Qatar * Saudi Arabia * Syria * Turkey * timeline * United Arab Emirates * Yemen Europe United Kingdom * * timeline * January–June 2020 * July–December 2020 * 2021 * government response * social impact * economic impact * education impact * Operation Rescript * England * 2020 timeline * 2021 timeline * London * Northern Ireland * 2020 timeline * 2021 timeline * Scotland * 2020 timeline * 2021 timeline * Wales * 2020 timeline * 2021 timeline * Crown dependencies * Isle of Man * Jersey * Guernsey * Overseas territories * Akrotiri and Dhekelia * Gibraltar * response Eastern * Armenia * Azerbaijan * Belarus * Georgia * Kazakhstan * Moldova * Gagauzia * Transnistria * Russia * timeline * government responses * Crimea * Sevastopol * Ukraine * Crimea * Sevastopol * Donetsk * Luhansk Balkans * Albania * Bosnia and Herzegovina * Kosovo * Montenegro * North Macedonia * Serbia * Turkey * timeline Microstates * Andorra * San Marino * Vatican City * Monaco European Union EFTA countries * Austria * Belgium * Bulgaria * Croatia * timeline * Cyprus * Northern Cyprus * Czech Republic * Denmark * Faroe Islands * Estonia * Finland * Åland Islands * France * Guadeloupe * French Guiana * Réunion * Martinique * Mayotte * Saint Martin * Germany * North Rhine-Westphalia * Greece * Hungary * Iceland * Ireland * timeline * January–June 2020 * July–December 2020 * economic impact * social impact * Italy * lockdown * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Netherlands * Norway * Poland * Portugal * Romania * timeline * Piatra Neamț hospital fire * Slovakia * Slovenia * Spain * timeline * Asturias * Canary Islands * Ceuta * Community of Madrid * Melilla * Sweden * timeline * government response * Switzerland North America Mexico * timeline Central America * Belize * Costa Rica * El Salvador * Guatemala * Honduras * Nicaragua * Panama Canada * * timeline * economic impact * Alberta * British Columbia * Manitoba * New Brunswick * Newfoundland and Labrador * Northwest Territories * Nova Scotia * Nunavut * Ontario * timeline * Peel Region * Toronto * Prince Edward Island * Quebec * Montreal * Saskatchewan * Yukon Caribbean * Antigua and Barbuda * Bahamas * Barbados * British Overseas Territories * Anguilla * British Virgin Islands * Cayman Islands * Montserrat * Turks and Caicos Islands * response * Cuba * Guantanamo Bay Naval Base * Dominica * Dominican Republic * Dutch Caribbean * Aruba * Curaçao * Sint Maarten * Caribbean Netherlands * Bonaire * Saba * Sint Eustatius * French West Indies * Guadeloupe * Martinique * Saint Barthélemy * Saint Martin * Grenada * Haiti * Jamaica * Saint Kitts and Nevis * Saint Lucia * Saint Vincent and the Grenadines * Trinidad and Tobago * US insular areas * Puerto Rico * U.S. Virgin Islands United States * * timeline * social impact * economic impact * federal government response * state and local government responses * Regional responses * Eastern States Multi-state Council * Midwest Governors Regional Pact * Western States Pact * Trump administration communication * Alabama * Alaska * American Samoa * Arizona * Navajo Nation * Arkansas * California * timeline * S.F. Bay Area * Colorado * Connecticut * Delaware * Florida * Georgia * Guam * Hawaii * Idaho * Illinois * Indiana * Iowa * Kansas * Kentucky * Louisiana * Maine * Maryland * Massachusetts * timeline * Boston * timeline * Michigan * Minnesota * Mississippi * Missouri * Montana * Nebraska * Nevada * New Hampshire * New Jersey * New Mexico * New York * New York City * North Carolina * North Dakota * Northern Mariana Islands * Ohio * impact * Columbus * Oklahoma * Oregon * Portland * Pennsylvania * Philadelphia * Puerto Rico * Rhode Island * South Carolina * South Dakota * Tennessee * Texas * timeline * U.S. Virgin Islands * Utah * Vermont * Virginia * Washington * Washington, D.C. * White House * West Virginia * Wisconsin * statistics * Wyoming Atlantic * Bermuda * Greenland * Saint Pierre and Miquelon Oceania * American Samoa * Australia * Easter Island * Federated States of Micronesia * Fiji * French Polynesia * Guam * Hawaii * Marshall Islands * New Caledonia * New Zealand * timeline * government response * Northern Mariana Islands * Papua New Guinea * Bougainville * Samoa * Solomon Islands * Vanuatu * Wallis and Futuna South America * Argentina * timeline * human rights * Bolivia * Brazil * São Paulo * Chile * Easter Island * Colombia * Ecuador * Falkland Islands * French Guiana * Guyana * Paraguay * Peru * Suriname * Uruguay * timeline * Venezuela Other * Antarctica * Cruise ships * Diamond Princess * Grand Princess * Naval ships * Charles de Gaulle * USS Theodore Roosevelt Impacts Culture and entertainment * Arts and cultural heritage * Cinema * films affected * Disney * Education * Ireland * United Kingdom * Events affected * Fashion industry * Music industry * Performing arts * Sports * By country * Ireland * Philippines * By sport * association football * cricket * disc golf * Gaelic games * motorsport * NBA * rugby league * Television * U.S. * programs affected * Video games Society and rights * Social * social media * stigma * COVID-19 parties * Children * foster care in the United States * Gender * Healthcare workers * Hospitals * Human rights * Legal * abortion in the U.S. * crime * crime in Ireland * domestic violence * prisons * U.S. immigration detention * LGBT community * Long-term care facilities * Public transport * Religion * Catholic Church * Hajj * Strikes * Xenophobia and racism Economic * Aviation * Airlines * Cannabis industry * Charitable activity * COVID-19 recession * Financial markets * Food industry * meat industry in Canada * meat industry in the U.S. * restaurant industry in the U.S. * Global stock market crash * Hospitals * Mink farming * Oil price war * Retail * Tourism * Travel restrictions Information * Journalism * Media coverage * Misinformation * Wikipedia's response Politics * National responses * Legislation * Protests * New Zealand * Serbia * United Kingdom * United States * International relations * Aid * European Union * Ireland Language * Doomscrolling * Flattening the curve * Long-hauler * Quarantini * Social distancing * Superspreader * Zoom Others * Anthropause * Environment * Military * Science and technology * Food security Health issues Problems and restrictions * Transmission * Death rates by country * Cancer * Evacuations * Falsified medical methods * Management * Mental health * Shortages * medical oxygen * ventilator * open-source ventilator * extracorporeal membrane oxygenation * Raise the line * COVID fatigue * Non-COVID-19-related health issues * Variants of SARS-CoV-2 Prevention * Pandemic Severity Assessment Framework * Public Health Emergency of International Concern * Non-pharmaceutical intervention * Great Barrington Declaration * Social distancing * Measures * Face masks * United States * N95 * Flattening the curve * Disease testing * breathalyzer * Datasets * Coronavirus apps * careFIJI * COVID Alert * COVIDSafe * COVID Tracker Ireland * Coronavirus Australia * Aarogya Setu * NZ COVID Tracer * TraceTogether * BlueTrace * Decentralized Privacy-Preserving Proximity Tracing * NHS COVID-19 * Nearby Spot * TCN Protocol * Exposure Notification * Workplace hazard controls * Surveillance * Lockdowns * Immunity passports * International aid * Safe Hands Challenge * Wastewater surveillance Treatments and research * Pregnancy * Treatment research * Drug repurposing research * Dexamethasone * Drug development * Vaccine research * Ad5-nCoV * AZD1222 * BBIBP-CorV * CoronaVac * Covaxin * mRNA-1273 * RBD-Dimer * Sputnik V * Pfizer-BioNTech * V451 * Operation Warp Speed (U.S.) * RECOVERY Trial (UK) * Solidarity trial (WHO) Institutions Hospitals and related * Hospital ships * Central Hospital of Wuhan * Dabie Mountain Regional Medical Centre * Fangcang Hospitals * Huoshenshan Hospital * Wuhan Jinyintan Hospital * Leishenshan Hospital * Xinjia Express Hotel * COVID-19 Hospital in Mumbai * Kemayoran Athletes Village * Malaysia Agro Exposition Park Serdang * COVID-19 hospitals in the United Kingdom * Canberra Coronavirus Field Hospital * Hospital El Salvador * Pyongyang General Hospital * Sancaktepe Prof. Dr. Feriha Öz Emergency Hospital * Yeşilköy Prof. Dr. Murat Dilmener Emergency Hospital * We Heal As One Center * Dragon's Heart Hospital * NHS Nightingale Hospitals * NHS Nightingale Hospital Birmingham * NHS Nightingale Hospital London * NHS Nightingale Hospital North East * NHS Nightingale Hospital North West * NHS Nightingale Hospital Yorkshire and the Humber * NHS Louisa Jordan Hospital * Kandakadu Treatment and Rehabilitation Centre Organizations * Coalition for Epidemic Preparedness Innovations * World Health Organization * United Nations * resolutions * International Committee on Taxonomy of Viruses * Wuhan Institute of Virology (China) * Central Epidemic Command Center (Taiwan) * Taiwan Centers for Disease Control (Taiwan) * COVID-19 Response Acceleration Task Force (Indonesia) * White House Coronavirus Task Force (United States) * Great American Economic Revival Industry Groups (United States) * Coronavirus Tech Handbook * Inter-Agency Task Force on Emerging Infectious Diseases (Philippines) * PM CARES Fund (India) * Artist Relief (United States) * Covid Watch * SAARC COVID-19 Emergency Fund (India) * Outbreak Management Team (Netherlands) * COVID-19 Solidarity Response Fund * MusiCares COVID-19 Relief Fund * Imperial College COVID-19 Response Team (UK) * SAGE (UK) * Independent SAGE (UK) * National Cabinet (Australia) * National COVID-19 Coordination Commission (Australia) * UN COVID-19 Supply Chain Task Force (WHO) * COVID-19 Supply Council (Canada) * PREPARE (European Union) * National Public Health Emergency Team (Ireland) * Africa Centres for Disease Control and Prevention (African Union) * Ghana Infectious Disease Centre (Ghana) * COVID-19 Immunity Task Force (Canada) * Novel Coronavirus Expert Meeting (Japan) * Coronavirus Scientific Advisory Board (Turkey) * Crisis Preparedness and Response Centre (Malaysia) * Korea Disease Control and Prevention Agency (Korea) People Medical professionals * Ai Fen * Li Wenliang * Liu Wen * Corona Rintawan * Xie Linka * Zhang Wenhong Researchers * Roberto Burioni * Awang Bulgiba Awang Mahmud * Chen Wei * Andrea Crisanti * Christian Drosten * Neil Ferguson * George F. Gao * Azra Ghani * Sarah Gilbert * Guan Yi * Kentaro Iwata * Trudie Lang * Li Lanjuan * W. Ian Lipkin * Ma Xiaowei * Allison McGeer * Luc Montagnier * Shi Zhengli * Moncef Slaoui * John Todd * Wang Chen * Wang Guangfa * Yuen Kwok-yung * Zeng Guang * Zhong Nanshan Officials WHO * Tedros Adhanom (Director-General of the WHO) * Bruce Aylward (Team lead of WHO-China COVID-19 mission) * Maria Van Kerkhove (Technical Lead for COVID-19 response) * Michael J. Ryan (Executive Director of the WHO Health Emergencies Programme) Countries * Alma Möller (Iceland) * Domenico Arcuri (Italy) * Frank Atherton (Wales) * Scott Atlas (United States) * Deborah Birx (United States) * Ashley Bloomfield (New Zealand) * Angelo Borrelli (Italy) * Catherine Calderwood (Scotland) * Carmen Deseda (Puerto Rico) * Jaap van Dissel (the Netherlands) * Shan-chwen Chang (Taiwan) * Chen Shih-chung (Taiwan) * Chuang Yin-ching (Taiwan) * Francisco Duque (Philippines) * Anthony Fauci (United States) * Graça Freitas (Portugal) * Hamad Hasan (Lebanon) * Tony Holohan (Ireland) * Jeong Eun-kyeong (South Korea) * Fahrettin Koca (Turkey) * Li Keqiang (China) * Michael McBride (Northern Ireland) * Oriol Mitjà (Andorra) * Doni Monardo (Indonesia) * Noor Hisham Abdullah (Malaysia) * Ali Pilli (Northern Cyprus) * Jérôme Salomon (France) * Fernando Simón (Spain) * Gregor Smith (Scotland) * Ih-Jen Su (Taiwan) * Łukasz Szumowski (Poland) * Theresa Tam (Canada) * Nelu Tătaru (Romania) * Anders Tegnell (Sweden) * Sotiris Tsiodras (Greece) * Víðir Reynisson (Iceland) * Carla Vizzotti (Argentina) * Chris Whitty (United Kingdom) * Lawrence Wong (Singapore) * Þórólfur Guðnason (Iceland) Others * Chen Qiushi * Brett Crozier * Fang Bin * Fang Fang * Li Zehua * Qiu Menghuang * Ren Zhiqiang * Captain Tom Deaths List Data (templates) Global * Cases, deaths, recoveries by country * Tests, cases, tests per capita, cases per capita by country * Tests, cases, tests per capita, cases per capita by country subdivision * WHO situation reports * cases * deaths * World map by countries: confirmed per capita * China * Hospital beds by country * Lockdowns * Mainland China Africa * Algeria * chart * Angola * chart * Burkina Faso * chart * Burundi * chart * Cameroon * chart * Egypt * chart * Eswatini * chart * Ethiopia * chart * Ghana * chart * Ivory Coast * chart * Kenya * chart * Libya * chart * Malawi * chart * Mali * chart * Mauritania * chart * Mauritius * chart * Morocco * chart * Nigeria * chart * Senegal * chart * Sierra Leone * chart * South Africa * chart * South Sudan * chart * Sudan * chart * Tanzania * chart * Togo * chart * Tunisia * chart Americas * Argentina * chart * Bolivia * chart * Brazil * chart * Canada * by province * chart * Chile * by commune * chart * Colombia * chart * Costa Rica * chart * Cuba * chart * Dominican Republic * chart * Ecuador * chart * El Salvador * chart * Guatemala * chart * Haiti * chart * Honduras * chart * Mexico * chart * Nicaragua * chart * Panama * chart * Paraguay * chart * Peru * chart * United States * by state * chart * Uruguay * chart * Venezuela * chart Asia * Afghanistan * chart * Armenia * chart * Azerbaijan * chart * Bahrain * chart * Bangladesh * chart * Bhutan * chart * summary * Brunei * chart * Cambodia * chart * summary * Mainland China * aggregate * chart * Georgia * chart * Hong Kong * chart * India * chart * summary * Indonesia * chart * Iran * chart * Iraq * chart * Israel * chart * Japan * chart * Jordan * chart * Kazakhstan * chart * South Korea * chart * Kuwait * graph * chart * Kyrgyzstan * chart * Laos * chart * Lebanon * chart * Malaysia * chart * Myanmar * chart * Nepal * chart * by district * PCR tests * Oman * chart * Pakistan * chart * Palestine * chart * Philippines * chart * areas of quarantine * Qatar * chart * Russia/North Asia * by federal subject * chart * Saudi Arabia * chart * Singapore * chart * Sri Lanka * chart * Syria * chart * Taiwan * chart * Tajikistan * chart * Thailand * chart * summary * Turkey * by province * chart * United Arab Emirates * chart * Uzbekistan * chart * Vietnam * chart * Yemen * chart Europe (chart) * Albania * chart * Austria * chart * Belarus * chart * Belgium * chart * Bosnia and Herzegovina * chart * Bulgaria * chart * Croatia * chart * Cyprus * chart * Czech Republic * chart * Denmark * chart * Estonia * chart * Faroe Islands * chart * Finland * chart * France * chart * Germany * chart * Greece * chart * Hungary * chart * Iceland * chart * Ireland * chart * Italy * chart * Kosovo * chart * Latvia * chart * Lithuania * chart * Luxembourg * chart * Malta * chart * Moldova * chart * Monaco * chart * Montenegro * chart * Netherlands * chart * North Macedonia * chart * Norway * chart * Poland * chart * Portugal * chart * Romania * chart * Russia * by federal subject * chart * San Marino * chart * Serbia * chart * Slovakia * by region * chart * Slovenia * chart * Spain * chart * Asturias * Community of Madrid * Sweden * chart * Switzerland * chart * Turkey * by province * chart * Ukraine * chart * Donetsk People's Republic * Luhansk People's Republic * United Kingdom * Scotland * chart * Vatican City * chart Oceania * Australia * chart * by state/territory * Fiji * chart * French Polynesia * chart * New Caledonia * chart * New Zealand * chart * Papua New Guinea * chart * Solomon Islands * Solomon Islands Others * Cruise ships * Diamond Princess * Category * Portal * v * t * e COVID-19 pandemic in Africa Africa Northern * Algeria * Canary Islands * Ceuta * Egypt * Libya * Mauritania * Melilla * Morocco * Sudan * Tunisia * Western Sahara * Sahrawi Arab Democratic Republic Eastern * Burundi * Comoros * Djibouti * Eritrea * Ethiopia * Kenya * Madagascar * Mauritius * Mayotte * Réunion * Rwanda * Seychelles * Somalia * Puntland * Somaliland * South Sudan * Tanzania * Uganda Southern * Angola * Botswana * Eswatini * Lesotho * Malawi * Mozambique * Namibia * South Africa * Zambia * Zimbabwe Central * Cameroon * Central African Republic * Chad * Democratic Republic of the Congo * Republic of the Congo * Gabon * São Tomé and Príncipe Western * Benin * Burkina Faso * Cape Verde * Equatorial Guinea * Gambia * Ghana * Guinea * Guinea-Bissau * Ivory Coast * Liberia * Mali * Niger * Nigeria * Senegal * Sierra Leone * Togo Notable deaths * Suleiman Adamu * Abba Kyari * Gita Ramjee [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	COVID-19 pandemic in Africa	None	26,628	wikipedia	https://en.wikipedia.org/wiki/COVID-19_pandemic_in_Africa	2021-01-18T18:38:53	{"wikidata": ["Q86694873"]}
A number sign (#) is used with this entry because Darier-White disease (DAR) is caused by heterozygous mutation in the ATP2A2 gene (108740), which encodes the sarcoplasmic reticulum Ca(2+)-ATPase-2, on chromosome 12q24. Description Darier-White disease, also known as keratosis follicularis, is an autosomal dominant skin disorder characterized by warty papules and plaques in seborrheic areas (central trunk, flexures, scalp, and forehead), palmoplantar pits, and distinctive nail abnormalities (Sakuntabhai et al., 1999). Onset is usually before the third decade, and penetrance is complete in adults, although expressivity is variable. Involvement may be severe, with widespread itchy malodorous crusted plaques, painful erosions, blistering, and mucosal lesions. Secondary infection is common. Sun, heat, and sweating exacerbate the symptoms. Darier disease never remits, but oral retinoids may reduce hyperkeratosis. Neuropsychiatric abnormalities, including mild mental retardation and epilepsy, have been described in association with Darier disease in a few families (Burge and Wilkinson, 1992); whether this is an association based on pleiotropism of the mutant gene or reflects coincidence is not clear. Histologic findings are (1) mild nonspecific perivascular infiltration in the dermis; (2) dermal villi protruding into the epidermis; (3) suprabasal detachment of the spinal layer leading to the formation of lacunae containing acantholytic cells; (4) in the more superficial epidermis, dyskeratotic round epidermal cells ('corps ronds'), the most distinctive feature; and (5) in the stratum corneum, 'grains' that resemble parakeratotic cells embedded in a hyperkeratotic horny layer. Electron microscopy reveals loss of desmosomal attachments, perinuclear aggregations of keratin filaments, and cytoplasmic vacuolization. Ultrastructural and immunologic studies suggest the disease results from an abnormality in the desmosome-keratin filament complex leading to a breakdown in cell adhesion. Clinical Features Hitch et al. (1941) reported a family with affected members in 5 generations. See acrokeratosis verruciformis (101900) for discussion of phenotypic overlap with that condition. When bullous lesions are present, the condition is difficult to distinguish from benign familial pemphigus (Hailey-Hailey disease; 169600). Indeed, Niordson and Sylvest (1965) suggested that familial benign pemphigus is simply a bullous variant of Darier-White keratosis follicularis and that both may be variants of acrokeratosis verruciformis. They observed one patient with clinical and histopathologic features of all 3 entities. The father, brother, sister, and son had acrokeratosis verruciformis. Over 70 cases were observed in 1 kindred by Beck et al. (1977). Burge and Wilkinson (1992) suggested that Darier disease is associated with mild mental retardation in some families and also with an increased prevalence of epilepsy. Other mental illnesses, such as psychosis and affective disorder, have been reported in association with Darier disease. Castori et al. (2009) reported a 14-year-old girl with an unusual combination of Darier disease and aniridia (106210) due to double de novo heterozygous mutations in the ATP2A2 and PAX6 (607108) genes, respectively. In addition to classic manifestations of both disorders, she had multiple bone cysts resulting in nontraumatic fractures of the long bones. Bone cysts were also present in the calvarium. Intelligence was normal. A review of the literature indicated that variable bone lesions had been reported in association with Darier disease, suggesting that skeletal changes may represent rare pleiotropic manifestations of ATP2A2 mutations. ### Darier Disease, Acral Hemorrhagic Type Ruiz-Perez et al. (1999) identified asn767-to-ser (108740.0004) and cys268-to-phe (108740.0004) mutations in ATP2A2 in 4 Darier disease families. Affected members in these families showed the acral hemorrhagic type of Darier disease, in which hemorrhage into acantholytic vesicles on the palms and dorsal aspects of the fingers gives rise to black macules. These findings suggested that certain mutations may be specifically disruptive to ATP2A2 function not only in keratinocytes but also in vascular endothelium cells, or that the mutant protein has a secondary effect in the blood vessels. ### Segmental Darier Disease As patients with acantholytic dyskeratotic nevi often give a history of worsening after sun exposure, and the lesions are typical of Darier disease, numerous authors have proposed that these patients have segmental Darier disease. Sakuntabhai et al. (2000) investigated the involvement of ATP2A2 in acantholytic dyskeratotic nevi following Blaschko lines in 2 patients. They identified a nonsense mutation (tyr894 to ter; 108740.0009) in the first patient and a nonconservative glycine-to-arginine mutation at codon 769 (108740.0010) in the other patient. These mutations were present in affected skin, and were not detected in unaffected skin or in leukocytes. Sakuntabhai et al. (2000) concluded that acantholytic dyskeratotic nevi can arise from a somatic mutation in ATP2A2 and suggested that the term 'acantholytic dyskeratotic nevus' might be replaced by 'segmental Darier disease induced by postzygotic mosaicism.' Mapping In a linkage study of 2 large British kindreds, Munro et al. (1992) found a suggestion of linkage to the Duffy blood group locus (FY; 110700) at 1q21-q22. Family B showed a maximum lod of 0.807 at theta = 0.0. While the lod scores for this marker were negative in family A, a computer program showed no significant heterogeneity in the scores between the families, and the pooled data still showed positive lod scores (maximum lod = 0.218 at theta = 0.20). In 2 separate studies of British families, Bashir et al. (1993) and Craddock et al. (1993) demonstrated linkage to markers in the 12q23-q24.1 region. Craddock et al. (1993) found a maximum 2-point lod score of 4.29 with marker D12S84 at theta = 0.0. Parfitt et al. (1994) defined flanking markers for the disease, namely D12S78 and D12S79, which are 12 cM apart. In addition, Parfitt et al. (1994) increased the lod score with D12S86 to 6.11 at theta = 0.0. In an additional 10 families of European and Middle Eastern ancestry, Ikeda et al. (1994) sublocalized the DAR gene to a 5-cM region in the 12q23-q24.1 region. The combined lod score was in excess of 20. The site on chromosome 12 of this disorder of keratinization is distal to that of the type II keratin gene cluster at 12q11-q13 (Buxton, 1993). In a study of 4 large British pedigrees, Carter et al. (1994) provided further evidence for locus homogeneity by showing statistically significant linkage of all 4 families to a 4-cM region of 12q23-q24.1 between the D12S105 and D12S129 markers. In 6 Canadian families, Kennedy et al. (1995) likewise found linkage to 12q; the peak lod score on multipoint analysis was 5.5 in the interval between D12S58 and D12S84. The Canadian families were of varied European ancestry. Using microsatellite markers, Wakem et al. (1996) localized the DAR gene to a 2-cM interval between D12S234 and D12S129. Using a polymorphic intronic marker for nitric oxide synthase-1 (163731), they excluded that gene as the Darier disease gene. Monk et al. (1998) presented linkage analysis showing, in 4 families, key recombination events that refined the location of the DAR locus to a region of less than 1 cM in 12q24.1 and constructed a high resolution PAC. Ikeda et al. (1998) narrowed the Darier disease locus to an interval of approximately 3.3 Mb on chromosome 12. Craddock et al. (1993) reported a family in which Darier disease and major affective disorder cosegregated. The pedigree provided a maximum lod score of 2.1 for linkage between the Darier disease gene and a putative major dominant susceptibility locus for affective disorder. Population Genetics Sakuntabhai et al. (1999) stated that the prevalence of Darier disease had been estimated at 1 in 55,000. Molecular Genetics Monk et al. (1998) constructed a 2.4-Mb, P1-derived artificial chromosome contig spanning the DAR candidate region on 12q23-q24.1. Using a combination of EST database searching, cDNA selection, and sequence analysis of bacterial clones of the contig, Sakuntabhai et al. (1999) identified 12 genes in this interval. After screening several of these genes, they identified mutations in the ATP2A2 gene (108740), which encodes the sarco/endoplasmic reticulum Ca(2+)-ATPase type 2 isoform (SERCA2) and is highly expressed in keratinocytes. Thirteen mutations were identified, including frameshift deletions, in-frame deletions or insertions, splice site mutations, and nonconservative missense mutations in functional domains. The results demonstrated that mutations in ATP2A2 cause Darier disease and disclosed a role for the SERCA2 pump in the Ca(2+)-signaling pathway that regulates cell-to-cell adhesion and differentiation of the epidermis. Peacocke and Christiano (1999) discussed the significance of the findings of Sakuntabhai et al. (1999). In previous years, mutations in many genes contributing to structural integrity had been shown to underlie inherited disorders of the skin. Genes encoding a variety of keratins were found to be responsible for epidermolysis bullosa simplex, epidermolytic hyperkeratosis, ichthyosis bullosa of Siemens, palmoplantar keratoderma, and pachyonychia congenita. Mutations in the LOR gene (152445), which encodes loricrin (the major component of the cornified cell envelope), had been implicated in 2 keratinizing genodermatoses, and the enzyme that crosslinks the cornified cell envelope, transglutaminase I, had been implicated in the pathogenesis of the recessively inherited lamellar ichthyosis. Plakophilin (PKP1; 601975), plectin (PLEC1; 601282), and desmoplakin (DSP; 125647) had been implicated in skin disease causation. While it seemed likely that mutations underlying Darier disease and the related disorder, Hailey-Hailey disease (169600), would affect a structural component, both disorders were mapped to chromosomal regions devoid of any known candidate genes. The first hints that the Darier disease gene might not directly concern the 'bricks and mortar' of the skin surfaced when, most unexpectedly, mutations in the connexin-31 gene (GJB3; 603324) were found to cause erythrokeratodermia variabilis. Combined with the discovery that mutations in the connexin-26 gene (GJB2; 121011) cause palmoplantar keratoderma with deafness, this finding suggested that intercellular communication is crucial for epidermal differentiation. Sakuntabhai et al. (1999) reported an additional 24 mutations in the ATP2A2 gene among 19 DD families and 6 sporadic cases. Over 50% of the mutations led to a premature termination codon, leading the authors to propose that haploinsufficiency is a common molecular mechanism for DD. However, marked inter- and intrafamilial phenotypic variability of the disease was observed, suggesting that additional factors may contribute to the clinical phenotype. INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Recurrent parotid gland swelling \- Oral mucosal lesions (15% of patients) SKIN, NAILS, & HAIR Skin \- Brown, warty keratotic papules (trunk, scalp, forehead, flexural areas) \- Palmar pits \- Plantar pits \- Odoriferous,, hypertrophic plaques \- Keratotic plaques (palms) \- Hemorrhagic palmar and plantar macules (uncommon) \- Acrokeratosis verruciformis-like lesions on dorsum of hands Skin Histology \- Acantholysis (cell separation) in the suprabasal layer of the epidermis with premature differentiation and hyperkeratinization of the epidermis Electron Microscopy \- Loss of desmosomal attachments and perinuclear aggregation of keratin filaments Nails \- Fingernails involved more often than toenails \- Longitudinal white or red subungual streaks \- Distal V-shaped notching \- Nail fragility \- Longitudinal ridging \- Subungual hyperkeratotic fragments NEUROLOGIC Central Nervous System \- Mental retardation, mild \- Seizures Behavioral Psychiatric Manifestations \- Schizophrenia \- Bipolar disorder MISCELLANEOUS \- Age of onset, 6-20 years \- Skin lesions exacerbated by heat, exercise (sweating), and sunlight \- Acral hemorrhagic variant \- Itch, pain, and body malodor often \- Allelic to acrokeratosis verruciformis ( 101900 ) MOLECULAR BASIS \- Caused by mutation in the ATPase, Ca++ dependent, slow-twitch, cardiac muscle-2 gene (ATP2A2, 108740.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DARIER-WHITE DISEASE	c0022595	26,629	omim	https://www.omim.org/entry/124200	2019-09-22T16:42:35	{"doid": ["2734"], "mesh": ["D007644"], "omim": ["124200"], "icd-10": ["E50.8"], "orphanet": ["218"], "synonyms": ["Alternative titles", "KERATOSIS FOLLICULARIS", "DARIER DISEASE"]}
Barbiturate overdose Other namesBarbiturate poisoning, barbiturate toxicity Molecular diagram of phenobarbital SpecialtyEmergency medicine SymptomsDecreased breathing, decreased level of consciousness[1] ComplicationsNoncardiogenic pulmonary edema[2] Duration6-12 hours[2] CausesAccidental, suicide[3] Diagnostic methodBlood or urine tests[4] Treatmentmedical support support, activated charcoal[5][6] FrequencyUncommon[7] Barbiturate overdose is poisoning due to excessive doses of barbiturates.[8] Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe (respiratory depression).[1] Complications of overdose can include noncardiogenic pulmonary edema.[2] If death occurs this is typically due to a lack of breathing.[3] Barbiturate overdose may occur by accident or purposefully in an attempt to cause death.[3] The toxic effects are additive to those of alcohol and benzodiazepines.[3] The lethal dose varies with a person's tolerance and how the drug is taken.[3] The effects of barbiturates occur via the GABA neurotransmitter.[2] Exposure may be verified by testing the urine or blood.[4] Treatment involves supporting a person's breathing and blood pressure.[2][5] While there is no antidote, activated charcoal may be useful.[5][6] Multiple doses of charcoal may be required.[7] Hemodialysis may occasionally be considered.[6] Urine alkalinisation has not been found to be useful.[6] While once a common cause of overdose, barbiturates are now a rare cause.[7] ## Contents * 1 Mechanism * 2 Treatment * 3 Notable cases * 4 Differential diagnosis * 5 References * 6 External links ## Mechanism[edit] Barbiturates increase the time that the chloride pore of the GABAA receptor is opened, thereby increasing the efficacy of GABA. In contrast, benzodiazepines increase the frequency with which the chloride pore is opened, thereby increasing GABA's potency.[9] ## Treatment[edit] Treatment involves supporting a person's breathing and blood pressure.[2][5] While there is no antidote, activated charcoal may be useful.[5][6] Multiple doses of charcoal may be required.[7] Hemodialysis may occasionally be considered.[6] Urine alkalinisation has not been found to be useful.[6] If a person is drowsy but awake and can swallow and breathe without difficulty, the treatment can be as simple as monitoring the person closely. If the person is not breathing, it may involve mechanical ventilation until the drug has worn off. Psychiatric consult is generally recommended. ## Notable cases[edit] People who are known to have committed suicide by barbiturate overdose include, Gillian Bennett,[10] Charles Boyer, Ruan Lingyu, Dalida,[11][12] Jeannine "The Singing Nun" Deckers, Felix Hausdorff, Abbie Hoffman, Phyllis Hyman, C. P. Ramanujam, George Sanders, Jean Seberg, Lupe Vélez and the members of Heaven's Gate cult. Others who have died as a result of barbiturate overdose include Pier Angeli, Brian Epstein, Judy Garland, Jimi Hendrix, Marilyn Monroe, Inger Stevens, Dinah Washington, Ellen Wilkinson, and Alan Wilson; in some cases these have been speculated to be suicides as well. Those who died of a combination of barbiturates and other drugs include Rainer Werner Fassbinder, Dorothy Kilgallen, Malcolm Lowry, Edie Sedgwick and Kenneth Williams. Dorothy Dandridge died of either an overdose or an unrelated embolism. Ingeborg Bachmann may have died of the consequences of barbiturate withdrawal (she was hospitalized with burns, the doctors treating her not being aware of her barbiturate addiction). Maurice Chevalier unsuccessfully attempted suicide in March 1971 by swallowing a large amount of barbiturates and slitting his wrists; however, he suffered severe organ damage as a result and died from multiple organ failure nine months later. ## Differential diagnosis[edit] The differential diagnosis should include intoxication by other substances with sedative effects, such as benzodiazepines, anticonvulsants (carbamazepine), alcohols (ethanol, ethylene glycol, methanol), opioids, carbon monoxide, sleep aids, and gamma-Hydroxybutyric acid (GHB – a known date rape drug). Natural disease that can result in disorientation may be in the differential, including hypoglycemia and myxedema coma. In the right setting, hypothermia should be ruled out.[13] ## References[edit] 1. ^ a b Weaver, MF (3 September 2015). "Prescription Sedative Misuse and Abuse". The Yale Journal of Biology and Medicine. 88 (3): 247–56. PMC 4553644. PMID 26339207. 2. ^ a b c d e f Marx, John A. Marx (2014). "165". Rosen's emergency medicine : concepts and clinical practice (8th ed.). Philadelphia, PA: Elsevier/Saunders. pp. Sedative Hypnotics. ISBN 978-1455706051. 3. ^ a b c d e Sadock, Benjamin J.; Sadock, Virginia A. (2008). Kaplan & Sadock's Concise Textbook of Clinical Psychiatry. Lippincott Williams & Wilkins. p. 149. ISBN 9780781787468. Archived from the original on 2016-11-04. 4. ^ a b Baren, Jill M. (2008). Pediatric Emergency Medicine. Elsevier Health Sciences. p. 955. ISBN 978-1416000877. Archived from the original on 2016-11-04. 5. ^ a b c d e Carroll, Robert G. (2010). Problem-based Physiology. Elsevier Health Sciences. p. 99. ISBN 978-1416042174. Archived from the original on 2016-11-04. 6. ^ a b c d e f g Roberts, DM; Buckley, NA (January 2011). "Enhanced elimination in acute barbiturate poisoning - a systematic review". Clinical Toxicology. 49 (1): 2–12. doi:10.3109/15563650.2010.550582. PMID 21288146. S2CID 41375480. 7. ^ a b c d Müller, D; Desel, H (October 2013). "Common causes of poisoning: etiology, diagnosis and treatment". Deutsches Ärzteblatt International. 110 (41): 690–9, quiz 700. doi:10.3238/arztebl.2013.0690. PMC 3813891. PMID 24194796. 8. ^ Publishing, Bloomsbury (2009). Dictionary of Medical Terms. Bloomsbury Publishing. p. 37. ISBN 9781408102091. Archived from the original on 2016-11-04. 9. ^ Lafferty, KA; Bonhomme, K; Kopinski, P; Lee, DC; Abdel-Kariem, R (14 January 2017). Tarabar, A; VanDeVoort, JT; Burns, MJ (eds.). "Barbiturate Toxicity: Pathophysiology". eMedicine. New York, USA: WebMD. Archived from the original on 26 August 2017. Retrieved 26 August 2017. 10. ^ "DeadAtNoon". deadatnoon.com. Retrieved 2020-06-23. 11. ^ "Dalida". New York Times. 5 May 1987. Archived from the original on 26 May 2012. Retrieved 28 February 2008. 12. ^ Simmonds, Jeremy (2008). v. Chicago Review Press. p. 225. ISBN 978-1-55652-754-8. Archived from the original on 2016-05-18. 13. ^ Suddock, Jolee T.; Cain, Matthew D. (2020), "Barbiturate Toxicity", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 29763050, retrieved 2020-08-05 ## External links[edit] Classification D * ICD-10: F13.0, T42.3 * ICD-9-CM: 969 External resources * eMedicine: article/813155 * v * t * e Psychoactive substance-related disorder General * SID * Substance intoxication / Drug overdose * Substance-induced psychosis * Withdrawal: * Craving * Neonatal withdrawal * Post-acute-withdrawal syndrome (PAWS) * SUD * Substance abuse / Substance-related disorders * Physical dependence / Psychological dependence / Substance dependence Combined substance use * SUD * Polysubstance dependence * SID * Combined drug intoxication (CDI) Alcohol SID Cardiovascular diseases * Alcoholic cardiomyopathy * Alcohol flush reaction (AFR) Gastrointestinal diseases * Alcoholic liver disease (ALD): * Alcoholic hepatitis * Auto-brewery syndrome (ABS) Endocrine diseases * Alcoholic ketoacidosis (AKA) Nervous system diseases * Alcohol-related dementia (ARD) * Alcohol intoxication * Hangover Neurological disorders * Alcoholic hallucinosis * Alcoholic polyneuropathy * Alcohol-related brain damage * Alcohol withdrawal syndrome (AWS): * Alcoholic hallucinosis * Delirium tremens (DTs) * Fetal alcohol spectrum disorder (FASD) * Fetal alcohol syndrome (FAS) * Korsakoff syndrome * Positional alcohol nystagmus (PAN) * Wernicke–Korsakoff syndrome (WKS, Korsakoff psychosis) * Wernicke encephalopathy (WE) Respiratory tract diseases * Alcohol-induced respiratory reactions * Alcoholic lung disease SUD * Alcoholism (alcohol use disorder (AUD)) * Binge drinking Caffeine * SID * Caffeine-induced anxiety disorder * Caffeine-induced sleep disorder * Caffeinism * SUD * Caffeine dependence Cannabis * SID * Cannabis arteritis * Cannabinoid hyperemesis syndrome (CHS) * SUD * Amotivational syndrome * Cannabis use disorder (CUD) * Synthetic cannabinoid use disorder Cocaine * SID * Cocaine intoxication * Prenatal cocaine exposure (PCE) * SUD * Cocaine dependence Hallucinogen * SID * Acute intoxication from hallucinogens (bad trip) * Hallucinogen persisting perception disorder (HPPD) Nicotine * SID * Nicotine poisoning * Nicotine withdrawal * SUD * Nicotine dependence Opioids * SID * Opioid overdose * SUD * Opioid use disorder (OUD) Sedative / hypnotic * SID * Kindling (sedative–hypnotic withdrawal) * benzodiazepine: SID * Benzodiazepine overdose * Benzodiazepine withdrawal * SUD * Benzodiazepine use disorder (BUD) * Benzodiazepine dependence * barbiturate: SID * Barbiturate overdose * SUD * Barbiturate dependence Stimulants * SID * Stimulant psychosis * amphetamine: SUD * Amphetamine dependence Volatile solvent * SID * Sudden sniffing death syndrome (SSDS) * Toluene toxicity * SUD * Inhalant abuse * v * t * e * Poisoning * Toxicity * Overdose History of poison Inorganic Metals Toxic metals * Beryllium * Cadmium * Lead * Mercury * Nickel * Silver * Thallium * Tin Dietary minerals * Chromium * Cobalt * Copper * Iron * Manganese * Zinc Metalloids * Arsenic Nonmetals * Sulfuric acid * Selenium * Chlorine * Fluoride Organic Phosphorus * Pesticides * Aluminium phosphide * Organophosphates Nitrogen * Cyanide * Nicotine * Nitrogen dioxide poisoning CHO * alcohol * Ethanol * Ethylene glycol * Methanol * Carbon monoxide * Oxygen * Toluene Pharmaceutical Drug overdoses Nervous * Anticholinesterase * Aspirin * Barbiturates * Benzodiazepines * Cocaine * Lithium * Opioids * Paracetamol * Tricyclic antidepressants Cardiovascular * Digoxin * Dipyridamole Vitamin poisoning * Vitamin A * Vitamin D * Vitamin E * Megavitamin-B6 syndrome Biological1 Fish / seafood * Ciguatera * Haff disease * Ichthyoallyeinotoxism * Scombroid * Shellfish poisoning * Amnesic * Diarrhetic * Neurotoxic * Paralytic Other vertebrates * amphibian venom * Batrachotoxin * Bombesin * Bufotenin * Physalaemin * birds / quail * Coturnism * snake venom * Alpha-Bungarotoxin * Ancrod * Batroxobin Arthropods * Arthropod bites and stings * bee sting / bee venom * Apamin * Melittin * scorpion venom * Charybdotoxin * spider venom * Latrotoxin / Latrodectism * Loxoscelism * tick paralysis Plants / fungi * Cinchonism * Ergotism * Lathyrism * Locoism * Mushrooms * Strychnine 1 including venoms, toxins, foodborne illnesses. * Category * Commons * WikiProject [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Barbiturate overdose	c0572916	26,630	wikipedia	https://en.wikipedia.org/wiki/Barbiturate_overdose	2021-01-18T19:00:09	{"icd-9": ["969"], "icd-10": ["T42.3", "F13"], "wikidata": ["Q1184752"]}
## Summary ### Clinical characteristics. PRSS1-related hereditary pancreatitis (HP) is characterized by episodes of acute pancreatitis (AP) and recurrent acute pancreatitis (RAP: >1 episode of AP), with frequent progression to chronic pancreatitis (CP). Manifestations of acute pancreatitis can range from vague abdominal pain lasting one to three days to severe abdominal pain lasting days to weeks and requiring hospitalization. ### Diagnosis/testing. The diagnosis of PRSS1-related hereditary pancreatitis is established in a proband with episodes of AP, RAP, and/or CP and a heterozygous pathogenic gain-of-function variant in PRSS1 identified by molecular genetic testing. Note that, due to incomplete penetrance, identification of a disease-associated PRSS1 variant in an asymptomatic individual is not sufficient for a clinical diagnosis. High-penetrance PRSS1 pathogenic variants include p.Asn29Ile and p.Arg122His, and lower-penetrance pathogenic variants include p.Arg16Val and p.Arg122Cys. Other pathogenic PRSS1 variants are recognized; these latter variants typically require additional risk factors to cause disease and do not cause autosomal dominant hereditary pancreatitis. ### Management. Treatment of manifestations: AP episodes are treated with rapid assessment of severity and fluid resuscitation as needed. Individuals with HP should be counseled not to delay in being assessed for AP since hypovolemia and shock leads to serious organ dysfunction and failure. For chronic pancreatitis, continue strategies to prevent RAP attacks. Antioxidants may have some benefit. Pancreatic enzyme replacement therapy to improve digestion in those with pancreatic insufficiency and bloating, steatorrhea, diarrhea, unexplained weight loss, and/or micronutrient deficiencies (e.g., vitamins A, D, B12); treatment of glucose intolerance with a regimen typically including metformin. Management of pain can be challenging but should begin with medical therapy, with endoscopic therapies for obstructions and surgery for more severe pain – including total pancreatectomy with islet autotransplantation in selected individuals. Prevention of primary manifestations: Avoid smoking, alcohol abuse. Recommended: a healthy diet that is low in red meat, multiple small meals if it improves symptoms, good hydration (especially during exercise), vitamins, and antioxidants. Some individuals report that moderate exercise helps control episodes of pain and reduce pain severity. Surveillance: Referral to a surveillance program. Agents/circumstances to avoid: Alcohol and tobacco use; dehydration; physical and emotional stress. Evaluation of relatives at risk: Molecular genetic testing for the family-specific germline PRSS1 pathogenic variant to allow early diagnosis and prevention and/or management of symptoms. ### Genetic counseling. HP caused by gain-of-function PRSS1 pathogenic variants is inherited in an autosomal dominant manner. The proportion of PRSS1-related HP caused by a de novo pathogenic variant is unknown. Each child of an individual with autosomal dominant PRSS1-related HP has a 50% chance of inheriting the variant. Prenatal diagnosis for pregnancies at increased risk is possible if the pathogenic variant of an affected family member has been identified. A number of other variants in the coding and noncoding regions of the PRSS1 locus are associated with risk for pancreatitis, but they typically do not cause autosomal dominant hereditary pancreatitis. ## Diagnosis The clinical features of PRSS1-related hereditary pancreatitis (HP) are clinically indistinguishable from other forms of acute and chronic pancreatitis. ### Suggestive Findings PRSS1-related HP should be suspected in individuals with the following: * Acute pancreatitis occurring in childhood * Recurrent acute attacks of pancreatitis of unknown cause * Chronic pancreatitis of unknown cause, particularly with onset before age 25 years * A family history of recurrent acute pancreatitis, chronic pancreatitis, and/or childhood pancreatitis consistent with autosomal dominant inheritance * A family history of pancreatitis, diabetes mellitus, or pancreatic cancer Acute pancreatitis (AP) is characterized by sudden onset of typical epigastric abdominal pain that may radiate to the back, serum pancreatic digestive enzymes (e.g., amylase, lipase) that are more than threefold the upper limits of normal, and/or characteristic findings of pancreatic inflammation on abdominal imaging [Banks et al 2013]. Recurrent acute pancreatitis (RAP) is defined as a syndrome of multiple distinct acute inflammatory responses originating within the pancreas in individuals with genetic, environmental, traumatic, morphologic, metabolic, biologic, and/or other risk factors who experienced two or more episodes of documented acute pancreatitis, separated by at least three months [Guda et al 2018]. Chronic pancreatitis (CP) is defined as a pathologic fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress [Whitcomb et al 2016]. The features of established and advanced chronic pancreatitis include pancreatic atrophy, fibrosis, pain syndromes, duct distortion and strictures, and calcifications; pancreatic exocrine dysfunction; and pancreatic endocrine dysfunction and dysplasia [Whitcomb et al 2016]. ### Establishing the Diagnosis The diagnosis of PRSS1-related HP is established in a proband by identification of a heterozygous pathogenic variant in PRSS1 by molecular genetic testing (see Table 1). Molecular genetic testing approaches can include a combination of single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of PRSS1 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. * A multigene panel that includes PRSS1 and other genes of interest (see Differential Diagnosis) may also be considered to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. ### Table 1. Molecular Genetic Testing Used in PRSS1-Related Hereditary Pancreatitis View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method PRSS1Sequence analysis 3≥94% 4 Gene-targeted deletion/duplication analysis 5≤6% 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. One of two pathogenic variants (p.Asn29Ile or p.Arg122His) is identified in 90% of affected individuals [Rebours et al 2009]. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Masson et al [2008a]. Among copy number variants identified: duplication and triplication of a 605-kb segment containing PRSS1 and PRSS2 [Le Maréchal et al 2006, Masson et al 2008b]. ## Clinical Characteristics ### Clinical Description In PRSS1-related hereditary pancreatitis (HP) the range of symptoms and disease course vary from person to person. On average, acute pancreatitis occurs by age ten years, chronic pancreatitis by age 20 years, and the incidence of pancreatic cancer rises at age 50 years. Acute pancreatitis (sudden onset; duration <6 months) can be mild, moderate, or severe, depending on the local and systemic complications [Banks et al 2013]. Findings can range from vague abdominal pain lasting three to four days to sudden onset of severe upper abdominal pain radiating to the back with nausea, vomiting, orthostatic hypotension, confusion, and shortness of breath. Mild cases typically require one to two days of hospitalization. Severe cases may require intensive care management, result in prolonged hospitalization, and/or require six months or more to recover. Persons with a PRSS1-related HP may also have other risk factors for pancreatitis, such as gallstones, alcohol consumption, smoking, and/or pathogenic variants in other pancreatitis-associated genes. Of note, persons with hereditary pancreatitis report that even small amounts of alcohol may sometimes trigger episodes of pain or acute pancreatitis. Chronic pancreatitis. Approximately half of individuals with PRSS1-related HP progress to chronic inflammation and/or irreversible morphologic changes classified as chronic pancreatitis (CP). The characteristics of CP include variable features of pancreatic atrophy, fibrosis, pain, duct distortion and strictures, and calcifications; pancreatic exocrine dysfunction; and pancreatic endocrine dysfunction and dysplasia [Whitcomb et al 2016]. Long-standing inflammation results in complications that can include the following: * Episodic or continuous mild-to-severe abdominal pain. Pain is usually sharp and stabbing in initial attacks, becoming deep and burning as the syndrome progresses. The most psychologically distressing pain is constant chronic pain, regardless of intensity [Machicado et al 2017]. * Exocrine pancreatic insufficiency leading to maldigestion with symptoms of gas and bloating and the appearance of diarrhea, oil in the stool (steatorrhea), and/or floating stools. Other signs of maldigestion include weight loss, fat-soluble-vitamin deficiency, and protein deficiency with low albumin, prealbumin, or retinol-binding protein detected on blood testing. * Pancreatic endocrine insufficiency manifesting initially as inappropriately elevated levels of blood glucose (glucose intolerance). Up to 48% of persons with PRSS1-related HP develop diabetes mellitus [Howes et al 2004, Rebours et al 2009], which is similar to the rates in other types of chronic pancreatitis [Bellin et al 2017]. Type 3c diabetes mellitus (pancreatogenic diabetes mellitus) is caused by loss of pancreatic tissue as a result of surgery or chronic pancreatitis; type 3c is associated with loss of both the insulin-producing beta cells and the glucagon-producing alpha cells, which results in loss of counter-regulatory hormones and risk of hypoglycemia. It is not clear what percentage of individuals with pancreatitis and diabetes have complete loss of islet cells versus beta cell dysfunction and/or peripheral insulin resistance as in typical type 2 diabetes mellitus. Pancreatic cancer. Chronic inflammation of the pancreas is associated with an increased risk for pancreatic cancer. Persons with HP are at increased risk for pancreatic cancer because the onset of chronic pancreatitis is 20-30 years earlier than in the general population [Rebours et al 2008]. The risk of developing pancreatic cancer by age 70 years was reported to be 18.8%-40%, but a more recent study suggested that the cumulative risk of pancreatic cancer in individuals with PRSS1-related HP by age 70 years is 7.2% [Zhan et al 2018]. ### Genotype-Phenotype Correlations Four gain-of-function PRSS1 variants have been associated with autosomal dominant hereditary pancreatitis. These include high-penetrance PRSS1 pathogenic variants p.Asn29Ile and p.Arg122His and lower-penetrance pathogenic variants p.Ala16Val and p.Arg122Cys. Other PRSS1 variants have been associated with disease, but typically require additional risk factors to cause disease and do not segregate as autosomal dominant hereditary pancreatitis. ### Penetrance The reported penetrance of PRSS1-related HP varies: * 40% in Spain for p.Arg122Cys [de las Heras-Castaño et al 2009] * 43% in Europe for p.Ala16Val [Grocock et al 2010] * 80% in the US for p.Asn29Ile and p.Arg122His [Sossenheimer et al 1997] * 93% in France for p.Asn29Ile and p.Arg122His [Rebours et al 2009] * 80% [Sibert 1978] to 96% in England [Howes et al 2004] for p.Asn29Ile and p.Arg122His The median age for diagnosis of pancreatitis in a large multifamily US cohort was seven years (IQR 3-16; range <1-73) [Shelton et al 2018]. ### Nomenclature In some instances, PRSS1-related hereditary pancreatitis has been described as chronic calcific pancreatitis, familial pancreatitis, or recurrent or relapsing acute or chronic pancreatitis; however, these are clinical diagnoses and do not describe the molecular basis of the disorder. ### Prevalence A report from France estimated a population prevalence of 0.3:100,000 persons with PRSS1-related hereditary pancreatitis [Rebours et al 2009]. PRSS1-related HP is found at highly variable rates in different populations of individuals with chronic pancreatitis. In Germany 5.0% of individuals with chronic pancreatitis had PRSS1 pathogenic variants p.Asn29Ile or p.Arg122His; additional reported variants included p.Ala16Val (2.1%), p.Arg122Cys (0.8%), and other rare variants [Rosendahl et al 2013]. In Denmark, of 12.4% of persons initially classified as having idiopathic acute and chronic pancreatitis, 9% were found to have a PRSS1 pathogenic variant (1% of all individuals with pancreatitis) [Joergensen et al 2010]. In Spain, 7.7% of individuals with chronic pancreatitis had PRSS1 pathogenic variant p.Asn29Ile [Mora et al 2009]. In the North American Pancreatitis Study II about 5% of individuals had PRSS1 variants [Phillips et al 2018]. Among children with pancreatitis, the incidence of PRSS1 pathogenic variants varies: Poland 9.6% [Sobczyńska-Tomaszewska et al 2006], Mexico 1.1% [Sánchez-Ramírez et al 2012], China 9.3% [Wang et al 2013], and Korea 9.6% [Cho et al 2016]. In India, PRSS1 variants are rare [Chandak et al 2004, Poddar et al 2017]. In the INSPPIRE cohort of 301 children primarily from the United States, 17% of individuals with recurrent acute pancreatitis and 46% of children with chronic pancreatitis had a PRSS1 pathogenic variant [Kumar et al 2016]. Furthermore, the children with a PRSS1 pathogenic variant had a younger age of onset than children with CP of other etiologies [Giefer et al 2017]. ## Differential Diagnosis The morphologic features and laboratory findings of PRSS1-related hereditary pancreatitis are the same as those of other causes of hereditary (Table 2) and non-hereditary pancreatitis. ### Table 2. Other Causes of Hereditary Pancreatitis: Genes and Distinguishing Clinical Features View in own window Gene 1MOIDistinguishing Clinical FeaturesReferences / Selected OMIM Links CASRAD 2 * Hypercalcemia * RAP/CP OMIM 601199; see Pancreatitis Overview CELAD * Diabetes mellitus * Pancreatic lipomatosis * Pancreatic exocrine insufficiency * Chronic pancreatitis w/out severe malnutrition * RAP/CP Fjeld et al [2015] CFTRAR 2 * Features of cystic fibrosis * RAP/CP CFTR-related disorders CLDN2XLAlcoholic pancreatitisWhitcomb et al [2012], Derikx et al [2015], Giri et al [2016] CPA1ADEarly-onset, nonalcoholic chronic pancreatitisOMIM 114850 CTRCAD 2 * RAP/CP * History of smoking See Pancreatitis Overview SPINK1AR 2 * ↑ risk for chronic pancreatitis following acute pancreatitis * Also AR early-onset, aggressive pancreatitis See Pancreatitis Overview AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; RAP/CP = recurrent acute pancreatitis and/or chronic pancreatitis 1\. Genes are listed in alphabetic order. 2\. Predisposition to hereditary pancreatitis caused by pathogenic variants in this gene may be polygenic and/or multifactorial. Non-hereditary causes of acute, recurrent acute, and chronic pancreatitis to consider. Most acute pancreatitis is caused by gallstones (biliary), alcohol, or hypertriglyceridemia, or is idiopathic. Non-hereditary recurrent acute pancreatitis and chronic pancreatitis can be simple or complex disorders and typically are associated with one or more factors on the TIGAR-O list [adapted from Etemad & Whitcomb 2001]. * Toxic-metabolic * Alcohol * Smoking * Hypercalcemia * Hypertriglyceridemia * Medications (e.g., azothioprine) * Toxins (e.g., due to chronic renal failure) * Idiopathic * Early onset (age <35 years) * Late onset (age ≥35 years) * Autoimmune * Type 1 (IgG4-related disease) * Type 2 * Recurrent or severe acute pancreatitis. Postnecrotic (severe acute pancreatitis) * Obstructive * Pancreatic divisum * Ampullary stenosis * Duct obstruction (e.g., tumor) * Post-traumatic pancreatic duct scars ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with PRSS1-related hereditary pancreatitis (HP), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended: * Referral to a gastroenterologist for evaluation of pancreatic exocrine function using invasive or noninvasive testing * Fecal elastase-1 analysis. It can be falsely positive with diarrhea but can be used while an individual is taking pancreatic enzyme replacement therapy. The test is insensitive for mild pancreatic exocrine insufficiency. * Secretin-stimulated pancreatic bicarbonate secretion testing, which requires intubation of the duodenum and careful measure of pancreatic bicarbonate secretion over about an hour (depending on the method). It is considered very sensitive, but only assesses duct function. * Cholecystokinin (CCK) and its analogs (e.g., CCK-8) or receptor agonists (e.g., cerulean); have also been used to assess acinar cell function. * Serum trypsinogen levels to measure pancreatic acinar cell mass [Couper et al 1995]. Levels are useful if the individual is not experiencing pain and/or an acute pancreatitis flair, as levels will be increased along with amylase and lipase [Pezzilli et al 2000]. * Diffusion-weighted MRI. Various "functional" tests have been advocated using abdominal imaging techniques, including secretin-stimulated MRI. Although diffusion-weighted MRI is probably better at detecting the structural changes of chronic pancreatitis than standard MRI [Akisik et al 2009], it does not measure function, and fluid volume cannot measure bicarbonate output. * Referral to an endocrinologist for evaluation of pancreatic endocrine function (i.e., assessment of glucose tolerance) * Referral to a pancreatic cancer surveillance program in persons with chronic pancreatitis and/or risk factors for pancreatic cancer (e.g., age >40 years, family history of pancreatic cancer, history of smoking) * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Medical treatment and management for PRSS1-related HP are similar to those for non-hereditary pancreatitis. #### Acute Pancreatitis Treatment of acute pancreatitis usually focuses on acute fluid and pain management. Discontinuation of smoking and alcohol use reduces the frequency of recurrent attacks, slows the rate of progression, and decreases the likelihood of complications, including diabetes mellitus and pancreatic cancer. Pancreatic pain can result from pancreatic duct obstruction, parenchyma hypertension, pancreatic ischemia, inflammation, neuropathy, and central pain. * Analgesics are offered when pancreatic enzyme replacement therapy is not sufficient to control pain. * Antioxidants have been reported to improve pain control in a few individuals with hereditary pancreatitis. In India, antioxidant treatment was associated with better pain control and outcomes [Shalimar et al 2017]. * Endoscopic or surgical interventions may be useful for treating obstructive pain [Clarke et al 2012], pseudocysts, bile duct or duodenal obstruction, infected pancreatic necrosis, and malignancy. * Total pancreatectomy with islet autotransplantation may be considered in individuals with severe pain and/or inflammation that cannot be controlled by other approaches. Efficacy increases when this is done approximately two years before chronic pain develops [Anderson et al 2016, Drewes et al 2017]. It is recommended that persons in whom pancreatectomy is being considered be referred to expert centers. In persons with adequate endocrine pancreatic function, islet cell isolation and autotransplantation may be considered at the time of total pancreatectomy [Bellin et al 2008, Bellin et al 2018]. Consideration of individuals for total pancreatectomy with islet transplantation should include age and disease duration, both of which adversely affect postsurgical outcomes [Bellin et al 2018]. Note: Islet autotransplantation should not be offered to older adults with long-standing chronic pancreatitis and diabetes mellitus because the implanted cells may be malignant. In addition to severe pain, endoscopic and surgical interventions are reserved for complications such as pseudocysts, bile duct or duodenal obstruction, infected pancreatic necrosis, and malignancy. Obstructions or calcifications in the pancreatic ducts may be relieved by procedures such as endoscopic retrograde cholangiopancreatography (ERCP), in which endoscopic cannulation of the common bile duct and pancreatic duct is followed by injection of radiographic dye. Decompressing/clearing of blockage decreases pain as well as the number of hospitalizations and recurrent attacks in many persons with HP [Dever et al 2010]. Note: Because of the risk of acute pancreatitis following ERCP, it is only recommended for obtaining brushings (for evaluation of strictures) and for therapeutic intervention, not diagnosis. Although a variety of surgical approaches are used for noncancerous pancreatic disorders that cause pain or obstruction from multiple strictures, pancreatic drainage surgeries in those with hereditary pancreatitis are unlikely to stop the underlying inflammatory process. Furthermore, pancreatic surgery often reduces the number of islet cells, which are essential in pancreatic endocrine function [Sutton et al 2010, Kobayashi et al 2011]. Because total pancreatectomy with islet cell auto-transplantation is an option for some persons with HP, retaining as many islet cells as possible is an important consideration before proceeding with any pancreatic surgery [Bellin et al 2014]. #### Chronic Pancreatitis Treatment of chronic pancreatitis focuses on improving quality of life by managing pancreatic pain, maldigestion, and diabetes mellitus. Pain is a variable complication of recurrent and chronic inflammation and ranges from minimal to severe and disabling. Pain can result from inflammation, ischemia, obstructed ducts, pseudocysts, and/or maldigestion [Fasanella et al 2007]. * One small study from Italy suggested that vitamins and antioxidants reduced pain in PRSS1-related hereditary pancreatitis [Uomo et al 2001]. * Pain from maldigestion is improved with pancreatic digestive enzymes [Burton et al 2011]. * If the main pancreatic duct is obstructed, a trial of endoscopic treatment is often used for diagnostic, therapeutic, and prognostic reasons in determining longer-term therapy. * Surgery has been reported to be helpful by many individuals; however, surgical approaches should be postponed if islet autotransplantation is being considered. * Several expert groups (e.g., University of Minnesota, University of Pittsburgh) are offering pancreatic islet autotransplantation in an effort to both control severe pain and delay the development of diabetes mellitus [Sutton et al 2010, Kobayashi et al 2011]. It is recommended that physicians and affected individuals work closely with expert centers since the process is irreversible. Maldigestion due to pancreatic exocrine insufficiency: * Pancreatic enzyme replacement therapy improves digestion in those with pancreatic insufficiency who have pain with eating, steatorrhea (fat in the stool), and/or diarrhea [Burton et al 2011]. * The amount of pancreatic enzyme replacement necessary depends on the diet and on the amount of residual pancreatic function (which diminishes over time). The normal amount of lipase secreted is about 750,000-1,000,000 units (USP) per meal. (Note that earlier papers used IU, and 1 IU = 3 USP units) [Pongprasobchai & DiMagno 2005]. Since a minimum of 10% of normal pancreatic enzyme output is needed to digest a meal, about 70,000-80,000 USP units of lipase are required for an average-sized adult (70 kg) with total pancreatic insufficiency. The amount can be reduced for smaller persons and those with residual pancreatic exocrine function – while monitoring symptoms and nutritional parameters. Pancreatic endocrine insufficiency occurs in individuals with chronic pancreatitis and is associated with a gradual loss of function resulting in diabetes mellitus. * Monitor for glucose intolerance. * Optimize nutrient digestion with pancreatic enzyme replacement therapy to stimulate foregut hormone release and minimize hindgut hormone release. Metformin is recommended as an oral antidiabetic agent [Decensi et al 2010]. * Synchronize the digestion and absorption of nutrients with insulin therapy delivery, with special attention to hypoglycemia due to loss of glucagon cells. ### Prevention of Primary Manifestations The ability to prevent the primary manifestations of PRSS1-related HP is limited. The following recommendations are for individuals with (or at risk for) PRSS1-related HP. Following these recommendations from early childhood may help prevent attacks of acute pancreatitis: * Low-fat diet. No formal guidelines for amount of dietary fat exist; however, some physicians recommend a low-fat diet to minimize pancreatic stimulation. If a low-fat diet is chosen, extra attention to providing fat-soluble vitamins (A, D, E, K) is needed. * Multiple small meals. No evidence-based guidelines exist; however, small meals may minimize pancreatic exocrine stimulation. * Good hydration. Maintaining good hydration may be helpful in minimizing attacks, especially since nausea, vomiting, and loss of appetite limit oral intake during an attack. Recognition of acute pancreatitis and prompt medical treatment with adequate intravenous hydration can be beneficial in decreasing the severity of the attack [de-Madaria et al 2018]. * Antioxidants. One small study suggested that antioxidants may be useful in reducing the likelihood of acute pancreatitis in persons at risk for hereditary pancreatitis [Uomo et al 2001]. * Exercise, yoga, and other relaxation techniques may increase quality of life in persons with pancreatitis [Sareen et al 2007]. Some individuals report that regular exercise, such as running, helps reduce the frequency of episodes of pancreatitis [Authors, unpublished]. ### Surveillance Surveillance for pancreatic cancer may benefit individuals with PRSS1-related HP age 40 years and older who have long-standing chronic pancreatitis and a strong family history of pancreatic cancer [Chang et al 2014]. Because long-standing chronic pancreatitis results in pancreatic scarring and fibrosis that make assessment of abnormalities difficult [Ulrich 2001, Brand et al 2007], it is recommended that concerned individuals be referred to a surveillance program that includes biomarker research and other new techniques. ### Agents/Circumstances to Avoid Alcohol and tobacco. Smoking doubles the risk for all forms of pancreatitis, including hereditary pancreatitis [Maisonneuve et al 2005, Yadav et al 2009]. In combination, smoking and alcohol use increases the risk of developing pancreatitis eightfold [Yadav et al 2009]. Tobacco use also doubles the risk of pancreatic cancer and is associated with earlier-onset pancreatic cancer [Lowenfels et al 2001]. Dehydration worsens episodes of acute pancreatitis, and in severe cases can contribute to complications such as acute kidney injury and cardiovascular shock. Physical and emotional stresses aggravate pancreatitis [Applebaum et al 2000]. Avoiding these stressors in individuals with PRSS1-related HP may prevent or delay worsening of symptoms and progression of disease. ### Evaluation of Relatives at Risk It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual by molecular genetic testing for the PRSS1 pathogenic variant in the family in order to identify as early as possible those who would benefit from screening for pancreatic exocrine and endocrine dysfunction. Note: Predictive testing of children is appropriate in families with early-onset symptoms (i.e., onset age <25 years). In families with onset at or later than age 25 years, predictive genetic testing of asymptomatic children younger than age 16 years is not thought to be of medical benefit [Ellis et al 2001]. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation A recognition of the need for new treatments and the challenges in developing classic pharmaceutical trials for rare diseases led to an NIH workshop during PancreasFest 2018 [Abbruzzese et al 2018, Abu-El-Haija et al 2018, Forsmark et al 2018, Lowe et al 2018, Uc et al 2018]. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PRSS1-Related Hereditary Pancreatitis	None	26,631	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK84399/	2021-01-18T21:05:03	{"synonyms": []}
"Sinophobia" and "Sinophobe" redirects here. It is not to be confused with Xenophobia and Sinophone. Sentiment against China, its people, overseas Chinese, or Chinese culture Part of a series on Discrimination General forms * Age * Class (Caste) * Physical Disability * Education * Economic * Employment * Genetics * Hair texture * Height * Housing * Language * Looks * Race / Ethnicity / Nationality * Rank * Religion * Sanity * Sex * Sexual orientation * Size * Skin color Specific forms Social * Acephobia * Adultism * Amatonormativity * Anti-albinism * Anti-autism * Anti-homelessness * Anti-intellectualism * Anti-intersex * Anti-left handedness * Anti-Masonry * Antisemitism (Judeophobia) * Aporophobia * Audism * Biphobia * Clannism * Cronyism * Drug use * Elitism * Ephebiphobia * Fatism * Gerontophobia * Heteronormativity * Heterosexism * HIV/AIDS stigma * Homophobia * Leprosy stigma * Lesbophobia * Misandry * Misogyny * Nepotism * Pedophobia * Perpetual foreigner * Pregnancy * Reverse * Sectarianism * Supremacism * Black * White * Transphobia * Non-binary * Transmisogyny * Vegaphobia * Xenophobia Religious * Ahmadiyya * Atheism * Baháʼí Faith * Buddhism * Catholicism * Christianity * post–Cold War era * Druze * Falun Gong * Hinduism * Persecution * Islam * Persecution * Jehovah's Witnesses * Judaism * Persecution * LDS or Mormon * Neopaganism * Eastern Orthodox * Oriental Orthodox * Copts * Protestantism * Rastafarianism * Shi'ism * Sufism * Sunnism * Zoroastrianism Ethnic/national * African * Albanian * American * Arab * Armenian * Australian * Austrian * Azerbaijani * British * Canadian * Catalan * Chechen * Chilean * Chinese * Croat * Dutch * English * Estonian * European * Filipino * Finnish * French * Georgian * German * Greek * Haitian * Hazara * Hispanic * Hungarian * Igbo * Indian * Indonesian * Iranian * Irish * Israeli * Italian * Japanese * Jewish * Khmer * Korean * Kurdish * Malay * Manchu * Mexican * Middle Eastern * Mongolian * Montenegrin * Pakistani * Pashtun * Polish * Portuguese * Quebec * Romani * Romanian * Russian * Scottish * Serb * Slavic * Somali * Soviet * Tatar * Thai * Tibetan * Turkish * Ukrainian * Venezuelan * Vietnamese * Western Manifestations * Blood libel * Bullying * Compulsory sterilization * Counter-jihad * Cultural genocide * Defamation * Democide * Disability hate crime * Dog-whistle politics * Eliminationism * Ethnic cleansing * Ethnic conflict * Ethnic hatred * Ethnic joke * Ethnocide * Forced conversion * Freak show * Gay bashing * Gendercide * Genital modification and mutilation * Genocide * examples * Glass ceiling * Hate crime * Hate group * Hate speech * online * Homeless dumping * Indian rolling * Lavender scare * LGBT hate crimes * Lynching * Mortgage * Murder music * Occupational segregation * Persecution * Pogrom * Purge * Red Scare * Religious persecution * Religious terrorism * Religious violence * Religious war * Scapegoating * Segregation academy * Sex-selective abortion * Slavery * Slut-shaming * Trans bashing * Victimisation * Violence against women * White flight * White power music * Wife selling * Witch-hunt Policies * Age of candidacy * Blood purity * Blood quantum * Crime of apartheid * Disabilities * Catholic * Jewish * Ethnocracy * Ethnopluralism * Gender pay gap * Gender roles * Gerontocracy * Gerrymandering * Ghetto benches * Internment * Jewish quota * Jim Crow laws * Law for Protection of the Nation * McCarthyism * MSM blood donation restrictions * Nonpersons * Numerus clausus (as religious or racial quota) * Nuremberg Laws * One-drop rule * Racial quota * Racial steering * Redlining * Same-sex marriage (laws and issues prohibiting) * Segregation * age * racial * religious * sexual * Sodomy law * State atheism * State religion * Ugly law * Voter suppression Countermeasures * Affirmative action * Anti-discrimination law * Cultural assimilation * Cultural pluralism * Diversity training * Empowerment * Feminism * Fighting Discrimination * Hate speech laws by country * Human rights * Intersex rights * LGBT rights * Masculism * Multiculturalism * Nonviolence * Racial integration * Reappropriation * Self-determination * Social integration * Toleration Related topics * Allophilia * Anti-cultural, anti-national, and anti-ethnic terms * Bias * Christian privilege * Civil liberties * Cultural assimilation * Dehumanization * Diversity * Ethnic penalty * Eugenics * Internalized oppression * Intersectionality * Male privilege * Masculism * Medical model of disability * autism * Multiculturalism * Net bias * Neurodiversity * Oikophobia * Oppression * Police brutality * Political correctness * Polyculturalism * Power distance * Prejudice * Prisoner abuse * Racial bias in criminal news * Racism by country * Religious intolerance * Second-generation gender bias * Snobbery * Social exclusion * Social model of disability * Social stigma * Stereotype * threat * The talk * White privilege * v * t * e Results of 2019 Pew Research Center poll. Views of China by country[1][2] Sorted by Pos-Neg Country polled Positive Negative Neutral Pos-Neg Japan 14% 85% 1 –71 Sweden 25% 70% 5 –45 Canada 27% 67% 6 –40 United States 26% 60% 14 –34 Czech Republic 27% 57% 16 –30 France 33% 62% 5 –29 South Korea 34% 63% 3 –29 Taiwan 35% 61% 4 –26 Germany 34% 56% 10 –22 Netherlands 36% 58% 6 –22 Australia 36% 57% 7 –21 Italy 37% 57% 6 –20 United Kingdom 38% 55% 7 –17 Spain 39% 53% 8 –14 Philippines 42% 54% 4 –12 Slovakia 40% 48% 12 –8 Indonesia 36% 36% 28 0 Hungary 40% 37% 23 +3 South Africa 46% 35% 19 +11 Lithuania 45% 33% 22 +12 Poland 47% 34% 19 +13 Greece 51% 32% 17 +19 Argentina 47% 24% 29 +23 Brazil 51% 27% 22 +24 Mexico 50% 22% 28 +28 Kenya 58% 25% 17 +33 Bulgaria 55% 20% 25 +35 Israel 66% 25% 9 +41 Ukraine 57% 14% 29 +43 Lebanon 68% 22% 10 +46 Tunisia 63% 16% 21 +47 Nigeria 70% 17% 13 +53 Russia 71% 18% 11 +53 Results of 2017 BBC World Service poll. Views of China's influence by country[3] Sorted by Pos-Neg Country/Region polled Positive Negative Pos-Neg Spain 15% 68% –53 United States 22% 70% –48 India 19% 60% –41 Turkey 29% 54% –25 France 35% 60% –25 Indonesia 28% 50% –22 United Kingdom 37% 58% –21 Germany 20% 35% –15 Canada 37% 51% –14 Australia 46% 47% –1 World (excl. China) 41% 42% –1 Brazil 45% 38% 7 Greece 37% 25% 12 Peru 49% 34% 15 Russia 44% 23% 21 Mexico 55% 26% 29 Kenya 63% 27% 36 Pakistan 63% 12% 51 Nigeria 83% 9% 74 China 88% 10% 78 Results of 2017 Eurobarometer poll. Views of China by country[4] Sorted by Pos-Neg Country polled Positive Negative Pos-Neg Czech Republic 25% 69% –44 France 21% 63% –42 Luxembourg 24% 61% –37 Germany 26% 61% –35 Sweden 31% 64% –33 Italy 29% 60% –31 Spain 29% 59% –30 Netherlands 32% 60% –28 Denmark 32% 59% –27 Belgium 34% 61% –27 Austria 34% 57% –23 Finland 36% 55% –19 Malta 30% 47% –17 Slovenia 41% 53% –12 Poland 37% 48% –11 Hungary 40% 50% –10 Portugal 36% 45% –9 Slovakia 36% 44% –8 Ireland 39% 47% –8 Greece 45% 49% –4 United Kingdom 39% 41% –2 Estonia 43% 35% 8 Lithuania 49% 36% 13 Croatia 54% 39% 15 Bulgaria 47% 31% 16 Romania 56% 34% 22 Latvia 51% 29% 22 Cyprus 58% 27% 31 Anti-Chinese sentiment or Sinophobia (from Late Latin Sinae "China" and Greek φόβος, phobos, "fear") involves sentiments such as hatred or fear of China (and related countries), its people, its diaspora, or its culture.[5] It often targets Chinese minorities living outside of China and involves immigration, development of national identity in neighboring countries, disparity of wealth, the past central tributary system, majority-minority relations, discrimination and racism.[6][7][8] Its opposite is Sinophilia. ## Contents * 1 Statistics and background * 2 History * 3 Regional antipathy * 3.1 East Asia * 3.1.1 Japan * 3.1.2 Korea * 3.1.3 Hong Kong * 3.1.4 Mongolia * 3.1.5 Taiwan * 3.2 Central Asia * 3.2.1 Afghanistan * 3.2.2 Kazakhstan * 3.2.3 Tajikistan * 3.2.4 Kyrgyzstan * 3.3 Within mainland China * 3.3.1 Xinjiang * 3.3.2 Tibet * 3.4 Southeast Asia * 3.4.1 Singapore * 3.4.2 Malaysia * 3.4.3 Cambodia * 3.4.4 Philippines * 3.4.5 Indonesia * 3.4.6 Myanmar * 3.4.7 Thailand * 3.4.8 Vietnam * 3.5 South Asia * 3.5.1 Nepal * 3.5.2 Bhutan * 3.5.3 Sri Lanka * 3.5.4 India * 3.6 Pacific Islands * 3.6.1 Papua New Guinea * 3.6.2 Tonga * 3.6.3 Solomon Islands * 3.7 Eurasia, former Soviet Union and the Middle East * 3.7.1 Israel * 3.7.2 Russia * 3.7.3 Turkey * 3.7.4 Syria * 3.8 Western world and Latin America * 3.8.1 Czech Republic * 3.8.2 Australia * 3.8.3 France * 3.8.4 Germany * 3.8.5 Italy * 3.8.6 Spain * 3.8.7 Sweden * 3.8.8 Peru * 3.8.9 Canada * 3.8.10 Brazil * 3.8.11 United Kingdom * 3.8.12 Portugal * 3.8.13 Mexico * 3.8.14 New Zealand * 3.8.15 United States * 3.8.16 Venezuela * 3.9 Africa * 3.9.1 Kenya * 3.9.2 Ghana * 3.9.3 Zambia * 3.9.4 South Africa * 4 Depiction of China and Chinese in media * 5 Business * 6 Historical Sinophobia-led violence * 6.1 Australia * 6.2 Canada * 6.3 Mexico * 6.4 Dutch East Indies * 6.5 Indonesia * 6.6 Malaysia * 6.7 Japan * 6.8 By Koreans * 6.9 United States * 6.10 Vietnam * 7 Derogatory terms * 7.1 In English * 7.2 In Filipino * 7.3 In French * 7.4 In Indonesian * 7.5 In Japanese * 7.6 In Korean * 7.7 In Mongolian * 7.8 In Portuguese * 7.9 In Russian * 7.10 In Spanish * 7.11 In Italian * 7.12 In Vietnamese * 7.13 In Cantonese * 7.14 In Min-nan * 7.15 In Burmese * 8 Chinese response * 9 Sinophobia during the COVID-19 pandemic * 10 See also * 11 References * 12 Further reading ## Statistics and background[edit] In 2013, Pew Research Center from the United States conducted a survey over Sinophobia, finding that China was viewed favorably in half (19 of 38) of the nations surveyed, excluding China itself. Beijing's strongest supporters were in Asia, in Malaysia (81%) and Pakistan (81%); African nations of Kenya (78%), Senegal (77%) and Nigeria (76%); as well as Latin America, particularly in countries heavily engaging with the Chinese market, such as Venezuela (71%), Brazil (65%) and Chile (62%).[9] However, anti-China sentiment has remained permanent in the West and other Asian countries: only 28% of Germans and Italians and 37% of Americans viewed China favorably while in Japan, just 5% of respondents had a favorable opinion of the country. But in just 11 of the 38 nations surveyed was China actually viewed unfavorably by at least half of those surveyed. Japan was polled to have the most anti-China sentiment, where 93% see the People's Republic in a negative light, including 48% of Japanese who have a very unfavorable view of China. There were also majorities in Germany (64%), Italy (62%) and Israel (60%) who held negative views of China. The rise in anti-China sentiment in Germany was particularly striking: from 33% disfavor in 2006 to 64% under the 2013 survey, with such views existing despite Germany's success exporting to China.[9] Despite China's general appeal to the young, half or more of those people surveyed in 26 of 38 nations felt that China acted unilaterally in international affairs, notably increasing tensions between China and other neighboring countries, excluding Russia, over territorial disputes. This concern about Beijing's failure to consider other countries' interests when making foreign policy decisions was particularly strong in the Asia-Pacific – in Japan (89%), South Korea (79%) and Australia (79%) – and in Europe – in Spain (85%), Italy (83%), France (83%) and Britain (82%). About half or more of those in the seven Middle Eastern nations surveyed also thought China acted unilaterally. This includes 79% of Israelis, 71% of Jordanians and 68% of Turks. There was relatively less concern about this issue in the U.S. (60%). African nations – in particular strong majorities in Kenya (77%), Nigeria (70%), South Africa (67%) and Senegal (62%) – believed Beijing considered their interests when making foreign policy decisions.[9] When asked in 2013 whether China had the respect it should have, 56% of Chinese respondents felt China should have been more respected.[9] ## History[edit] While historical records document the existence of anti-Chinese hostilities during China's imperial wars,[10] modern Sinophobia first emerged in the 19th century.[citation needed] Lord Palmerston, who was responsible for orchestrating the First Opium War with Qing China, considered the Chinese civilization "uncivilized", and his negative views on China played a significant role in his decision to issue a declaration of war.[11] The trend became commonly popular throughout the Second Opium War (1856-1860), when repeated attacks against foreign traders in China inflamed anti-Chinese sentiment.[citation needed] With the defeat of China in both wars, and violent behavior of Chinese towards foreigners, Lord Elgin upon his arrival in Peking in 1860 ordered the sacking and burning of China's Summer Palace in vengeance, highlighting the deep Sinophobic sentiment existing in the West.[12] In 1882 the Chinese Exclusion Act further deepened[citation needed] Sinophobic sentiment in the U.S., which escalated into tensions. Chinese workers were forbidden and treated as second-class citizens.[13] Meanwhile, during the mid-19th century in Peru, Chinese were used as slave laborers and they were not allowed to hold any positions in Peruvian society.[14] Japanese illustration depicting the beheading of Chinese captives. Sino-Japanese War of 1894–5. On the other hand, the Empire of Japan was also known for its strong Sinophobia. After the violence in Nagasaki caused by Chinese sailors, it stemmed anti-Chinese sentiment in Japan and following Qing China's non-apology, it even strained further. After the end of the First Sino-Japanese War, Japan defeated China and soon acquired colonial possessions of Taiwan and Ryukyu Islands.[citation needed] Throughout the 1920s, Sinophobia was still common in Europe. Chinese workers had been a fixture on London's docks since the mid-eighteenth century, when they arrived as sailors who were employed by the East India Company, importing tea and spices from the Far East. Conditions on those long voyages were so dreadful that many sailors decided to abscond and take their chances on the streets rather than face the return journey. Those who stayed generally settled around the bustling docks, running laundries and small lodging houses for other sailors or selling exotic Asian produce. By the 1880s, a small but recognizable Chinese community had developed in the Limehouse area, increasing Sinophobic sentiments from other Londoners, who feared the Chinese workers displacing their traditional jobs by willing to work for much lower wages and longer hours than other workers in the same industries. The entire Chinese population of London was only in the low hundreds—in a city whose entire population was roughly estimated to be seven million—but nativist feelings ran high, as was evidenced by the Aliens Act of 1905, a bundle of legislation which sought to restrict entry to poor and low-skilled foreign workers.[15] Chinese Londoners also became involved with illegal criminal organisations, spurring Sinophobic sentiments.[15] World War II era massacres like the Nanking Massacre and widespread human rights abuses caused rifts between China and Japan which still exist today.[16] During the Cold War, anti-Chinese sentiment became permanent in the media of the Western world and anti-communist countries, largely after the establishment of the People's Republic of China in 1949. From the 1950s to the 1980s, anti-Chinese sentiment was so high in South Korea, where the Korean War was fought and the Chinese subsequently intervened against the South Korean army. To this day, many Koreans believe that China perpetrated the division of Korea into two countries.[17] Even in the Soviet Union, anti-Chinese sentiment was so high due to the differences which existed between China and the USSR[clarification needed] which nearly resulted in war between the two countries. The "Chinese threat" as it was described in a letter by Alexander Solzhenitsyn prompted expressions of anti-Chinese sentiment in the conservative Russian samizdat movement.[18] Since the 1990s, China's economic reforms have turned the country into a global power. Nonetheless, distrust of China and Chinese is sometimes attributed[by whom?] to the backlash which exists against the historical memory of Sinicization which was first pursued by Imperial China and was later pursued by the Republic of China, and the additional backlash which exists against the modern policies of the Chinese government, both of which are permanent in many countries like India, Korea, Japan and Vietnam.[19][20] ## Regional antipathy[edit] ### East Asia[edit] #### Japan[edit] See also: Anti-Chinese sentiment in Japan, Nanjing Massacre, and China–Japan relations After the end of the Second Sino-Japanese War and World War II in 1945, the relationship between China and Japan gradually improved. However, since 2000, Japan has seen a gradual resurgence of anti-Chinese sentiment. Many Japanese believe that China is using the issue of the countries' checkered history, such as the Japanese history textbook controversies, many past war crimes committed by Japan's military, and official visits to the Yasukuni Shrine (in which a number of war criminals are enshrined), as both a diplomatic card and a tool to make Japan a scapegoat in domestic Chinese politics.[21] The Anti-Japanese Riots in the Spring of 2005 were another source of more anger towards China among the Japanese public. Anti-Chinese sentiments have been on a sharp rise in Japan since 2002. According to the Pew Global Attitude Project (2008), 84% of Japanese people held an unfavorable view of China and 73% of Japanese people held an unfavorable view of Chinese people, which was a higher percentage than all the other countries surveyed.[22] A survey in 2017 suggested that 51% of Chinese respondents had experienced tenancy discrimination.[23] Another report in the same year noted a significant bias against Chinese visitors from the media and some of the Japanese locals.[24] #### Korea[edit] See also: Anti-Chinese sentiment in Korea and History of Sino-Korean relations Korea has had a long history of both resistance against and subordination to China.[25][26] Until the arrival of Western powers in the 19th century, Korea had been part of the sinocentric East Asian regional order.[27] In the early 2000s, a dispute over the history of Goguryo, which both Koreas and China claim as their own, caused tension between the two countries.[27] Anti-Chinese riots in Pyongyang, Korea in the aftermath of the Wanpaoshan Incident In 1931, while Korea was dominated by Imperial Japan, there was a dispute between Chinese and Korean farmers in Wanpaoshan, Manchuria. It was highly sensationalized in the Japanese and Korean press, and used as propaganda to increase anti-Chinese sentiment. It caused a series of anti-Chinese riots throughout Korea, starting in Incheon on July 3 and spreading rapidly to other cities. Chinese sources estimate that 146 people were killed, 546 wounded, and a considerable number of properties were destroyed.[citation needed] The worst riot occurred in Pyongyang on July 5. In this effect, the Japanese had a considerable influence on sinophobia in Korea.[28] Starting in October 1950, the People's Volunteer Army fought in the Korean War (1950–1953) on the side of North Korea against South Korean and United Nations troops. The participation of the PVA made the relations between South Korea and China hostile. Throughout the Cold War, there were no official relations between capitalist South Korea and communist China until August 24, 1992, when formal diplomatic relations were established between Seoul and Beijing.[citation needed] Anti-Chinese sentiments in South Korea have been on a steady rise since 2002. According to Pew opinion polls, favorable view of China steadily declined from 66% in 2002 to 48% in 2008, while unfavorable views rose from 31% in 2002 to 49% in 2008.[29] According to surveys by the East Asia Institute, positive view of China's influence declined from 48.6% in 2005 to 38% in 2009, while negative view of it rose from 46.7% in 2005 to 50% in 2008.[30] Relations further strained with the deployment of THAAD in South Korea in 2017, in which China started its boycott against Korea, making Koreans to develop anti-Chinese sentiment in South Korea over reports of economic retaliation by Beijing.[31] According to a poll from the Institute for Peace and Unification Studies at Seoul National University in 2018, 46 percent of South Koreans found China as the most threatening country to inter-Korean peace (compared to 33 percent for North Korea), marking the first time China was seen as a bigger threat than North Korea since the survey began in 2007.[32] Discriminatory views of Chinese people have been reported or implied in some sources,[33][34] and ethnic-Chinese Koreans have faced prejudices including what is said to be a widespread criminal stigma.[35][36][37] #### Hong Kong[edit] See also: Hong Kong–Mainland China conflict 2019–20 Hong Kong protests. The sign reads, "We stand united against China". Although Hong Kong's sovereignty was returned to China in 1997, only a small minority of its inhabitants consider themselves to be exclusively and simply Chinese. According to a 2014 survey from the University of Hong Kong , 42.3% of respondents identified themselves as "Hong Kong citizens", versus only 17.8% who identified themselves as "Chinese citizens", and 39.3% who chose to give themselves a mixed identity (a Hong Kong Chinese or a Hong Konger who was living in China).[38] The number of mainland Chinese visitors to the region has surged since the handover (reaching 28 million in 2011), and is perceived by many locals to be the cause of their housing and job difficulties. Negative perceptions have been exacerbated by posts and recirculations of alleged mainlander misbehaviour on social media,[39] as well as discriminatory discourse in major HK newspapers.[40][41] In 2013, polls from the University of Hong Kong suggested that 32 to 35.6 per cent of locals had "negative" feelings for mainland Chinese people.[42] However, a 2019 survey of Hong Kong residents has suggested that there are also some who attribute positive stereotypes to visitors from the mainland.[43][44] In 2012, a group of Hong Kong residents published a newspaper advertisement depicting mainland visitors and immigrants as locusts.[45] In February 2014, about 100 Hong Kongers harassed mainland tourists and shoppers during what they styled an "anti-locust" protest in Kowloon. In response, the Equal Opportunities Commission of Hong Kong proposed an extension of the territory's race-hate laws to cover mainlanders.[46] Strong anti-mainland sentiment has also been documented amidst the 2019 protests,[47] with reported instances of protesters attacking Mandarin-speakers and mainland-linked businesses.[48][49][50][51] #### Mongolia[edit] See also: Occupation of Mongolia and Inner Mongolian independence movement Inner Mongolia used to be part of Greater Mongolia, until Mongolia was absorbed into China at 17th century following the Qing conquest. For three centuries, Mongolia was marked with little interests even during the expansion of Russian Empire. With the Qing collapse, China attempted to retake Mongolia only to see its rule fallen with the Mongolian Revolution of 1921, overthrowing the Chinese rule; but it was proposed that Zhang Zuoling's domain (the Chinese "Three Eastern Provinces") take Outer Mongolia under its administration by the Bogda Khan and Bodo in 1922 after pro-Soviet Mongolian Communists seized control of Outer Mongolia.[52] However, China failed to take Outer Mongolia (which would become modern Mongolia) but successfully maintained their presence in Inner Mongolia. For this reason, it has led to a strong anti-Chinese sentiment among the native Mongol population in Inner Mongolia which have rejected assimilation, which prompted Mongolian nationalists and Neo-Nazi groups to be hostile against China.[53] One of the most renown unrest in modern China is the 2011 Inner Mongolia unrest, following the murder of two ethnic Mongolians in separate incidents.[54] Mongolians traditionally hold very unfavorable views of China.[55] The common stereotype is that China is trying to undermine Mongolian sovereignty in order to eventually make it part of China (the Republic of China has claimed Mongolia as part of its territory, see Outer Mongolia ). Fear and hatred of erliiz (Mongolian: эрлийз, [ˈɛrɮiːt͡sə], literally, double seeds), a derogatory term for people of mixed Han Chinese and Mongol ethnicity,[56] is a common phenomena in Mongolian politics. Erliiz are seen as a Chinese plot of "genetic pollution" to chip away at Mongolian sovereignty, and allegations of Chinese ancestry are used as a political weapon in election campaigns – though not always with success.[57][58] Several Neo-Nazi groups opposing Chinese influence and mixed Chinese couples are present within Mongolia, such as Tsagaan Khas.[53] #### Taiwan[edit] See also: Cross-Strait relations, Taiwan independence movement, and Taiwanese identity Due to historical reasons dating back to the de facto end of the Chinese Civil War, the relationship between the two majority ethnic Chinese and Mandarin Chinese-speaking regions has been tense due to the fact that the People's Republic of China has threatened repeatedly to invade if Taiwan were to declare independence, shedding the status quo of existing legally as the Republic of China and replacing a Chinese national identity with a distinctly Taiwanese identity. This creates strong divisions between mainland China and Taiwan[59] and further strains the relationship between two nations. Anti-Chinese sentiment in Taiwan also comes from the fact that many Taiwanese, especially those in their 20s, choose to identify solely as "Taiwanese",[60] and are against having closer ties with the Chinese mainland, like those in the Sunflower Student Movement.[61] A number of Taiwanese have also viewed mainlanders as backwards or uncivilised, according to Peng Ming-min, a Taiwanese politician.[62] According to a 2020 survey 76% of Taiwanese consider China to be "unfriendly" towards Taiwan.[63] ### Central Asia[edit] #### Afghanistan[edit] Recently, the Xinjiang conflict has strained the relations between Afghanistan and China.[64] #### Kazakhstan[edit] In 2018 massive land reform protests were held in Kazakhstan. The protesters demonstrated against leasing land to Chinese companies and the perceived economic dominance of Chinese companies and traders.[65][66] Other issues leading to rise of Sinophobia in Kazakhstan is also over the Xinjiang conflict and Kazakhstan hosting a significant number of Uyghur separatists.[citation needed] #### Tajikistan[edit] Resentment against China and Chinese also increased in Tajikistan recent years due to accusation of China's land grab from Tajikistan.[67] In 2013, Tajik Popular Social-Democrat Party leader, Rakhmatillo Zoirov, claimed Chinese troops were entering to Tajikistan deeper than it got from land ceding.[68] #### Kyrgyzstan[edit] Kyrgyzstan is traditionally non-aligned and somewhat positive of China. There are historical grievances, however, such as occupation by Qing China, ethnic cleansing. A Kyrgyz farmer claimed "We always run the risk of being colonized by the Chinese,", in fear of future being colonized by China.[69] Meanwhile, like in other Central Asian nations, Kyrgyz people mostly sympathize with Uyghur separatism in China, further complicated relations.[69] ### Within mainland China[edit] #### Xinjiang[edit] See also: Terrorism in China, July 2009 Ürümqi riots, and Al-Qaeda in Xinjiang After China took over control of Xinjiang under Mao Zedong to establish the PRC in 1949, there have been considerable ethnic tensions arising between the Han Chinese and Turkic Muslim Uyghurs.[70][71][72][73][74] This manifested itself in the 1997 Ghulja incident,[75] the bloody July 2009 Ürümqi riots,[76] and the 2014 Kunming attack.[77] This has prompted China to suppress the native population and create re-education camps for purported counter-terrorism efforts, which have reportedly fuelled resentment in the region.[78][79] Al Jazeera has reported that many Uyghurs during the COVID-19 pandemic felt the virus as a divine punishment against China.[80] #### Tibet[edit] See also: Sino-Tibetan War and Self-immolation protests by Tibetans in China Anti-China protest by Tibetans in India in 2008 Tibet has a complicated relations with China. Both are part of the Sino-Tibetan language family and share a long history. Tang dynasty and Tibetan Empire did enter into a military conflict.[citation needed] and had a major effect on the rise of Sinophobia among Tibetans. In the 13th century, Tibet fell into the rule of Yuan dynasty but it soon broke out with the collapse of Yuan dynasty. Relationship between Tibet with China remains complicated until Tibet was invaded again by the Qing dynasty. Following the British expedition to Tibet at 1904, many Tibetans look back to it as an exercise of Tibetan self-defence and an act of independence from the Qing dynasty as the dynasty was falling apart.[81] and has left a dark chapter in their modern relations. The Republic of China failed to reconquer Tibet but the later People's Republic of China retook Tibet and incorporated it as Tibet Autonomous Region within China. Despite 14th Dalai Lama and Mao Zedong had together signed Seventeen Point Agreement for the Peaceful Liberation of Tibet, China was accused for not honoring the treaty[82] and led to 1959 Tibetan uprising which was totally suppressed by China[83] and Dalai Lama escaped to India.[84] Tibetans again rioted against Chinese rule twice, the 1987–89 unrest[85] and 2008 unrest, where they directed their angers against Han and Hui Chinese.[86] Both have been suppressed by China and China has increased their military presence in the region, despite self-immolations against China are still ongoing.[87] ### Southeast Asia[edit] #### Singapore[edit] To counteract the city state's low birthrate, Singapore's government has been offering financial incentives and a liberal visa policy to attract an influx of migrants. Chinese immigrants to the nation grew from 150,447 in 1990 to 448,566 in 2015 to make up 18% of the foreign-born population, next to Malaysian immigrants at 44%.[88][89] The xenophobia towards mainland Chinese is reported to be particularly severe compared to other foreign residents,[90] as they are generally looked down on as country bumpkins and blamed for stealing desirable jobs and driving up housing prices.[91] There have also been reports of housing discrimination against mainland Chinese tenants,[92] and a 2019 YouGov poll has suggested Singapore to have the highest percentage of locals prejudiced against Chinese travellers out of the many countries surveyed.[93][94] #### Malaysia[edit] Due to race-based politics and Bumiputera policy, there had been several incidents of racial conflict between the Malays and Chinese before the 1969 riots. For example, in Penang, hostility between the races turned into violence during the centenary celebration of George Town in 1957 which resulted in several days of fighting and a number of deaths,[95] and there were further disturbances in 1959 and 1964, as well as a riot in 1967 which originated as a protest against currency devaluation but turned into racial killings.[96][97] In Singapore, the antagonism between the races led to the 1964 Race Riots which contributed to the expulsion of Singapore from Malaysia on August 9, 1965. The 13 May Incident was perhaps the deadliest race riot to have occurred in Malaysia with an official combined death toll of 196[98] (143 Chinese, 25 Malays, 13 Indians, and 15 others of undetermined ethnicity),[99] but with higher estimates by other observers reaching around 600-800+ total deaths.[100][101][102] It was reported in 2019 that relations between ethnic Chinese Malaysians and indigenous Malays were "at their lowest ebb", and fake news posted online of mainland Chinese indiscriminately receiving citizenship in the country had been stoking racial tensions. The primarily Chinese-based Democratic Action Party in Malaysia has also reportedly faced an onslaught of fake news depicting it as unpatriotic, anti-Malay and anti-Muslim.[103] Amidst the COVID-19 pandemic, there have been social media posts claiming the initial outbreak is "divine retribution" for China's treatment of its Muslim Uygurs population.[104] #### Cambodia[edit] See also: Chinese Cambodians and Cambodia–China relations During the late 1960s an estimated 425,000 ethnic Chinese lived in Cambodia. By 1984, as a result of the Khmer Rouge genocide and emigration, only about 61,400 Chinese remained in the country.[105][106][107] The hatred for Chinese was projected on the ethnic Chinese of Cambodia during 80s. A Vietnamese report had noted "In general, the attitude of young people and intellectuals is that they hate Cambodian-Chinese."[108] Recent influx of Chinese investment, especially in Sihanoukville Province, has led to rising anti-Chinese rhetoric.[109] #### Philippines[edit] See also: Philippines, Province of China banners; Chinese gambling workers in the Philippines; Iisang Dagat; and Philippines v. China The Spanish introduced the first anti-Chinese laws in the Philippine archipelago. The Spanish massacred or expelled Chinese several times from Manila, and the Chinese responded by fleeing either to La Pampanga or to territories outside colonial control, particularly the Sulu Sultanate, which they in turn supported in their wars against the Spanish authorities.[110] The Chinese refugees not only ensured that the Sūg people were supplied with the requisite arms, but also joined their new compatriots in combat operations against the Spaniards during the centuries of Spanish–Moro conflict.[111] The standoff in Spratly Islands and Scarborough Shoal between China and the Philippines contributes to anti-China sentiment among Filipinos. Campaigns to boycott Chinese products began in 2012. People protested in front of the Chinese Embassy and it had led the Chinese embassy to issue travel warning for its citizens to the Philippines for a year.[112] Amidst the COVID-19 pandemic, scholar Jonathan Corpuz Ong has lamented that there is a great deal of hateful and racist speech on Philippine social media which "many academics and even journalists in the country have actually justified as a form of political resistance" to the Chinese government. There have been jokes and memes reposted of supposedly Chinese people defecating in public.[113] #### Indonesia[edit] See also: Discrimination against Chinese Indonesians Anti-Chinese sentiment reached its peak in May 1998, when major riots swept over Jakarta. The Dutch introduced anti-Chinese laws in the Dutch East Indies. The Dutch colonialists started the first massacre of Chinese in the 1740 Batavia massacre in which tens of thousands died. The Java War (1741–43) followed shortly thereafter.[114][115][116][117][118] The asymmetrical economic position between ethnic Chinese Indonesians and indigenous Indonesians has incited anti-Chinese sentiment among the poorer majorities. During the Indonesian killings of 1965–66, in which more than 500,000 people died (mostly non-Chinese Indonesians),[119] ethnic Chinese were killed and their properties looted and burned as a result of anti-Chinese racism on the excuse that Dipa "Amat" Aidit had brought the PKI closer to China.[120][6] In the May 1998 riots of Indonesia following the fall of President Suharto, many ethnic Chinese were targeted by Indonesian rioters, resulting in a large number of looting. However, most of the deaths suffered when Chinese owned supermarkets were targeted for looting were not Chinese, but the Indonesian looters themselves, who were burnt to death by the hundreds when a fire broke out.[121][122] In recent years, China's increasing aggression in South China Sea has led to the renewal of tensions, although Indonesia is much a latecomer. At first, the conflict stemmed mostly between China to Vietnam, the Philippines and Malaysia, with Indonesia chose to stay neutral but soon escalated when China attempted to claim Natuna Regency from Indonesia, in which triggered outrages in Indonesia.[123]Accusations about Indonesia's lack of activities to protect its fishermen from China's increasing aggressive behaviors and multiple fake news about Chinese foreign workers contribute further to the deterioration of China's image in Indonesia.[124][125] #### Myanmar[edit] See also: China–Myanmar relations, Sino-Burmese wars, and Chinese people in Myanmar Although both countries share the exact same ancestor, the infamous Ongoing Ethnic insurgency in Myanmar and the 1967 riots in Burma against the Chinese community had sparked angers among Chinese, led to the arming of ethnic and political rebels by China against Burma. In the present day, resentment towards Chinese investments[126][127] and their perceived exploitation of natural resources have also hampered the Sino-Burmese relationship.[128] Chinese people in Myanmar have also been subject to discriminatory laws and rhetoric in Burmese media and popular culture.[129] #### Thailand[edit] See also: China–Thailand relations and Thai Chinese Historically, Thailand and previous Siam is and was seen as China-friendly country, owning by the fact China and Siam enjoyed a close relations, a large portion of Thai population have Chinese descent and strong cooperation, with Thai Chinese have been assimilated to mainstream Thai society. However, at the 20th century, Plaek Phibunsongkhram launched a massive Thaification, including oppression of Thailand's Chinese population and hampered Thai Chinese communities, banning teaching Chinese language, and forcing them to adopt Thai names.[130] Plaek's obsession toward creating a pan-Thai nationalist agenda caused heavy resentment by Thai Chinese until he was removed at 1944.[131] After that, Thai Chinese do not experience anti-Chinese incidents, although the Cold War almost inflamed hostility toward Chinese community in Thailand.[citation needed] Hostility towards the mainland Chinese increased with the influx of visitors from China in 2013.[132][133] It has also been worsened by Thai news reports and social media postings on misbehaviour from a portion of the tourists,[134] with the accuracy of some of the postings in dispute.[135][136] In spite of this, two reports have suggested that there are still some Thais who have positive impressions of Chinese tourists.[137][138] #### Vietnam[edit] See also: China–Vietnam relations and Sino-Vietnamese Wars Although both nations share a similar culture, there are strong anti-Chinese sentiments among the Vietnamese population, due in part to a past thousand years of Chinese rule in Northern Vietnam, a later series of Sino-Vietnamese wars in the history between two nations and recent territory disputes in the Paracel and Spratly Islands.[139][140][141] Though current relations are peaceful, numerous wars fought between the two nations in the past, from the time of Early Lê Dynasty (10th century)[142] to the Sino-Vietnamese War from 1979 to 1989. The conflict fueled racist discrimination against and consequent emigration by the country's ethnic Chinese population. From 1978 to 1979, some 450,000 ethnic Chinese left Vietnam by boat (mainly former South Vietnam citizens fleeing the Vietcong) as refugees or were expelled across the land border with China.[143] These mass emigrations and deportations only stopped in 1989 following the Đổi mới reforms in Vietnam.[citation needed] Anti-Chinese sentiments had spiked in 2007 after China formed an administration in the disputed islands,[140] in 2009 when the Vietnamese government allowed the Chinese aluminium manufacturer Chinalco the rights to mine for bauxite in the Central Highlands,[144][145][146] and when Vietnamese fishermen were detained by Chinese security forces while seeking refuge in the disputed territories.[147] In 2011, following a spat in which a Chinese Marine Surveillance ship damaged a Vietnamese geologic survey ship off the coast of Vietnam, some Vietnamese travel agencies boycotted Chinese destinations or refused to serve customers with Chinese citizenship.[148] Hundreds of people protested in front of the Chinese embassy in Hanoi and the Chinese consulate in Ho Chi Minh City against Chinese naval operations in the South China Sea before being dispersed by the police.[149] In May 2014, mass anti-Chinese protests against China moving an oil platform into disputed waters escalated into riots in which many Chinese factories and workers were targeted. In 2018, thousands of people nationwide protested against a proposed law regarding Special Economic Zones that would give foreign investors 99 year leases on Vietnamese land, fearing that it would be dominated by Chinese investors.[150] According to journalist Daniel Gross, Sinophobia is omnipresent in modern Vietnam, where "from school kids to government officials, China-bashing is very much in vogue." He reports that a majority of Vietnamese resent the import and usage of Chinese products, considering them distinctly low status.[151] A 2013 book on varying host perceptions in global tourism has also referenced negativity from Vietnamese hosts towards Chinese tourists, where the latter were seen as "making a lot more requests, complaints and troubles than other tourists"; the views differed from the much more positive perceptions of young Tibetan hosts at Lhasa towards mainland Chinese visitors in 2011.[152] ### South Asia[edit] #### Nepal[edit] See also: Sino-Nepalese War The relationship between two only began in the 18th century when the Qing dynasty expanded near the Nepalese border, but this resulted in war between two nations, at the time concentrated mostly in Tibet.[153] After the war, Nepal and China signed a peace treaty, which made Nepal a vassal of China; but with the Anglo-Nepalese War and China's failure to assist Nepal, it inflamed the hatred, and Nepal contributed Gorkha troops to help the British during the wars with China, known as the Opium Wars.[154] In modern relations, during the COVID-19 pandemic, Nepalese media, most notably Kathmandu Post, has published questions regarding Chinese transparency, and accused the Chinese government of open threat against Nepal due to its report, which hampers the relationship between two.[155] It became further complicated after CCTV's foreign outlet CGTN published on Twitter a tweet about the Mount Everest and called it Mount Qomolangma in the Tibetan language (Tibet is currently part of China), which caused widespread enrages from the Nepalese public that China is trying to claim the mount from Nepal.[156] #### Bhutan[edit] The relation between Bhutan and China has historically been tense and past events have led to anti-Chinese sentiment within the country. Notably the Chinese government's destruction of Tibetan Buddhist institutions in Tibet in 1959 led to a wave of anti-Chinese sentiment in the country.[157] Similarly, the publishing of a controversial map in the book, A Brief History of China which illustrated a large portion of Bhutanese territory belonging to China and the statement released by China in 1960 which claimed the Bhutanese "form a united family in Tibet" and "they must once again be united and taught the communist doctrine" all led to hostile responses from Bhutan including the closing of its border, trade and all diplomatic contact with China. Bhutan and China have not established diplomatic relations.[158] #### Sri Lanka[edit] Although there is a lot of favorable opinions about China because they helped to finish the civil war in Sri Lanka there are anti-Chinese sentiment among some people over Chinese investment in the country.[159][160][161] #### India[edit] See also: China–India relations, Persecution of Chinese Indians, Sino-Indian border dispute, 1987 Sino-Indian skirmish, Sino-Indian War, and Nathu La and Cho La clashes During the Sino-Indian War, the Chinese faced anti-national sentiment unleashed by the Indian National Congress-dominated government. Chinese businesses were investigated for links to the Chinese government and many people of Chinese origin were interned in prisons in North India.[162] The Indian government passed the Defence of India Act in December 1962,[163] permitting the "apprehension and detention in custody of any person [suspected] of being of hostile origin." The broad language of the act allowed for the arrest of any person simply for having a Chinese surname or a Chinese spouse.[164] The Indian government incarcerated thousands of Chinese-Indians in an internment camp in Deoli, Rajasthan, where they were held for years without trial. The last internees were not released until 1967. Thousands more Chinese-Indians were forcibly deported or coerced to leave India. Nearly all internees had their properties sold off or looted.[163] Even after their release, the Chinese Indians faced many restrictions in their freedom. They could not travel freely until the mid-1990s.[163] On 2014, India in conjunction with Tibet have called for a joint campaign to boycott Chinese goods due to border intrusion incidents. Similarly to the Philippines and Vietnam the call for the boycott of Chinese goods by India is related to the contested territorial disputes India has with China.[165][166] The 2020 China–India skirmishes killed 20 Indian soldiers, in hand-to-hand combat with Chinese troops using barbed wire bats. No specific casualties numbers were represented from China, though they acknowledged they had experienced deaths. India claims the deaths of 40-45 Chinese soldiers.[167] Following the skirmishes, a company from Jaipur, India developed an app named "Remove China Apps" and released it on the Google Play Store, gaining 5 millon downloads in less than 2 weeks. It discouraged software dependence on China and promoted apps developed in India. Following the 2020 skirmishes, people were concerned about their privacy. Amid tensions, TikTok began censoring anti-China content on its platform and banning users,[citation needed] prompting people to uninstall apps like SHAREit, ES File Explorer etc.[168] ### Pacific Islands[edit] #### Papua New Guinea[edit] In May 2009, Chinese-owned businesses were pillaged by looters in several cities across Papua New Guinea, amid increasing anti-Chinese sentiment reported in the country.[169] Thousands of people were reportedly involved in the riots.[170] #### Tonga[edit] In 2000, Tongan noble Tu'ivakano of Nukunuku banned Chinese stores from his Nukunuku District in Tonga. This followed complaints from other shopkeepers regarding competition from local Chinese.[171] In 2001, Tonga's Chinese community (a population of about three or four thousand people) was hit by a wave racist assaults.[citation needed] The Tongan government did not renew the work permits of more than 600 Chinese storekeepers, and has admitted the decision was in response to "widespread anger at the growing presence of the storekeepers".[172] In 2006, rioters damaged shops owned by Chinese-Tongans in Nukuʻalofa.[173][174] #### Solomon Islands[edit] In 2006, Honiara's Chinatown suffered damage when it was looted and burned by rioters following a contested election. Ethnic Chinese businessmen were falsely blamed for bribing members of the Solomon Islands' Parliament. The government of Taiwan was the one that supported the then current government of the Solomon Islands. The Chinese businessmen were mainly small traders from mainland China and had no interest in local politics.[173] ### Eurasia, former Soviet Union and the Middle East[edit] #### Israel[edit] See also: Kaifeng Jews Israel and China are seen to have a friendly relationship, and a 2018 survey suggests that a significant percentage of the Israeli population have a positive view of the Chinese culture and people.[175] It is also historically preceded by the support from local Chinese to Jewish refugees fleeing from Nazi persecution amidst the World War II.[176] The Jews also gained praise on their successful integration within the mainstream Chinese society.[177] However, the rise of communist China made the relationship less positive. The rise of Xi Jinping hampered the relations, with the Jews suffering a crackdown since 2016, which has been reported in Israeli media.[178][179] This has led to some Sinophobic sentiments in Israel, with Israeli nationalists viewing China a despotic and authoritarian regime, given the ongoing repression of Jews in China.[178] Another problem in regard to the struggling relationship is Israel's lack of trust in China, given China's strong tie to Iran, which is also viewed as a despotic nation and accusation that China is backing Iran against Israel, including the COVID-19 pandemic, had led to the deterioration of the positive image of China.[180] #### Russia[edit] See also: History of Sino-Russian relations and Sino-Soviet relations After the Sino-Soviet split the Soviet Union produced propaganda which depicted the PRC and the Chinese people as enemies. In Central Asia Soviet propaganda specifically framed the PRC as an enemy of Islam and all Turkic peoples. These phobias have been inherited by the post-Soviet states in Central Asia.[181] Russia inherited a long-standing dispute over territory with China over Siberia and the Russian Far East with the breakup of the Soviet Union, these disputes were formerly resolved in 2004. Russia and China no longer have territorial disputes and China does not claim land in Russia; however, there has also been a perceived fear of a demographic takeover by Chinese immigrants in sparsely populated Russian areas.[182][183] Both nations have become increasingly friendlier however, in the aftermath of the 1999 US bombing of Serbia, which the Chinese embassy was struck with a bomb, and have become increasingly united in one similar stance of hatred on the West, with both countries are being besieged.[184][185] A 2019 survey of online Russians has suggested that in terms of sincerity, trustfulness, and warmth, the Chinese are not viewed especially negatively or positively compared to the many other nationalities and ethnic groups in the study.[186][187] #### Turkey[edit] On July 4, 2015, a group of around 2,000 Turkish ultra-nationalists from the Grey Wolves linked to MHP protesting against China's fasting ban in Xinjiang mistakenly attacked South Korean tourists in Istanbul,[188][189] which led to China issuing a travel warning to its citizens traveling to Turkey.[190] A Uyghur employee at a Chinese restaurant was beaten by the Turkish Grey Wolves-linked protesters. Devlet Bahçeli, a leader from Turkey's MHP (Nationalist Movement Party), said that the attacks by MHP affiliated Turkish youth on South Korean tourists was "understandable", telling the Turkish newspaper Hurriyet that: "What feature differentiates a Korean from a Chinese? They see that they both have slanted eyes. How can they tell the difference?".[191] According to a November 2018 INR poll, 46% of Turks view China favourably, up from less than 20% in 2015. A further 62% thought that it is important to have strong trade relationship with China.[192] #### Syria[edit] Although Sinophobia is not widely practiced in Syria, the Syrian opposition has accused China for supporting the Government of Bashar al-Assad as China has vetoed UN resolutions condemning Assad's alleged war crimes; Syrian and Lebanese nationalists have burnt Chinese flag in response.[193] ### Western world and Latin America[edit] See also: Yellow Peril, The Chinese in Latin America and the Caribbean, and Stereotypes of East Asians in the Western world Cover of the third edition of G. G. Rupert's The Yellow Peril, depicting Uncle Sam engaged in a sword fight with a stereotypical pigtailed Chinese warrior. Like China's perception in other countries, China's large population, long history and size has been the subject of fear somewhat. China has figured in the Western imagination in a number of different ways as being a very large civilization existing for many centuries with a very large population; however the rise of the People's Republic of China after the Chinese Civil War has dramatically changed the perception of China from a relatively positive light to negative because of the anti-communism in the West, and reports of human rights abuses from China. Sinophobia became more common as China was becoming a major source of immigrants for the west (including the American West).[7] Numerous Chinese immigrants to North America were attracted by wages offered by large railway companies in the late 19th century as the companies built the transcontinental railroads. Sinophobic policies (such as the Chinese Exclusion Act, the Chinese Immigration Act of 1923, anti-Chinese zoning laws and restrictive covenants, the policies of Richard Seddon, and the White Australia policy) and pronouncements on the "yellow peril" were in evidence as late as the mid-20th century in the Australia, United States, Canada, and New Zealand. #### Czech Republic[edit] In 2016, Czechs and pro-Tibetan activists had defaced Chinese flag ahead of Xi Jinping's visit to the country, showing their strong resentment against China's growing influence and its perceived oppression on Tibetans.[194] Anti-Chinese sentiment has experienced a new growth due to closer tie between Czech Republic and Taiwan led to deterioration of Czech Republic's relations with China.[195] Chinese government retaliated by issuing warning travel to Czech Republic, using the lament of rising COVID-19 infection and racism in the country.[196] Czech politicians have demanded China to replace its ambassador and criticizing Chinese government for its open threat on Czech Republic, further worsens China's perception in Czech Republic.[197][198] #### Australia[edit] See also: History of Chinese Australians The Chinese population was active in political and social life in Australia. Community leaders protested against discriminatory legislation and attitudes, and despite the passing of the Immigration Restriction Act in 1901, Chinese communities around Australia participated in parades and celebrations of Australia's Federation and the visit of the Duke and Duchess of York. Although the Chinese communities in Australia were generally peaceful and industrious, resentment flared up against them because of their different customs and traditions. In the mid-19th century, terms such as "dirty, disease ridden, [and] insect-like" were used in Australia and New Zealand to describe the Chinese.[199] A poll tax was passed in Victoria in 1855 to restrict Chinese immigration. New South Wales, Queensland, and Western Australia followed suit. Such legislation did not distinguish between naturalised, British citizens, Australian-born and Chinese-born individuals. The tax in Victoria and New South Wales was repealed in the 1860s, In the 1870s and 1880s, the Growing trade union movement began a series of protests against foreign labour. Their arguments were that Asians and Chinese took jobs away from white men, worked for "substandard" wages, lowered working conditions and refused unionisation.[200] Objections to these arguments came largely from wealthy land owners in rural areas.[200] It was argued that without Asiatics to work in the tropical areas of the Northern Territory and Queensland, the area would have to be abandoned.[201] Despite these objections to restricting immigration, between 1875 and 1888 all Australian colonies enacted legislation which excluded all further Chinese immigration.[201] Asian immigrants already residing in the Australian colonies were not expelled and retained the same rights as their Anglo and Southern compatriots. In 1888, following protests and strike actions, an inter-colonial conference agreed to reinstate and increase the severity of restrictions on Chinese immigration. This provided the basis for the 1901 Immigration Restriction Act and the seed for the White Australia Policy, which although relaxed over time, was not fully abandoned until the early 1970s. Number of cases have been reported, related to Sinophobia in the country.[202] Recently, in February 2013, a Chinese football team had reported about the abuses and racism they suffered on Australia Day.[8] There have been a spate of racist anti-Chinese graffiti and posters in universities across Melbourne and Sydney which host a large number of Chinese students. In July and August 2017, hate-filled posters were plastered around Monash University and University of Melbourne which said, in Mandarin, that Chinese students were not allowed to enter the premises, or else they would face deportation, while a "kill Chinese" graffiti, decorated with swastikas was found at University of Sydney.[203][204] The Antipodean Resistance, a white supremacist group that identifies itself as pro-Nazi, claimed responsibility for the posters on Twitter. The group's website contains anti-Chinese slurs and Nazi imagery.[205] Anti-Chinese sentiment has witnessed a steady rise in Australia, after China was accused of sending spies and trying to manipulate Australian politics.[206] #### France[edit] See also: China–France relations In France, anti-Chinese sentiment has become an issue, with recent poor treatments of Chinese minority in France like the killing of Chinese people in Paris, causing uproar among Chinese in France;[207] joint alliance with India against China;[208] and land grabs from Chinese investors.[209] A 2018 survey by Institut Montaigne has suggested that Chinese investments in France are viewed more negatively than Chinese tourism to the country, with 50% of respondents holding negative views of the former.[210][211] It was reported in 2017 that there was some negativity among Parisians towards Chinese visitors,[212] but other surveys have suggested that they are not viewed worse than a number of other groups.[213][214][215] #### Germany[edit] See also: Persecution of Chinese people in Nazi Germany In 2016, Günther Oettinger, the former European Commissioner for Digital Economy and Society, called Chinese people derogatory names, including "sly dogs," in a speech to executives in Hamburg and had refused to apologize for several days.[216] Two surveys have suggested that a percentage of Germans hold negative views towards Chinese travellers, although it is not as bad as a few other groups.[217][218][219] #### Italy[edit] See also: Sino-Roman relations Although historical relations between two were friendly and even Marco Polo paid a visit to China, during the Boxer Rebellion, Italy was part of Eight-Nation Alliance against the rebellion, thus this had stemmed anti-Chinese sentiment in Italy.[220] Italian troops looted, burnt and stole a lot of Chinese goods to Italy, whom many are still being displayed in Italian museums.[221] In modern era, Sinophobia still exists in Italy. In 2007, an anti-Chinese unrest occurred when Italian residents of Milan and Rome had complained that, as Chinese neighbourhoods expand, Italian stores are being squeezed out by merchants who obtain licences for retail shops but then open up wholesale distribution operations for goods flooding in from China.[222] In 2010, Italian town of Prato became increasingly anti-Chinese, accusing them for not obeying Italian law.[223] #### Spain[edit] Spain first issued anti-Chinese legislation when Limahong, a Chinese pirate, attacked Spanish settlements in the Philippines. One of his famous actions was a failed invasion of Manila in 1574, which he launched with the support of Chinese and Moro pirates.[224] The Spanish conquistadors massacred the Chinese or expelled them from Manila several times, notably the autumn 1603 massacre of Chinese in Manila, and the reasons for this uprising remain unclear. Its motives range from the desire of the Chinese to dominate Manila, to their desire to abort the Spaniards' moves which seemed to lead to their elimination. The Spaniards quelled the rebellion and massacred around 20,000 Chinese. The Chinese responded by fleeing to the Sulu Sultanate and supporting the Moro Muslims in their war against the Spanish. The Chinese supplied the Moros with weapons and joined them in directly fighting against the Spanish during the Spanish–Moro conflict. Spain also upheld a plan to conquer China, but it never materialized.[225] #### Sweden[edit] See also: China–Sweden relations In 2018, a family of Chinese tourists were removed from a hostel in Stockholm, which led to a diplomatic spat between China and Sweden. China accused the Swedish police of maltreatment as Stockholm's chief prosecutor chose not to investigate the incident.[226] A comedy skit later aired on Svenska Nyheter mocking the tourists and playing on racial stereotypes of Chinese people.[227][228] After the producers uploaded the skit to Youku, it drew anger and accusations of racism on Chinese social media,[229] the latter of which was also echoed in a letter to the editor from a Swedish-Chinese scholar[230] to Dagens Nyheter.[231] Chinese citizens were called on to boycott Sweden.[232] The next year, Jesper Rönndahl, the host of the skit, was honoured by Swedish newspaper Kvällsposten as "Scanian of the Year".[233] Relations further worsened after the reported kidnap and arrest of China-born Swedish citizen and bookseller Gui Minhai by Chinese authorities,[234] which led to 3 Swedish opposition parties to call for the expulsion of China's ambassador to Sweden, Gui Congyou, who had been accused of threatening several Swedish media outlets.[235][236] Several Swedish cities in February 2020 cut ties with China's cities amid deteriorating relations.[237] In May 2020, Sweden had decided to shut down all Confucius Institutes in the country, stating the Chinese government's meddling in education affairs.[238] Some Chinese in Sweden have also reported increased stigmatisation during the coronavirus outbreak.[239] #### Peru[edit] See also: Chinese Peruvians and China–Peru relations Peru was a popular destination for Chinese immigrants at 19th century, mainly due to its vulnerability over slave market and subsequent needed for Peru over military and laborer workforce. However, relations between Chinese workers and Peruvian owners have been tense, due to mistreatments over Chinese laborers and anti-Chinese discrimination in Peru.[14] Due to the Chinese support for Chile throughout the War of the Pacific, relations between Peruvians and Chinese became increasingly tenser in the aftermath. After the war, armed indigenous peasants sacked and occupied haciendas of landed elite criollo "collaborationists" in the central Sierra – majority of them were of ethnic Chinese, while indigenous and mestizo Peruvians murdered Chinese shopkeepers in Lima; in response to Chinese coolies revolted and even joined the Chilean Army.[240][241] Even in 20th century, memory of Chinese support for Chile was so deep that Manuel A. Odría, once dictator of Peru, issued a ban against Chinese immigration as a punishment for their betrayal.[242] This caused a deep wound still relevant today in Peru. #### Canada[edit] See also: History of Chinese immigration to Canada In the 1850s, sizable numbers of Chinese immigrants came to British Columbia seeking gold; the region was known to them as Gold Mountain. Starting in 1858, Chinese "coolies" were brought to Canada to work in the mines and on the Canadian Pacific Railway. However, they were denied by law the rights of citizenship, including the right to vote, and in the 1880s, "head taxes" were implemented to curtail immigration from China. In 1907, a riot in Vancouver targeted Chinese and Japanese-owned businesses. In 1923, the federal government passed the Chinese Immigration Act, commonly known as the Exclusion Act, prohibiting further Chinese immigration except under "special circumstances". The Exclusion Act was repealed in 1947, the same year in which Chinese Canadians were given the right to vote. Restrictions would continue to exist on immigration from Asia until 1967, when all racial restrictions on immigration to Canada were repealed, and Canada adopted the current points based immigration system. On June 22, 2006, Prime Minister Stephen Harper offered an apology and compensation only for the head tax once paid by Chinese immigrants.[243] Survivors or their spouses were paid approximately CAD$20,000 in compensation.[244] Sinophobia in Canada has been fueled by allegations of extreme real estate price distortion resulting from Chinese demand, purportedly forcing locals out of the market.[245] #### Brazil[edit] There is Sinophobic sentiment in Brazil, largely due to the issue over economic and political manipulation from China over Brazil. Recently, Chinese have been accused for grabbing land in Brazil, involving on unclean political ties, further deepens Sinophobia in Brazil.[246] Chinese investments in Brazil have been largely influenced by this negative impression.[247] Current Brazilian President Jair Bolsonaro has shown distrust towards China during his presidential campaign, saying claiming they "[want to] buy Brazil."[248][249] #### United Kingdom[edit] See also: British Chinese, China–United Kingdom relations, and Opium Wars The United Kingdom developed a strong Sinophobic sentiment dated back at 1800s when China and the British Empire fought for influence in Asia. It resulted with the First Opium War which Qing China suffered a tremendous defeat and was forced to pay a fee.[250] Since then, due to strong anti-British sentiment in China, anti-Chinese sentiment grew in the U.K. as a response. Today, negative impressions of China and its people continues to be an issue in the United Kingdom. The Chinese emigrants in Britain often posit themselves to be among the most discriminated people out of all minorities,[251] and there is a lack of reporting over anti-Chinese discrimination in the U.K. as consequence, notably violence against Chinese Britons.[252] Further, British Chinese even claimed they had been "ignored" from such discrimination.[253] #### Portugal[edit] See also: China–Portugal relations and Malayan–Portuguese War In the 16th century, increasing sea trades between Europe to China had led Portuguese merchants to China, however Portuguese military ambitions for power and its fear of China's interventions and brutality had led to the growth of Sinophobia in Portugal. Galiote Pereira, a Portuguese Jesuit missionary who was imprisoned by Chinese authorities, claimed China's juridical treatment known as bastinado was so horrible as it hit on human flesh, becoming the source of fundamental anti-Chinese sentiment later; as well as brutality, cruelty of China and Chinese tyranny.[254] With Ming China's brutal reactions on Portuguese merchants following the conquest of Malacca,[255] Sinophobia became widespread in Portugal, and widely practiced until the First Opium War, which Qing China was forced to cede Macau for Portugal.[256] #### Mexico[edit] See also: Chinese immigration to Mexico Anti-Chinese sentiment was first recorded in Mexico at 1880s. Similar to most Western countries at the time, Chinese immigration and its large business involvement has always been a fear for native Mexicans. Violence against Chinese occurred such as in Sonora, Baja California and Coahuila, the most notable was the Torreón massacre,[257] although it was sometimes argued to be different than other Western nations.[258] #### New Zealand[edit] Anti-Chinese sentiment in New Zealand grew with the idea of a "Yellow Peril" in the 19th century, as Chinese citizens began to immigrate to New Zealand. Official discrimination began with the Chinese Immigration Acts in 1881, limiting Chinese emigration to New Zealand and excluding Chinese citizens from major jobs, to even anti-Chinese organizations.[259] Today, mostly anti-Chinese sentiment in New Zealand is about the labor issue.[259] K. Emma Ng reported that "One in two New Zealanders feel the recent arrival of Asian migrants is changing the country in undesirable ways"[259] Attitudes on Chinese in New Zealand is suggested to have remained fairly negative, with some Chinese still considered to be less respected people in the country.[260] #### United States[edit] See also: Anti-Chinese sentiment in the United States, China–United States relations, Fresh off the boat, and Citizens Against Government Waste § "Chinese Professor" ad Chinese immigrants portrayed as locusts invading Uncle Sam's farm, fleeing the shadow of famine, 1878 A political cartoon criticizing the United States' protest against the anti-Jewish pogroms in the Russian Empire despite the Chinese Exclusion Act. Starting with the California Gold Rush in the late 19th century, the United States—particularly the West Coast states—imported large numbers of Chinese migrant laborers. Employers believed that the Chinese were "reliable" workers who would continue working, without complaint, even under destitute conditions.[261] The migrant workers encountered considerable prejudice in the United States, especially among the people who occupied the lower layers of white society, because Chinese "coolies" were used as a scapegoat for depressed wage levels by politicians and labor leaders.[262] Cases of physical assaults on the Chinese include the Chinese massacre of 1871 in Los Angeles and the murder of Vincent Chin on June 23, 1982. The 1909 murder of Elsie Sigel in New York, for which a Chinese person was suspected, was blamed on the Chinese in general and it immediately led to physical violence against them. "The murder of Elsie Sigel immediately grabbed the front pages of newspapers, which portrayed Chinese men as dangerous to "innocent" and "virtuous" young white women. This murder led to a surge in the harassment of Chinese in communities across the United States."[263] The emerging American trade unions, under such leaders as Samuel Gompers, also took an outspoken anti-Chinese position,[264] regarding Chinese laborers as competitors to white laborers. Only with the emergence of the international trade union, IWW, did trade unionists start to accept Chinese workers as part of the American working-class.[265] Denver's anti-Chinese riot in 1880 In the 1870s and 1880s various legal discriminatory measures were taken against the Chinese. These laws, in particular the Chinese Exclusion Act of 1882, were aimed at restricting further immigration from China.[13] although the laws were later repealed by the Chinese Exclusion Repeal Act of 1943. In particular, even in his lone dissent against Plessy v. Ferguson (1896), then-Supreme Court Justice John Marshall Harlan wrote of the Chinese as: "a race so different from our own that we do not permit those belonging to it to become citizens of the United States. Persons belonging to it are, with few exceptions, absolutely excluded from our country. I allude to the Chinese race."[266] In the 2010 United States elections, a significant number[267] of negative advertisements from both major political parties focused on a candidates' alleged support for free trade with China which were criticized by Jeff Yang for promoting anti-Chinese xenophobia.[268] Some of the stock images that accompanied ominous voiceovers about China were actually of Chinatown, San Francisco.[268] These advertisements included one produced by Citizens Against Government Waste called "Chinese Professor," which portrayed a 2030 conquest of the West by China and an ad by Congressman Zack Space attacking his opponent for supporting free trade agreements like NAFTA, which the ad had claimed caused jobs to be outsourced to China.[269] In October 2013, a child actor on Jimmy Kimmel Live! jokingly suggested in a skit that the U.S. could solve its debt problems by "kill[ing] everyone in China."[270][271] Donald Trump, the 45th President of the United States, was accused of promoting Sinophobia throughout his campaign for the Presidency in 2016.[272][273] and it was followed by his imposition of trade tariffs on Chinese goods, which was seen as a declaration of a trade war and another anti-Chinese act.[274] The deterioration of relations has led to a spike in anti-Chinese sentiment in the US.[275][276] According to a Pew Research Center poll released in August 2019, 60 percent of Americans had negative opinions about China, with only 26 percent holding positive views. The same poll found that the country was named as America's greatest enemy by 24 percent of respondents in USA, tied along with Russia.[277] It has been noted that there is a negative bias in American reporting on China.[278][279][280] And many Americans, including American-born Chinese, have continuously held prejudices toward mainland Chinese people[281][282][283] which include perceived rudeness and unwillingness to stand in line,[284][285] even though there are sources that have reported contrary to those stereotypes.[286][287][288][289][290][291] A survey in 2019 though has suggested that some Americans still hold positive views of Chinese visitors to the US.[292] #### Venezuela[edit] A recent increasing Sinophobic sentiment sparked in Venezuela in the 2010s as for the direct consequence of Venezuelan crisis, which China was accused for looting and exploiting Venezuelan natural resources and economic starvation in the country, as well as its alliance to the current Venezuelan government of Nicolás Maduro.[293] ### Africa[edit] Anti-Chinese populism has been an emerging presence in some African countries.[294] There have been reported incidents of Chinese workers and business-owners being attacked by locals in some parts of the continent.[295][296] Recent reports of evictions, discrimination and other mistreatment of Africans in Guangzhou during the COVID-19 pandemic[297] has led to expressed animosity from some African politicians towards Chinese ambassadors.[298] #### Kenya[edit] Anti-Chinese sentiment broke out in Kenya when Kenyans accused Chinese for looting and stealing jobs from Kenyans, thus attacking Chinese workers and Chinese immigrants inside the country in 2016.[299] #### Ghana[edit] Ghanaians have alleged Chinese miners of illegally seizing jobs, polluting community water supplies, and disturbing agricultural production through their work. A sixteen-year-old illegal Chinese miner was shot in 2012, while trying to escape arrest.[300] #### Zambia[edit] In 2006, Chinese businesses were targeted in riots by angry crowds after the electoral defeat of the anti-China Patriotic Front.[301] In 2018, a reported spate of violent incidents targeting the Chinese community was allegedly linked to local politics.[302] Presidential candidate Michael Sata frequently invoked anti-Chinese rhetoric prior to winning his election in 2011,[303] once describing the Chinese in Zambia as not investors but "invaders". A 2016 study from the Hong Kong University of Science and Technology suggested though that locals held more nuanced views of Chinese people, ranking them not as highly as Caucasians, but also less negatively than Lebanese, and to some extent, Indian people.[304] #### South Africa[edit] Anti-Chinese sentiment in South Africa began with Chinese immigration in the 19th century, with rising fears of the "Yellow Peril". Under apartheid, Chinese South Africans were subject to discriminatory laws as well. Recent rise of Sinophobic sentiment in South Africa is largely contributed to by economic looting from China and growing Chinese influence in the country. In 2015, South Africa planned to allow for Mandarin to be taught in schools in South Africa solicited umbrage from the teachers' union and set social media and comment sections ablaze with fears of a Chinese "imperialism" in Africa and a new "colonialism"; as well as recent increasing Chinese immigration to the country.[305] A hate speech case was brought to light in 2017 for the Facebook comments found on a Carte Blanche animal abuse video, with 12 suspects on trial.[306] In 2017, violence against Chinese immigrants and other foreign workers broke out in Durban, then quickly spread out in other major cities in South Africa as for the result of Chinese fears over taking South Africa.[307] Xenophobia towards the Chinese has sometimes manifested in the form of robberies or hijackings,[308] ## Depiction of China and Chinese in media[edit] Depiction of China and Chinese in official media have been somewhat under subject in general, but overall, the majority of depiction over China and Chinese are surrounded about coverages, mainly, as negative. In 2016, Hong Kong's L. K. Cheah said to South China Morning Post that Western journalists who regard China's motives with suspicion and cynicism are cherry-picking facts based on a biased view, and the misinformation they produce as a result is unhelpful, and sympathetic of the resentment against China.[309] Many Chinese consider this is "war of information". According to China Daily, a nationalist press of China, Hollywood is accused for its negative portrayal of Chinese in movies, such as bandits, thugs, criminals, gangsters, dangerous, cold-blood, weak and cruel;[310] while the Americans as well as several European or Asians like Filipino, Taiwanese, Korean, Hong Konger, Vietnamese, Indian and Japanese characters in general are depicted as saviors, even anti-Chinese whitewashing in film is common. Matt Damon, the American actor who appeared in The Great Wall, had also faced criticism that he had participated in "whitewashing" through his involvement in forthcoming historical epic The Great Wall, a large-scale Hollywood-Chinese co-production, which he denied.[311] Several another examples is the depiction of ancient Tang Chinese in Yeon Gaesomun, a Korean historical drama, as "barbaric, inhuman, violent" seeking to conquer Goguryeo and subjecting Koreans.[312][313][314] In practice, anti-Chinese political rhetoric usually puts emphasis on highlighting policies and alleged practices of the Chinese government that are criticised internally - corruption, human rights issues, unfair trades, censorship, violence, military expansionism, political interferences and historical imperialist legacies. It is often in line with independent media opposing Chinese Government in Mainland China as well as in the Special Administrative Regions of China, Hong Kong and Macau.[315] In defence of this rhetoric, some sources critical of the Chinese government claim that it is Chinese state-owned media and administration who attempt to discredit the "neutral" criticism by generalizing it into indiscriminate accusations of the whole Chinese population and targeting those who criticize the regime[316] \- or Sinophobia.[315][317][318][319] Some have argued, however, that the Western media, similar to Russia's case, doesn't make enough distinction between CPC's regime and China and the Chinese, thus effectively vilifying the whole nation.[320] ## Business[edit] Due to the deep resentment over China-made business as well as alleged unfair trades from Chinese corporations, several countries have taken measures to ban or limit Chinese companies from investing in its markets. Notably is the case of Huawei and ZTE, which were banned from operating or doing business with American companies in the United States due to alleged involvements from Chinese Government and security concerns.[321][322][323] It was seen as discrimination against China. Some countries like India also moves closer to full ban or limit operations of Chinese corporations inside their countries for the exact reasons.[324][325] According to The Economist, many Western as well as non-Chinese investors still think that anything to do with China is somewhat "dirty" and unfresh[326] as most look on China as a country which often interferes on other businesses. Alexandra Stevenson from The New York Times also noted that "China wants its giant national companies to be world leaders in sectors like electric cars, robotics and drones, but the authorities are accused of curtailing foreign firms' access to Chinese consumers."[327] ## Historical Sinophobia-led violence[edit] List of non-Chinese "sinophobia-led" violence against ethnic Chinese ### Australia[edit] * Lambing Flat riots * Buckland Riot ### Canada[edit] * Vancouver anti-Chinese riots, 1886 ### Mexico[edit] * Torreón massacre ### Dutch East Indies[edit] * 1740 Batavia massacre ### Indonesia[edit] * 1740 Batavia massacre * 1918 Kudus riot * Mergosono massacre * Indonesian mass killings of 1965–66 * 1967 Mangkuk Merah Tragedy [id] * 1980 Jawa Tengah Racial Riot [id] * Situbondo Riot [id] * Banjarmasin riot of May 1997 * May 1998 riots of Indonesia * November 2016 Jakarta protests ### Malaysia[edit] * 13 May incident ### Japan[edit] Japanese war crimes against Chinese POWs in Nanjing, c. 1937 * Kantō Massacre * Nanking Massacre * Sook Ching massacre ### By Koreans[edit] * Wanpaoshan Incident, on July 1, 1931 ### United States[edit] * Chinese massacre of 1871 * Rock Springs massacre * Issaquah riot of 1885 * Tacoma riot of 1885 * Seattle riot of 1886 * Anti-Chinese violence in Washington * Hells Canyon Massacre ### Vietnam[edit] * 2014 Vietnam anti-China protest ## Derogatory terms[edit] There are a variety of derogatory terms referring to China and Chinese people. Many of these terms are viewed as racist. However, these terms do not necessarily refer to the Chinese ethnicity as a whole; they can also refer to specific policies, or specific time periods in history. ### In English[edit] * Eh Tiong – refers specifically to Chinese nationals. Primarily used in Singapore to differentiate between the Singaporeans of Chinese heritage and Chinese nationals. From Hokkien 中, an abbreviation of 中國 ("China"). Considered offensive. * Cheena – same usage as 'Eh Tiong' in Singapore. * Chinaman – the term Chinaman is noted as offensive by modern dictionaries, dictionaries of slurs and euphemisms, and guidelines for racial harassment. * Ching chong – Used to mock people of Chinese descent and the Chinese language, or other East and Southeast Asian looking people in general. * Ching chang chong – same usage as 'ching chong'. * Chink – racial slur referring to a person of Chinese ethnicity, but could be directed towards anyone of East and Southeast Asian descent in general. * Chinky – the name "Chinky" is the adjectival form of Chink and, like Chink, is an ethnic slur for Chinese occasionally directed towards other East and Southeast Asian people. * Chonky – refers to a person of Chinese heritage with white attributes whether being a personality aspect or physical aspect.[328][329] * Corona \- recently used in 2020 because of the COVID-19 pandemic, in assumptions that everyone of Chinese descent contracts the virus. * Coolie – means Laborer in reference to Chinese manual workers in the 19th and early 20th century. * Slope – used to mock people of Chinese descent and the sloping shape of their skull, or other East Asians. Used commonly during the Vietnam War. * Chicom – used to refer to a Communist Chinese. * Panface – used to mock the flat facial features of the Chinese and other people of East and Southeast Asian descent. * Lingling – used to call someone of Chinese descent in the West. * Chinazi – a recent anti-Chinese abusive sentiment which compares China to Nazi Germany, combining the word "China" and "Nazi". First published by Chinese dissident Yu Jie,[330][331] it became frequently used during Hong Kong protests against the Chinese government.[332][333] * Made in China – used to mock a purported low quality product, which can extend to other pejoratively perceived aspects of the country.[104] ### In Filipino[edit] * Intsik (Cebuan: Insik) is used to refer to refer people of Chinese ancestry including Chinese Filipinos. (The standard term is Tsino, derived from the Spanish chino, with the colloquial Tsinoy referring specifically to Chinese Filipinos.) The originally neutral term recently gained negative connotation with the increasing preference of Chinese Filipinos not to be referred to as Intsik. The term originally came from in chiek, a Hokkien term referring to one's uncle. The term has variations, which may be more offensive in tone such as Intsik beho and may used in a deregatory phrase, Intsik beho tulo-laway ("old Chinaman with drooling saliva").[334][335] * Tsekwa (sometimes spelled chekwa) – is a slang term used by the Filipinos to refer to Chinese people.[336] ### In French[edit] * Chinetoque (m/f) – derogatory term referring to Asian people. ### In Indonesian[edit] * Cokin, derogatory term to Asian people[337] * Panlok (Panda lokal/local panda): derogatory term referring to Chinese female or female who look like Chinese, particularly prostitute[338] ### In Japanese[edit] * Dojin (土人, dojin) – literally "earth people", referring either neutrally to local folk or derogatorily to indigenous peoples and savages, used towards the end of the 19th century and early 20th century by Japanese colonials, being a sarcastic remark regarding backwardsness.[citation needed] * Tokuajin (特亜人, tokuajin) – literally "particular Asian people", derogatory term used against Koreans and Chinese.[citation needed] * Shina (支那 or シナ, shina) – Japanese reading of the Chinese character compound "支那" (Zhina in Mandarin Chinese), originally a Chinese transcription of an Indic name for China that entered East Asia with the spread of Buddhism. Its effect when a Japanese person uses it to refer to a Chinese person is considered by some people to be similar to the American connotation of the word "negro", a word that has harmless etymologies but has gained derogative connotations due to historical context, where the phrase shinajin (支那人, lit. "Shina person") was used refer to Chinese.[citation needed] The slur is also extended towards left-wing activists by right-wing people.[339] * Chankoro (チャンコロ or ちゃんころ, chankoro) – derogatory term originating from a corruption of the Taiwanese Hokkien pronunciation of 清国奴 Chheng-kok-lô͘, used to refer to any "Chinaman", with a meaning of "Qing dynasty's slave". ### In Korean[edit] * Jjangkkae (Korean: 짱깨) – the Korean pronunciation of 掌櫃 (zhǎngguì), literally "shopkeeper", originally referring to owners of Chinese restaurants and stores;[340] derogatory term referring to Chinese people. * Seom jjangkkae (Korean: 섬짱깨) – literally "island shopkeeper"; referring to Taiwanese people. * Jjangkkolla (Korean: 짱꼴라) – this term has originated from Japanese term chankoro (淸國奴, lit. "slave of Qing Manchurian"). Later, it became a derogatory term that indicates people in China.[341] * Jung-gong (Korean: 중공; Hanja: 中共) – literally "Chinese communist", it is generally used to refer to Chinese communists and nationalists, since the Korean War (1950–1953). * Orangkae (Korean: 오랑캐) – literally "Barbarian", derogatory term used against Chinese, Mongolian and Manchus. * Dwoenom (Korean: 되놈) – It originally was a demeaning word for Jurchen meaning like 'barbarians' because Koreans looked down and treat Jurchen as inferior. But Jurchen (1636) invaded Korea (Joseon) and caused longterm hatred. Then Jurchen would take over China and make the Qing Dynasty. Koreans completely changed the view of China that China has now become taken over by hateful Dwoenom 'barbarians', so Koreans now called all of China as 'Dwoenom' not just Jurchen/Manchu.[342] * Ttaenom (Korean: 때놈) – literally "dirt bastard", referring to the perceived "dirtiness" of Chinese people, who some believe do not wash themselves. It was originally Dwoenom but changed over time to Ddaenom. ### In Mongolian[edit] * Hujaa (Mongolian: хужаа) – derogatory term referring to Chinese people. * Jungaa – a derogatory term for Chinese people referring to the Chinese language. ### In Portuguese[edit] * Xing líng (星零) - literal translation of the Portuguese expression "zero estrela" ("0 star"), to name a rip-off product, associated with Chinese products.[343][344] ### In Russian[edit] * Kitayoza (Russian: китаёза kitayóza) (m/f) – derogatory term referring to Chinese people. * Uzkoglazy (Russian: узкоглазый uzkoglázy) (m) – generic derogatory term referring to Asian people (lit. "narrow-eyed"). ### In Spanish[edit] * Chino cochino – (coe-chee-noe, N.A. "cochini", SPAN "cochino", literally meaning "pig") is an outdated derogatory term meaning dirty Chinese. Cochina is the feminine form of the word. ### In Italian[edit] * Muso giallo – literally "yellow muzzle". It is an offensive term used to refer to Chinese people, sometimes to Asian in general, with intent to point out their yellowish complexion as an indication of racial inferiority. The use of the word "muzzle" is in order not to consider them humans, but animals. ### In Vietnamese[edit] * Tàu – literally "boat". It is used to refer to Chinese people in general, can be construed as derogatory but very rarely does. This usage is derived from the fact that many Chinese refugees came to Vietnam in boats during the Qing dynasty. * Khựa – neologism, derogatory term for Chinese people and combination of two words above is called Tàu Khựa, that is a common word * Tung Của or Trung Của or Trung Cẩu (lit. Dog Chinese) – the parody spelling of the word "中国" (China) which spells as "zhong guó" in a scornful way, but rarely used. * Trung Cộng or Tàu Cộng (Chinese communists or Communist China) – used by Vietnamese anti-communists, mostly in exile, as a mockery toward China's political system and its imperialist desires.[345][346][347] ### In Cantonese[edit] * Wong choong (Chinese: 蝗蟲; Jyutping: wong4cung4) – literally "locust"; derogatory neologism used to refer to mainland visitors to Hong Kong accused of bad behavior.[45] ### In Min-nan[edit] * Si-a-liok (Written in traditional Chinese: 死阿陸; Taiwanese Romanization: Sí-a-lio̍k or Sí-a-la̍k) – literally "damn mainland Chinese", sometimes uses "四二六" (426, "sì-èr-liù") in Mandarin as word play. See also: 阿陸仔. ### In Burmese[edit] * Taruk (တရုပ်) – literally mean "Turks". It is used as derogatory term about Chinese people in general. First issued during the First Mongol invasion of Burma, the Chinese are widely seen as barbarian hordes from the north. That reflected the geographical and political dimensions at the time, when the Mongols ruled mainland China and the Turks formed the largest of Mongol Army. Now rarely used due to warm Sino-Burmese relations. ## Chinese response[edit] Main articles: Anti-Western sentiment in China and 50 Cent Army In the aftermath of the United States bombing of the Chinese embassy in Belgrade during the NATO bombing of Yugoslavia in 1999, there was a significant surge in Chinese nationalist sentiment, and it was intensified by the growth of patriotic movements in China, which, like patriotic movements in Russia, believe that China is engaged in a clash of civilizations or a "a global struggle between the materialistic, individualistic, consumerist, cosmopolitan, corrupt, and decadent West which is led by the United States and the idealist, collectivist, morally and spiritually superior Asia which is led by China," where the West is viewed as trying to tear China up so it can use its natural resources to satisfy its own interests and needs.[348][349] A 2020 study among Chinese students studying abroad in the United States found that after facing anti-Chinese racism, their support for the Chinese government increased and their support for political reform in China decreased.[350] ## Sinophobia during the COVID-19 pandemic[edit] Main article: List of incidents of xenophobia and racism related to the COVID-19 pandemic An unofficial[351] anti-xenophobia poster at a subway station in New York City amid the COVID-19 pandemic The COVID-19 pandemic, in which the virus originated from Wuhan, has caused prejudice and racism towards people of Chinese ancestry. Some people expressed how Chinese people deserve to get it.[352][353][354][355] Several citizens across the globe also demanded a ban of Chinese people from their countries.[356][357][358] Racist abuse and assaults among the Asian groups in the UK and US are also reported to increase.[359][360] U.S. President Donald Trump also repeatedly called the coronavirus 'Chinese virus' and 'Kung Flu',[361][362] however, he denied racist connotation of the terms.[363] ## See also[edit] * Anti-Qing sentiment * Anti-Western sentiment in China * Anti-Russian sentiment * Boycott Chinese products * China–United States trade war * Chinese imperialism * Desinicization * Ethnic issues in China * Fu Manchu * List of anti-ethnic and anti-national terms * List of ethnic slurs * List of incidents of xenophobia and racism related to the COVID-19 pandemic * List of phobias * List of religious slurs * Sinophile * Sinicization * Sinocentrism * Yellow Peril ## References[edit] 1. ^ "People around the globe are divided in their opinions of China". Pew Research Center. September 30, 2019. 2. ^ "In Taiwan, Views of Mainland China Mostly Negative". Pew Research Center. May 12, 2020. 3. ^ "BBC World Service poll" (PDF). BBC. July 4, 2017. p. 36. 4. ^ "China's Image in Greece (page 33)" (PDF). December 2017. p. 33. 5. ^ Company, Houghton Mifflin Harcourt Publishing. "The American Heritage Dictionary entry: Sinophobic". ahdictionary.com. Retrieved October 25, 2020. 6. ^ a b "BBC News – Analysis – Indonesia: Why ethnic Chinese are afraid". Retrieved May 9, 2015. 7. ^ a b Kazin, Michael; Edwards, Rebecca; Rothman, Adam (2010). "Immigration Policy". The Princeton Encyclopedia of American Political History. Princeton University Press. "Compared to its European counterparts, Chinese immigration of the late nineteenth century was minuscule (4 percent of all immigration at its zenith), but it inspired one of the most brutal and successful nativist movements in U.S. history. Official and popular racism made Chinese newcomers especially vulnerable; their lack of numbers, political power, or legal protections gave them none of the weapons that enabled Irish Catholics to counterattack nativists." 8. ^ a b Chinese Aussie rules players suffer abuse, racism, Herald Sun 9. ^ a b c d Chapter 3. Attitudes toward China \- Pew Global Attitudes. Posted on July 18, 2013. 10. ^ Billé, Franck (October 31, 2014). "Sinophobia: Anxiety, Violence, and the Making of Mongolian Identity". University of Hawaii Press – via www.degruyter.com. 11. ^ Lovell, Julia (November 10, 2015). The Opium War: Drugs, Dreams, and the Making of Modern China. ISBN 9781468313239. 12. ^ Lord Elgin and the Burning of the Summer Palace. Posted by E.W.R. Lumby, in History Today. Volume 10, Issue 7, July 1960. 13. ^ a b "An Evidentiary Timeline on the History of Sacramento's Chinatown: 1882 – American Sinophobia, The Chinese Exclusion Act and "The Driving Out"". Friends of the Yee Fow Museum, Sacramento, California. Retrieved March 24, 2008. 14. ^ a b Justina Hwang. Chinese in Peru in the 19th century \- Modern Latin American, Brown University Library. 15. ^ a b Unspeakable Affections \- Paris Review. May 5, 2017. 16. ^ Haruko Satoh (August 7, 2006). The Odd Couple: Japan and China, The Politics of History and Identity. Yale Global University. 17. ^ Sah Dong-seok (2016-08-26, at 14:48). THAAD and anti-Chinese sentiment. The Korea Times. 18. ^ Zisserman-Brodsky, D. (July 3, 2003). Constructing Ethnopolitics in the Soviet Union: Samizdat, Deprivation and the Rise of Ethnic Nationalism. ISBN 9781403973627. 19. ^ The Chinese Government's claims that the Chinese rise is peaceful have been viewed with skepticism. 20. ^ Peaceful rise of India and China. Post on Washington Post. 21. ^ Matthew Forney, "Why China Loves to Hate Japan". Time Magazine, December 10, 2005.Why China Bashes Japan. Accessed June 1, 2008 22. ^ 24-Nation Pew Global Attitudes Survey(2008) Archived July 4, 2008, at the Wayback Machine 35p, Pew Research 23. ^ "Joint Civil Society Report on Racial Discrimination in Japan (page 33)" (PDF). August 2018. 24. ^ "Issues related to the increase in tourists visiting Japan from abroad (sections titled 'How foreign tourists are portrayed' and 'Acts of hate?')". www.japanpolicyforum.jp. November 2017. Retrieved January 1, 2020. 25. ^ Niv, Horesh; Jin, Kim Hyun; Peter, Mauch (October 27, 2014). Superpower, China? Historicizing Beijing's New Narratives of Leadership and East Asia's Response Thereto. ISBN 9789814619172. 26. ^ THAAD and anti-Chinese sentiment. Posted on The Korea Times. Posted by Sah Dong-seok on August 26, 2016. 27. ^ a b Gries, Peter Hays (Winter 2005). "The Koguryo Controversy, National Identity, and Sino-Korean relations Today" (PDF). East Asia. 22 (4): 9. doi:10.1007/s12140-005-0001-y. S2CID 144129470. Archived from the original (PDF) on August 20, 2017. 28. ^ 만보산사건 (in Korean). Naver/Doosan Encyclopedia. 29. ^ World Public Opinion surveys, 2002–2008 www.worldpublicopinion.org 30. ^ East Asia Institute Foreign Perception Survey 2005–2009, some in collaboration with BBC World Service Polls 2005–2008 www.eai.or.kr 31. ^ Beijing's Anti-THAAD Moves Sour China Views in South Korea. Posted by Brian Padden on March 21, 2017. 32. ^ "China, not North Korea, is biggest threat to peace, South Koreans say". South China Morning Post. October 3, 2018. Retrieved July 14, 2019. 33. ^ Tai, Crystal. "The strange, contradictory privilege of living in South Korea as a Chinese-Canadian woman". Quartz. Retrieved January 1, 2020. 34. ^ "A Peek into Chinese Views of other Countries \| Daxue Consulting". daxueconsulting.com. Retrieved January 1, 2020. 35. ^ "Too Different to Be Chinese, Not Good Enough to Be Korean". KOREA EXPOSÉ. September 20, 2018. Retrieved January 1, 2020. 36. ^ "Ethnic Korean-Chinese fight 'criminal' stigma in Korea". AsiaOne. October 4, 2017. Retrieved January 1, 2020. 37. ^ 이해아 (March 22, 2011). "(News Focus) Ethnic Koreans from China grow resentful over discrimination in homeland". Yonhap News Agency. Retrieved January 1, 2020. 38. ^ "HKU POP releases latest survey on Hong Kong people's ethnic identity". Hong Kong University. December 22, 2014. Retrieved January 14, 2015. 39. ^ jim.smith (August 27, 2013). "Phone cams and hate speech in Hong Kong". Gates Cambridge. Retrieved January 1, 2020. 40. ^ Leung, Wing Yeung Vivian (July 18, 2018). "Discriminatory Media Reports Against Mainland Chinese New Immigrants in Hong Kong". ISA World Congress Of Sociology. Cite journal requires `\|journal=` (help) 41. ^ Holdstock, Nick (June 13, 2019). China's Forgotten People: Xinjiang, Terror and the Chinese State. Bloomsbury Publishing. ISBN 978-1-78831-982-9. 42. ^ "Hongkongers still 'negative' about mainland visitors, HKU poll shows". South China Morning Post. December 4, 2013. Retrieved April 19, 2020. 43. ^ "The Tourist Stereotype Model: Positive and Negative Dimensions". ResearchGate. Retrieved March 16, 2020. 44. ^ Tung, Vincent Wing Sun; King, Brian Edward Melville; Tse, Serene (January 23, 2019). "The Tourist Stereotype Model: Positive and Negative Dimensions". Journal of Travel Research. 59 (1): 37–51. doi:10.1177/0047287518821739. ISSN 0047-2875. S2CID 150395266. 45. ^ a b Liu, Juliana (February 8, 2012). "Surge in anti-China sentiment in Hong Kong". BBC. Retrieved October 4, 2013. 46. ^ Buddle, Cliff (February 26, 2014). "Anti-mainlander protest a reminder of the limits of free speech". South China Morning Post. Retrieved February 27, 2014. 47. ^ Jing Wu, Nelson Moura (August 30, 2019). "Corrected: Mainland Chinese uni students in Macau afraid of discrimination in HK". Macau News Agency - DeFicção Multimedia Projects. Retrieved April 19, 2020. 48. ^ "The dirty secret of Hong Kong's protests: hatred of mainlanders". South China Morning Post. October 11, 2019. Retrieved January 1, 2020. 49. ^ "Will violence kill Hong Kong's pro-democracy movement? (at 22:07 minutes)". DW News. November 2019. 50. ^ "Hong Kong Protesters Are Alienating Mainland Chinese Allies". Bloomberg. November 2019. 51. ^ "Chinese students flee HK in fear of attack after death". Bangkok Post. Retrieved January 1, 2020. 52. ^ Lattimore, Owen; Nachukdorji, Sh (1955). Nationalism and Revolution in Mongolia. Brill Archive. pp. 171–. GGKEY:4D2GY636WK5. 53. ^ a b Tania Branigan (August 2, 2010). "Mongolian neo-Nazis: Anti-Chinese sentiment fuels rise of ultra-nationalism". The Guardian. 54. ^ China's Inner Mongolia 'under heavy security'. Posted on BBC News. Posted on May 3, 2011. 55. ^ Billé (2015). Sinophobia: Anxiety, Violence, and the Making of Mongolian Identity. 56. ^ Avery, Martha (2003). The Tea Road: China and Russia Meet Across the Steppe. China Intercontinental Press. p. 91. 57. ^ Bulag, Uradyn E. (December 2004). "Mongolian Modernity and Hybridity". Minpaku. National Museum of Ethnology (Osaka) (19): 1–3. 58. ^ NZZ: Die Mongolen bestimmen einen neuen Präsidenten (in German): "Die Kampagne des bisherigen Amtsinhabers Enkhbayar hatte an chauvinistische Gefühle appelliert und dem Gegenkandidaten Elbegdorj mehr oder weniger direkt unterstellt, chinesische Vorfahren und damit «kein reines mongolisches Blut» zu haben." 59. ^ "What's behind the China-Taiwan divide?". BBC. December 3, 2016. 60. ^ "Three out of four Taiwanese do not consider themselves to be Chinese (youths even less so)". March 26, 2018. 61. ^ Anderlini, Jamil (March 30, 2014). "Thousands of Taiwanese rally against closer ties with China". Financial Times. 62. ^ Civilized Taiwanese vs Uncivilized Mainlanders: Peng Mingmin and Anti-Chinese Rhetoric. Posted on The Greater China Journal. Posted by / Aris Teon on February 26, 2017. 63. ^ Everington, Keoni. "76% of Taiwanese consider China 'unfriendly': MAC poll". www.taiwannews.com.tw. Taiwan News. Retrieved April 15, 2020. 64. ^ Sinophilia and Sinophobia in Afghanistan. Posted on The Diplomat. Posted by Tamin Asey on December 10, 2014. 65. ^ "Kazakhstan's land reform protests explained – BBC News". BBC News. April 28, 2016. Retrieved February 28, 2018. 66. ^ Catherine Putz, The Diplomat. "Land Protests Persist in Kazakhstan". The Diplomat. Retrieved February 28, 2018. 67. ^ "Archived copy". Archived from the original on July 26, 2018. Retrieved July 25, 2018.CS1 maint: archived copy as title (link) 68. ^ Tajik social-democrats leader: China grabs more Tajik land than agreed. Posted by Ferghana International Agency, on April 16, 2013. 69. ^ a b The China-Pakistan Economic Corridor Between Hope and Fear. Posted by Mushtaq A. Kaw on April 26, 2017. 70. ^ Holdstock, Nick (June 13, 2019). China's Forgotten People: Xinjiang, Terror and the Chinese State. Bloomsbury Publishing. ISBN 978-1-78831-982-9. 71. ^ Holdstock, Nick (June 13, 2019). China's Forgotten People: Xinjiang, Terror and the Chinese State. Bloomsbury Publishing. ISBN 978-1-78831-981-2. 72. ^ Svanberg, Ingvar; Westerlund, David (1999). Islam Outside the Arab World. Routledge. ISBN 978-1-136-11322-2. 73. ^ Fallows, James (July 13, 2009). "On Uighurs, Han, and general racial attitudes in China". The Atlantic. Retrieved January 1, 2020. 74. ^ "China's model village of ethnic unity shows cracks in facade". AP NEWS. November 22, 2018. Retrieved January 1, 2020. 75. ^ 10 killed in ethnic clash in western China. Posted on CNN. Posted on February 10, 1997. 76. ^ China locks down western province after ethnic riots kill 140. Posted on The Guardian.com. Posted on July 6, 2009. 77. ^ Why is there tension between China and the Uighurs?. Posted on BBC News. Posted on September 26, 2014. 78. ^ China Xinjiang police state: Fear and resentment. Posted on BBC News. Posted on February 1, 2018. 79. ^ "Wanted: cadres to hold Beijing's line in Xinjiang as Han Chinese exit". South China Morning Post. December 4, 2019. Retrieved April 19, 2020. 80. ^ Suleiman, Omar. "Don't forget the Uighur amid the coronavirus crisis". www.aljazeera.com. Retrieved March 16, 2020. 81. ^ "China Seizes on a Dark Chapter for Tibet", by Edward Wong, The New York Times, August 9, 2010 (August 10, 2010 p. A6 of NY ed.). Retrieved August 10, 2010. 82. ^ How the Dalai Lama Works - People. Posted on HowStuffWorks 83. ^ Events Leading to the 1959 Tibetan Uprising. Posted on ThoughtCo. Posted by Kallie Szczepanski on July 16, 2018. 84. ^ Dalai Lama Escapes From Tibet: How and Why It Happened. Posted on Time. Posted on March 17, 2015. 85. ^ HEROD IN TIBET. Posted on Tibetan Review. Posted on January 2, 2018. 86. ^ TIBETAN UPRISING IN 2008. Posted on Facts and Details 87. ^ Self-immolation protests. Posted on Free Tibet 88. ^ "Immigration, Population, and Foreign Workforce in Singapore: An Overview of Trends, Policies, and Issues (page 2)" (PDF). 89. ^ "Singapore: Asian immigrant stock by country of origin 2019". Statista. Retrieved March 16, 2020. 90. ^ "Part 1 of 2: Chinese Xenophobia in Singapore Rises \| GRI". Global Risk Insights. July 28, 2013. Retrieved March 16, 2020. 91. ^ Jacobs, Andrew (July 27, 2012). "New York Times: In Singapore, Vitriol Against Chinese Newcomers". Nytimes.com. Retrieved April 22, 2020. 92. ^ Cheung, Helier (May 1, 2014). "'No Indians No PRCs': Singapore's rental discrimination". Retrieved January 1, 2020. 93. ^ "Britons make worst tourists, say Britons (and Spaniards and Germans) \| YouGov". yougov.co.uk. Retrieved January 1, 2020. 94. ^ Gebicki, Michael (September 19, 2019). "The world's most hated tourists revealed". Traveller. Retrieved January 1, 2020. 95. ^ Horowitz, Donald L. (2003). The Deadly Ethnic Riot. University of California Press. p. 275. ISBN 978-0520236424. 96. ^ "Penang's forgotten protest: The 1967 Hartal". Penang Monthly. August 25, 2014. 97. ^ Horowitz, Donald L. (2003). The Deadly Ethnic Riot. University of California Press. p. 255. ISBN 978-0520236424. 98. ^ Hwang, p. 72. 99. ^ von Vorys 1975, p. 364. 100. ^ "Race War in Malaysia". Time. 23 May 1969.[1] 101. ^ von Vorys 1975, p. 368. 102. ^ Slimming 1969, pp. 47–48. 103. ^ "In Malaysia, fake news of Chinese nationals getting citizenship stokes racial tensions". South China Morning Post. September 10, 2019. Retrieved April 19, 2020. 104. ^ a b "Coronavirus spreads anti-Chinese racism through Asia like a disease". South China Morning Post. January 29, 2020. Retrieved March 16, 2020. 105. ^ "GENOCIDE – CAMBODIA". Archived from the original on October 30, 2014. Retrieved May 9, 2015. 106. ^ "The Cambodian Genocide and International Law". 107. ^ "Cambodia the Chinese". Retrieved May 9, 2015. 108. ^ "Cambodia after the Khmer Rouge: inside the politics of nation building", p. 174, by Evan Gottesman 109. ^ Ellis-Petersen, Hannah (July 31, 2018). "'No Cambodia left': how Chinese money is changing Sihanoukville". The Guardian. Retrieved June 3, 2020. 110. ^ Tantingco, Robby (March 15, 2010). "Tantingco: What your surname reveals about your past". Sunstar. 111. ^ James Francis Warren (2007). The Sulu zone, 1768–1898: the dynamics of external trade, slavery, and ethnicity in the transformation of a Southeast Asian maritime state (2, illustrated ed.). NUS Press. pp. 129, 130, 131. ISBN 978-9971-69-386-2. 112. ^ Tiezzi, Shannon (September 17, 2014). "China Warns Citizens to Stay Away from Philippines". The Diplomat. 113. ^ "Coronavirus concerns fuel anti-Chinese sentiment in the Philippines". South China Morning Post. February 7, 2020. Retrieved March 16, 2020. 114. ^ History: October 9, 1740: Chinezenmoord, The Batavia Massacre. Posted on History Headline. Posted by Major Dan on October 9, 2016. 115. ^ 海外汉人被屠杀的血泪史大全. woku.com (in Chinese).[permanent dead link] 116. ^ "Archived copy" 十七﹒八世紀海外華人慘案初探 (in Chinese). Taoyuan Department of Education. Archived from the original on January 2, 2017. Retrieved March 17, 2018.CS1 maint: archived copy as title (link) 117. ^ "ǻܵļɱ". Retrieved May 9, 2015. 118. ^ 南洋华人被大规模屠杀不完全记录 (in Chinese). The Third Media. 119. ^ Indonesian academics fight burning of books on 1965 coup, smh.com.au 120. ^ Vickers (2005), p. 158 121. ^ "Inside Indonesia – Digest 86 – Towards a mapping of 'at risk' groups in Indonesia". Archived from the original on September 20, 2000. Retrieved May 9, 2015. 122. ^ "[INDONESIA-L] DIGEST – The May Riot". Archived from the original on March 25, 2017. Retrieved May 9, 2015. 123. ^ "Why Is China Pressing Indonesia Again Over the Natuna Islands?". www.worldpoliticsreview.com. 124. ^ Beech, Hannah; Suhartono, Muktita; Dean, Adam (March 31, 2020). "China Chases Indonesia's Fishing Fleets, Staking Claim to Sea's Riches" – via NYTimes.com. 125. ^ "Indonesian students continue protests against Chinese workers". South China Morning Post. July 16, 2020. Retrieved September 4, 2020. 126. ^ Yhome, K. "The BRI and Myanmar's China debate". Observer Research Foundation. Retrieved April 19, 2020. 127. ^ "Opinion \| How China Fuels Myanmar's Wars". The New York Times. Retrieved March 4, 2015. 128. ^ "Animosity in a Burmese Hub Deepens as Chinese Get Richer". The New York Times. Retrieved November 27, 2016. 129. ^ Nicholas Farrelly, Stephanie Olinga-Shannon. "Establishing Contemporary Chinese Life in Myanmar (pages 24, 25)" (PDF). ISEAS Publishing. 130. ^ Luang Phibunsongkhram. Posted in Encyclopedia Britannica. 131. ^ "Nation-building and the Pursuit of Nationalism under Field Marshal Plaek Phibunsongkhram". 2bangkok.com. July 15, 2004. Retrieved April 22, 2020. 132. ^ Harrison, David; Sharpley, Richard (May 26, 2017). Mass Tourism in a Small World. CABI. ISBN 978-1-78064-854-5. 133. ^ "Chinese, Russian tourists not 'preferred', says Phuket poll". The Phuket News. August 1, 2015. Retrieved January 2, 2020. 134. ^ Farrell, James Austin. "Thailand's hostility to Chinese tourists traces all the way back to its history of immigration". Business Insider. Retrieved January 1, 2020. 135. ^ Charuvastra, Teeranai; Chief, News (June 19, 2019). "'Chinese Tourist' Who Took a Dump in Chinatown Not Chinese After All". Khaosod English. Retrieved January 1, 2020. 136. ^ "Viral video of Chinese tourists' buffet frenzy shot 2 years ago, Thai restaurant claims". Shanghaiist. March 23, 2016. Retrieved January 1, 2020. 137. ^ "Cross-cultural Differences and Cultural Stereotypes in Tourism - Chinese Tourists in Thailand" (PDF). 138. ^ Beech, Hannah (February 28, 2020). "He Drove Her to the Hospital. She Gave Him the Coronavirus". The New York Times. ISSN 0362-4331. Retrieved March 16, 2020. 139. ^ Martha Ann Overland (April 16, 2009). "In Vietnam, New Fears of a Chinese 'Invasion'". Time Magazine. Retrieved October 27, 2009. 140. ^ a b "Vietnamese in second anti-China rally over disputed islands". The Australian. Agence France-Presse. December 16, 2007. Archived from the original on December 18, 2007. Retrieved October 27, 2009. 141. ^ Ask The Vietnamese About War, And They Think China, Not The U.S. Posted Michael Sullivan on May 1, 2015. 142. ^ "overseas chinese in vietnam". Retrieved May 9, 2015. 143. ^ Griffin, Kevin. Vietnamese Archived February 28, 2003, at the Wayback Machine. Discover Vancouver. 144. ^ Agence France Presse (April 20, 2009). "Vietnam's China mining plans spark rare criticism". AsianOne News. Retrieved October 27, 2009. 145. ^ "Vietnam's nationalist bloggers: Getting if off your chest". The Economist. September 10, 2009. Retrieved October 27, 2009. 146. ^ Martha Ann Overland (September 5, 2009). "Vietnam to Its Journalists: Don't Tread on China". Time Magazine. Retrieved October 27, 2009. 147. ^ Pham, Nga (August 12, 2009). "China releases Vietnam fishermen". BBC News. Retrieved October 27, 2009. 148. ^ "Tourist Agencies Abandon China". Radio Free Asia. June 3, 2011. 149. ^ "Vietnamese hold anti-Chinese protest". BBC News. June 5, 2011. Retrieved June 5, 2011. 150. ^ "Vietnam protesters clash with police over new economic zones". BBC News. June 10, 2018. Retrieved June 10, 2018. 151. ^ Gross, Daniel. Cheap Trade. Newsweek. 152. ^ Moufakkir, Omar; Reisinger, Yvette (2013). The Host Gaze in Global Tourism. CABI. ISBN 978-1-78064-021-1. 153. ^ http://himalaya.socanth.cam.ac.uk/collections/journals/kailash/pdf/kailash_15_0102_03.pdf 154. ^ Mosca, Matthew (February 20, 2013). From Frontier Policy to Foreign Policy: The Question of India and the Transformation of Geopolitics in Qing China. ISBN 9780804785389. 155. ^ "Nepalese newspaper accuses China of 'veiled threats against editor'". South China Morning Post. February 20, 2020. 156. ^ Francis, Xavier (May 10, 2020). "After Claiming Mount Everest, China Now Says Mount Qomolangma is located on Nepal-China Border". EurAsian Times: Latest Asian, Middle-East, EurAsian, Indian News. 157. ^ Garver, John W. (July 1, 2011). Protracted Contest: Sino-Indian Rivalry in the Twentieth Century – John W. Garver – Google Books. ISBN 9780295801209. Retrieved February 28, 2018. 158. ^ Brian Benedictus, The Diplomat. "Bhutan and the Great Power Tussle". The Diplomat. Retrieved February 28, 2018. 159. ^ "Sri Lanka protest over Chinese investment turns ugly". BBC. January 7, 2017. 160. ^ Shephard, Wade (January 8, 2017). "Violent Protests Against Chinese 'Colony' In Sri Lanka Rage On". Forbes. 161. ^ How Beijing won Sri Lanka's civil war. Posted on The Independent. Posted on 23 may. 2010. 162. ^ Sen, Tansen (April 13, 2005). "Go for a slight change of route". Telegraph. Retrieved September 26, 2006. 163. ^ a b c Mazumdar, Jaideep (November 20, 2010). "The 1962 jailing of Chinese Indians". OPEN. Retrieved November 17, 2013. 164. ^ Schiavenza, Matt (August 9, 2013). "India's Forgotten Chinese Internment Camp". The Atlantic. Retrieved November 17, 2013. 165. ^ "Indo". Retrieved October 20, 2014. 166. ^ "Boycott Chinese products, says prominent cleric in Eid sermon". Zee News. October 6, 2014. Retrieved October 20, 2014. 167. ^ "India says China's Galwan Valley claims 'untenable, exaggerated'". aljazeera. 168. ^ "Google Removes Viral Indian App That Deleted Chinese Ones: 10 Points". NDTV Gadgets 360. 169. ^ "PNG riots hit Chinese businesses". BBC. May 18, 2009. Retrieved April 19, 2020. 170. ^ "Overseas and under siege". The Economist. ISSN 0013-0613. Retrieved April 19, 2020. 171. ^ "No More Chinese!" Archived June 30, 2012, at the Wayback Machine, Tongatapu.net 172. ^ "Tonga announces the expulsion of hundreds of Chinese immigrants" Archived March 16, 2008, at the Wayback Machine, John Braddock, WSWS, December 18, 2001 173. ^ a b "The Pacific Proxy: China vs Taiwan" Archived November 4, 2007, at the Wayback Machine, Graeme Dobell, ABC Radio Australia, February 7, 2007 174. ^ "Chinese stores looted in Tonga riots", People's Daily, November 17, 2006 175. ^ Kuo, Mercy A. "Israeli Perceptions of China: Implications for the United States". The Diplomat. Retrieved April 19, 2020. 176. ^ Pompilio, Natalie (July 15, 2019). "How Shanghai Saved 20,000 Jews from the Nazis". Thedailybeast.com. Retrieved April 22, 2020. 177. ^ "China's Kaifeng Jews date back 1,400 years and have an unlikely ambassador – a teenager from Hong Kong". South China Morning Post. March 8, 2020. Retrieved April 22, 2020. 178. ^ a b "Chinese authorities crack down on tiny Jewish community". The Times of Israel. September 25, 2016. Retrieved April 22, 2020. 179. ^ Gilbert, Lela (February 15, 2019). "Tiny Kaifeng Jewish community faces Orwellian future". The Jerusalem Post. Retrieved April 22, 2020. 180. ^ Gambrell, Jon (March 22, 2020). "Iran leader refuses US help, citing conspiracy theory that virus man-made". The Times of Israel. Retrieved April 22, 2020. 181. ^ Peyrouse, Sebastien. "Understanding Sinophobia in Central Asia". thediplomat.com. The Diplomat. Retrieved May 4, 2020. 182. ^ Santoli, Al (January 29, 2001). "Russian far east residents fear takeover by China; Sino-Russian "strategic cooperation" pact aimed at US". American Foreign Policy Council. Archived from the original on November 16, 2007. Retrieved March 25, 2008. 183. ^ Baker, Peter (August 2, 2003). "Russians fear Chinese 'takeover' of Far East regions". Dawn. Archived from the original on November 16, 2007. Retrieved March 25, 2008. 184. ^ Weitz, Richard (2012). "SUPERPOWER SYMBIOSIS: The Russia-China Axis". World Affairs. 175 (4): 71–78. JSTOR 41639036. 185. ^ Libman, Alexander; Vollan, Björn (2019). "Anti-Western Conspiracy Thinking in China and Russia: Empirical Evidence and its Link to Expectations of Collusion". Homo Oeconomicus. 36 (3–4): 135–163. doi:10.1007/s41412-019-00082-9. 186. ^ "Mapping Ethnic Stereotypes and Their Antecedents in Russia (chart)". www.ncbi.nlm.nih.gov. Retrieved January 1, 2020. 187. ^ Grigoryev, Dmitry; Fiske, Susan T.; Batkhina, Anastasia (July 16, 2019). "Mapping Ethnic Stereotypes and Their Antecedents in Russia: The Stereotype Content Model". Frontiers in Psychology. 10: 1643. doi:10.3389/fpsyg.2019.01643. ISSN 1664-1078. PMC 6646730. PMID 31379677. 188. ^ "VIDEO: Turkish nationalists protesting China attack Korean tourists in Istanbul". Hurriyet Daily News. Doğan News Agency. July 4, 2015. 189. ^ "Turks protesting against China attack Koreans 'by mistake'". Malay Mail. Agence France-Presse. July 5, 2014. 190. ^ "China says tourists attacked in Turkey during anti-China protests". Reuters. July 5, 2015. 191. ^ Lefevre, Amy Sawitta; Dikmen, Yesim (July 9, 2015). "Thai PM defends decision to send Uighurs back to China". Reuters. 192. ^ "Turks embrace Russia, China, reject U.S. - U.S. State Dept poll". Ahval. Retrieved January 16, 2020. 193. ^ China Will not 'Protect Any Party' in Syria Violence. Posted by Daniel Tovrov on 02/14/12 aT 10:59 AM. 194. ^ "Chinese flags defaced in Prague ahead of Xi visit". BBC News. March 26, 2016. Retrieved April 22, 2020. 195. ^ "'Heavy price': China threatens Czech official over Taiwan visit". www.aljazeera.com. 196. ^ "China warns tourists against visiting the Czech Republic". news.expats.cz. September 14, 2020. 197. ^ Mackinnon, Colum Lynch, Amy. "Document of the Week: Czech Pol to China: Piss Off". 198. ^ "China influence aggravates Czech Republic's political war". Nikkei Asia. 199. ^ Young, Jason. "Review of East by South: China in the Australasian Imagination". Victoria University of Wellington. Archived from the original (.doc) on April 14, 2008. Retrieved March 24, 2008. 200. ^ a b Markey, Raymond (January 1, 1996). "Race and organized labor in Australia, 1850–1901". Highbeam Research. Archived from the original on October 19, 2017. Retrieved June 14, 2006. 201. ^ a b Griffiths, Phil (July 4, 2002). "Towards White Australia: The shadow of Mill and the spectre of slavery in the 1880s debates on Chinese immigration" (RTF). 11th Biennial National Conference of the Australian Historical Association. Retrieved June 14, 2006. 202. ^ "China Outrage Over Sydney Train Assault". The Sydney Morning Herald. April 26, 2012. Retrieved May 9, 2015. 203. ^ Lord, Kathy (July 25, 2017). "Offensive flyers targeting Chinese students found at Melbourne universities". 204. ^ Riordan, Primrose (August 2, 2017). "Chinese social media outraged by racist graffiti at Sydney University". 205. ^ Kwai, Isabella; Xu, Vicky Xiuzhong (July 25, 2017). "Anti-Chinese Posters at Melbourne Universities Are Tied to White Supremacists". The New York Times. 206. ^ "SCOTT BURCHILL. Resuscitating Sinophobia in Australia". Johnmenadue.com. September 4, 2019. Retrieved April 22, 2020. 207. ^ Ponniah, Kevin (October 26, 2016). "A killing in Paris: Why French Chinese are in uproar". BBC. 208. ^ "France ready to join India's anti-China front". Asia Times. November 2, 2017. 209. ^ Mulholland, Rory (February 22, 2018). "Emmanuel Macron promises to stop foreign investors buying up French farms after China land grab". The Telegraph. 210. ^ "How the French Are Waking Up to the Rise of Chinese Power". Belfer Center for Science and International Affairs. Retrieved January 1, 2020. 211. ^ "La Chine vue par les Français : menace ou opportunité ?". Institut Montaigne (in French). Retrieved January 1, 2020. 212. ^ [email protected], Nik Fes. "Chinese Tourists – Parisians Not Only Happy about the Tourism Boom \| .TR". www.tourism-review.com. Retrieved January 1, 2020. 213. ^ "Survey Finds Americans Are Most Annoying Airline Passengers". TravelPulse. Retrieved January 1, 2020. 214. ^ "Stats: Speaking Louder, Slower Picked as Most Ignorant Tourist Habit". Travel Agent Central. Retrieved January 1, 2020. 215. ^ "Chinese Tourists' Behavior Improving, Study by Chinese Tourism Authority Finds". Jing Daily. February 23, 2017. Retrieved January 1, 2020. 216. ^ Germany Defends Itself Against Chinese M&A Onslaught. Posted on Real Money. Posted by Alex Frew Mcmillan on November 5, 2016. 217. ^ WELT (September 3, 2019). "Globale Umfrage: Deutsche Touristen im Ausland eher unbeliebt". Retrieved January 1, 2020. 218. ^ Seipp, Bettina (June 6, 2014). "Umfrage : Warum Russen die unbeliebtesten Touristen sind". Retrieved January 1, 2020. 219. ^ AFP. "Don't worry: German tourists hate sunbed grabbers too". TheJournal.ie. Retrieved January 1, 2020. 220. ^ How did the Boxer Rebellion unite Imperial Powers and create Chinese Nationalism?. Posted on Daily History. 221. ^ Carbone, Iside (January 12, 2015). China in the Frame: Materialising Ideas of China in Italian Museums. ISBN 9781443873062. 222. ^ Italy's first major ethnic riot sparked by parking fine. Posted on The Guardian.com on 13 abr. 2007. 223. ^ Ancient Italian Town Turns Against Chinese Migrants. Posted on VOA News. Posted by Henry Ridgwell on October 22, 2010. 224. ^ The story of Li-ma-hong and his failed attempt to conquer Manila in 1574. Posted on Wednesday October 24, 2012. 225. ^ Samuel Hawley. The Spanish Plan to Conquer China. 226. ^ "China says Swedish police 'brutally abused' tourists ejected from a hostel". ABC. September 18, 2018. Retrieved September 7, 2020. 227. ^ "'Vicious attack': Comedy skit deepens China and Sweden's diplomatic spat". ABC. September 29, 2018. Retrieved September 7, 2020. 228. ^ "Touristes expulsés et blagues racistes : tensions entre la Suede et la Chine". Le Monde (via Youtube). 229. ^ "A Swedish TV Show Said Chinese Tourists Poop In Public And People Are Pissed". BuzzFeed News. Retrieved September 7, 2020. 230. ^ "Aili Tang - Örebro University School of Business". www.oru.se. Retrieved September 7, 2020. 231. ^ "Sveriges Television sprider rasism om kineser". DN.SE (in Swedish). September 26, 2018. Retrieved September 7, 2020. 232. ^ Tomas Haupt. "Sweden Avoided by Chinese Tourists". www.tourism-review.com. 233. ^ "Scanian of the Year: Jesper Rönndahl gets his portrait at Malmö Airport". www.swedavia.com. Retrieved September 7, 2020. 234. ^ Board, Editorial. "Opinion - China kidnapped Gui Minhai. Now it wants to lock him away". Washington Post. 235. ^ Flittner, Sofia (May 11, 2020). "Hostility between China and Sweden at an all-time high". ScandAsia. 236. ^ "How Sweden copes with Chinese bullying". The Economist. ISSN 0013-0613. Retrieved September 7, 2020. 237. ^ "Swedish cities cut China links after increase in tension". www.ft.com. February 2020. 238. ^ News, Taiwan. "Sweden shutters all China-sponsored Confucius Institutes". Taiwan News. 239. ^ Russell, Dave. "Chinese in Sweden report increased stigmatisation since corona virus outbreak" – via sverigesradio.se. 240. ^ Taylor, Lewis. Indigenous Peasant Rebellions in Peru during the 1880s 241. ^ Bonilla, Heraclio. 1978. The National and Colonial Problem in Peru. Past and Present 242. ^ López-Calvo, Ignacio; Chang-Rodríguez, Eugenio (2014). Dragons in the Land of the Condor: Writing Tusán in Peru. University of Arizona Press. ISBN 9780816531110. Retrieved April 22, 2020 – via Google Books. 243. ^ Canada (2006). "Address by the Prime Minister on the Chinese Head Tax Redress". Government of Canada. Archived from the original on April 19, 2012. Retrieved August 8, 2006. 244. ^ Sympatico / MSN : News : CTV.ca: PM apologizes in House of Commons for head tax Archived February 20, 2012, at the Wayback Machine 245. ^ Anti-Chinese sentiment partly governments' fault: Steves. Posted on Richmond News. Posted by Graeme Wood on November 23, 2016, at 12:52 PM. 246. ^ Can Brazil learn to manipulate China?. Posted on Post Western World. Posted by Oliver Stuenkel on February 4, 2012. 247. ^ Oliveira, Gustavo de L. T. (2018). "Chinese land grabs in Brazil? Sinophobia and foreign investments in Brazilian soybean agribusiness". Globalizations. 15: 114–133. doi:10.1080/14747731.2017.1377374. S2CID 158910046. 248. ^ "Presidential candidates present a drastic turn in foreign policy Jair Bolsonaro (PSL) promises to break Brazil's traditional diplomatic positions while Fernando Haddad". Retrieved October 27, 2018. 249. ^ "Os compromissos de Bolsonaro em Taiwan". Jair Bolsonaro. March 4, 2018. Retrieved October 29, 2018. 250. ^ The Opium War. Posted on National Army Museum. 251. ^ Chinese report highest levels of racial harassment in UK. Posted by The Guardian.com Posted on November 18, 2017. 252. ^ Violence against Chinese in the UK widespread and under-reported. Posted on China Daily. Posted by Angus McNeice in London, August 18, 2016 at 10:12. 253. ^ British Chinese people say racism against them is 'ignored'. Posted on BBC. Posted by Emily Thomas on 5 ene. 2015. 254. ^ Ricardo Padron (2014).Sinophobia vs. Sinofilia in the 16th Century Iberian World. Instituto Cultural do Governo da R.A.E de Macau. 255. ^ Cameron, Nigel (1976). Barbarians and mandarins: thirteen centuries of Western travelers in China. Volume 681 of A phoenix book (illustrated, reprint ed.). University of Chicago Press. p. 143. ISBN 978-0-226-09229-4. Retrieved July 18, 2011. "envoy, had most effectively poured out his tale of woe, of deprivation at the hands of the Portuguese in Malacca; and he had backed up the tale with others concerning the reprehensible Portuguese methods in the Moluccas, making the case (quite truthfully) that European trading visits were no more than the prelude to annexation of territory. With the tiny sea power at this time available to the Chinese" 256. ^ Duarte Drumond Braga (2017). de portugal a macau: FILOSOFIA E LITERATURA NO DIÁLOGO DAS CULTURAS. Universidade do Porto, Faculdade de Letras. 257. ^ An antichinese mob in Mexico. Posted by NyTimes 258. ^ Chino: Anti-Chinese Racism in Mexico. Department of History. Prof. Jason Oliver Chang (Asian American Studies & History, University Of Connecticut). Posted on Monday, March 20, 2017. 259. ^ a b c K. Emma Ng (11 ago. 2015). Old Asian, New Asian. The Pantograph Punch. 260. ^ Katherine Dolan (September 16, 2016). New Zealand is no paradise: Rugby, racism and homophobia. Stuff. 261. ^ Norton, Henry K. (1924). The Story of California From the Earliest Days to the Present. Chicago: A.C. McClurg & Co. pp. 283–296. 262. ^ See, e.g., "Our Misery and Despair": Kearney Blasts Chinese Immigration. Posted on History Matters: The U.S. Survey course on the web. Posted by Dennis Kearney, President, and H.L Knight, Secretary. 263. ^ Ling, Huping (2004). Chinese St. Louis: From Enclave to Cultural Community. Temple University Press. p. 68. "The murder of Elsie Sigel immediately grabbed the front pages of newspapers, which portrayed Chinese men as dangerous to "innocent" and "virtuous" young white women. This murder led to a surge in the harassment of Chinese in communities across the United States." 264. ^ Gompers, Samuel; Gustadt, Herman (1902). Meat vs. Rice: American Manhood against Asiatic Coolieism: Which Shall Survive?. American Federation of Labor. 265. ^ Lai, Him Mark; Hsu, Madeline Y. (2010). Chinese American Transnational Politics. University of Illinois Press. pp. 53–54. 266. ^ Chin, Gabriel J. "Harlan, Chinese and Chinese Americans". University of Dayton Law School. 267. ^ Chi, Frank (November 8, 2010). "In campaign ads, China is fair game; Chinese-Americans are not". The Boston Globe. 268. ^ a b Lyden, Jacki (October 27, 2010). "Critics Say Political Ads Hint Of Xenophobia". NPR. Retrieved December 5, 2010. 269. ^ Yang, Jeff (October 27, 2010). "Politicians Play The China Card". Tell Me More. NPR. Retrieved December 5, 2010. 270. ^ News, Bloomberg (November 7, 2013). "Did protesters overreact to Jimmy Kimmel's jokes about Chinese people?". The Denver Post. Retrieved January 1, 2020. 271. ^ "'Kill everyone in China': Outrage over comment during Jimmy Kimmel skit". South China Morning Post. October 23, 2013. 272. ^ Summers, Ann (July 3, 2016). "all Trump has left is Islamophobia and Sinophobia in the swing-states". Flowers For Socrates. 273. ^ Anti-China rhetoric in campaign suggests change under a new president. Posted on Washington Post. Posted on September 23, 2015. 274. ^ It isn't only Trump who loves a trade war. Posted on Spiked. Posted on March 6, 2018. 275. ^ Swanson, Ana (July 20, 2019). "A New Red Scare Is Reshaping Washington". The New York Times. ISSN 0362-4331. Retrieved August 14, 2019. 276. ^ "Caught in the middle: Chinese-Americans feel heat as tensions flare". South China Morning Post. September 25, 2018. Retrieved August 14, 2019. 277. ^ Silver, Laura; Devlin, Kat; Huang, Christine (August 13, 2019). "U.S. Views of China Amid Trade War Turn Sharply Negative". Pew Research Center's Global Attitudes Project. Retrieved August 14, 2019. 278. ^ "Dealing with the Scourge of "Schadenfreude" in Foreign Reporting on China". China-US Focus. Retrieved January 1, 2020. 279. ^ "Is the World Against China? \| BU Today". Boston University. Retrieved January 1, 2020. 280. ^ "Search Results for chinese \| FAIR - Page 2". Retrieved January 1, 2020. 281. ^ "Why I care about the Chinese". SFChronicle.com. July 25, 2019. Retrieved January 1, 2020. 282. ^ Zhou, Min (April 7, 2009). Contemporary Chinese America: Immigration, Ethnicity, and Community Transformation. Temple University Press. ISBN 978-1-59213-859-3. 283. ^ Snider, Mike. "Steve Bannon learned to harness troll army from 'World of Warcraft'". USA TODAY. Retrieved January 1, 2020. 284. ^ "Why Won't the Chinese Line Up?". HuffPost. May 25, 2014. Retrieved January 1, 2020. 285. ^ "Black in Beijing: How Transient Black Foreigners Create Community in China (page 106)". 286. ^ Rathi, Akshat. "My trip to China shattered my biases about developing nations". Quartz India. Retrieved January 1, 2020. 287. ^ "Why Chinese Tourists Absolutely Love This Luxury Outlet 46 Minutes Outside London". Time. Retrieved January 1, 2020. 288. ^ Kaiman, Jonathan. "At Shanghai Disney, there are fans and then there are superfans". baltimoresun.com. Retrieved January 1, 2020. 289. ^ "Rain doesn't dampen the mood of opening day at Shanghai Disney". Los Angeles Times. June 16, 2016. Retrieved January 1, 2020. 290. ^ Smith, Mikey (October 17, 2014). "The Chinese iPhone 6 launch was very well behaved". mirror. Retrieved January 1, 2020. 291. ^ "Sichuan's Race Against Time". Radio Free Asia. Retrieved January 1, 2020. 292. ^ "Americans Love Canadian Visitors. British Tourists? Not So Much". TravelPulse. Retrieved January 1, 2020. 293. ^ What's next for Venezuela? Sinophobia. Posted bu Post Western World. Posted by Oliver Stuenkel on 10 dic. 2015. 294. ^ Aidoo, Richard (2018). "Go Global, Meet the Locals: Pragmatism, Plunder, and Anti-Chinese Populism in Africa" (PDF). Seton Hall University Journal of Diplomacy and International Relations. 295. ^ White, Edward (August 5, 2016). "ANALYSIS: Unpacking Attacks on Chinese Workers in Africa". The News Lens Taiwan (International Edition). Retrieved April 19, 2020. 296. ^ "Feared rise in anti-Chinese attacks in Africa". AFP News Agency. June 2013. 297. ^ "Africans in One of China's Major Cities Say They Are Targets After a Spike in COVID-19". Time. Retrieved April 19, 2020. 298. ^ Olusegun Adeniyi (April 15, 2020). "China, COVID-19 and African Anger". THISDAY Nigeria. Retrieved April 19, 2020. 299. ^ Rise in anti-Chinese violence in Kenya forces halt of major rail project. Posted on International Business Times. Posted by Elsa Buchanan, on August 19, 2016 14:32 BST. 300. ^ TSG IntelBrief: Rising Sinophobia in Africa Archived December 29, 2013, at the Wayback Machine, July 31, 2013 301. ^ Negi, Rohit (January 1, 2008). "Beyond the "Chinese Scramble": The Political Economy of Anti-China Sentiment in Zambia". African Geographical Review. 27. doi:10.1080/19376812.2008.9756209 (inactive January 16, 2021).CS1 maint: DOI inactive as of January 2021 (link) 302. ^ "Zambia blames opposition for anti-China attacks". The Jakarta Post. Retrieved April 19, 2020. 303. ^ "Opposition leader wins Zambia election". Retrieved May 9, 2015. 304. ^ Eric Olander, Cobus van Staden (September 2016). "Sinophobia In Zambia Is More Complex Than The International Press Presents". HuffPost. 305. ^ Brent Meersman (September 1, 2015).South Africa's latest disease: Sinophobia. ThisisAfrica. 306. ^ "Chinese hate speech case: 'They made me feel deeply hurt and helpless,' says SA man". News24. November 27, 2019. Retrieved January 1, 2020. 307. ^ Shannon Tiezzi (April 17, 2015). China's South African Ties Complicated By Recent Violence.The Diplomat Magazine. 308. ^ Kuo, Lily. "Chinese migrants have changed the face of South Africa. Now they're leaving". Quartz Africa. Retrieved January 1, 2020. 309. ^ Western media should rethink its distorted portrayal of China’s rise. Posted on South China Morning Post. Posted by L. K. Cheah on Jun 5, 2016, at 1:04pm. 310. ^ Negative Portrayal of Chinese in Hollywood Movies. China daily Blog. Posted on July 11, 2016. 311. ^ Matt Damon on Great Wall whitewashing: 'I didn't take role from Chinese actor'. Posted by Andrew Pulver on December 7, 2016. 312. ^ "YeonGaesomun(연개소문): Battle of Ansiseong Part I". Retrieved April 22, 2020 – via YouTube. 313. ^ "YeonGaesomun(연개소문): Battle of Ansiseong Part II". Retrieved April 22, 2020 – via YouTube. 314. ^ "YeonGaesomun(연개소문): Battle of Ansiseong Part III". Retrieved April 22, 2020 – via YouTube. 315. ^ a b Opinion \| Beijing's Propaganda Crisis. NyTimes. Posted by Murong Xuecun on March 17, 2014. 316. ^ China's secret internet police target critics with web of propaganda. Posted on The Guardian.com 317. ^ Propaganda and Censorship Are Reaching Fever Pitch on the Eve of China’s Big Leadership Reshuffl. Posted on Time. Posted by Charlie Campbell, Beijing, on October 17, 2017. 318. ^ Nyland, Chris; Forbes-Mewett, Helen; Thomson, S. Bruce (2011). "Sinophobia as Corporate Tactic and the Response of Host Communities". Journal of Contemporary Asia. 41 (4): 610–631. doi:10.1080/00472336.2011.610617. S2CID 153335960. 319. ^ China's state broadcaster struggles to silence criticism it is a propaganda machine. Posted on ABC. Posted by Lisa Millar on November 16, 2014. 320. ^ Why Do We Keep Writing About Chinese Politics As if We Know More Than We Do? Posted on China File.com Posted on October 16, 2017. 321. ^ US ban on sales to China's ZTE opens fresh front as tensions. Posted on Reuters. Posted by Steve Stecklow, Karen Freifeld and Sijia Jiang on April 16, 2018. 322. ^ Huawei and ZTE Hit Hard as U.S. Moves Against Chinese Tech Firms. Posted on NYTimes. Posted by Raymond Zhong, Paul Mozur and Jack Nicas on April 17, 2018. 323. ^ ZTE faces export ban from US Commerce Dept over lying. Posted on CNET. Posted by ALFRED NG and ROGER CHENG, on April 16, 2018, at 7:29 AM PDT. 324. ^ Hello Indian telcos: Heard the US warning on Huawei, ZTE?. Posted on firstpost.com. Posted on December 20, 2014. 325. ^ Chinese telecom giants in India's security spotlight. Posted on The Sunday Guardian Live. Posted by Abhinandan Mishra, on August 20, 2017. 326. ^ "Dirty business". The Economist. September 30, 2010. 327. ^ China Says It’s Open for Business. Foreign Firms Find It’s Not That Simple. Posted on The New York Times. Posted by Alexandra Stevenson, on December 6, 2017. 328. ^ Fontes, Lisa Aronson (May 23, 2008). ?. ISBN 978-1-59385-710-3. 329. ^ Robert Lee, A (January 28, 2008). ?. ISBN 9789042023512. Retrieved August 23, 2010. 330. ^ 納粹中國 #Chinazi \| 楊繼昌. 眾新聞 (in Chinese). Retrieved September 5, 2019. 331. ^ VanderKlippe, Nathan (August 29, 2019). "In Hong Kong, protesters employ Nazi imagery as demonstrations erupt again". The Globe and Mail Inc. 332. ^ Wong, Chun Han (September 30, 2019). "Hong Kong Protesters Taunt Beijing in Bid to Spoil Communist China's Birthday". Wall Street Journal. ISSN 0099-9660. Retrieved April 19, 2020. 333. ^ "Protesters drop Nazi term after Western input - RTHK". 334. ^ "Pinoy or Tsinoy, What is the Problem?". September 13, 2013. Retrieved May 9, 2015. 335. ^ "Intsik – INQUIRER.net". Archived from the original on February 19, 2014. Retrieved May 9, 2015. 336. ^ "Archived copy". Archived from the original on December 2, 2008. Retrieved July 23, 2013.CS1 maint: archived copy as title (link) 337. ^ "Archived copy". Archived from the original on February 2, 2017. Retrieved January 25, 2017.CS1 maint: archived copy as title (link) 338. ^ "Kamus Slang Mobile". kamusslang.com. Archived from the original on February 2, 2017. 339. ^ "Police officer dispatched from Osaka insults protesters in Okinawa". The Japan Times Online. October 19, 2016. Retrieved November 25, 2019. 340. ^ 중국, 질문 좀 할게 (in Korean). 좋은땅. April 22, 2016. p. 114. ISBN 9791159820205. Retrieved April 21, 2017. 341. ^ (in Korean) Jjangkkolla – Naver encyclopedia 342. ^ "떼놈. 때놈. 뙤놈?". December 13, 2014. 343. ^ "Celulares Xing-Ling: o que são e por que não comprá-los". TechTudo (in Portuguese). Retrieved April 19, 2020. 344. ^ "Xing ling". Dicionário inFormal. Retrieved April 21, 2020. 345. ^ "Trung Cộng - Wiktionary". en.wiktionary.org. 346. ^ "Cảnh giác trước lời đe doạ của Trung Cộng". Radio Free Asia. 347. ^ "Vietlive.tv". www.facebook.com. 348. ^ Ponniah, Kevin; Marinkovic, Lazara (May 7, 2019). "The night the US bombed a Chinese embassy". BBC News. 349. ^ Zhao, Suisheng (1998). "A State-Led Nationalism: The Patriotic Education Campaign in Post-Tiananmen China". Communist and Post-Communist Studies. 31 (3): 287–302. doi:10.1016/S0967-067X(98)00009-9. 350. ^ Fan, Yingjie; Pan, Jennifer; Shao, Zijie; Xu, Yiqing (June 29, 2020). "How Discrimination Increases Chinese Overseas Students' Support for Authoritarian Rule". Social Science Research Network. SSRN 3637710. Cite journal requires `\|journal=` (help) 351. ^ O'Hara, Mary Emily. "Mock Subway Posters Urge New Yorkers to Curb Anti-Asian Hate". www.adweek.com. Retrieved July 12, 2020. 352. ^ "Virus-induced racism does no one any good". Bangkok Post. Retrieved July 1, 2020. 353. ^ "'You deserve the coronavirus': Chinese people in UK abused over outbreak". Sky News. February 2020. Retrieved October 28, 2020. 354. ^ "The Coronavirus and the Search for Scapegoats". Psychology Today. Retrieved July 1, 2020. 355. ^ Smith, Nicola; Torre, Giovanni (February 1, 2020). "Anti-Chinese racism spikes as virus spreads globally". The Telegraph. ISSN 0307-1235. Retrieved July 1, 2020. "'Some Muslims were claiming the disease was "divine retribution" for China's oppression of the Uighur minority. The problem lay in confusing the Chinese population with the actions of an authoritarian government known for its lack of transparency,' he said." 356. ^ Solhi, Farah (January 26, 2020). "Some Malaysians calling for ban on Chinese tourists \| New Straits Times". NST Online. 357. ^ "Fears of new virus trigger anti-China sentiment worldwide". AP NEWS. February 2, 2020. 358. ^ "South Koreans call in petition for Chinese to be barred over virus". January 28, 2020 – via www.reuters.com. 359. ^ Tavernise, Sabrina; Jr, Richard A. Oppel (March 23, 2020). "Spit On, Yelled At, Attacked: Chinese-Americans Fear for Their Safety". The New York Times. ISSN 0362-4331. Retrieved July 1, 2020. 360. ^ "Hunt for racist coronavirus attackers: Police release CCTV after assault". ITV News. Retrieved July 1, 2020. 361. ^ Rogers, Katie; Jakes, Lara; Swanson, Ana (March 18, 2020). "Trump Defends Using 'Chinese Virus' Label, Ignoring Growing Criticism". The New York Times. ISSN 0362-4331. Retrieved July 1, 2020. 362. ^ "Trump: Asian-Americans not responsible for virus, need protection". Reuters. March 24, 2020. Retrieved July 1, 2020. 363. ^ "'Not racist at all': Donald Trump defends calling coronavirus the 'Chinese virus'". The Guardian -- YouTube. Retrieved July 1, 2020. ## Further reading[edit] * Aarim-Heriot, Najia (2003). Chinese Immigrants, African Americans, and Racial Anxiety in the United States, 1848–82. University of Illinois Press. * Chua, Amy. (2004). World on Fire: How Exporting Free Market Democracy Breeds Ethnic Hatred and Global Instability. Random House Digital, Inc. * Ferrall, Charles; Millar, Paul; Smith, Keren. (eds) (2005). East by South: China in the Australasian imagination. Victoria University Press. * Hong, Jane H. Opening the Gates to Asia: A Transpacific History of How America Repealed Asian Exclusion (University of North Carolina Press, 2019) online review * McClain, Charles J. (1996). In Search of Equality: The Chinese Struggle Against Discrimination in Nineteenth-Century America. University of California Press. * Mungello, David E. (2009). The Great Encounter of China and the West, 1500–1800. Rowman & Littlefield. * Slimming, John (1969). The Death of a Democracy. John Murray Publishers Ltd. ISBN 978-0-7195-2045-7. Book written by an Observer/UK journalist, who was in Kuala Lumpur at the time. * von Vorys, Karl (1975). Democracy Without Consensus: Communalism and Political Stability in Malaysia. Princeton University Press. ISBN 978-0-691-07571-6. Paperback reprint (2015) ISBN 9780691617640. * Ward, W. Peter (2002). White Canada Forever: Popular Attitudes and Public Policy Toward Orientals in British Columbia. McGill-Queen's Press. 3rd edition. * v * t * e Anti-Chinese sentiment (Sinophobia) Background * Chinese emigration * Japanese nationalism By persecutor * Adriaan Valckenier * Hideki Tojo * Suharto * Pol Pot * Plaek Phibunsongkhram * Hamengkubuwono IX By country * India * Indonesia * Japan * Korea * Laos * Malaysia * Myanmar * Nazi Germany * Philippines * Singapore * Thailand * United States * Vietnam By group * Tsagaan Khas * Uyoku dantai By incident * 13 May incident (Malaysia) * 1740 Batavia massacre * 1964 race riots in Singapore * 1969 race riots of Singapore * Banjarmasin riot of May 1997 * Buckland Riot * Cambodian genocide * Changkiao massacre * Chinese massacre of 1871 * Indonesian mass killings of 1965–66 * Issaquah riot of 1885 * Lambing Flat riots * Nanking Massacre * May 1998 riots of Indonesia * Rock Springs massacre * Seattle riot of 1886 * Sook Ching massacre * Tacoma riot of 1885 * Vancouver anti-Chinese riots, 1886 * Wanpaoshan Incident * COVID-19 pandemic incidents * Boycotts of Chinese products By victim * Ita Martadinata Haryono * v * t * e Anti-cultural, -national or -ethnic sentiment * African * Albanian * American * Arab * Armenian * Australian * Austrian * Azerbaijani * British * Buddhist * Canadian * Catalan * Chechen * Chilean * Chinese * Christian * Croat * Czech * Dutch * English * Estonian * European * Filipino * Finnish * French * Georgian * German * Greek * Haitian * Hazara * Hindu * Hispanic * Hungarian * Igbo * Indian * Indonesian * Iranian * Irish * Israeli * Italian * Japanese * Jewish * Khmer * Korean * Kurdish * Malay * Manchu * Mexican * Middle Eastern * Mongolian * Montenegrin * Muslim * Pakistani * Pashtun * Polish * Portuguese * Quebec * Romani * Romanian * Russian * Scottish * Serb * Shia * Slavic * Somali * Soviet * Sufi * Sunni * Swede * Tatar * Thai * Tibetan * Turkish * Ukrainian * Venezuelan * Vietnamese * Western * v * t * e Racism Types of racism * Antisemitism * Aversive * Among White people * Among LGBT people * Among US minorities * Colorism * Sinophobia * Negrophobia * Among hipsters * Consumer * Covert * Cultural * Environmental * Gendered * Institutional * Internalized * Nationalist * Reverse * Romantic * Sexual * Scientific * Societal * Symbolic Manifestations of racism * Anti-miscegenation laws * Expression * in the media * in Charles Dickens' works * in music * in early US films * Censored Eleven * in horror films * in porn * online * on Wikipedia * in sport * baseball * martial arts * soccer * in school curricula * Jokes * Slurs * Racial antagonism * Racial determinism * Racial hatred * Racial hierarchy * Casta * Racial polarization * Racial quota * Racial vilification * Racial violence * Race war Racism by region * Africa * Arab world * Asia * Australia * Europe * Middle East * North America * South America Related topics * Anti-racism * Psychological impact * Psychoanalysis * Racial transformation * Passing * Racial democracy * Racial fetishism * Race traitor * List of racism-related articles * List of anti-ethnic terms Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Anti-Chinese sentiment	None	26,632	wikipedia	https://en.wikipedia.org/wiki/Anti-Chinese_sentiment	2021-01-18T18:43:24	{"wikidata": ["Q1144708"]}
For a phenotypic description and a discussion of genetic heterogeneity of periventricular heterotopia, see 300049. Mapping Sheen et al. (2003) described 2 individuals from unrelated families in whom periventricular nodular heterotopia was associated with anomalies of chromosome 5p. Both individuals had complex partial seizures. Magnetic resonance imaging demonstrated bilateral nodular periventricular heterotopia, with subcortical heterotopia or focal gliosis. FISH identified a duplication of 5p15.1 (46,XX,dup(5)(p15.1p15.1)) in one patient. In the other, FISH showed trisomy of 5p15.33 (46,XY,der(14)t(5;14)(p15.33;p11.2)mat). These findings indicated the existence of a novel periventricular heterotopia locus along the telomeric end of chromosome 5p. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PERIVENTRICULAR NODULAR HETEROTOPIA 3	c1868720	26,633	omim	https://www.omim.org/entry/608098	2019-09-22T16:08:22	{"doid": ["0050454"], "mesh": ["D054091"], "omim": ["608098"], "orphanet": ["98892", "2149"], "synonyms": ["Alternative titles", "HETEROTOPIA, PERIVENTRICULAR, ASSOCIATED WITH CHROMOSOME 5p ANOMALIES"]}
A number sign (#) is used with this entry because of evidence that Adams-Oliver syndrome-6 (AOS6) is caused by heterozygous mutation in the DLL4 gene (605185) on chromosome 15q15. Description Adams-Oliver syndrome is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly). In addition, vascular anomalies such as cutis marmorata telangiectatica congenita, pulmonary hypertension, portal hypertension, and retinal hypervascularization are recurrent findings. Congenital heart defects have been estimated to be present in 20% of AOS patients; reported malformations include ventricular septal defects, anomalies of the great arteries and their valves, and tetralogy of Fallot (summary by Stittrich et al., 2014). For a discussion of genetic heterogeneity of Adams-Oliver syndrome, see AOS1 (100300). Molecular Genetics Meester et al. (2015) screened 91 families with Adams-Oliver syndrome for mutations in the candidate gene DLL4 and identified heterozygous nonsense and missense mutations in 9 families (see, e.g., 605185.0001-605185.0006). Noting the marked intrafamilial variability in phenotypic expression, with some parents exhibiting isolated aplasia cutis congenita whereas their offspring were severely affected, Meester et al. (2015) suggested that other genetic, epigenetic, or environmental factors might be involved in the clinical expression of the disease. Incomplete penetrance was also observed in some families. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Aplasia congenita cutis of the scalp vertex CARDIOVASCULAR Heart \- Tricuspid insufficiency \- Ventricular septal defect Vascular \- Truncus arteriosus ABDOMEN Liver \- Hepatic fibrosis (rare) \- Portal hypertension (rare) Spleen \- Congenital splenomegaly (rare) Gastrointestinal \- Esophageal varices (rare) GENITOURINARY Kidneys \- Small kidneys (rare) SKELETAL Skull \- Skull defect (underlying aplasia cutis congenita) Hands \- Brachydactyly \- Symphalangism Feet \- Brachydactyly \- Syndactyly \- Brachysyndactyly \- Symbrachydactyly \- Missing toes SKIN, NAILS, & HAIR Skin \- Scalp defect (aplasia cutis congenita) \- Bald area on scalp (in some patients) \- Cutis marmorata (in some patients) Nails \- Hypoplastic toenails (in some patients) MISCELLANEOUS \- Marked intrafamilial variability of clinical features \- Incomplete penetrance in some families MOLECULAR BASIS \- Caused by mutation in the delta-like-4 gene (DLL4, 605185.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	ADAMS-OLIVER SYNDROME 6	c0265268	26,634	omim	https://www.omim.org/entry/616589	2019-09-22T15:48:26	{"omim": ["616589"], "orphanet": ["974"]}
Palmoplantar keratoderma with deafness is a disorder characterized by skin abnormalities and hearing loss. Affected individuals develop unusually thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma) beginning in childhood. Hearing loss ranges from mild to profound. It begins in early childhood and gets worse over time. Affected individuals have particular trouble hearing high-pitched sounds. The signs and symptoms of this disorder may vary even within the same family, with some individuals developing only skin abnormalities and others developing only hearing loss. ## Frequency Palmoplantar keratoderma with deafness is a rare disorder; its prevalence is unknown. At least 10 affected families have been identified. ## Causes Palmoplantar keratoderma with deafness can be caused by mutations in the GJB2 or MT-TS1 genes. The GJB2 gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. Gap junctions made with connexin 26 transport potassium ions and certain small molecules. Connexin 26 is found in cells throughout the body, including the inner ear and the skin. In the inner ear, channels made from connexin 26 are found in a snail-shaped structure called the cochlea. These channels may help to maintain the proper level of potassium ions required for the conversion of sound waves to electrical nerve impulses. This conversion is essential for normal hearing. In addition, connexin 26 may be involved in the maturation of certain cells in the cochlea. Connexin 26 also plays a role in the growth, maturation, and stability of the outermost layer of skin (the epidermis). The GJB2 gene mutations that cause palmoplantar keratoderma with deafness change single protein building blocks (amino acids) in connexin 26. The altered protein probably disrupts the function of normal connexin 26 in cells, and may interfere with the function of other connexin proteins. This disruption could affect skin growth and also impair hearing by disturbing the conversion of sound waves to nerve impulses. Palmoplantar keratoderma with deafness can also be caused by a mutation in the MT-TS1 gene. This gene provides instructions for making a particular type of RNA, a molecule that is a chemical cousin of DNA. This type of RNA, called transfer RNA (tRNA), helps assemble amino acids into full-length, functioning proteins. The MT-TS1 gene provides instructions for a specific form of tRNA that is designated as tRNASer(UCN). This molecule attaches to a particular amino acid, serine (Ser), and inserts it into the appropriate locations in many different proteins. The tRNASer(UCN) molecule is present only in cellular structures called mitochondria. These structures convert energy from food into a form that cells can use. Through a process called oxidative phosphorylation, mitochondria use oxygen, simple sugars, and fatty acids to create adenosine triphosphate (ATP), the cell's main energy source. The tRNASer(UCN) molecule is involved in the assembly of proteins that carry out oxidative phosphorylation. The MT-TS1 gene mutation that causes palmoplantar keratoderma with deafness leads to reduced levels of tRNASer(UCN) to assemble proteins within mitochondria. Reduced production of proteins needed for oxidative phosphorylation may impair the ability of mitochondria to make ATP. Researchers have not determined why the effects of the mutation are limited to cells in the inner ear and the skin in this condition. ### Learn more about the genes associated with Palmoplantar keratoderma with deafness * GJB2 * MT-TS1 ## Inheritance Pattern Palmoplantar keratoderma with deafness can have different inheritance patterns. When this disorder is caused by GJB2 gene mutations, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. When palmoplantar keratoderma with deafness is caused by mutations in the MT-TS1 gene, it is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mitochondrial DNA (mtDNA). Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Palmoplantar keratoderma with deafness	c1835672	26,635	medlineplus	https://medlineplus.gov/genetics/condition/palmoplantar-keratoderma-with-deafness/	2021-01-27T08:25:02	{"gard": ["3094"], "mesh": ["C536152"], "omim": ["148350"], "synonyms": []}
Multicentric carpotarsal osteolysis syndrome Other namesMCTO[1] This condition is inherited in an autosomal dominant manner. SpecialtyMedical genetics Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare autosomal dominant condition.[2] This condition is also known as idiopathic multicentric osteolysis with nephropathy. It is characterised by carpal-tarsal destruction and kidney failure. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Pathogenesis * 4 Diagnosis * 4.1 Differential diagnosis * 4.2 Classification * 5 Treatment * 6 History * 7 References ## Signs and symptoms[edit] The presentation is of gradual loss of the small bones in the carpus and tarsus. This may lead to joint subluxation and instability.The kidney failure, when present, usually presents as the presence of protein in the urine. In some cases, there may also be craniofacial abnormalities including[citation needed] * Triangular facies * Micrognathia * Maxillary hypoplasia * Exophthalmos Histology of renal biopsies show glomerulosclerosis and severe tubulointerstitial fibrosis. Intellectual disability may occur. ## Genetics[edit] This condition is caused by mutations in the transcription factor MafB, or V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), gene.[3] This gene encodes a basic leucine zipper (bZIP) transcription factor. The gene is located on the long arm of chromosome 20 (20q11.2-q13.1). ## Pathogenesis[edit] How this mutation causes the clinical picture is not currently clear.[citation needed] ## Diagnosis[edit] The diagnosis may be suspected on the basis of the constellation of clinical features. It is made by sequencing the MAFB gene. ### Differential diagnosis[edit] The condition should be differentially diagnosed from juvenile rheumatoid arthritis. ### Classification[edit] This condition has been classified into five types.[4] * Type 1: hereditary multicentric osteolysis with dominant transmission * Type 2: hereditary multicentric osteolysis with recessive transmission * Type 3: nonhereditary multicentric osteolysis with nephropathy * Type 4: Gorham–Stout syndrome * Type 5: Winchester syndrome – defined as a monocentric disease with autosomal recessive inheritance ## Treatment[edit] Optimal treatment for this condition is unclear. Bisphosphonates and denosumab may be of use for the bone lesions. Cyclosporine A may be of use for treating the nephropathy. Steroids and other immunosuppressant drugs do not seem to be of help. ## History[edit] This condition was first described by Shurtleff et al. in 1964.[2] ## References[edit] 1. ^ "OMIM Entry - # 166300 - MULTICENTRIC CARPOTARSAL OSTEOLYSIS SYNDROME; MCTO". omim.org. Retrieved 27 April 2019. 2. ^ a b Shurtleff DB, Sparkes RS, Clawson DK, Guntheroth WG, Mottet NK (1964) Hereditary osteolysis with hypertension and nephropathy. JAMA 188:363–368 3. ^ Zankl A, Duncan EL, Leo PJ, Clark GR, Glazov EA, Addor M-C, Herlin T, Kim CA, Leheup BP, McGill J, McTaggart S, Mittas S, Mitchell, AL, Mortier GR, Robertson SP, Schroeder M, Terhal P, Brown MA (2012) Multicentric carpotarsal osteolysis is caused by mutations clustering in the amino-terminal transcriptional activation domain of MAFB. Am J Hum Genet 90: 494-501 4. ^ Hardegger F, Simpson LA, Segmueller G (1985) The syndrome of idiopathic osteolysis. Classification, review, and case report. J Bone Joint Surg Br 67(1):88-93 Classification D * OMIM: 166300 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Multicentric carpotarsal osteolysis syndrome	c2674705	26,636	wikipedia	https://en.wikipedia.org/wiki/Multicentric_carpotarsal_osteolysis_syndrome	2021-01-18T18:49:03	{"mesh": ["C567171"], "umls": ["C2674705"], "wikidata": ["Q56297474"]}
Peroxisomal acyl-CoA oxidase deficiency is a rare neurodegenerative disorder that belongs to the group of inherited peroxisomal disorders and is characterized by hypotonia and seizures in the neonatal period and neurological regression in early infancy. ## Epidemiology Acyl-CoA oxidase deficiency is a rare disease with only 30-40 patients identified world-wide so far. ## Clinical description The disease manifests in the neonatal period with hypotonia (92%) and seizures (91%) as dominant features. Facial dysmorphism (50%) with hypertelorism, epicanthus, low nasal bridge, and low-set ears may be present. Some children have polydactyly and hepatomegaly. Psychomotor development is delayed, but children are usually able to walk and say a few words. However, neurological regression occurs usually at the age of 1-3 years (mean age: 28 months). Hypotonia is replaced by hypertonia with hyperreflexia. Epilepsy may become more severe and sensorineural hearing loss may appear. Strabismus, nystagmus, and optic atrophy can also occur. ## Etiology Peroxisomal acyl-CoA oxidase deficiency is caused by mutations in the ACOX1 gene (17q25.1) encoding peroxisomal straight-chain acyl-CoA oxidase. ## Diagnostic methods Diagnosis is based on laboratory studies revealing increased serum very-long chain fatty acids (VLCFA) and markedly reduced acyl-CoA oxidase activity in fibroblasts. MRI examination of the brain shows abnormal white matter signals. Diagnosis can be confirmed by the presence of mutations in the ACOX1 gene. ## Differential diagnosis Differential diagnoses include Usher syndrome (see this term) and all causes of neonatal hypotonia. The other peroxisomal disorders should also be discarded, especially neonatal adrenoleukodystrophy (see this term), which presents similar clinical manifestations. ## Antenatal diagnosis Antenatal diagnosis is possible through biochemical and/or molecular analysis of amniocytes or chorionic villus cells. ## Genetic counseling Transmission is autosomal recessive. Genetic counseling should be offered to the families of patients. ## Management and treatment No specific treatment is available. Multidisciplinary supportive care should be offered. ## Prognosis Prognosis is unfavorable; death usually occurs at around 5 years from respiratory issues. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Peroxisomal acyl-CoA oxidase deficiency	c1849678	26,637	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2971	2021-01-23T17:13:26	{"gard": ["4543"], "mesh": ["C536662"], "omim": ["264470"], "umls": ["C0342871", "C1849678"], "icd-10": ["E71.3"], "synonyms": ["Pseudo-NALD", "Pseudo-neonatal adrenoleukodystrophy", "Pseudoadrenoleukodystrophy"]}
Primary inoculation tuberculosis Other namesCutaneous primary complex,[1] Primary tuberculous complex,[2] and Tuberculous chancre[1] Primary inoculation tuberculosis is a skin condition that develops at the site of inoculation of tubercle bacilli into a tuberculosis-free individual.[2]:334 ## See also[edit] * Tuberculosis verrucosa cutis * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 1114, 1116. ISBN 978-1-4160-2999-1. 2. ^ a b James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. * v * t * e Gram-positive bacterial infection: Actinobacteria Actinomycineae Actinomycetaceae * Actinomyces israelii * Actinomycosis * Cutaneous actinomycosis * Tropheryma whipplei * Whipple's disease * Arcanobacterium haemolyticum * Arcanobacterium haemolyticum infection * Actinomyces gerencseriae Propionibacteriaceae * Propionibacterium acnes Corynebacterineae Mycobacteriaceae M. tuberculosis/ M. bovis * Tuberculosis: Ghon focus/Ghon's complex * Pott disease * brain * Meningitis * Rich focus * Tuberculous lymphadenitis * Tuberculous cervical lymphadenitis * cutaneous * Scrofuloderma * Erythema induratum * Lupus vulgaris * Prosector's wart * Tuberculosis cutis orificialis * Tuberculous cellulitis * Tuberculous gumma * Lichen scrofulosorum * Tuberculid * Papulonecrotic tuberculid * Primary inoculation tuberculosis * Miliary * Tuberculous pericarditis * Urogenital tuberculosis * Multi-drug-resistant tuberculosis * Extensively drug-resistant tuberculosis M. leprae * Leprosy: Tuberculoid leprosy * Borderline tuberculoid leprosy * Borderline leprosy * Borderline lepromatous leprosy * Lepromatous leprosy * Histoid leprosy Nontuberculous R1: * M. kansasii * M. marinum * Aquarium granuloma R2: * M. gordonae R3: * M. avium complex/Mycobacterium avium/Mycobacterium intracellulare/MAP * MAI infection * M. ulcerans * Buruli ulcer * M. haemophilum R4/RG: * M. fortuitum * M. chelonae * M. abscessus Nocardiaceae * Nocardia asteroides/Nocardia brasiliensis/Nocardia farcinica * Nocardiosis * Rhodococcus equi Corynebacteriaceae * Corynebacterium diphtheriae * Diphtheria * Corynebacterium minutissimum * Erythrasma * Corynebacterium jeikeium * Group JK corynebacterium sepsis Bifidobacteriaceae * Gardnerella vaginalis This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Primary inoculation tuberculosis	c0007943	26,638	wikipedia	https://en.wikipedia.org/wiki/Primary_inoculation_tuberculosis	2021-01-18T18:49:57	{"umls": ["C0007943"], "wikidata": ["Q7243141"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Tomato leaf mold" – news · newspapers · books · scholar · JSTOR (December 2014) (Learn how and when to remove this template message) Tomato leaf mold Scientific classification Domain: Eukaryota Kingdom: Fungi Phylum: Ascomycota Class: Dothideomycetes Order: Capnodiales Family: Mycosphaerellaceae Genus: Mycovellosiella Species: Mycovellosiella fulva Binomial name Cladosporium fulvum, Fulvia fulva, Passalora fulva (Pers.) (1816) Link (1816) Cladosporium fulvum is an Ascomycete called Passalora fulva, a non-obligate pathogen that causes the disease on tomato known as the Tomato leaf mold.[1] P. fulva only attacks tomato plants, especially the foliage, and it is a common disease in greenhouses, but can also occur in the field.[2] The pathogen is likely to grow in humid and cool conditions. In greenhouses, this disease causes big problems during the fall, in the early winter and spring, due to the high relative humidity of air and the temperature,[3] that are propitious for the leaf mold development. This disease was first described in the North Carolina, by Mordecai Cubitt Cooke (1883),[4] on cultivated tomato (Cooke 1883), although it is originally from South and Central America. The causal fungus of tomato leaf mold may also be referred to as Cladosporium fulvum (Cooke 1883), a former name.[4] ## Contents * 1 Hosts and Symptoms * 2 Environment * 3 Disease Cycle * 4 Reproduction * 5 Management * 5.1 Culture * 5.2 Sanitation * 5.3 Resistance * 5.4 Chemical Control * 6 Importance * 7 References ## Hosts and Symptoms[edit] Symptoms on Tomato Leaf. Photograph provided by Elizabeth Bush, Virginia Polytechnic Institute and State University. The tomato leaf mold fungus is a specific pathogen of tomato plant Lycopersicon, this pathogen has restricted host range (host specific pathogen) that only infects tomatoes, mainly in greenhouses. The symptoms of this disease commonly occurs on foliage, and it develops on both sides of the leaf on the adaxial and abaxial surface. The older leaves are infected first and then the disease moves up towards young leaves.[2] Symptoms of tomato leaf mold appear usually with foliage, but fruit infection is rare. The primary symptom appear on the upper surface of infected leaves as a small spot pale green or yellowish with indefinite margins, and on corresponding area of the lower surface, the fungus begins to sporulate.[5] The diagnostic symptom develops on lower surface as an olive green to grayish purple and velvety appearance, which are composed of spores (conidia).[6] Continuously, the color of the infected leaf changes to yellowish brown and the leaf begins to curl and dry. The leaves will drop upon reaching a premature stage, and the defoliation of the infected host will cause further infection. This disease develops well in relative humidity levels above 85%. When the temperature reaches optimum level for germinating, the host will be infected by the pathogen. Occasionally, this pathogen causes disease on the fruit or blossoms with various symptoms.[7] Fruits such as green and ripe one will develop dark rot on the stem. The blossoms will be killed before fruits grow. ## Environment[edit] Free water is required for Cladosporium fulvum to germinate, spores are unable to infect the perfectly dried leaf. Spores germinate in the leaf surface with free water and humidity with above 85%.[8] This pathogen can survive at least one year without a host which is called non-obligate. The temperature must be between 40°~94 °F (4°~34 °C) for germinating spore. The pathogen usually infects the leaves by penetrating through stomata in a high humidity level. ## Disease Cycle[edit] The life cycle starts with the fungus overwintering as sclerotia on plants debris, in seeds and in soils as a saprophyte. Conidia also play an important role as a survival structure, once they are resistant to drying, and might survive up to one year in the absence of a susceptible host. When condition are favorable the sclerotia produce new conidia, which act as primary inoculum to infect plants. The conidia produce mycelium that infects the plant through stomata when humidity is 85% or higher and produce conidiophores on the abaxial leaf surface of infected leaves. The symptoms usually start to appear 10 days after inoculation with spore formation, a large number of conidia are produced and these spores are easily spread from plant to plant by the wind, splash water, on tools, clothing of workers and also by insects. Spores are highly dependent on weather condition to germinate, thus they only geminate in water films or when the humidity level are superior than 85%, at temperature among 40° and 94 °F (4° and 34 °C). However the optimum temperature for germination is among 75° and 78 °F (24° and 26 °C). ## Reproduction[edit] Although it was previously considered that C. fulvum only reproduces asexually, the discovery of mating type genes indicated a capability for sexual reproduction.[9] These mating type genes have high similarity to homologous genes in other ascomycete fungi. ## Management[edit] The disease management or control can be divided into two main groups: disease control in greenhouse and disease control in the field. Both controls are very similar. The differences are presented in few controls adopted in greenhouse in which some environmental conditions are controlled such as humidity and temperature as well sanitization of the greenhouse. ### Culture[edit] The first strategy of management is the cultural practices for reducing the disease. It includes adequating row and plant spacing that promote better air circulation through the canopy reducing the humidity; preventing excessive nitrogen on fertilization since nitrogen out of balance enhances foliage disease development; keeping the relatively humidity below 85% (suitable on greenhouse), promote air circulation inside the greenhouse, early planting might to reduce the disease severity and seed treatment with hot water (25 minutes at 122 °F or 50 °C).[4] ### Sanitation[edit] The second strategy of management is the sanitization control in order to reduce the primary inoculum. Remove and destroy (burn) all plants debris after the harvest, scout for disease and rogue infected plants as soon as detected and steam sanitization the greenhouse between crops.[2] ### Resistance[edit] The most effective and widespread method of disease control is to use resistant cultivars. However, only few resistant cultivar to tomato leaf mold are known such as Caruso, Capello, Cobra (race 5), Jumbo and Dombito (races 1 and 2). Moreover, this disease is not considered an important disease for breeding field tomatoes.[2] ### Chemical Control[edit] The least but not the less important management is the chemical control that ensure good control of the disease. The chemical control is basically spraying fungicide as soon as the symptoms are evident. Compounds registered for using are: chlorothalonil, maneb, mancozeb and copper.[2] ## Importance[edit] Tomato leaf mold is a plant disease originated from the South and Central America.[1] In 1883, Cooke first discovered the tomato leaf mold in North Carolina.[2] This disease is not common on the fruit, but if the control is not run, the foliage can be greatly damaged and result in significant yield losses. Once the spores of this fungi are spread by air, water, tools and insects,[10] the development of the disease is quick, moving from lower to upper leaves; the controlling must be done as soon as possible. It includes avoiding water on the surface of leaves, handling plants in high humidity, and in the worst case, disinfecting the whole greenhouse. ## References[edit] 1. ^ a b Cladosporium fulvum–Tomato Pathosystem: Fungal Infection Strategy and Plant Responses Bilal ¨Okmen and Pierre J. G. M. de Wit 2. ^ a b c d e f Dr. Sharon M. Douglas Department of Plant Pathology and Ecology The Connecticut Agricultural Experiment Station. LEAF MOLD AND POWDERY MILDEW OF TOMATO. 3. ^ University of Illinois Extension. LAEF MOLD OF GREENHOUSE TOMATOES. 4. ^ a b c Cooke, MC. (1883). New American fungi. Grivillea XII: 32. De Jong, CF, Takken, FLW, Cai, XH, De Wit, PJGM, Joosten, MHAJ. (2002). Attenuation of Cf-mediated defence responses at elevated temperatures correlates with a decrease in elicitor-binding sites. MPMI 15: 1040–9. 5. ^ "Tomato Leaf Mould". Plantwise Knowledge Bank. Retrieved 2 November 2013. 6. ^ AVRDC - The World Vegetable Center. Tomato Diseases Leaf Mold. 7. ^ "Tomato Diseases & Disorders". Clemson University. Retrieved 14 November 2014. 8. ^ High Plains IPM Guide, a cooperative effort of the University of Wyoming, University of Nebraska, Colorado State University and Montana State University. Cladosporium Leaf Mold. 9. ^ Stergiopoulos I, Groenewald M, Staats M, Lindhout P, Crous PW, De Wit PJ. Mating-type genes and the genetic structure of a world-wide collection of the tomato pathogen Cladosporium fulvum. Fungal Genet Biol. 2007 May;44(5):415-29. Epub 2006 Dec 18. PMID: 17178244 10. ^ Tomato Leaf Mold, Helen Margaret Griffiths http://www.ballpublishing.com/growertalks/ViewArticle.aspx?articleid=20665 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Tomato leaf mold	None	26,639	wikipedia	https://en.wikipedia.org/wiki/Tomato_leaf_mold	2021-01-18T19:05:46	{"wikidata": ["Q20720363"]}
The Mad Gasser of Mattoon (also known as the "Anesthetic Prowler," Friz, the "Phantom Anesthetist," or simply the "Mad Gasser")[1] was the name given to the person or people believed to be responsible for a series of apparent gas attacks that occurred in Mattoon, Illinois, during the mid-1940s. More than two dozen separate cases of gassings were reported to police over the span of two weeks, in addition to many more reported sightings of the suspected assailant. The gasser's supposed victims reported smelling strange odors in their homes which were soon followed by symptoms such as paralysis of the legs, coughing, nausea and vomiting. No one died or had serious medical consequences. Police remained skeptical of the accounts throughout the entire incident.[2]:235 No physical evidence was ever found,[3]:175 and many reported gassings had simple explanations, such as spilled nail polish or odors emanating from animals or local factories.[2]:237 Victims made quick recoveries from their symptoms and suffered no long-term effects.[3]:175 Nevertheless, local newspapers ran alarmist articles about the reported attacks and treated the accounts as fact.[2]:234 The attacks are widely considered to be a case of mass hysteria.[2][3] However, others maintain that the Mad Gasser actually existed, or that the perceived attacks have another explanation, such as industrial pollution. ## Contents * 1 Appearance * 2 Reported attacks * 3 Explanations * 3.1 Mass hysteria * 3.2 Toxic waste or pollution * 3.3 Actual assailant * 3.4 Other suggestions * 4 Popular culture * 5 See also * 6 References * 7 Further reading * 8 External links ## Appearance[edit] Most contemporary descriptions of the Mad Gasser are based on the testimony of Mr. and Mrs. Bert Kearney of 1408 Marshall Avenue, the victims of the first Mattoon case to be reported by the media. They described the gasser as being a tall, thin man dressed in dark clothing and wearing a tight-fitting cap.[4][5] Another report, made some weeks later, described the gasser as being a female dressed as a man.[6] The Gasser had also been described as carrying a flit gun, an agricultural tool for spraying pesticide, which he purportedly used to expel the gas.[7] ## Reported attacks[edit] The first of the 1944 gasser incidents occurred at a house on Grant Ave., Mattoon, on August 31, 1944. Urban Raef was awakened during the early hours of the morning by a strange odor. He felt nauseated and weak, and suffered from a fit of vomiting. Suspecting that he was suffering from domestic gas poisoning, Raef's wife tried to check the kitchen stove to see if there was a problem with the pilot light, but found that she was partially paralyzed and unable to leave her bed.[6][4][8][9] Later that night (some contemporary accounts refer to the time as the morning of the following day), a similar incident was also reported by a young mother living close by. She was awakened by the sound of her daughter coughing but found herself unable to leave her bed.[6] The next day, September 1, there was a third reported incident. A Mrs. Kearney, of Marshall Avenue, Mattoon, reported smelling a strong, sweet odor around 11:00 pm. At first she dismissed the smell, believing it to be from flowers outside of the window, but the odor soon became stronger and she began to lose feeling in her legs. Mrs. Kearney panicked and her calls attracted her sister, Mrs. Ready, who was in the house at the time. Mrs. Ready also noticed the odor, and determined that it was coming from the direction of the bedroom window, which was open at the time. The police were contacted, but no evidence of a prowler was found. At around 12:30 am, Bert Kearney, Mrs. Kearney's husband (a local taxi driver who had been absent during the time of the attack), returned home to find an unidentified man hiding close to one of the house's windows. The man fled and Kearney was unable to catch him. Kearney's description of the prowler was of a tall man dressed in dark clothing, wearing a tight fitting cap. This description was reported in the local media, and became the common description of the gasser throughout the Mattoon incident.[4][8][9] After the attack, Mrs. Kearney reported suffering from a burning sensation on her lips and throat, which were attributed to the effects of the gas.[6][9] Initially, it was suspected that robbery was the primary motive for the attack. At the time of the incidents, the Kearneys had a large sum of money in the house, and it was surmised that the prowler could have seen Mrs. Kearney and her sister counting it earlier that evening.[4][8] Local newspapers incorrectly reported this incident as being the first gasser attack.[4] In the days following the Kearney attack, there were half a dozen similar attacks (See table), though none of the purported victims were able to provide a clear description of the prowler, and no clues were found at the scene of the attacks. The first specimen of physical evidence was found on the night of September 5, when Carl and Beulah Cordes of North 21st Street returned home around 10:00 pm. After spending a few minutes in the house they noticed a piece of white cloth, slightly larger than a man's handkerchief, sitting on their porch next to the screen door. Beulah Cordes picked up the cloth and smelled it. As soon as she inhaled, she became violently ill. She described the effect as being similar to an electric shock. Her face quickly began to swell, she experienced a burning sensation in her mouth and throat, and began to vomit. As with other victims, she also reported feeling weak and experiencing partial paralysis of her legs. Beulah Cordes later hypothesized that the cloth had been left on the porch in order to knock out the family dog, which usually slept there, so that the prowler could gain access to the house unnoticed.[10] In addition to the cloth, a skeleton key, described as looking "well used," was reportedly found on the sidewalk adjacent to the porch, along with a large, almost empty, tube of lipstick. The cloth was analyzed by the authorities, but they found no chemicals on it that could explain Beulah Cordes' reaction.[6][7] The same night a second incident was reported, this time in North 13th Street, at the home of Mrs. Leonard Burrell. She reported seeing a stranger break in through her bedroom window and then attempt to gas her. Public concern over the alleged gassings quickly rose, the FBI became involved, and the local police issued a statement calling on residents to avoid lingering in residential areas, and warning that groups set up to patrol for the gasser should be disbanded for reasons of public safety. Chief of Police C.E. Cole also warned concerned citizens to exercise due restraint when carrying or discharging firearms.[11] During this period, there was also an increase in physical evidence of attacks being reported, ranging from footprints allegedly being discovered underneath windows to tears being found in window screens.[8][9] By September 12, local police had received so many false alarms (mostly from citizens believing that they smelled gas, or that they had seen a prowler) that they reduced the priority afforded to gasser reports and announced that the entire incident was likely the result of explainable occurrences exacerbated by public fears, and a sign of the anxiety felt by women while local men were on war service.[8][11][12] After the police announcement, gasser reports declined. The only incident of arguable note after that date was the case of Bertha Burch, who claimed she saw a gasser who was a woman dressed as a man.[6] Date Victim(s) Location Notes Aug 31, 1944 Mr. and Mrs. Urban Raef Grant Avenue Sept 1 Unnamed Name not reported in the media Sept 1 Mrs. Charles Rider Prairie Avenue Sept 1 Mrs. Bert Kearney Marshall Avenue First case reported in the media;[6] most Gasser descriptions derive from this case Sept 5 Mrs. Beulah Cordes North 21st Street Became ill after smelling cloth found on porch Sept 5 Mrs. Leonard Burrell North 13th Street Sept 6 Mrs. Laura Junken Richmond Avenue Sept 6 Ardell Spangle North 15th Street Sept 6 Mr. Fred Goble Saw prowler believed to be Gasser Sept 6 Mrs. Glenda Hendershott South 14th Street Sept 6 Mr. Daniel Spohn North 19th street Sept 6 Mrs. Cordie Taylor Charleston Avenue Sept 6 Miss Frances Smith Miss Maxine Smith Moultrie Ave Sept 7 As Above As Above Saw blue vapor and heard a motorized buzzing sound believed to be from gassing machinery Sept 8 Mr C.W. Driskell DeWitt Avenue Sept 9 Mrs. Genevieve Haskell Grayson Wayne Haskell Mrs. Russell Bailey Miss Katherine Tuzzo Westwood Sept 9 Mrs. Lucy Stephens North 32nd Street Sept 10 Unnamed Champaign Avenue Name not reported in the media Sept 10 Unnamed 2112 Moultrie Avenue Name not reported in the media Sept 10 Miss Frances Smith Miss Maxine Smith Moultrie Ave Third reported attack Sept 13 Bertha Burch Described gasser as being a woman dressed as a man; woman's footprints found at scene (List incomplete) [6][4][5][8][9][13][14] ## Explanations[edit] There are three primary theories about the Mattoon Mad Gasser incident: mass hysteria, industrial pollution, or an actual physical assailant. The events have also been written about by authors on the paranormal. ### Mass hysteria[edit] Almost two weeks after the Mattoon attacks began, the local Commissioner of Public Health, Thomas V. Wright, announced that there had undoubtedly been a number of gassing incidents, but that many instances were likely due to hysteria: residents hearing of alarming events, and then panicking when confronted by an out-of-place odor or a shadow at the window; Wright stated:[8] > There is no doubt that a gas maniac exists and has made a number of attacks. But many of the reported attacks are nothing more than hysteria. Fear of the gas man is entirely out of proportion to the menace of the relatively harmless gas he is spraying. The whole town is sick with hysteria. On September 12, local Chief of Police C. E. Cole took Wright's hypothesis a step further, announcing that there had likely been no gas attacks at all, and that the reported incidents had probably been triggered by chemicals carried on the wind from nearby industrial facilities and then exacerbated by public panic.[6] Wright and Cole's diagnosis was given further validity in 1945 when the Journal of Abnormal and Social Psychology published "The 'phantom anesthetist' of Mattoon: a field study of mass hysteria" by Donald M. Johnson, which documented the Mattoon incident as a case study in mass hysteria.[3] In 1959, his opinion was seconded by psychologist James P. Chaplin,[15] and went on to form the basis for several subsequent studies of the phenomena of mass hysteria.[16] Most of the physical symptoms recorded during the Botetourt and Mattoon incidents (including choking, swelling of mucus membranes, and weakness/temporary paralysis) have all been suggested symptoms of hysteria.[17] Some experts believe that the mass hysteria was fueled by the headline in the Mattoon Journal-Gazette, "Mrs. Kearney and Daughter First Victims," which assumed there would be more attacks. ### Toxic waste or pollution[edit] On September 12, Chief of Police Cole told a press conference that odors and symptoms reported may have been the result of pollutants or toxic waste released by nearby industrial plants, and speculated that carbon tetrachloride or trichloroethylene, both of which have a sweet odor and can induce symptoms similar to those reported by purported gasser victims, may have been the substance released.[6][12] In response to Cole's statement, Atlas-Imperial, the primary company implicated in this affair, released a statement of its own saying that their facility had only five gallons of carbon tetrachloride in stock, which was contained in firefighting equipment. Atlas-Imperial officials also denied that any quantities of trichloroethylene (an industrial solvent used by Atlas) could be responsible for sickness in the town, reasoning that it would have taken significant quantities of the chemical to sicken the townspeople, and that factory workers would have experienced similar symptoms long before anybody outside of the factory was affected.[12] At the time of the gassing, the Atlas plant had been certified as safe by the State Department of Health.[12] ### Actual assailant[edit] After analyzing events, some researchers have concluded that at least some of the gasser incidents were the work of an actual attacker who carried out a series of gassings as reported by witnesses.[13] ### Other suggestions[edit] Some writers on the paranormal have covered the events. Clark (1993) describes an illustration of the Gasser from Loren Coleman's Mysterious America: "[the artist] depicts him as a not-quite-human, possibly extraterrestrial, being".[18] ## Popular culture[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (June 2017) (Learn how and when to remove this template message) * Monster in My Pocket action figure * The Mad Gasser is the subject of numerous podcasts, including a 2018 episode of Do Go On,[19] a 2016 episode of the Futility Closet,[20] a 2015 episode of The Dollop,[21] and a 2009 episode of The Memory Palace.[22] * In the video game Shin Megami Tensei IV The Mad Gasser of Mattoon appears as a recruitable demon for the player's party. * In the science-fiction novel The Body Snatchers by Jack Finney, the story of the Mad Gasser of Mattoon is briefly discussed as one of the characters hypothesizes that the widespread panic which is spreading among the local population about potential alien invaders is nothing but mass hysteria.[23] ## See also[edit] * Fortean phenomena * Nocebo * Placebo * Spring-heeled Jack * Pérák, the Spring Man of Prague * London Monster ## References[edit] 1. ^ Graddon, Nigel (1 August 2018). THE LANDING LIGHTS OF MAGNOLIA. ISBN 9781948803021. Retrieved 24 May 2020. 2. ^ a b c d Bartholomew, Robert E.; Victor, Jeffrey S. (Spring 2004). "A Social-Psychological Theory of Collective Anxiety Attacks: The "Mad Gasser" Reexamined". The Sociological Quarterly. 45 (2): 229–248. doi:10.1111/j.1533-8525.2004.tb00011.x. S2CID 145607562. 3. ^ a b c d Johnson, Donald M (1945). "The 'phantom anesthetist' of Mattoon: a field study of mass hysteria". Journal of Abnormal and Social Psychology. 40 (2): 175–186. doi:10.1037/h0062339. 4. ^ a b c d e f "Aesthetic Prowler" on the loose Mrs. Kearney and daughter first victims". Daily Journal-Gazette (Mattoon). 1944-09-02. Archived from the original on 2007-09-27. Retrieved 2006-11-01. 5. ^ a b "Victims of gas prowler now 25". Charleston Daily Courier. 1944-09-09. Archived from the original on 2006-06-20. Retrieved 2006-11-01. 6. ^ a b c d e f g h i j Clark, Jerome (1993). Unexplained! 347 Strange Sightings, Incredible Occurrences, and Puzzling Physical Phenomena. Detroit: Visible Ink Press. ISBN 0-8103-9436-7. 7. ^ a b "At Night in Mattoon". Time Magazine. 1944-09-18. 0040-781X. Retrieved 2006-11-01. 8. ^ a b c d e f g Taylor, Troy (2002). "The mad gasser of Virginia and & Mattoon, Illinois". Ghosts of the Prairie. Archived from the original on 2006-08-27. Retrieved 2006-10-01. 9. ^ a b c d e Taylor, Troy (2002). Into the shadows. Whitechapel Productions. ISBN 1-892523-21-3. 10. ^ "Anesthetic prowler adds victim: Mrs. C. Cordes burned, Ill two hours". Daily Journal-Gazette (Mattoon). 1944-09-06. Archived from the original on 2007-09-27. Retrieved 2006-11-10. 11. ^ a b "Many Prowler Reports; few Real - To all citizens of Mattoon". Daily Journal-Gazette (Mattoon). 1944-09-11. Archived from the original on 2007-09-27. Retrieved 2006-11-01. 12. ^ a b c d "Police get two false alarms during night". Daily Journal-Gazette (Mattoon). 1944-09-13. Archived from the original on 2007-09-27. Retrieved 2006-11-01. 13. ^ a b Clark, Jerome; Coleman Loren (1972-02-01). "The Mad Gasser of Mattoon". Fate. 25 (2). 14. ^ Mio, Leslie (2001). "Location of "Gasser Attacks"". Eastern Illinois University. Archived from the original on 2006-09-25. Retrieved 2006-11-10. 15. ^ Chaplin, J. P. (1959). Rumor, Fear and The Madness of Crowds. Ballantine Books. ASIN B000AMUL5M. 16. ^ Dash, Mike (2000). Borderlands: The ultimate exploration of the unknown. Overlook. ISBN 0-87951-724-7. 17. ^ Janet, Pierre (1965). "Major Symptoms of Hysteria (2nd edition)". Macmillan Pub Co. Cite journal requires `\|journal=` (help) 18. ^ Clark, Jerome (1993). Unexplained! 347 Strange Sightings, Incredible Occurrences, and Puzzling Physical Phenomena. Detroit: Visible Ink Press. pp. 239. ISBN 0-8103-9436-7. 19. ^ Do Go On. "146 - The Mad Gasser of Mattoon". Archived from the original on 25 August 2018. Retrieved 24 August 2018. 20. ^ "Futility Closet 132: The Mad Gasser of Mattoon". 21. ^ "Episode 120:Dollop:The Mad Gasser". 22. ^ "A Gas Gas Gas". The Memory Palace. 23. ^ Finney, Jack (2010). The Body Snatchers. UK: Hachette UK. pp. 68–71. ISBN 9780575089167. ## Further reading[edit] * Coleman, Loren (2004). Mysterious America. New York: Paraview. ISBN 1-931044-84-8. * Maruna, Scott (2003). The Mad Gasser of Mattoon: Dispelling the Hysteria. Jacksonville, Ill.: Swamp Gas Book Co. ISBN 978-0-9728605-0-5. * Van Huss, William B. (2017) The Mad Gasser of Botetourt County ISBN 978-1979589246 ## External links[edit] * "The Mad Gasser of Mattoon: how the press created an imaginary chemical weapons attack" from Skeptical Inquirer, 7/1/2002 * Site with newspaper headlines and a list of victims and locations of incidents [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mad Gasser of Mattoon	None	26,640	wikipedia	https://en.wikipedia.org/wiki/Mad_Gasser_of_Mattoon	2021-01-18T18:34:14	{"wikidata": ["Q1883081"]}
Gastrocutaneous syndrome Other namesPeptic ulcer/hiatal hernia, multiple lentigines/cafe-au-lait spots, hypertelorism, myopia [1] SpecialtyDermatology Gastrocutaneous syndrome is a rare autosomal dominant cutaneous condition characterized by multiple lentigines.[2] ## See also[edit] * Gardner's syndrome * List of cutaneous conditions ## References[edit] 1. ^ "Gastrocutaneous syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 17 March 2019. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. ## External links[edit] Classification D * OMIM: 137270 * MeSH: C535651 External resources * Orphanet: 2069 This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Gastrocutaneous syndrome	c1850899	26,641	wikipedia	https://en.wikipedia.org/wiki/Gastrocutaneous_syndrome	2021-01-18T18:45:50	{"gard": ["2438"], "mesh": ["C535651"], "umls": ["C1850899"], "orphanet": ["2069"], "wikidata": ["Q5526827"]}
A number sign (#) is used with this entry because autosomal recessive spondylocostal dysostosis-1 (SCDO1) is caused by homozygous or compound heterozygous mutation in the DLL3 gene (602768) on chromosome 19q13. Description The spondylocostal dysostoses are a heterogeneous group of axial skeletal disorders characterized by multiple segmentation defects of the vertebrae (SDV), malalignment of the ribs with variable points of intercostal fusion, and often a reduction in rib number. The term 'spondylocostal dysostosis' is best applied to those phenotypes with generalized SDV and a broadly symmetric thoracic cage (summary by Gucev et al., 2010). ### Genetic Heterogeneity of Spondylocostal Dysostosis Other forms of SCDO include SCDO2 (608681), caused by mutation in the MESP2 gene (605195) on chromosome 15q26; SCDO3 (609813), caused by mutation in the LFNG gene (602576) on chromosome 7p22; SCDO4 (613686), caused by mutation in the HES7 gene (608059) on chromosome 17p13; SCDO5 (122600), caused by mutation in the TBX6 gene (602427) on chromosome 16p11; and SCDO6 (616566), caused by mutation in the RIPPLY2 gene (609891) on chromosome 6q14. Clinical Features Lavy et al. (1966) observed 4 of 7 offspring of a third-cousin marriage who had characteristic vertebral anomalies including hemivertebrae and block vertebrae accompanied by deformity of the ribs. All affected children died of respiratory infection under 1 year of age. Moseley and Bonforte (1969) described the same disorder in 2 apparently unrelated children of nonconsanguineous Puerto Rican parents. Caffey (1967) described brother and sister with short neck and trunk in contrast to extremities of normal length. Both showed 'hemivertebrae at practically all levels in the spine.' The skeletons were otherwise normal. Norum (1969) observed 4 similar cases in 2 related sibships in an inbred community in eastern Kentucky. Fused ribs also occurred in affected persons. See 122600 for an autosomal dominant form of spondylocostal dysostosis. Eller and Morton (1970) described similar deformity of the chest and spine, with additional craniolacunia, rachischisis, and urinary tract anomalies, in the offspring of a woman who admitted to a single exposure to LSD about the time of conception. Cantu et al. (1971) described 5 cases in an inbred kindred. Castroviejo et al. (1973) reported spondylothoracic dysplasia in 3 Spanish sisters who showed the typically short thorax, short neck with limited mobility, winged scapulae, and scoliosis or kyphoscoliosis. Particularly noteworthy were the vertebral anomalies, including hemivertebrae and vertebral fusions affecting the whole vertebral column. Rib abnormalities in form and number were seen. One sister showed decreased mental function and another showed incompletely formed odontoid process. Bartsocas et al. (1974) described 3 affected sibs (2 of them identical twin sisters). Satar et al. (1992) described this disorder in identical twins whose parents were first cousins. Van Thienen and Van der Auwera (1994) described monozygotic twins discordant for this syndrome, either due to a postzygotic mutation or to a phenocopy. Jarcho and Levin (1938) are credited with first describing this syndrome, in a black brother and sister in Baltimore, but they mistakenly spoke of the condition as the same as the Klippel-Feil syndrome (118100). Perez-Comas and Garcia-Castro (1974) described 6 cases in Puerto Ricans, including 2 affected sibs. Their designation, occipito-facial-cervico-thoracic-abdomino-digital dysplasia, seems in the first place ridiculously long, but really unwarranted since all changes seem to be secondary or tertiary to the primary changes in the spine. Several authors refer to a typical 'crab-like' radiologic appearance of the thoracic skeleton. Conceivably the early lethal form represented by the cases of Jarcho and Levin (1938) and the cases with survival to a later age, e.g., the cases of Norum (1969) and Cantu et al. (1971) are produced by homozygosity for alleles at the same locus. Devos et al. (1978) described associated abnormalities of ureters and renal pelvis. Gassner and Grabs (1982) described 8 affected persons in 4 interrelated families. One also had Down syndrome and died at the age of 7 days. The others showed no decrease in life expectancy and no other malformations. Autosomal recessive inheritance was well documented. Young and Moore (1984) reported a case in a child of first-cousin parents. They claimed it to be the first report of the condition in the United Kingdom. Cassidy et al. (1984) reported observations on a Puerto Rican child living in Connecticut. Giacoia and Say (1991) found diastematomyelia, spina bifida, and open meningocele in an American Indian infant with the features of the Jarcho-Levin syndrome. Turnpenny et al. (1991) indicated the wide variability in 7 affected members of an inbred Israeli-Arab family. Romeo et al. (1991) reported 2 affected brothers and 2 affected sisters related to each other as first cousins once removed. Karnes et al. (1991) reported 4 new cases. They supported the classification of Solomon et al. (1978) into 2 subtypes: spondylocostal dysostosis and spondylothoracic dysostosis. McCall et al. (1994) described the case of a Puerto Rican child with unusually long survival to age 11 years. Aurora et al. (1996) reported a newborn with characteristic features of Jarcho-Levin syndrome in addition to complex congenital heart disease (situs solitus, double outlet right ventricle, atrial septal defect) and hypospadias. Mortier et al. (1996) analyzed 26 new patients with multiple vertebral segmentation defects and reviewed 115 previously reported cases. They recognized 3 distinct entities based on radiographic and clinical findings: Jarcho-Levin syndrome, a lethal autosomal recessive form, characterized by a symmetric crab-chest; spondylocostal dysostosis (122600), a benign autosomal dominant condition; and spondylothoracic dysostosis, which shows considerable clinical and radiographic overlap with spondylocostal dysostosis and has an autosomal recessive mode of inheritance. The authors noted that intrafamilial variability is striking (Cantu et al., 1971; Franceschini et al., 1974; Trindade and de Nobrega, 1977; Turnpenny et al., 1991); affected individuals either die in infancy of respiratory failure or survive into adulthood with minimal symptoms. Associated anomalies are not common and are only observed in lethal cases. Mortier et al. (1996) stated that sporadic cases of vertebral segmentation defects are difficult to classify as to etiology, genetic versus nongenetic, and concluded that they probably represent a heterogeneous group. Associated anomalies are more common in this group than in the familial types and may involve both mesodermally and ectodermally derived structures. Mortier et al. (1996) also concluded that the body segment in which the nonvertebral malformations occur corresponds to the site of the vertebral segmentation defects. Bannykh et al. (2003) reported 2 affected Caucasian sibs and provided a review of the Jarcho-Levin syndrome and related disorders. Biochemical Features Because vertebral development is controlled by a limited number of master genes including PAX1 (167411) and PAX9 (167416), Bannykh et al. (2003) analyzed protein expression from these genes in 2 sibs with Jarcho-Levin syndrome and in age-matched controls. Immunochemical analysis showed a significant reduction in levels of protein expression on chondrocytes of the vertebral column. Molecular Genetics Turnpenny et al. (1999) performed genomewide scanning by homozygosity mapping in a large consanguineous Arab-Israeli family in which there were 6 definite cases of autosomal recessive spondylocostal dysostosis. Significant linkage was found to 19q13, with a lod score of 6.9. This was confirmed in a second Pakistani family with 3 affected members, with a lod score of 2.4. The combined haplotype data identified a critical region between D19S570 and D19S908, an interval of 8.5 cM on 19q13.1-q13.3. Using homology of synteny and linkage data suggesting that the SCDO1 locus is on chromosome 19q13.1-q13.3 and that a mouse region containing the Notch ligand delta-like-3 gene is mutated in the x-ray-induced mouse mutant 'pudgy,' causing a variety of vertebral costal defects similar to the SCDO1 phenotype, Bulman et al. (2000) cloned and sequenced human DLL3 to evaluate it as a candidate gene for SCDO1. They identified mutations in 3 autosomal recessive SCDO1 families. Two of the mutations (602768.0001 and 602768.0002) predicted truncations within conserved extracellular domains; the third (602768.0003) was a missense mutation in a highly conserved glycine residue of the fifth epidermal growth factor repeat, which revealed an important functional role for this domain. These were the first mutations in a human delta homolog, thus highlighting the critical role of the Notch signaling pathway and its components in patterning the mammalian axial skeleton. Turnpenny et al. (2003) sequenced the DLL3 gene in a series of spondylocostal dysostosis patients from 14 families and identified 12 mutations, 2 of which occurred twice. The patients represented diverse ethnic backgrounds and 6 came from traditionally consanguineous communities. In all affected individuals, the radiologic phenotype was abnormal segmentation throughout the entire vertebral column with smooth outlines to the vertebral bodies in childhood, for which Turnpenny et al. (2003) suggested the term 'pebble beach sign.' This appeared to be a very consistent phenotype-genotype correlation. Turnpenny et al. (2003) suggested the designation SCD type 1 for the autosomal recessive form caused by mutation in the DLL3 gene. Day and Fryer (2003) reported 2 pregnancies in 1 family in which diaphragmatic hernia and preaxial polydactyly accompanied spondylothoracic dysplasia. The first pregnancy was monozygous male twins and the second was a female sib. The pregnancies were terminated. The authors suggested that spondylothoracic dysplasia and spondylocostal dysostosis may be allelic. In a family with spondylocostal dysostosis, previously reported by Floor et al. (1989) and believed to represent autosomal dominant inheritance, Whittock et al. (2004) performed haplotype analysis which suggested pseudodominant transmission with segregation of 2 distinct disease alleles. Direct sequencing of the DLL3 gene revealed that the affected father was homozygous and all 4 sibs were heterozygous for a 1440delG mutation (602768.0007), whereas the unaffected mother and 2 affected sibs were heterozygous for a G504D substitution (602768.0008), thus confirming autosomal recessive inheritance in all affected members of the family. Heterogeneity In a family segregating autosomal recessive spondylocostal dysplasia, Iughetti et al. (2000) could find no evidence of linkage to 19q, indicating genetic heterogeneity in this disorder. Whittock et al. (2004) demonstrated a mutation in the basic helix-loop-helix transcription factor gene, MESP2 (605195), in a consanguineous family with 2 children affected by spondylocostal dysostosis (SCDO2; 608681). The phenotype was milder than that of DLL3 mutation-positive spondylocostal dysostosis, and not all vertebrae were affected. Both the DLL3 and MESP2 genes are important components of the Notch signaling pathway, which has multiple roles in development and disease. Sparrow et al. (2006) used a candidate-gene approach to identify mutation in a third Notch pathway gene, lunatic fringe (LFNG; 602576.0001), in a family with autosomal recessive spondylocostal dysostosis (SCDO3; 609813). In 5 children with short stature and congenital scoliosis from 4 Taiwanese Han Chinese families, Wang et al. (2011) analyzed the DLL3, MESP2, LFNG, and HES7 genes but identified no causative mutations. Apart from abnormal vertebral segmentation defects, the children had no other systemic anomalies, and all achieved normal developmental milestones. Two sisters whose parents were descendants of the same minor aboriginal tribe in Taiwan showed marked phenotypic similarity, including decreased size of vertebral bodies, hypoplasia of disc spaces throughout the thoracic spine, thoracic scoliosis, and block lumbar vertebrae. The other 3 unrelated patients displayed varying degrees of block vertebrae and hemivertebrae in the thoracic spine, with asymmetric fusion, bifid ribs, and butterfly vertebrae. Noting that none of their patients completely fulfilled the criteria for the strictest definition of SCD, which requires contiguous involvement of at least 10 spinal segments and aberrant rib alignment, with some asymmetry in rib alignment and irregular points of rib fusions, but basic overall symmetry in the shape of the thorax, Wang et al. (2011) suggested that these patients might represent a subtype of SCD occurring in the Taiwanese population. Nomenclature The terms dysostosis and dysplasia are used here interchangeably. Both words refer to abnormal development or formation. A distinction between the 2 terms has some usefulness, however. The dysostoses, in the usage and interpretation of Spranger (1997), referred to disorders due to defects in genes that are active predominantly in early stages of development and only at that stage are likely to result in the 'frozen' type of malformation. On the other hand, defects in genes that are active later in development or in extrauterine life cause dysplasia. Some disorders, such as fibrodysplasia ossificans progressiva (135100), show characteristics of a malformation (dysostosis) in the malformation of the thumbs and toes and characteristics of a dysplasia in the form of the ectopic ossification which develops in the first decade of life. INHERITANCE \- Autosomal recessive GROWTH Height \- Dwarfism \- Short trunk Other \- Normal length limbs HEAD & NECK Neck \- Short neck RESPIRATORY \- Respiratory infection CHEST Ribs Sternum Clavicles & Scapulae \- Rib anomalies \- Fused ribs SKELETAL Spine \- Hemivertebrae \- Vertebral fusion \- Block vertebrae \- Abnormal odontoid process Limbs \- Normal length limbs MISCELLANEOUS \- Infantile death MOLECULAR BASIS \- Caused by mutation in the delta like canonical Notch ligand 3 gene (DLL3, 602768.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SPONDYLOCOSTAL DYSOSTOSIS 1, AUTOSOMAL RECESSIVE	c0265343	26,642	omim	https://www.omim.org/entry/277300	2019-09-22T16:21:23	{"doid": ["0050568"], "mesh": ["C537565"], "omim": ["277300"], "orphanet": ["2311"], "synonyms": ["Alternative titles", "VERTEBRAL ANOMALIES", "JARCHO-LEVIN SYNDROME", "SPONDYLOTHORACIC DYSPLASIA", "COSTOVERTEBRAL DYSPLASIA", "SPONDYLOTHORACIC DYSOSTOSIS"], "genereviews": ["NBK8828"]}
A rare type of inherited epidermolysis bullosa characterized by aplasia cutis congenita on the extremities, leaving behind hypopigmentation and atrophy in a whirled pattern. Generalized blistering persists during childhood and heals with cutaneous and follicular atrophy, linear and stellate scars, and hypopigmentation. Skin fragility decreases with adulthood. Adult patients exhibit dyspigmentation and atrophy of the skin, scars, follicular atrophoderma, sparse body hair, progressive diffuse alopecia of the scalp, diffuse palmoplantar keratoderma, and nail changes. Ultrastructurally, intraepidermal splitting appears at the level of the basal keratinocytes, above the hemidesmosomes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Generalized basal epidermolysis bullosa simplex with skin atrophy, scarring and hair loss	c4310631	26,643	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=508529	2021-01-23T18:54:45	{"omim": ["617294"]}
X-linked visceral heterotaxy type 1 is a very rare form of heterotaxy that has only been reported in a few families. Heterotaxy is the right/left transposition of thoracic and/or abdominal organs. This condition is caused by mutations in the ZIC3 gene, is inherited in an X-linked recessive fashion, and is usually seen in males. Physical features include heart abnormalities such as dextrocardia, transposition of great vessels, ventricular septal defect, patent ductus arteriosus, pulmonic stenosis; situs inversus, and missing (asplenia) and/or extra spleens (polysplenia). Affected individuals can also experience abnormalities in the development of the midline of the body, which can cause holoprosencephaly , myelomeningocele, urological anomalies, widely spaced eyes (hypertelorism), cleft palate, and abnormalities of the sacral spine and anus. Heterotaxia with recurrent respiratory infections are called primary ciliary dyskinesia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	X-linked visceral heterotaxy 1	c1844020	26,644	gard	https://rarediseases.info.nih.gov/diseases/8591/x-linked-visceral-heterotaxy-1	2021-01-18T17:57:01	{"mesh": ["C538116"], "omim": ["306955"], "umls": ["C1844020"], "orphanet": ["450"], "synonyms": ["HTX1", "Laterality, X-linked", "Situs inversus, complex cardiac defects, and splenic defects, X-linked", "Heterotaxy, visceral, 1, X-linked", "Heterotaxy, visceral, X-linked"]}
Subnormal intellectual functioning (cognitive disorder) There are a variety of disabilities affecting cognitive ability. This is a broad concept encompassing various intellectual or cognitive deficits, including intellectual disability (formerly called mental retardation), deficits too mild to properly qualify as intellectual disability, various specific conditions (such as specific learning disability), and problems acquired later in life through acquired brain injuries or neurodegenerative diseases like dementia. Many of these disabilities have an effect on memory, which is the ability to recall what has been learned over time. Typically memory is moved from sensory memory to working memory, and then finally into long-term memory. People with cognitive disabilities typically will have trouble with one of these types of memory.[1] ## Contents * 1 Intellectual disability * 2 Specific learning disability * 3 Acquired brain injuries * 4 Neurodegenerative diseases * 5 Living with cognitive disability * 6 References ## Intellectual disability[edit] Main article: Intellectual disability Intellectual disability, also known as general learning disability,[2] and previously known as mental retardation (a term now considered offensive),[3][4] is a generalized disorder characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors that appears before adulthood. It has historically been defined as an Intelligence Quotient (IQ) score under 70, but the definition now includes both one component relating to mental functioning and one relating to individuals' functional skills in their environment, so IQ is not the only factor. Intellectual disability must have appeared in the developmental period, not only as an adult. By contrast, people with cognitive impairment have, or previously had, normal IQ, but now show confusion, forgetfulness and difficulty concentrating; cognitive impairment is typical of brain injuries, side effects from medications, and dementia. ## Specific learning disability[edit] Main article: Specific learning disability A specific learning disability is a classification including several disorders in which a person has difficulty learning in a typical manner, usually caused by an unknown factor or factors, but sometimes caused by stroke or other medical problems. Specific learning disabilities include dyslexia and developmental coordination disorder and other disorders of psychological development.[5] Unlike other intellectual disabilities, it is not indicative of general intelligence level, and many experts consequently do not consider it to be a true intellectual disability. Rather, people with a specific learning disability have trouble performing specific types of cognitive skills or if taught in conventional ways. A specific learning disability cannot be cured or fixed, but the effects can be mitigated by the use of different learning strategies. Individuals with specific learning disabilities face some challenges throughout life. Social support can be a crucial component for students with specific learning disabilities in the school system. With the right support and intervention, people with specific learning disabilities can succeed in school and be successful later in life. Conversely, many individuals who have struggled at school or who were considered 'lazy' or 'stupid' at school, may have had unrecognised specific learning disability instead of character flaws or low IQ. ## Acquired brain injuries[edit] Main article: Acquired brain injury An acquired brain injury (ABI) is brain damage caused by events after birth, rather than as part of a genetic or congenital disorder. It usually affects cognitive, physical, emotional, social or independent functioning. ABIs can result from either a traumatic brain injury or a non-traumatic injury such as stroke, infection or substance abuse. Most definitions of ABI exclude neurodegenerative disorders. People with a brain injury may have difficulty controlling, coordinating and communicating their thoughts and actions. They may or may not retain their intellectual abilities, depending on the type and extent of the injury. However, the intellectual abilities of a person with a brain injury are likely to be interfered with by the resulting thought coordination and communication difficulties, which can make it difficult for them to express themselves in a manner intelligible to others. This may give the false impression of a damaged intelligence even in people with normal intellectual capacity. ## Neurodegenerative diseases[edit] Main article: Neurodegeneration Neurodegenerative diseases all involve the progressive loss of structure or function of neurons, including the death of neurons. Many neurodegenerative diseases including Parkinson's, Alzheimer's, and Huntington's occur as a result of neurodegenerative processes. As research progresses, many similarities appear which relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging. Both dementia and intellectual disability are defined by neurologists as having an IQ that is two standard deviations below median (below about 70, when 100 is the median); the difference between these two classifications for intellectual disability is whether the low IQ represents a lifelong condition (intellectual disability), or a condition that is acquired later (dementia).[6] Dementia may be static, the result of a unique global brain injury, or progressive, resulting in long-term decline due to damage or disease in the body. In the early stages of Alzheimer's disease, whose symptoms of dementia are called mild cognitive impairment, the person typically loses 8 to 10 IQ points per year, with the result that a person of previously normal intelligence usually becomes intellectually disabled in less than five years.[7] ## Living with cognitive disability[edit] Research documents the importance of providing those with intellectual disabilities alternative spaces and contexts where they feel included and can assert their own definitions of ability and what it is to be "normal."[8] ## References[edit] 1. ^ "Teachers Without Borders Resources / Inclusive Education". twbonline.pbworks.com. Retrieved 24 October 2017. 2. ^ Special Education Support Service General Learning Disabilities 3. ^ Kaufman, Alan S. (2009). IQ Testing 101. New York: Springer Publishing. pp. 114–115. ISBN 978-0-8261-0629-2. Lay summary (10 August 2010). 4. ^ Plomin, Robert; DeFries, John C.; Knopik, Valerie S.; Neiderhiser, Jenae M. (2012). Behavioral Genetics. Shaun Purcell (Appendix: Statistical Methods in Behavioral Genetics). Worth Publishers. p. 163. ISBN 978-1-4292-4215-8. Lay summary (4 September 2013). "However, the term mental retardation is now considered pejorative," 5. ^ "International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) Version for 2010". World Health Organization. Retrieved 12 March 2013. 6. ^ Jessica L. Schultz; Davis, Larry E.; Molly K. King (2005). Fundamentals of Neurologic Disease. Demos Medical Publishing. pp. 115. ISBN 1-888799-84-6. OCLC 57316700. 7. ^ Dalton, A. J.; Janicki, Matthew P. (1999). Dementia, aging, and intellectual disabilities: a handbook. New York: Brunner/Mazel. p. 12. ISBN 0-87630-916-3. OCLC 39223703. 8. ^ Adkins, B.; Summerville, J.; Knox, M.; Brown, A. R.; Dillon, S. (2012). "Digital technologies and musical participation for people with intellectual disabilities". New Media & Society. 15 (4): 501–518. doi:10.1177/1461444812457338. hdl:10072/47764. OCLC 829241491. * v * t * e Disability Main topics * Disability * Disability studies * Medical model * Social model * Society for Disability Studies Approaches * Freak show * IEP * Inclusion * Learning disability * Mainstreaming * Physical therapy * driver rehabilitation * Special needs * school * education Rights, law, support Rights * Ableism/disablism * Disability rights * Pejorative terms Law * AODA * ADA * Convention on the Rights of Persons with Disabilities * Declaration on the Rights of Disabled Persons * International Classification of Functioning, Disability and Health Services * Services for mental disorders * Services for the disabled Support * DLA * ODSP * Rail * SSDI * SSI * Students * CNIB Activist groups * CCD * DPI * MINDS * Reach Canada * Visitability Structural and assistive * Activities of daily living * Assistive technology * Independent living * Mobility aid * Orthotics and braces * Personal Care Assistant * Physical accessibility * Prosthetics * Universal design * Web accessibility Social issues * Augmentative and alternative communication * Emotional or behavioral disability * Invisible disability * Disability and religion * Disability and poverty * Disability and sexuality Arts, media, culture, sport * Disability culture * Disability art * Disability in the arts * Disability in the media * Disabled sports * Deaflympics * Paralympics * Special Olympics * Category * Lists * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Disabilities affecting intellectual abilities	None	26,645	wikipedia	https://en.wikipedia.org/wiki/Disabilities_affecting_intellectual_abilities	2021-01-18T18:56:57	{"wikidata": ["Q3317827"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-15 (DFNA15) is caused by heterozygous mutation in the POU4F3 gene (602460) on chromosome 5q32. Description Autosomal dominant deafness-15 is a form of progressive nonsyndromic sensorineural hearing loss with postlingual onset between the second and sixth decades of life (summary by Kim et al., 2013). Clinical Features Vahava et al. (1998) studied progressive hearing loss in an Israeli Jewish family that traced its ancestry to Italy and to subsequent migrations through various North African and Middle Eastern countries, including Tunisia, Libya, and Egypt, with branches of the family now living in Israel, the United States, and Belgium. Five generations demonstrated autosomal dominant inheritance of progressive deafness. Earliest record of a hearing-impaired family member concerned an individual born in 1843 in Libya. He had 4 children, only 1 of whom was affected. Hearing loss in this kindred, referred to as family H, began between ages 18 and 30, with a moderate to severe defect in hearing by age 50. Collin et al. (2008) reported a large Dutch family in which multiple members had hearing loss. The was large clinical variability in terms of age at onset, levels of progression, and shape of audiograms. For example, 1 patient reported subjective onset around puberty, whereas another had onset at 20 years of age. Lee et al. (2010) reported a 44-year-old Korean woman with progressive sensorineural hearing loss beginning at age 20 years. Family history revealed affected family members spanning 4 generations. Kim et al. (2013) reported a large 6-generation Korean family in which multiple individuals had postlingual onset of sensorineural hearing loss. The age at onset ranged from the early teens to late fifties, and no patients had additional syndromic features. Pure tone audiograms showed bilateral minimal to moderate sensorineural hearing loss with flat to gently downward-sloping audiograms. Inheritance The transmission pattern of DFNA15 in the families reported by Vahava et al. (1998) and Kim et al. (2013) was consistent with autosomal dominant inheritance. Mapping By linkage analysis of a large family with hearing loss, Vahava et al. (1998) identified a locus, termed DFNA15, on chromosome 5q31-q33. The candidate 25-cM region was bounded by D5S1979 and D5S422. Analysis of the maximum-likelihood genetic model for deafness in this family indicated a rare autosomal dominant allele with full penetrance by age 40 and 0.05 probability of deafness from other causes by age 40 (in other words, 5% phenocopies). Molecular Genetics In searching for candidate genes in the DFNA15-linked region, Vahava et al. (1998) noted that the class 4 POU domain transcription factor-3 gene (POU4F3) may lie on 5q, on the basis of the localization of mouse Pou4f3 and the homology of human chromosomes 5 and 18 with mouse chromosome 18. POU4F3 was considered an excellent candidate for a gene causing human deafness because targeted deletion of both alleles of Pou4f3 caused complete deafness in mice. To map POU4F3 more precisely, they synthesized primers for the human POU4F3 cDNA sequence and used these to amplify pools of the CEPH3 yeast artificial chromosome (YAC) library. In this way, YACs containing markers linked to deafness in family H were found, indicating that POU4F3 must lie within the DFNA15-linked region. Using primers designed to amplify and sequence the entire coding region, they found an 8-bp deletion (602460.0001) in exon 2 of the POU4F3 gene. The predicted result of this deletion was a frameshift beginning at codon 295 and a premature translation stop at position 299. Deletion was not found in the POU4F3 gene of 114 unrelated individuals of various North African and Middle Eastern Jewish ancestry selected to represent the contribution of various ethnic Jewish populations to family H. In affected members of 2 unrelated Dutch families with autosomal dominant hearing loss, Collin et al. (2008) identified 2 different heterozygous mutations in the POU4F3 gene (602460.0002 and 602460.0003, respectively). In a 44-year-old Korean woman with DFNA15, Lee et al. (2010) identified a heterozygous truncating mutation in the POU4F3 gene (602460.0005). In vitro expression studies showed that the mutant protein lost most of its nuclear localization as well as transcriptional activity. The proband was 1 of 42 unrelated Korean patients with autosomal dominant nonsyndromic hearing loss who were sequenced for POU4F3 mutations. Using a combination of linkage analysis and whole-exome sequencing, Kim et al. (2013) identified a heterozygous missense mutation in the POU4F3 gene (R326K; 602460) in affected members of a large Korean family with DFNA15. Animal Model By comparing inner ear gene expression profiles of embryonic day 16.5 wildtype and Pou4f3-mutant deaf mice, Hertzano et al. (2004) identified the GFI1 gene (600871) as a target gene regulated by Pou4f3. Deficiency of Pou4f3 led to a reduction in Gfi1 expression levels, and the dynamics of Gfi1 mRNA abundance closely followed the pattern of expression for Pou4f3. Immunohistochemical and ultrastructural analyses revealed that loss of Gfi1 resulted in outer hair cell degeneration, which appeared comparable to that observed in Pou4f3 mutants. Hertzano et al. (2004) concluded that Gfi1 is the first downstream target of a hair cell-specific transcription factor, and they suggested that outer hair cell degeneration in Pou4f3 mutants may be largely or entirely a result of the loss of expression of Gfi1. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, postlingual sensorineural \- Downward sloping or flat audiogram MISCELLANEOUS \- Onset between the second and sixth decades \- Intrafamilial variability MOLECULAR BASIS \- Caused by mutation in the class 4 POU domain transcription factor 3 gene (POU4F3, 602460.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DEAFNESS, AUTOSOMAL DOMINANT 15	c1865366	26,646	omim	https://www.omim.org/entry/602459	2019-09-22T16:13:41	{"doid": ["0110546"], "mesh": ["C566545"], "omim": ["602459"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA", "Autosomal dominant non-syndromic sensorineural hearing loss type DFNA"], "genereviews": ["NBK1434"]}
Ventricular outflow tract obstruction Human heart SpecialtyCardiology A ventricular outflow tract obstruction is one type of congenital heart defect in which either the right or left ventricular outflow tract is blocked or obstructed. These obstructions represent a spectrum of disorders. ## Right side[edit] A right ventricular outflow tract obstruction (RVOTO) may be due to a defect in the pulmonic valve, the supravalvar region, the infundibulum, or the pulmonary artery.[1] * Pulmonary atresia * Pulmonary valve stenosis * Hypoplastic right heart syndrome * Tetralogy of Fallot ## Left side[edit] A left ventricular outflow tract obstruction (LVOTO) may be due to a defect in the aortic valve, or a defect located at the subvalvar or supravalvar level.[2] * Aortic valve stenosis * Supravalvar aortic stenosis * Coarctation of the aorta * Hypoplastic left heart syndrome ## References[edit] 1. ^ Bashore TM (2007). "Adult congenital heart disease: right ventricular outflow tract lesions". Circulation. 115 (14): 1933–1947. doi:10.1161/CIRCULATIONAHA.105.592345. PMID 17420363.CS1 maint: uses authors parameter (link) 2. ^ Gaynor JW, Elliott MJ (1993). "Congenital left ventricular outflow tract obstruction". Journal of Heart Valve Disease. 2 (1): 80–93. PMID 7505702.CS1 maint: uses authors parameter (link) * v * t * e Congenital heart defects Heart septal defect Aortopulmonary septal defect * Double outlet right ventricle * Taussig–Bing syndrome * Transposition of the great vessels * dextro * levo * Persistent truncus arteriosus * Aortopulmonary window Atrial septal defect * Sinus venosus atrial septal defect * Lutembacher's syndrome Ventricular septal defect * Tetralogy of Fallot Atrioventricular septal defect * Ostium primum Consequences * Cardiac shunt * Cyanotic heart disease * Eisenmenger syndrome Valvular heart disease Right * pulmonary valves * stenosis * insufficiency * absence * tricuspid valves * stenosis * atresia * Ebstein's anomaly Left * aortic valves * stenosis * insufficiency * bicuspid * mitral valves * stenosis * regurgitation Other * Underdeveloped heart chambers * right * left * Uhl anomaly * Dextrocardia * Levocardia * Cor triatriatum * Crisscross heart * Brugada syndrome * Coronary artery anomaly * Anomalous aortic origin of a coronary artery * Ventricular inversion This article about a medical condition affecting the circulatory system is a stub. You can help Wikipedia by expanding it. * v * t * e This article about a congenital malformation is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Ventricular outflow tract obstruction	c0035619	26,647	wikipedia	https://en.wikipedia.org/wiki/Ventricular_outflow_tract_obstruction	2021-01-18T18:37:00	{"mesh": ["D014694"], "umls": ["C0035619"], "wikidata": ["Q7920319"]}
This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (August 2015) (Learn how and when to remove this template message) Post-viral cerebellar ataxia also known as acute cerebellitis and acute cerebellar ataxia (ACA) is a disease characterized by the sudden onset of ataxia following a viral infection.[1] The disease affects the function or structure of the cerebellum region in the brain. ## Contents * 1 Diagnosis * 2 Differential diagnosis * 3 Symptoms * 4 Causes * 5 Treatment * 6 Outlook (prognosis) * 7 History * 8 See also * 9 References * 10 Further reading ## Diagnosis[edit] Since the majority of ACA cases result from a post-viral infection, the physician’s first question will be to ask if the patient has been recently ill. From this point a series of exclusion tests can determine if the current state of ataxia is a correct diagnosis or not. A CT (computed tomography) scan with normal results can rule out the possibility of the presence of a posterior fossa tumor and an acute hemorrhage, which would both have abnormal results. Other imaging tests like EEG (electroencephalographs) and MRI (magnetic resonance imaging) can also be performed to eliminate possible diagnoses of other severe diseases, such as neuroblastoma, drug intoxication, acute labyrinthitis, and metabolic diseases. A more complicated test that is performed for research analysis of the disease is to isolate viruses from the CSF (cerebrospinal fluid). This can show that the virus has attacked the nervous system of the patient and resulted in the ataxia symptoms.[citation needed] ## Differential diagnosis[edit] Differential diagnosis may include: * Opsoclonus-myoclonus-ataxia syndrome * Miller-Fisher syndrome * Meningoencephalitis * Cerebral abscess * Tumor * Hydrocephalus * Inner-ear disease * Acute vestibulitis * Acute labyrinthitis ## Symptoms[edit] Most symptoms of people with post-viral cerebellar ataxia deal to a large extent with the movement of the body. Some common symptoms that are seen are clumsy body movements and eye movements, difficulty walking, nausea, vomiting, and headaches.[citation needed] ## Causes[edit] Post-viral cerebellar ataxia is caused by damage to or problems with the cerebellum. It is most common in children, especially those younger than age 3, and usually occurs several weeks following a viral infection. Viral infections that may cause it include the following: chickenpox, Coxsackie disease (viral infection also called hand-foot-and-mouth disease), Epstein–Barr virus (a common human virus that belongs to the herpes family) and HIV.[2] ## Treatment[edit] Ataxia usually goes away without any treatment. In cases where an underlying cause is identified, medical treatment may be needed. In extremely rare cases, patients can have continuing and disabling symptoms. Treatment includes corticosteroids, intravenous immunoglobulin, or plasma exchange therapy. Drug treatment to improve muscle coordination has a low success rate. However, the following drugs may be prescribed: clonazepam, amantadine, gabapentin, or buspirone. Occupational or physical therapy may also alleviate lack of coordination. Changes to diet and nutritional supplements may also help. Treatment will depend on the cause. If the ataxia is due to bleeding, surgery may be needed. For a stroke, medication to thin the blood can be given. Infections may need to be treated with antibiotics. Steroids may be needed for swelling (inflammation) of the cerebellum (such as from multiple sclerosis). Cerebellar ataxia caused by a recent viral infection may not need treatment.[citation needed] ## Outlook (prognosis)[edit] People whose condition was caused by a recent viral infection should make a full recovery without treatment in a few months. Fine motor skills, such as handwriting, typically have to be practised in order to restore them to their former ability. In more serious cases, strokes, bleeding or infections may sometimes cause permanent symptoms.[citation needed] ## History[edit] Westphal reported the first documented case of post-viral cerebellar ataxia in 1872, where associations of reversible cerebellar syndrome were observed.[3] Another early case was documented in 1905. Batten described in detail cases of post-infectious cerebellar ataxia in five children. The cause of the disease was unknown until 1978 when Weiss and Guberman proposed that ACA could be due to direct invasion of the central nervous system by infectious agents. Since then many case studies have followed to understand the underlying conditions, symptoms and causes of the disease. The largest study of retrospective childhood ACA was done in 1994 by Connolly. This disease is still commonly used as a reference in clinical practice for other inflammatory and autoimmune disorders of the nervous system.[4] ## See also[edit] * Acute cerebellar ataxia of childhood ## References[edit] 1. ^ Nussinovitch, Moshe; Prais, Dario; Volovitz, Benjamin; Shapiro, Rivka; Amir, Jacob (2003). "Post-Infectious Acute Cerebellar Ataxia in Children". Clinical Pediatrics. 42 (7): 581–4. doi:10.1177/000992280304200702. PMID 14552515. 2. ^ Bergquist, Jennifer (September 12, 2005). "Childhood Ataxia" (PDF). University of Chicago. Archived from the original (PDF) on 10 July 2012. Retrieved 7 September 2012. 3. ^ Hinchey, Judy; Chaves, Claudia; Appignani, Barbara; Breen, Joan; Pao, Linda; Wang, Annabel; Pessin, Michael S.; Lamy, Catherine; Mas, Jean-Louis; Caplan, Louis R. (1996). "A Reversible Posterior Leukoencephalopathy Syndrome". New England Journal of Medicine. 334 (8): 494–500. doi:10.1056/NEJM199602223340803. PMID 8559202. 4. ^ Bae, Jong Seok; Kim, Byoung Joon (2005). "Cerebellar ataxia and acute motor axonal neuropathy associated with Anti GD1b and Anti GM1 antibodies". Journal of Clinical Neuroscience. 12 (7): 808–10. doi:10.1016/j.jocn.2004.09.019. PMID 16054817. ## Further reading[edit] * http://health.nytimes.com/health/guides/disease/acute-cerebellar-ataxia/overview.html[full citation needed] * https://web.archive.org/web/20111021044049/http://www.bettermedicine.com/article/cerebellar-ataxia-syndrome/symptoms%7B%7Bfull%7Cdate%3DAugust 2015}} * MedlinePlus Encyclopedia: Acute cerebellar ataxia * http://www.lifescript.com/Health/A-Z/Conditions_A-Z/Conditions/A/ Acute_cerebellar_ataxia.aspx[full citation needed] * v * t * e Symptoms and signs relating to movement and gait Gait * Gait abnormality * CNS * Scissor gait * Cerebellar ataxia * Festinating gait * Marche à petit pas * Propulsive gait * Stomping gait * Spastic gait * Magnetic gait * Truncal ataxia * Muscular * Myopathic gait * Trendelenburg gait * Pigeon gait * Steppage gait * Antalgic gait Coordination * Ataxia * Cerebellar ataxia * Dysmetria * Dysdiadochokinesia * Pronator drift * Dyssynergia * Sensory ataxia * Asterixis Abnormal movement * Athetosis * Tremor * Fasciculation * Fibrillation Posturing * Abnormal posturing * Opisthotonus * Spasm * Trismus * Cramp * Tetany * Myokymia * Joint locking Paralysis * Flaccid paralysis * Spastic paraplegia * Spastic diplegia * Spastic paraplegia * Syndromes * Monoplegia * Diplegia / Paraplegia * Hemiplegia * Triplegia * Tetraplegia / Quadruplegia * General causes * Upper motor neuron lesion * Lower motor neuron lesion Weakness * Hemiparesis Other * Rachitic rosary * Hyperreflexia * Clasp-knife response [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Post viral cerebellar ataxia	None	26,648	wikipedia	https://en.wikipedia.org/wiki/Post_viral_cerebellar_ataxia	2021-01-18T19:09:41	{"wikidata": ["Q7233757"]}
A number sign (#) is used with this entry because of evidence that cataract-36 (CTRCT36) is caused by homozygous mutation in the TDRD7 gene (611258) on chromosome 9q22. Mapping Lachke et al. (2011) ascertained a male patient (DGAP186) with juvenile cataract and hypospadias who had a de novo balanced paracentric inversion of chromosome 9, 46,XY,inv(9)(q22.33q34.11). The 9q34.11 breakpoint disrupted the gene NR5A1 (184757), which encodes the steroid nuclear receptor protein implicated in hypospadias in mouse and human mutants without cataract. Analysis of the 9q22.33 breakpoint revealed that the TDRD7 gene was disrupted, and TDRD7 haploinsufficiency was demonstrated in lymphoblastoid cells from this patient at both the RNA and protein levels. Molecular Genetics To confirm independently the involvement of TDRD7 in pediatric cataract, Lachke et al. (2011) identified a family (F3R) with autosomal recessive congenital cataract in which homozygosity mapping identified a single block of shared homozygosity between the 4 affected sibs that spanned the TDRD7 locus. Bidirectional sequencing of the TDRD7 gene uncovered a novel in-frame 3-bp deletion that removed a highly conserved amino acid, val618 (611258.0001). The val618 mutation was not identified in 320 ethnically matched controls and was predicted to disrupt the structure of TDRD7. Two of the 4 affected family members developed glaucoma with open-angle and increased intraocular pressure after cataract extraction. By homozygosity mapping of 83 Pakistani families with unmapped autosomal recessive cataract, followed by screening of 33 known candidate genes, Chen et al. (2017) identified mutations in 10 genes, including homozygosity for a frameshift mutation in the TDRD7 gene (611258.0002) in 1 family (60152). The mutation segregated with cataract in the family. It was not found in the 1000 Genomes Project or ExAC databases, and was present at a low frequency (8 x 10(-6)) in the dbSNP database. Inheritance The transmission pattern of congenital cataract in the family reported by Lachke et al. (2011) was consistent with autosomal recessive inheritance. Animal Model Lachke et al. (2011) observed that mice who were homozygous for a null mutation in TDRD7 developed congenital cataracts with lens capsule rupture and extrusion of fiber cell mass into the vitreous and eventually into the anterior chamber, causing glaucoma. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Cataract MISCELLANEOUS \- No clinical details provided MOLECULAR BASIS \- Caused by mutation in the tudor domain-containing protein 7 gene (TDRD7, 611258.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CATARACT 36	c3151304	26,649	omim	https://www.omim.org/entry/613887	2019-09-22T15:57:03	{"omim": ["613887"], "synonyms": ["Alternative titles", "CATARACT, AUTOSOMAL RECESSIVE CONGENITAL 4"]}
For a discussion of genetic heterogeneity of quantitative trait loci for stature (STQTL), see STQTL1 (606255). Mapping Sanna et al. (2008) reported extensive genomewide association studies of individuals in Finland and Sardinia that showed that common variants in the osteoarthritis-associated locus GDF5 (601146)-UQCC (611797) contribute to variation in height with an estimated additive effect of 0.44 cm. The results indicated that there may be a link between the genetic basis of height and osteoarthritis, potentially mediated through alterations in bone growth and development. To identify genetic variants influencing adult human height, Weedon et al. (2008) used genomewide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. They identified association with a SNP in the UQCC gene, rs6060373 (overall P = 1.7 x 10(-17)). In all, Weedon et al. (2008) identified 20 variants associated with adult height (p less than 5 x 10(-7), with 10 reaching p less than 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with an approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. Each of the robustly associated variants identified in the study altered height by between approximately 0.2 and 0.6 centimeters per allele. Weedon et al. (2008) noted that the rs6060373 SNP in UQCC is highly correlated (r(2) = 0.89) with a functional SNP in GDF5 (rs143383; 601146.0015) shown to alter the risk of osteoarthritis (Miyamoto et al., 2007). Weedon et al. (2008) listed GDF5 as the nearby candidate gene implicated by this SNP, based on the knockout mouse phenotype, associated monogenic human syndromes caused by mutations, and its role in bone formation. Lettre et al. (2008) carried out a metaanalysis of genomewide association study data of height for 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in greater than 10,000 subjects. A SNP in the UQCC gene, rs6060369, showed strong association (P = 1.4 x 10(-16)). Lettre et al. (2008) identified 12 loci in all that were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)) and that together accounted for approximately 2% of the population variation in height. Individuals with 8 or fewer height-increasing alleles and 16 or more height-increasing alleles differed in height by approximately 3.5 cm. The combined effect size of the rs6060369 C allele was 0.435 cm. Sanna et al. (2008) identified the rs6060369 allele in their genomewide association analysis and noted it to be in strong linkage disequilibrium with the SNP rs143383 identified by Miyamoto et al. (2007) associated with osteoarthritis (see OS5; 612400). The rs143383 A allele, associated with increased risk of osteoarthritis, was associated with a decrease in height in their studies (P = 5.01 x 10(-12)), and is also associated with decreased transcriptional activity of GDF5 in chondrogenic cells. Soranzo et al. (2009) performed a genomewide scan in 12,611 participants followed by replication in an additional 7,187 individuals. All participants were of British or Dutch descent. Soranzo et al. (2009) identified 2 SNPs in the 20q11.22 region associated with stature, rs4911494 (combined P = 1.2 x 10(-13)) and rs6088813 (combined P = 9.8 x 10(-14)). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	STATURE QUANTITATIVE TRAIT LOCUS 14	c2677124	26,650	omim	https://www.omim.org/entry/612228	2019-09-22T16:02:06	{"omim": ["612228"]}
A number sign (#) is used with this entry because X-linked cleft palate with or without ankyloglossia (CPX) is caused by mutation in the TBX22 gene (300307) on chromosome Xq21. Clinical Features In a British Columbia Indian family, Lowry (1970) found 12 males with incomplete cleft of the secondary palate. In some the cleft was submucous. Palatopharyngeal incompetence was a leading feature. The pedigree pattern suggested X-linked recessive inheritance. The high sex ratio for cleft palate in British Columbia Indians could be due to the existence of an X-linked form of submucous cleft palate (Lowry and Renwick, 1969). Lowry (1974) observed other cases born into this family. In an Italian-American kindred, Rushton (1979) reported 4 males with cleft palate in 4 generations in a typical X-linked recessive pedigree pattern. Rollnick and Kaye (1986) reported 2 families with cleft palate in a pattern consistent with X-linked recessive inheritance. Bifid uvula was found in 3 females in these families, 2 of them obligatory carriers. In family A there was an obligate affected but nonexpressing male who had 2 normal carrier daughters who had 3 affected sons. Hall (1987) described another possible instance of a nonexpressing obligate affected male in an X-linked cleft palate family. As pointed out by Rollnick and Kaye (1987), 'nonexpression' is not proved because the male in question was not examined for bifid uvula or submucous cleft palate. Bixler (1987) found 2 pedigrees consistent with X-linked inheritance among 956 Danish and 229 Indiana isolated cleft palate families. Mapping In an Icelandic kindred containing many persons with cleft palate and ankyloglossia ('tongue-tied') in an X-linked recessive pedigree pattern, Moore et al. (1987, 1988) localized the mutation to Xq13-q21 by linkage to a RFLP marker DXYS1 (lod = 3.07 at theta = about 0.0). The assignment of a cleft palate locus on the long arm of the X chromosome is supported by the finding of an interstitial deletion of Xq13-q21.3 in a male patient with cleft palate (Tabor et al., 1983). Ivens et al. (1987) found a considerable number of X-chromosome DNA markers to be absent from the DNA of a cell line derived from the patient of Tabor et al. (1983). These markers should be useful for linkage analysis in the Icelandic family in which Moore et al. (1987) demonstrated linkage to DXYS1. By the combination of deletion mapping and linkage analysis, Ivens et al. (1988) localized the X-linked cleft palate gene to a site between DXYS12 proximally and DXS17 distally. The findings were consistent with localization in Xq21. Moore et al. (1991) reported further mapping studies that placed the gene between markers DXYS12 and DXS17 (lod score = 4.1) at Xq21.3-q22. The distance between the 2 probes was estimated to be approximately 5 cM. Gorski et al. (1992) performed linkage studies in the large British Columbia Indian family first described by Lowry (1970). They found no recombination between CPX in this kindred and the DNA marker DXS72 (peak lod score = 7.44 at theta = 0.0), localized to Xq21.1. Recombination was observed between CPX and PGK1 (maximum lod = 7.35 at theta = 0.03) and between CPX and DXYS1 (maximum lod = 5.59 at theta = 0.04). Gorski et al. (1992) concluded that CPX lies between PGK1 and DXYS1 in the Xq13-q21.31 region. In further studies, Stanier et al. (1993) concluded that CPX lies within the interval Xq21.1-q21.31 between the markers DXYS1X distally and DXS326 proximally. Gorski et al. (1994) provided additional linkage analyses in the British Columbia native family and a newly identified Manitoba Mennonite family. The latter family showed mapping to the same region as in the Icelandic and B.C. families. Two-point analyses in the Manitoba family indicated a maximum lod score of 3.33 at theta = 0.0 for CPX and DXS349. A further refinement in the localization of CPX in the Icelandic kindred was provided by Forbes et al. (1995), who placed the gene in the interval between DXS95 and DXYS1X, a region estimated to be approximately 2 to 3 Mb. Forbes et al. (1996) created an approximately 3.1-Mb YAC contig for the proximal X-Y homology breakpoint within Xq21.3 and refined the map position of CPX to a region of approximately 2.0 Mb. Molecular Genetics Braybrook et al. (2001) identified 6 different missense, splice site, and nonsense mutations in the TBX22 gene (300307.0001-300307.0006) in families segregating X-linked cleft palate and ankyloglossia. Braybrook et al. (2002) reported 2 additional familial cases of cleft palate with ankyloglossia with novel missense and insertion mutations (300307.0007 and 300307.0008), each occurring within the DNA-binding T-box domain. Marcano et al. (2004) performed analysis of the TBX22 gene in a large sample of patients with cleft palate with no preselection for inheritance or ankyloglossia. They found coding mutations in 5 of 200 patients in North American and Brazilian cohorts, with an additional 4 putative splice site mutations. They also identified mutations in previously unreported CPX families (see, e.g., 300307.0004) and presented a combined genotype/phenotype analysis of previously reported familial cases. Males frequently exhibited cleft palate and ankyloglossia together (78%), as did a smaller percentage of carrier females. A range of severity was observed, including complete cleft of the secondary palate, submucous cleft, bifid uvula, absent tonsils, or high vaulted palate. Ankyloglossia was the sole phenotype in 4% of male patients and 45% of female carriers. Cleft palate was the sole presenting feature in 6% of female carriers. Not all female carriers escaped a cleft, which affected 16% regardless of tongue phenotype. Mutations within families could result in either cleft palate only, ankyloglossia only, or both, indicating that these defects are distinct parts of the phenotypic spectrum. Among 53 unrelated Thai patients with nonsyndromic cleft palate, Suphapeetiporn et al. (2007) identified 4 patients, each with a different potentially pathogenic mutation in the TBX22 gene (see, e.g., 300307.0010). Two of the patients were found to have a family history of the disorder. The authors concluded that TBX22 mutations are a cause of nonsyndromic isolated cleft palate in the Thai population. In the proband of a family segregating X-linked cleft palate, later shown to represent a branch of a family originally studied by Marcano et al. (2004), Pauws et al. (2013) identified a splice site mutation in the TBX22 gene (300307.0004). The proband had a submucous cleft palate, ankyloglossia, speech and language delay, and left-sided eustachian tube dysfunction. His carrier mother had ankyloglossia, which was widely present in the extended family; affected males in the family also had submucous or soft palate cleft. Pauws et al. (2013) also identified another TBX22 splice site mutation in a sporadic male patient with soft palate cleft and significant ankyloglossia. Neither variant was found in the dbSNP database or in 539 control chromosomes. Animal Model Barra (1990) described a new X-linked mutation in the mouse characterized by cleft palate, crooked tail, and polydactyly of the hind feet. The mutation was called ptd (for palate-tail-digits). The human CPX locus is situated proximal to the region on the X chromosome that is homologous to that on the mouse X chromosome occupied by the ptd mutation. Sponenberg and Bowling (1985) described a similar disorder in Australian shepherd dogs; the features were cleft palate, syndactyly, polydactyly, tibiofibular shortening, brachygnathism, and often scoliosis. All affected males died shortly after birth. Both the canine and the murine disorders suggest one of the otopalatodigital syndromes (311300, 303400). Pauws et al. (2009) generated a Tbx22-null mouse, which demonstrated a submucous cleft palate (SMCP) and ankyloglossia, similar to the human phenotype, with a small minority showing overt clefts. There was also persistence of the oronasal membranes or, in some mice a partial rupture, resulting in choanal atresia. Oronasal defects led to postnatal lethality in about 50% of Tbx-null mice. There was a marked reduction in intramembranous bone formation in the posterior hard palate, resulting in the classic notch associated with SMCP. Ossification was severely reduced after condensation of the palatal mesenchyme, resulting from a delay in the maturation of osteoblasts. Pauws et al. (2009) suggested that Tbx22 may play an important role in the osteogenic patterning of the posterior hard palate, rather than having a major role in palatal shelf closure. Misc \- Bifid uvula in heterozygous females Mouth \- Incomplete cleft palate \- Palatopharyngeal incompetence \- Ankyloglossia Inheritance \- X-linked ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CLEFT PALATE WITH OR WITHOUT ANKYLOGLOSSIA, X-LINKED	c1844830	26,651	omim	https://www.omim.org/entry/303400	2019-09-22T16:18:31	{"doid": ["0060613"], "mesh": ["C536426"], "omim": ["303400"], "orphanet": ["324601"], "synonyms": []}
"Hysterical blindness" redirects here. For other uses, see Hysterical blindness (disambiguation). Diagnostic category used in some psychiatric classification systems Conversion disorder Jean-Martin Charcot demonstrating hypnosis in a hysterical patient to his students. Hysteria as a clinical diagnosis was later replaced by conversion disorder SpecialtyPsychiatry SymptomsNumbness, weakness, paralysis, seizures, tremor, fainting, impaired hearing, swallowing and vision CausesLong term stress TreatmentCognitive behavioral therapy, antidepressants, physical/occupational therapy Conversion disorder (CD), or functional neurologic symptom disorder, is a diagnostic category used in some psychiatric classification systems. It is sometimes applied to patients who present with neurological symptoms, such as numbness, blindness, paralysis, or fits, which are not consistent with a well-established organic cause, which cause significant distress, and can be traced back to a psychological trigger. It is thought that these symptoms arise in response to stressful situations affecting a patient's mental health or an ongoing mental health condition such as depression. Conversion disorder was retained in DSM-5, but given the subtitle functional neurological symptom disorder. The new criteria cover the same range of symptoms, but remove the requirements for a psychological stressor to be present and for feigning to be disproved. ICD-10 classifies conversion disorder as a dissociative disorder[1] while DSM-IV classifies it as a somatoform disorder. ## Contents * 1 Signs and symptoms * 2 Diagnosis * 2.1 Definition * 2.2 Exclusion of neurological disease * 2.3 Exclusion of feigning * 2.4 Psychological mechanism * 3 Treatment * 4 Prognosis * 5 Epidemiology * 5.1 Frequency * 5.2 Culture * 5.3 Gender * 5.4 Age * 6 History * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] Conversion disorder begins with some stressor, trauma, or psychological distress. Usually the physical symptoms of the syndrome affect the senses or movement. Common symptoms include blindness, partial or total paralysis, inability to speak, deafness, numbness, difficulty swallowing, incontinence, balance problems, seizures, tremors, and difficulty walking. These symptoms are attributed to conversion disorder when a medical explanation for the afflictions cannot be found.[2] Symptoms of conversion disorder usually occur suddenly. Conversion disorder is typically seen in individuals aged 10 to 35,[3] and affects between 0.011% and 0.5% of the general population.[4] Conversion disorder can present with motor or sensory symptoms including any of the following: Motor symptoms or deficits: * Impaired coordination or balance * Weakness/paralysis of a limb or the entire body (hysterical paralysis or motor conversion disorders) * Impairment or loss of speech (hysterical aphonia) * Difficulty swallowing (dysphagia) or a sensation of a lump in the throat * Urinary retention * Psychogenic non-epileptic seizures or convulsions * Persistent dystonia * Tremor, myoclonus or other movement disorders * Gait problems (astasia-abasia) * Loss of consciousness (fainting) Sensory symptoms or deficits: * Impaired vision (hysterical blindness), double vision * Impaired hearing (deafness) * Loss or disturbance of touch or pain sensation Conversion symptoms typically do not conform to known anatomical pathways and physiological mechanisms. It has sometimes been stated that the presenting symptoms tend to reflect the patient's own understanding of anatomy and that the less medical knowledge a person has, the more implausible are the presenting symptoms.[3] However, no systematic studies have yet been performed to substantiate this statement.[citation needed] ## Diagnosis[edit] ### Definition[edit] Conversion disorder is now contained under the umbrella term functional neurological symptom disorder. In cases of conversion disorder, there is a psychological stressor. The diagnostic criteria for functional neurological symptom disorder, as set out in DSM-5, are: 1. The patient has at least one symptom of altered voluntary motor or sensory function. 2. Clinical findings provide evidence of incompatibility between the symptom and recognised neurological or medical conditions. 3. The symptom or deficit is not better explained by another medical or mental disorder. 4. The symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation. Specify type of symptom or deficit as: * With weakness or paralysis * With abnormal movement (e.g. tremor, dystonic movement, myoclonus, gait disorder) * With swallowing symptoms * With speech symptoms (e.g. dysphonia, slurred speech) * With attacks or seizures * With amnesia or memory loss * With special sensory loss symptoms (e.g. visual blindness, olfactory loss, or hearing disturbance) * With mixed symptoms. Specify if: * Acute episode: symptoms present for less than six months * Persistent: symptoms present for six months or more.[5] Specify if: * Psychological stressor (conversion disorder) * No psychological stressor (functional neurological symptom disorder) ### Exclusion of neurological disease[edit] Conversion disorder presents with symptoms that typically resemble a neurological disorder such as stroke, multiple sclerosis, epilepsy or hypokalemic periodic paralysis. The neurologist must carefully exclude neurological disease, through examination and appropriate investigations.[6] However, it is not uncommon for patients with neurological disease to also have conversion disorder.[7] In excluding neurological disease, the neurologist has traditionally relied partly on the presence of positive signs of conversion disorder, i.e. certain aspects of the presentation that were thought to be rare in neurological disease but common in conversion. The validity of many of these signs has been questioned, however, by a study showing they also occur in neurological disease.[8] One such symptom, for example, is la belle indifférence, described in DSM-IV as "a relative lack of concern about the nature or implications of the symptoms". In a later study, no evidence was found that patients with functional symptoms are any more likely to exhibit this than patients with a confirmed organic disease.[9] In DSM-V, la belle indifférence was removed as a diagnostic criteria. Another feature thought to be important was that symptoms tended to be more severe on the non-dominant (usually left) side of the body. There have been a number of theories about this, such as the relative involvement of cerebral hemispheres in emotional processing, or more simply, that it was "easier" to live with a functional deficit on the non-dominant side. However, a literature review of 121 studies established that this was not true, with publication bias the most likely explanation for this commonly held view.[10] Although agitation is often assumed to be a positive sign of conversion disorder, release of epinephrine is a well-demonstrated cause of paralysis from hypokalemic periodic paralysis.[11] Misdiagnosis does sometimes occur. In a highly influential[12] study from the 1960s, Eliot Slater demonstrated that misdiagnoses had occurred in one third of his 112 patients with conversion disorder.[13] Later authors have argued that the paper was flawed, however,[14][15] and a meta-analysis has shown that misdiagnosis rates since that paper was published are around four percent, the same as for other neurological diseases.[6] ### Exclusion of feigning[edit] Conversion disorder is unique in ICD-10 in explicitly requiring the exclusion of deliberate feigning. Unfortunately, this is likely to be demonstrable only where the patient confesses, or is "caught out" in a broader deception, such as a false identity.[16] One neuroimaging study suggested that feigning may be distinguished from conversion by the pattern of frontal lobe activation;[17] however, this was a piece of research, rather than a clinical technique. True rates of feigning in medicine remain unknown. However, it is believed that feigning of conversion disorder is no more likely than of other medical conditions.[citation needed] ### Psychological mechanism[edit] The psychological mechanism of conversion can be the most difficult aspect of a conversion diagnosis. Even if there is a clear antecedent trauma or other possible psychological trigger, it is still not clear exactly how this gives rise to the symptoms observed. Patients with medically unexplained neurological symptoms may not have any psychological stressor, hence the use of the term "functional neurological symptom disorder" in DSM-5 as opposed to "conversion disorder", and DSM-5's removal of the need for a psychological trigger. ## Treatment[edit] There are a number of different treatments available to treat and manage conversion syndrome. Treatments for conversion syndrome include hypnosis, psychotherapy, physical therapy, stress management, and transcranial magnetic stimulation. Treatment plans will consider duration and presentation of symptoms and may include one or multiple of the above treatments.[18] This may include the following:[19] 1. Explanation. This must be clear and coherent as attributing physical symptoms to a psychological cause is not accepted by many educated people in Western cultures. It must emphasize the genuineness of the condition, that it is common, potentially reversible and does not mean the sufferer is psychotic. Taking a neutral-cause-based stance by describing the symptoms as functional may be helpful, but further studies are required. Ideally, the patient should be followed up neurologically for a while to ensure the diagnosis has been understood. 2. Physiotherapy where appropriate; 3. Occupational Therapy to maintain autonomy in activities of daily living;[20] 4. Treatment of comorbid depression or anxiety if present. There is little evidence-based treatment of conversion disorder.[21] Other treatments such as cognitive behavioral therapy, hypnosis, EMDR, and psychodynamic psychotherapy, EEG brain biofeedback need further trials. Psychoanalytic treatment may possibly be helpful.[22] However, most studies assessing the efficacy of these treatments are of poor quality and larger, better controlled studies are urgently needed. Cognitive Behavioural Therapy is the most common treatment, however boasts a mere 13% improvement rate. ## Prognosis[edit] Empirical studies have found that the prognosis for conversion disorder varies widely, with some cases resolving in weeks, and others enduring for years or decades.[23][24] There is also evidence that there is no cure for conversion disorder, and that although patients may go into remission they can relapse at any point. Furthermore, many patients can get rid of their symptoms with time, treatments and reassurance. ## Epidemiology[edit] ### Frequency[edit] Information on the frequency of conversion disorder in the West is limited, in part due to the complexities of the diagnostic process. In neurology clinics, the reported prevalence of unexplained symptoms among new patients is very high (between 30 and 60%).[25][26][27] However, diagnosis of conversion typically requires an additional psychiatric evaluation, and since few patients will see a psychiatrist[28] it is unclear what proportion of the unexplained symptoms are actually due to conversion. Large scale psychiatric registers in the US and Iceland found incidence rates of 22 and 11 newly diagnosed cases per 100,000 person-years, respectively.[29] Some estimates claim that in the general population, between 0.011% and 0.5% of the population have conversion disorder.[4] ### Culture[edit] Although it is often thought that the frequency of conversion may be higher outside of the West, perhaps in relation to cultural and medical attitudes, evidence of this is limited.[30] A community survey of urban Turkey found a prevalence of 5.6%.[31] Many authors have found occurrence of conversion to be more frequent in rural, lower socio-economic groups, where technological investigation of patients is limited and individuals may be less knowledgeable about medical and psychological concepts.[29][32][33] ### Gender[edit] Historically, the concept of 'hysteria' was originally understood to be a condition exclusively affecting women, though the concept was eventually extended to men. In recent surveys of conversion disorder (formerly classified as "hysterical neurosis, conversion type"),[25][31] females predominate, with between two and six female patients for every male. ### Age[edit] Conversion disorder may present at any age but is rare in children younger than 10 years or in the elderly. Studies suggest a peak onset in the mid-to-late 30s.[25][29][31] ## History[edit] The first evidence of functional neurological symptom disorder dates back to 1900 BC, when the symptoms were blamed on the uterus moving within the female body. The treatment varied "depending on the position of the uterus, which must be forced to return to its natural position. If the uterus had moved upwards, this could be done by placing malodorous and acrid substances near the woman's mouth and nostrils, while scented ones were placed near her vagina; on the contrary, if the uterus had lowered, the document recommends placing the acrid substances near her vagina and the perfumed ones near her mouth and nostrils."[34] In Greek mythology, hysteria, the original name for functional neurological symptom disorder, was thought to be caused by a lack of orgasms, uterine melancholy and not procreating. Plato, Aristotle and Hippocrates believed a lack of sex upsets the uterus. The Greeks believed it could be prevented and cured with wine and orgies. Hippocrates argued that a lack of regular sexual intercourse led to the uterus producing toxic fumes and caused it to move in the body, and that this meant all women should be married and enjoy a satisfactory sexual life.[34] From the 13th century, women with hysteria were exorcised, as it was believed that they were possessed by the devil. It was believed that if doctors could not find the cause of a disease or illness, it must be caused by the devil.[34] At the beginning of the 16th century, women were sexually stimulated by midwives in order to relieve their symptoms. Gerolamo Cardano and Giambattista della Porta believed polluted water and fumes caused the symptoms of hysteria. Towards the end of the century, however, the role of the uterus was no longer thought central to the disorder, with Thomas Willis discovering that the brain and central nervous system were the cause of the symptoms. Thomas Sydenham argued that the symptoms of hysteria may have an organic cause. He also proved the uterus is not the cause of symptom.[34] In 1692, in the US town of Salem, Massachusetts, there was an outbreak of hysteria. This led to the Salem witch trials, where the women accused of being witches had symptoms such as sudden movements, staring eyes and uncontrollable jumping.[34] During the 18th century, there was a move from the idea of hysteria being caused by the uterus to it being caused by the brain. This led to an understanding that it could affect both sexes. Jean-Martin Charcot argued that hysteria was caused by "a hereditary degeneration of the nervous system, namely a neurological disorder".[34] In the 19th century, hysteria moved from being considered a neurological disorder to being considered a psychological disorder, when Pierre Janet argued that "dissociation appears autonomously for neurotic reasons, and in such a way as to adversely disturb the individual's everyday life".[34] However, as early as 1874, doctors including W. B. Carpenter and J. A. Omerod began to speak out against the hysteria phenomenon as there was no evidence to prove its existence.[35] Sigmund Freud referred to the condition as both hysteria and conversion disorder throughout his career. He believed those with the condition could not live in a mature relationship, and that those with the condition were unwell in order to achieve a "secondary gain", in that they are able to manipulate their situation to fit their needs or desires. He also found that both men and women could suffer from the disorder.[34] Freud's model[36] suggested the emotional charge deriving from painful experiences would be consciously repressed as a way of managing the pain, but that the emotional charge would be somehow "converted" into neurological symptoms. Freud later argued that the repressed experiences were of a sexual nature.[37] As Peter Halligan comments, conversion has "the doubtful distinction among psychiatric diagnoses of still invoking Freudian mechanisms".[38] Pierre Janet, the other great theoretician of hysteria, argued that symptoms arose through the power of suggestion, acting on a personality vulnerable to dissociation.[39] In this hypothetical process, the subject's experience of their leg, for example, is split off from the rest of their consciousness, resulting in paralysis or numbness in that leg. Later authors have attempted to combine elements of these various models, but none of them has a firm empirical basis.[40] In 1908, Steyerthal predicted that: "Within a few years the concept of hysteria will belong to history ... there is no such disease and there never has been. What Charcot called hysteria is a tissue woven of a thousand threads, a cohort of the most varied diseases, with nothing in common but the so-called stigmata, which in fact may accompany any disease."[41] However, the term "hysteria" was still being used well into the 20th century. Some support for the Freudian model comes from findings of high rates of childhood sexual abuse in conversion patients.[42] Support for the dissociation model comes from studies showing heightened suggestibility in conversion patients.[43] However, critics argue that it can be challenging to find organic pathologies for all symptoms, and so the practice of diagnosing patients who suffered with such symptoms as having hysteria led to the disorder being meaningless, vague and a sham diagnosis, as it does not refer to any definable disease.[41] Furthermore, throughout its history, many patients have been misdiagnosed with hysteria or conversion disorder when they had organic disorders such as tumours or epilepsy or vascular diseases. This has led to patient deaths, a lack of appropriate care and suffering for the patients. Eliot Slater, after studying the condition in the 1950s, stated: "The diagnosis of 'hysteria' is all too often a way of avoiding a confrontation with our own ignorance. This is especially dangerous when there is an underlying organic pathology, not yet recognised. In this penumbra we find patients who know themselves to be ill but, coming up against the blank faces of doctors who refuse to believe in the reality of their illness, proceed by way of emotional lability, overstatement and demands for attention ... Here is an area where catastrophic errors can be made. In fact it is often possible to recognise the presence though not the nature of the unrecognisable, to know that a man must be ill or in pain when all the tests are negative. But it is only possible to those who come to their task in a spirit of humility. In the main the diagnosis of 'hysteria' applies to a disorder of the doctor–patient relationship. It is evidence of non-communication, of a mutual misunderstanding ... We are, often, unwilling to tell the full truth or to admit to ignorance ... Evasions, even untruths, on the doctor's side are among the most powerful and frequently used methods he has for bringing about an efflorescence of 'hysteria'".[41] Much recent work has been done to identify the underlying causes of conversion and related disorders and to better understand why conversion disorder and hysteria appear more commonly in women. Current theoreticians tend to believe there is no single cause for these disorders. Instead, the emphasis tends to be on the individual understanding of the patient and a variety of therapeutic techniques. In some cases, the onset of conversion disorder correlates to a traumatic or stressful event. There are also certain populations that are considered at risk for conversion disorder, including people suffering from a medical illness or condition, people with personality disorder, and individuals with dissociative identity disorder.[2] However, no biomarkers have yet been found to support the idea that conversion disorder is caused by a psychiatric condition. There has been much recent interest in using functional neuroimaging to study conversion. As researchers identify the mechanisms which underlie conversion symptoms, it is hoped they will enable the development of a neuropsychological model. A number of such studies have been performed, including some which suggest the blood-flow in patients' brains may be abnormal while they are unwell. However, the studies have all been too small to be confident of the generalisability of their findings, so no neuropsychological model has been clearly established. An evolutionary psychology explanation for conversion disorder is that the symptoms may have been evolutionarily advantageous during warfare. A non-combatant with these symptoms signals non-verbally, possibly to someone speaking a different language, that she or he is not dangerous as a combatant and also may be carrying some form of dangerous infectious disease. This can explain that conversion disorder may develop following a threatening situation, that there may be a group effect with many people simultaneously developing similar symptoms (as in mass psychogenic illness), and the gender difference in prevalence.[44] The Lacanian model accepts conversion disorder as a common phenomenon inherent in specific psychical structures. The higher prevalence of it among women is based on somewhat different intrapsychic relations to the body from those of typical males, which allows the formation of conversion symptoms.[45] ## See also[edit] * Body-centred countertransference * Hysterical contagion * Mass hysteria * Posttraumatic stress disorder (PTSD) and Complex posttraumatic stress disorder (C-PTSD) * Somatization disorder * Functional neurological symptom disorder ## References[edit] 1. ^ International Statistical Classification of Diseases and Related Health Problems, 10th Revision. F44.9 2. ^ a b "Conversion disorder". National Center for Biotechnology Information, U.S. National Library of Medicine. 2012-11-17. Retrieved 25 October 2013. 3. ^ a b Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, American Psychiatric Association 4. ^ a b Tollison, C. David; Satterthwaite, John R.; Tollison, Joseph W. (2002-01-01). Practical Pain Management. Lippincott Williams & Wilkins. ISBN 9780781731607. 5. ^ "Conversion and somatic symptom disorders". Retrieved 25 November 2015. 6. ^ a b Stone J, Carson A, Sharpe M (2005). "Functional symptoms and signs in neurology: assessment and diagnosis". J. Neurol. Neurosurg. Psychiatry. 76 Suppl 1: i2–12. doi:10.1136/jnnp.2004.061655. PMC 1765681. PMID 15718217. 7. ^ Eames P (1992). "Hysteria following brain injury". J. Neurol. Neurosurg. Psychiatry. 55 (11): 1046–53. doi:10.1136/jnnp.55.11.1046. PMC 1015291. PMID 1469401. 8. ^ Gould R, Miller BL, Goldberg MA, Benson DF (1986). "The validity of hysterical signs and symptoms". J. Nerv. Ment. Dis. 174 (10): 593–7. doi:10.1097/00005053-198610000-00003. PMID 3760849. 9. ^ Stone J, Smyth R, Carson A, Warlow C, Sharpe M (2006). "La belle indifférence in conversion symptoms and hysteria: systematic review". Br J Psychiatry. 188: 204–9. doi:10.1192/bjp.188.3.204. PMID 16507959. 10. ^ Stone J, Sharpe M, Carson A, Lewis SC, Thomas B, Goldbeck R, Warlow CP (2002). "Are functional motor and sensory symptoms really more frequent on the left? A systematic review". J. Neurol. Neurosurg. Psychiatry. 73 (5): 578–81. doi:10.1136/jnnp.73.5.578. PMC 1738113. PMID 12397155. 11. ^ "Segal MM, Jurkat-Rott K, Levitt J, Lehmann-Horn F, Hypokalemic periodic paralysis—an owner's manual". Uni-ulm.de. 2009-06-05. Retrieved 2013-11-30. 12. ^ Slater E (1965). "Diagnosis of Hysteria". Br Med J. 1 (5447): 1395–9. doi:10.1136/bmj.1.5447.1395. PMC 2166300. PMID 14286998. 13. ^ Slater ET, Glithero E (1965). "A follow-up of patients diagnosed as suffering from "hysteria"". J Psychosom Res. 9 (1): 9–13. doi:10.1016/0022-3999(65)90004-8. PMID 5857619. 14. ^ Stone J, Warlow C, Carson A, Sharpe M (2005). "Eliot Slater's myth of the non-existence of hysteria". J R Soc Med. 98 (12): 547–8. doi:10.1258/jrsm.98.12.547. PMC 1299341. PMID 16319432. 15. ^ Ron M, "The Prognosis of Hysteria" In P. Halligan, C. Bass, J. Marshall (Eds.) Hysterical Conversion: clinical and theoretical perspectives (pp. 73–87). Oxford: Oxford University Press. 16. ^ Krahn LE, Li H, O'Connor MK (2003). "Patients who strive to be ill: factitious disorder with physical symptoms". Am J Psychiatry. 160 (6): 1163–8. doi:10.1176/appi.ajp.160.6.1163. PMID 12777276. 17. ^ Spence SA, Crimlisk HL, Cope H, Ron MA, Grasby PM (2000). "Discrete neurophysiological correlates in prefrontal cortex during hysterical and feigned disorder of movement". Lancet. 355 (9211): 1243–4. doi:10.1016/S0140-6736(00)02096-1. PMID 10770312. 18. ^ "Conversion disorder". Mayo Foundation for Medical Education and Research. Retrieved 25 October 2013. 19. ^ Stone J, Carson A, Sharpe M (2005). "Functional symptoms in neurology: management". J. Neurol. Neurosurg. Psychiatry. 76 Suppl 1: i13–21. doi:10.1136/jnnp.2004.061663. PMC 1765682. PMID 15718216. 20. ^ http://www.doctorsofusc.com/condition/document/96743[permanent dead link] 21. ^ Ganslev, Christina A.; Storebø, Ole Jakob; Callesen, Henriette E.; Ruddy, Rachel; Søgaard, Ulf (17 July 2020). "Psychosocial interventions for conversion and dissociative disorders in adults". The Cochrane Database of Systematic Reviews. 7: CD005331. doi:10.1002/14651858.CD005331.pub3. ISSN 1469-493X. PMC 7388313. PMID 32681745. 22. ^ Feinstein A (2011). "Conversion disorder: advances in our understanding". CMAJ. 183 (8): 915–20. doi:10.1503/cmaj.110490. PMC 3091899. PMID 21502352. 23. ^ Mace, CJ; Trimble, MR (September 1996). "Ten-year prognosis of conversion disorder". The British Journal of Psychiatry. 169 (3): 282–8. doi:10.1192/bjp.169.3.282. PMID 8879713. 24. ^ Couprie, W; Wijdicks, EF; Rooijmans, HG; van Gijn, J (June 1995). "Outcome in conversion disorder: a follow up study". Journal of Neurology, Neurosurgery, and Psychiatry. 58 (6): 750–2. doi:10.1136/jnnp.58.6.750. PMC 1073562. PMID 7608683. 25. ^ a b c Carson AJ, Ringbauer B, Stone J, McKenzie L, Warlow C, Sharpe M (2000). "Do medically unexplained symptoms matter? A prospective cohort study of 300 new referrals to neurology outpatient clinics". J. Neurol. Neurosurg. Psychiatry. 68 (2): 207–10. doi:10.1136/jnnp.68.2.207. PMC 1736779. PMID 10644789. 26. ^ Nimnuan C, Hotopf M, Wessely S (2001). "Medically unexplained symptoms: an epidemiological study in seven specialities". J Psychosom Res. 51 (1): 361–7. doi:10.1016/s0022-3999(01)00223-9. PMID 11448704. 27. ^ Snijders TJ, de Leeuw FE, Klumpers UM, Kappelle LJ, van Gijn J (2004). "Prevalence and predictors of unexplained neurological symptoms in an academic neurology outpatient clinic—an observational study". J. Neurol. 251 (1): 66–71. doi:10.1007/s00415-004-0273-y. PMID 14999491. 28. ^ Crimlisk HL, Bhatia KP, Cope H, David AS, Marsden D, Ron MA (2000). "Patterns of referral in patients with medically unexplained motor symptoms". J Psychosom Res. 49 (3): 217–9. doi:10.1016/s0022-3999(00)00167-7. PMID 11110993. 29. ^ a b c Stefánsson JG, Messina JA, Meyerowitz S (1976). "Hysterical neurosis, conversion type: clinical and epidemiological considerations". Acta Psychiatr Scand. 53 (2): 119–38. doi:10.1111/j.1600-0447.1976.tb00066.x. PMID 1251758. 30. ^ Akagi, H. & House, A.O., 2001, "The epidemiology of hysterical conversion". In P. Halligan, C. Bass, J. Marshall (Eds.) Hysterical Conversion: clinical and theoretical perspectives (pp. 73–87). Oxford: Oxford University Press. 31. ^ a b c Deveci A, Taskin O, Dinc G, Yilmaz H, Demet MM, Erbay-Dundar P, Kaya E, Ozmen E (2007). "Prevalence of pseudoneurologic conversion disorder in an urban community in Manisa, Turkey". Soc Psychiatry Psychiatr Epidemiol. 42 (11): 857–64. doi:10.1007/s00127-007-0233-9. PMID 17639308. 32. ^ Tomasson K, Kent D, Coryell W (1991). "Somatization and conversion disorders: comorbidity and demographics at presentation". Acta Psychiatr Scand. 84 (3): 288–93. doi:10.1111/j.1600-0447.1991.tb03146.x. PMID 1950631. 33. ^ Kuloglu M, Atmaca M, Tezcan E, Gecici O, Bulut S (2003). "Sociodemographic and clinical characteristics of patients with conversion disorder in Eastern Turkey". Soc Psychiatry Psychiatr Epidemiol. 38 (2): 88–93. doi:10.1007/s00127-003-0608-5. PMID 12563551. 34. ^ a b c d e f g h Tasca, Cecilia; Rapetti, Mariangela; Carta, Mauro Giovanni; Fadda, Bianca (2012-10-19). "Women And Hysteria In The History Of Mental Health". Clinical Practice and Epidemiology in Mental Health. 8: 110–119. doi:10.2174/1745017901208010110. ISSN 1745-0179. PMC 3480686. PMID 23115576. 35. ^ Webster, Richard. "The hysteria diagnosis: Freud, Charcot, Breuer and Anna O". www.richardwebster.net. Retrieved 2016-02-29. 36. ^ Josef Breuer & Sigmund Freud, Studies in Hysteria, 1895 37. ^ Freud S (1905). Fragment of an analysis of a case of hysteria. 38. ^ Halligan PW, Bass C, Wade DT (2000). "New approaches to conversion hysteria". BMJ. 320 (7248): 1488–9. doi:10.1136/bmj.320.7248.1488. PMC 1118088. PMID 10834873. 39. ^ Janet P (1920). The Major Symptoms of Hysteria (2nd ed.). 40. ^ Brown RJ (2004). "Psychological mechanisms of medically unexplained symptoms: an integrative conceptual model". Psychol Bull. 130 (5): 793–812. doi:10.1037/0033-2909.130.5.793. PMID 15367081. 41. ^ a b c Webster, Richard. "Sigmund Freud: hysteria, somatization, medicine and misdiagnosis". www.richardwebster.net. Retrieved 2016-02-21. 42. ^ Roelofs K, Keijsers GP, Hoogduin KA, Näring GW, Moene FC (2002). "Childhood abuse in patients with conversion disorder". Am J Psychiatry. 159 (11): 1908–13. doi:10.1176/appi.ajp.159.11.1908. hdl:1887/14240. PMID 12411227. S2CID 24809182. 43. ^ Roelofs K, Hoogduin KA, Keijsers GP, Näring GW, Moene FC, Sandijck P (2002). "Hypnotic susceptibility in patients with conversion disorder". J Abnorm Psychol. 111 (2): 390–5. doi:10.1037//0021-843x.111.2.390. hdl:1887/14289. PMID 12003460. 44. ^ Bracha HS (2006). "Human brain evolution and the "Neuroevolutionary Time-depth Principle:" Implications for the Reclassification of fear-circuitry-related traits in DSM-V and for studying resilience to warzone-related posttraumatic stress disorder" (PDF). Progress in Neuro-Psychopharmacology and Biological Psychiatry. 30 (5): 827–853. doi:10.1016/j.pnpbp.2006.01.008. PMC 7130737. PMID 16563589. 45. ^ Fink B (2000). A Clinical Introduction to Lacanian Psychoanalysis: Theory and Technique (3 ed.). Cambridge, Mass.: Harvard University Press. ISBN 978-0674135369. ## External links[edit] Classification D * ICD-10: F44 * ICD-9-CM: 300.11 * MeSH: D003291 * DiseasesDB: 1645 External resources * MedlinePlus: 000954 * eMedicine: emerg/112 med/1150 * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Conversion disorder	c0009946	26,652	wikipedia	https://en.wikipedia.org/wiki/Conversion_disorder	2021-01-18T19:05:43	{"gard": ["6191"], "mesh": ["D003291"], "umls": ["C0009946"], "wikidata": ["Q1051355"]}
A number sign (#) is used with this entry because Treacher Collins syndrome-1 (TCS1) is caused by heterozygous mutation in the 'treacle' gene (TCOF1; 606847) on chromosome 5q32. Description Treacher Collins syndrome is a disorder of craniofacial development. The features include antimongoloid slant of the eyes, coloboma of the lid, micrognathia, microtia and other deformity of the ears, hypoplastic zygomatic arches, and macrostomia. Conductive hearing loss and cleft palate are often present (Dixon, 1996). ### Genetic Heterogeneity of Treacher Collins Syndrome Treacher Collins syndrome-2 (TCS2; 613717) is caused by mutation in the POLR1D gene (613715) on chromosome 13q12. Treacher Collins syndrome-3 (TCS3; 248390) is caused by mutation in the POLR1C gene (610060) on chromosome 6p21. Clinical Features In 2 sisters in an inbred Hutterite kindred, Lowry et al. (1985) described mandibulofacial dysostosis and raised the question of an autosomal recessive form of Treacher Collins syndrome. The palpebral fissures were downward slanting, the outer third of the lower lids showed coloboma, and malar hypoplasia and abnormal pinnae were present. The parents had no signs of mandibulofacial dysostosis. Intraorbital hollowness and prominent ears in the father were considered familial traits. The father and relatives in 3 generations had an apparently isolated dental anomaly characterized by small, widely spaced primary teeth and complete lack of secondary dentition. This appeared to be an independent, autosomal dominant trait. In a 13-month-old girl who had been diagnosed with Treacher Collins syndrome at 1 month of age, Biebesheimer and Fredrick (2004) reported delayed-onset infantile cataracts. Teber et al. (2004) identified TCOF1 mutations in 28 of 36 (78%) patients with a clinically unequivocal diagnosis of TCS. The most frequent findings were downward-slanting palpebral fissures, hypoplasia of the zygomatic complex, hypoplasia of the mandible, conductive deafness, any degree of microtia, and atresia of the external ear canal. Although there was inter- and intrafamilial variation ranging from mild to severe, there were no genotype/phenotype correlations. Four clinically unaffected parents were heterozygous for the TCOF1 mutation. Teber et al. (2004) concluded that modifying factors are important for phenotypic expression. Li et al. (2009) described a patient with Treacher Collins syndrome who had additional features including encephalocele, marked malformation of the eyes, and several extracraniofacial anomalies that involved the thyroid, the thymus, the heart, an accessory spleen, ectopic adrenal gland tissue, and underdeveloped external genitalia. Vincent et al. (2016) compared the clinical features of their patients with TCS1 with those reported in the literature. In their 70 patients, they reported a frequency of 100% downward-slanting palpebral fissures; 99% malar hypoplasia; 91% conductive deafness; 87% mandibular hypoplasia; 72% had atresia of external ear canal; 71% microtia; 65% coloboma of the lower eyelid; 53% asymmetry; 48% projection of scalp hair onto the lateral cheek; 22% cleft palate; 14% choanal stenosis/atresia; 12% cardiac malformation. Brain, kidney, and limb anomalies were rare. Inheritance Treacher Collins syndrome 1 is an autosomal dominant disorder (Dixon, 1996), with variable expression (Edery et al., 1994). Rovin et al. (1964) observed 14 affected persons in 5 generations of a Kentucky family. Intrafamilial variation was wide. Intersib variation was small. There seemed to be a significant increase in affected offspring from affected females and a decrease in affected offspring from affected males. Fazen et al. (1967) described 10 affected persons in 4 generations. (They hyphenated Treacher Collins, which is not proper since Treacher was one of Dr. Collins's given names.) Jones et al. (1975) found evidence of paternal age effect in new mutations for this disorder. Hansen et al. (1996) observed extreme expression of Treacher Collins syndrome in a male infant with arhinia, anotia, absent zygomatic bones, hypoplastic mandibular rami, and bilateral coloboma of iris, choroid plexus, and optic nerve. The Treacher Collins phenotype was mildly expressed in the mother and moderately in a sister. The father had no signs and was not excluded as the father by DNA fingerprinting, thus making homozygosity by descent in the severely affected son very unlikely. In 10 cases of sporadic Treacher Collins syndrome, Splendore et al. (2003) determined that the pathogenic mutation was of paternal origin in 7 cases and maternal in 3. There was no preferential origin of new mutations in male gametogenesis, and there was no detectable parental age effect. Based on the finding of Treacher Collins syndrome in 2 Hutterite sisters whose parents were apparently unaffected, Lowry et al. (1985) had suggested either autosomal recessive inheritance or another explanation such as germinal mosaicism, chromosome rearrangement, or delayed mutation. Caluseriu et al. (2013) restudied the 2 Hutterite sisters as well as another Hutterite woman with TCS and found that the patients had classic TCS due to heterozygous mutation in the TCOF1 gene (see MOLECULAR GENETICS). The mutation present in the sisters was also found in their unaffected father, suggesting incomplete penetrance of the disorder. Diagnosis ### Differential Diagnosis Treacher Collins syndrome should not be confused with similar entities such as oculoauriculovertebral dysplasia, or Goldenhar syndrome (164210). Coloboma is present in the lower eyelid in Treacher Collins syndrome and in the upper eyelid in Goldenhar syndrome. ### Prenatal Diagnosis Crane and Beaver (1986) diagnosed this disorder by ultrasonography in a midtrimester fetus. Edwards et al. (1996) used 7 short tandem repeat polymorphic probes closely linked to the TCOF1 locus for prenatal diagnosis of the Treacher Collins syndrome in the fetus of an affected father. A chorionic villus sample was used as a source of fetal DNA. The at-risk fetus, his father, and half sister shared the same haplotype, indicating a very high probability that the fetus inherited the TCOF1 gene. Ultrasound examination at 20 weeks of gestation confirmed the diagnosis. Heterogeneity Arn et al. (1993) suggested that mandibulofacial dysostosis is a heterogeneous entity and that evaluation and counseling of affected persons should be undertaken with caution. Jabs et al. (1991) studied 8 affected families and concluded that there was no evidence for genetic heterogeneity among the 8 families despite variable expression of the disorder. Edery et al. (1994) provided further evidence of genetic homogeneity using linkage analysis in 8 affected families. Splendore et al. (2000) found that 2 of 28 families with Treacher Collins did not show apparent pathogenic mutation in the TCOF1 gene (606847). They suggested a possible different mechanism leading to Treacher Collins syndrome or genetic heterogeneity for this condition. The data confirmed the absence of genotype-phenotype correlation and reinforced the conclusion that the apparent anticipation often observed in Treacher Collins syndrome families is due to ascertainment bias. Pathogenesis Wise et al. (1997) postulated that the disorder results from defects in a nucleolar trafficking protein that is critically required during human craniofacial development. Marsh et al. (1998) suggested that the disorder results from aberrant expression of a nucleolar protein. They observed that mutations in the TCOF1 gene (606847) cause truncated proteins to be mislocalized within the cell. Lungarotti et al. (1987) described changes strikingly similar to those of vitamin A toxicity in both animals and humans in an infant born of a mother who took 2000 IU of vitamin A daily as a supplement during pregnancy. Facial changes resembled those of mandibulofacial dysostosis. Lungarotti et al. (1987) speculated that the mother might have had hypersensitivity to vitamin A. Calo et al. (2018) demonstrated that genetic perturbations associated with Treacher Collins syndrome lead to relocalization of DDX21 (606357) from the nucleolus to the nucleoplasm, its loss from chromatin targets, and inhibition of ribosomal RNA (rRNA) processing and downregulation of ribosomal protein gene transcription. These effects are cell type-selective, cell autonomous, and involve activation of p53 (191170) tumor suppressor protein. Calo et al. (2018) further showed that cranial neural crest cells are sensitized to p53-mediated apoptosis, but blocking DDX21 loss from the nucleolus and chromatin rescues both the susceptibility to apoptosis and the craniofacial phenotypes associated with Treacher Collins syndrome. This mechanism was not restricted to cranial neural crest cells, as blood formation was also hypersensitive to loss of DDX21 functions. Accordingly, ribosomal gene perturbations associated with Diamond-Blackfan anemia (105650) disrupted DDX21 localization. At the molecular level, Calo et al. (2018) demonstrated that impaired rRNA synthesis elicits a DNA damage response, and that ribosomal DNA damage results in tissue-selective and dosage-dependent effects on craniofacial development. Calo et al. (2018) concluded that their findings illustrated how disruption in general regulators that compromise nucleolar homeostasis can result in tissue-selective malformations. Mapping Balestrazzi et al. (1983) described Treacher Collins syndrome in a girl with a de novo balanced translocation t(5;13)(q11;p11). The level of hexosaminidase B was decreased; the HEXB locus is thought to be at 5q13. The possibility that the Treacher Collins locus is on 5q was raised by these findings. Arn et al. (1993) described a mild but entirely typical case of Treacher Collins syndrome in association with a small interstitial deletion of 3p: 46,XY,del(3)(p23p24.12). By the time Arn et al. (1993) reported this case, the TCS locus in familial cases had been assigned to 5q31.3. Because of the report by Balestrazzi et al. (1983) of a de novo balanced translocation involving chromosome 5 in a girl with the Treacher Collins syndrome, Jabs et al. (1991) studied linkage with chromosome 5 markers in 8 families with the disorder. They demonstrated positive lod scores with 4 loci which mapped to 5q31.3-q33.3. The most closely linked locus was D5S210, which is associated with a microsatellite polymorphism; maximum lod score = 8.65 at theta = 0.02. Dixon et al. (1991) demonstrated linkage of the TCS locus to markers in the region 5q31-q34. They concluded that it probably lies in the interval between the GRL locus (138040) and the anonymous marker D5S22. Dixon et al. (1992) refined the localization by linkage studies using hypervariable microsatellite markers and by fluorescence in situ hybridization. They concluded that the gene is in 5q32-q33.2 and described flanking markers. By linkage to 3 microsatellite markers, Dixon et al. (1993) further refined the assignment to 5q32-q33.1. Fluorescence in situ hybridization of a linked clone indicated that TCOF1 is flanked distally by SPARC (182120). Studying 8 independent families and using 12 microsatellite DNA markers at distal 5q, Edery et al. (1994) placed the TCOF1 locus between D5S434 and D5S412, thus corroborating the earlier linkage analyses. Molecular Genetics Dixon (1996) reviewed the clinical and molecular features of Treacher Collins syndrome. A total of 20 mutations in the TCOF1 gene (606847) had been identified, of which 2 were nonsense mutations, 5 were insertions, 11 were deletions, and 2 were splicing mutations. All of the mutations observed resulted in introduction of premature termination codons into the reading frame, suggesting haploinsufficiency as the molecular mechanism underlying the disorder. Edwards et al. (1997) reported 25 previously undescribed mutations throughout the TCOF1 gene in patients with Treacher Collins syndrome. This brought the total reported mutations to 35, which represented a detection rate of 60%. All but one of the mutations resulted in the introduction of a premature termination codon into the predicted protein. The mutational spectrum supported the hypothesis that TCS results from haploinsufficiency. In a 5-year-old girl with classic findings of Treacher Collins syndrome and craniosynostosis, choanal atresia, and esophageal regurgitation, Horiuchi et al. (2004) identified a de novo truncating mutation in exon 17 of the TCOF1 gene (606847.0007). The authors stated that this was the first case of Treacher Collins syndrome with molecular confirmation and craniosynostosis. Li et al. (2009) identified a pathogenic mutation in the TCOF1 gene (606847.0009) in a patient with Treacher Collins syndrome who had novel craniofacial and extracranial features. Bowman et al. (2012) identified pathogenic sequence variants in the TCOF1 gene in 92 (50.5%) of 182 unrelated patients with a clinical diagnosis consistent with Treacher Collins syndrome. Of those with a sequence change, 57% had a frameshift or mutation disrupting the start codon, 23% had a nonsense mutation, 16% had a splice site mutation, and 4% had a missense mutation. In addition, 5.2% of patients had an intragenic deletion of the TCOF1 gene. Thus, the majority of TCOF1 mutations lead to a loss of protein function and haploinsufficiency. In 2 Hutterite sisters with Treacher Collins syndrome, originally reported by Lowry et al. (1985) and thought to have an autosomal recessive form of the disorder, and in another Hutterite woman with TCS, Caluseriu et al. (2013) identified heterozygosity for 2 mutations in the TCOF1 gene, a previously reported 4-bp deletion (606847.0010) and a novel 1-bp duplication (606847.0011). The deletion mutation, which was found in both sisters, was also present in their unaffected father, supporting incomplete penetrance of the disorder. Vincent et al. (2016) performed extensive clinical and molecular studies in 146 Treacher Collins patients. They identified a mutation in TCOF1 in 92 of 146 (63%) and a pathogenic variant in POLR1D in 9 of 146 (6%). No patient had a variant in POL1C. Among the atypical negative patients (with intellectual disability or microcephaly), Vincent et al. (2016) identified 4 carrying a mutation in EFTUD2 (603892) and 2 with a 5q32 deletion encompassing TCOF1 and CAMK2A. Population Genetics Caluseriu et al. (2013) stated that the incidence of Treacher Collins syndrome is thought to be 1 in 50,000 individuals. History Dixon et al. (1991) identified a family in which a mother and 2 children who had the Treacher Collins syndrome also had a balanced translocation t(6;16)(p21.31;p13.11), which suggested the possibility that the mutation might be located at one of the translocation breakpoints. By in situ hybridization, they defined probes located at these breakpoints and then, by linkage analysis using these chromosome 6 and chromosome 16 probes in 12 other families with multiple cases of the Treacher Collins syndrome, excluded the TCS locus from proximity to either translocation breakpoint. The data were confirmed when a third affected child, who did not exhibit the translocation, was born to the mother of their index family. Jabs et al. (1991) observed a patient with severe manifestations of TCS and a de novo chromosomal deletion in region 4p15.32-p14. Several previously identified anonymous DNA sequences were mapped to the deleted region and several were excluded from the region, on the basis of being deleted or not deleted, respectively. Linkage analysis between 3 of these markers and TCS in 8 multiplex families excluded the TCS gene from this region. Animal Model Sulik et al. (1987) suggested that the malformations produced in mice by isotretinoin represent a useful model for the pathogenesis of Treacher Collins syndrome. Richter et al. (2010) used Tcof1 mutant mice to dissect the developmental mechanisms underlying congenital hearing loss. Effective cavitation of the middle ear was intimately linked to growth of the auditory bulla, the neural crest cell-derived structure that encapsulates all middle ear components, and defects in these processes had a profoundly detrimental effect on hearing. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Malar hypoplasia \- Projection of scalp hair onto the lateral cheek Ears \- Malformation of auricle \- Hearing loss, conductive \- Ear tags \- Blind fistulas Eyes \- Downslanting palpebral fissures \- Lower eyelid coloboma \- Partial absence of lower eyelashes Mouth \- Cleft palate (rare) \- Palatopharyngeal incompetence \- Mandibular hypoplasia \- Macrostomia MOLECULAR BASIS \- Caused by mutation in the treacle gene (TCOF1, 154500.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	TREACHER COLLINS SYNDROME 1	c0242387	26,653	omim	https://www.omim.org/entry/154500	2019-09-22T16:38:34	{"doid": ["2908"], "mesh": ["D008342"], "omim": ["154500"], "icd-10": ["Q75.4"], "orphanet": ["861"], "synonyms": ["Alternative titles", "TREACHER COLLINS-FRANCESCHETTI SYNDROME", "TREACHER COLLINS SYNDROME", "MANDIBULOFACIAL DYSOSTOSIS"], "genereviews": ["NBK1532"]}
A rare systemic disease characterized by progressive hyalinosis involving capillaries, arterioles and small veins of the digestive tract, kidneys, and retina, associated with idiopathic cerebral calcifications, manifesting with severe diarrhea (with rectal bleeding and malabsorption), nephropathy (with renal failure and systemic hypertension), chorioretinal scarring, and subarachnoid hemorrhage. Poikiloderma and premature greying of the hair may be additionally observed. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Retinal ischemic syndrome-digestive tract small vessel hyalinosis-diffuse cerebral calcifications syndrome	c2930864	26,654	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3018	2021-01-23T17:59:34	{"gard": ["4635"], "mesh": ["C535283"], "omim": ["277175"], "umls": ["C2930864"], "icd-10": ["E78.8"], "synonyms": ["Rambaud-Gallian syndrome", "Rambaud-Gallian-Touchard syndrome"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Arrhythmogenic cardiomyopathy" – news · newspapers · books · scholar · JSTOR (February 2009) (Learn how and when to remove this template message) Arrhythmogenic cardiomyopathy Other namesarrhythmogenic right ventricular cardiomyopathy (ARVC), arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), right ventricular dysplasia Photomicrograph of an ACM heart. SpecialtyCardiology Arrhythmogenic cardiomyopathy (ACM), arrhythmogenic right ventricular dysplasia (ARVD), or arrhythmogenic right ventricular cardiomyopathy (ARVC), is an inherited heart disease.[1] ACM is caused by genetic defects of the parts of heart muscle (also called myocardium or cardiac muscle) known as desmosomes, areas on the surface of heart muscle cells which link the cells together. The desmosomes are composed of several proteins, and many of those proteins can have harmful mutations. The disease is a type of non-ischemic cardiomyopathy that primarily involves the right ventricle, though cases of exclusive left ventricular disease have been reported. It is characterized by hypokinetic areas involving the free wall of the ventricle, with fibrofatty replacement of the myocardium, with associated arrhythmias often originating in the right ventricle. The nomenclature ARVD is currently thought to be inappropriate and misleading as ACM does not involve dysplasia of the ventricular wall. Cases of ACM originating from the left ventricle led to the abandonment of the name ARVC. ACM can be found in association with diffuse palmoplantar keratoderma, and woolly hair, in an autosomal recessive condition called Naxos disease, because this genetic abnormality can also affect the integrity of the superficial layers of the skin most exposed to pressure stress.[2]:513[3] ACM is an important cause of ventricular arrhythmias in children and young adults. It is seen predominantly in males, and 30–50% of cases have a familial distribution. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Pathogenesis * 3.1 Fatty infiltration * 3.2 Fibro-fatty infiltration * 3.3 The Role of Exercise * 4 Ventricular arrhythmias * 5 Diagnosis * 5.1 Electrocardiogram * 5.2 Echocardiography * 5.3 MRI * 5.4 Angiography * 5.5 Biopsy * 5.6 Genetic testing * 5.7 Diagnostic criteria * 6 Management * 6.1 Medications * 6.2 Catheter ablation * 6.3 Implantable cardioverter-defibrillator * 6.4 Heart transplant * 6.5 Family screening * 7 Prognosis * 8 Epidemiology * 9 Notable cases * 10 See also * 11 References * 12 External links ## Signs and symptoms[edit] Those affected by arrhythmogenic cardiomyopathy may not have any symptoms at all despite having significant abnormalities in the structure of their hearts.[4] If symptoms do occur, the initial presentation is often due to abnormal heart rhythms (arrhythmias) which in arrhythmogenic cardiomyopathy may take the form of palpitations, or blackouts.[5] Sudden death may be the first presentation of ACM without any preceding symptoms.[4] These symptoms often occur during adolescence and early adulthood, but signs of ACM may rarely be seen in infants. As ACM progresses, the muscle tissue within the ventricles may dilate and weaken. The right ventricle typically weakens first, leading to fatigue and ankle swelling. In the later stages of the disease in which both ventricles are involved shortness of breath may develop, especially when lying flat.[4] The first clinical signs of ACM are usually during adolescence and early adulthood. However, rarely, signs of ACM have been demonstrated in infants. ## Genetics[edit] ACM is usually inherited in an autosomal dominant pattern, with variable expression. Only 30% to 50% of individuals affected by ACM will test positive to one of the known genetic mutations in chromosomal loci associated with the disease.[6][7] Novel studies showed that mutations (point mutations) in genes encoding for desmosomal proteins (see intercalated disc) are the main causatives for the development of this disease. Recently it has been shown, that mutations in the desmin DES gene could cause ACM.[8] Desmin is an intermediate filament protein, which is linked to the desmosomes. Different DES mutations cause an abnormal aggregation of desmin and associated proteins.[9] The penetrance is 20–35% in general, but significantly higher in Italy. Seven gene loci have been implicated in ACM. It is unclear whether the pathogenesis varies with the different loci involved. Standard genetic screening test are currently tested and evaluated in different state of the art cardiovascular research centres and hospitals. Types include: Type OMIM Gene Locus Reference ARVD1lpl 107970 TGFB3 14q23-q24 [10] ARVD2 600996 RYR2 1q42-q43 [11] ARVD3 602086 ? 14q12-q22 ARVD4 602087 ? 2q32.1-q32.3 ARVD5 604400 TMEM43 3p23 [12][13] ARVD6 604401 ? 10p14-p12 ARVD7 609160 DES 10q22.3 [14][15] ARVD8 607450 DSP 6p24 [16] ARVD9 609040 PKP2 12p11 [17] ARVD10 610193 DSG2 18q12.1-q12 [18][19] ARVD11 610476 DSC2 18q12.1 [20][21] ARVD12 611528 JUP 17q21 [22][23] ILK 11p15.4 [24] LMNA [25] ## Pathogenesis[edit] The pathogenesis of ACM is largely unknown. Apoptosis (programmed cell death) appears to play a large role. It was previously thought that only the right ventricle is involved, but recent cohorts have shown many cases of left ventricular disease and biventricular disease. The disease process starts in the subepicardial region and works its way towards the endocardial surface, leading to transmural involvement (possibly accounting for the aneurysmal dilatation of the ventricles). Residual myocardium is confined to the subendocardial region and the trabeculae of the ventricles. These trabeculae may become hypertrophied. Aneurysmal dilatation is seen in 50% of cases at autopsy. It usually occurs in the diaphragmatic, apical, and infundibular regions (known as the triangle of dysplasia). The left ventricle is involved in 50–67% of individuals. If the left ventricle is involved, it is usually late in the course of disease, and confers a poor prognosis. There are two pathological patterns seen in ACM, Fatty infiltration and fibro-fatty infiltration. ### Fatty infiltration[edit] The first, fatty infiltration, is confined to the right ventricle. This involves a partial or near-complete substitution of myocardium with fatty tissue without wall thinning. It involves predominantly the apical and infundibular regions of the RV. The left ventricle and ventricular septum are usually spared. No inflammatory infiltrates are seen in fatty infiltration. There is evidence of myocyte (myocardial cell) degeneration and death seen in 50% of cases of fatty infiltration. ### Fibro-fatty infiltration[edit] The second, fibro-fatty infiltration, involves replacement of myocytes with fibrofatty tissue. A patchy myocarditis is involved in up to 2/3 of cases, with inflammatory infiltrates (mostly T cells) seen on microscopy. Myocardial atrophy is due to injury and apoptosis. This leads to thinning of the RV free wall (to < 3 mm thickness) Myocytes are replaced with fibrofatty tissue. The regions preferentially involved include the RV inflow tract, the RV outflow tract, and the RV apex. However, the LV free wall may be involved in some cases. Involvement of the ventricular septum is rare. The areas involved are prone to aneurysm formation. ### The Role of Exercise[edit] Recently, some studies have identified strenuous exercise as a novel risk for accelerated progression of the disease. One retrospective study on 301 patients conclusively demonstrated that the subpopulations participating in strenuous physical activity (professional athletes for example) had an earlier onset of symptoms and earlier mortality compared to other populations.[26] ## Ventricular arrhythmias[edit] Monomorphic ventricular tachycardia originating from the right ventricular outflow tract Ventricular arrhythmias due to ACM typically arise from the diseased right ventricle. The type of arrhythmia ranges from frequent premature ventricular complexes (PVCs) to ventricular tachycardia (VT) to ventricular fibrillation (VF). While the initiating factor of the ventricular arrhythmias is unclear, it may be due to triggered activity or reentry. Ventricular arrhythmias are usually exercise-related, suggesting that they are sensitive to catecholamines. The ventricular beats typically have a right axis deviation. Multiple morphologies of ventricular tachycardia may be present in the same individual, suggesting multiple arrhythmogenic foci or pathways. Right ventricular outflow tract (RVOT) tachycardia is the most common VT seen in individuals with ACM. In this case, the EKG shows a left bundle branch block (LBBB) morphology with an inferior axis. ## Diagnosis[edit] The differential diagnosis for the ventricular tachycardia due to ACM include: * Congenital heart disease * Repaired tetralogy of Fallot * Ebstein's anomaly * Uhl's anomaly * Atrial septal defect * Partial anomalous venous return * Acquired heart disease * Tricuspid valve disease * Pulmonary hypertension * Right ventricular infarction * Bundle-branch re-entrant tachycardia * Miscellaneous * Pre-excited AV re-entry tachycardia * Idiopathic RVOT tachycardia * Sarcoidosis In order to make the diagnosis of ACM, a number of clinical tests are employed, including the electrocardiogram (EKG), echocardiography, right ventricular angiography, cardiac MRI, and genetic testing. ### Electrocardiogram[edit] 90% of individuals with ARVD have some EKG abnormality. The most common EKG abnormality seen in ACM is T wave inversion in leads V1 to V3. However, this is a non-specific finding, and may be considered a normal variant in right bundle branch block (RBBB), women, and children under 12 years old. RBBB itself is seen frequently in individuals with ACM. This may be due to delayed activation of the right ventricle, rather than any intrinsic abnormality in the right bundle branch. The epsilon wave (marked by red triangle), seen in ARVD. The epsilon wave is found in about 50% of those with ACM. This is described as a terminal notch in the QRS complex. It is due to slowed intraventricular conduction. The epsilon wave may be seen on a surface EKG; however, it is more commonly seen on signal averaged EKGs. Ventricular ectopy seen on a surface EKG in the setting of ACM is typically of left bundle branch block (LBBB) morphology, with a QRS axis of −90 to +110 degrees. The origin of the ectopic beats is usually from one of the three regions of fatty degeneration (the "triangle of dysplasia"): the RV outflow tract, the RV inflow tract, and the RV apex. Signal averaged ECG (SAECG) is used to detect late potentials and epsilon waves in individuals with ACM. ### Echocardiography[edit] Echocardiography may reveal an enlarged, hypokinetic right ventricle with a paper-thin RV free wall. The dilatation of the RV will cause dilatation of the tricuspid valve annulus, with subsequent tricuspid regurgitation. Paradoxical septal motion may also be present. ### MRI[edit] MRI in a patient affected by ARVC/D (long axis view of the right ventricle): note the transmural diffuse bright signal in the RV free wall on spin echo T1 (a) due to massive myocardial atrophy with fatty replacement (b). In vitro MRI and corresponding cross section of the heart in ARVD show RV dilatation with anterior and posterior aneurysms (17-year-old asymptomatic male athlete who died suddenly during a soccer game). Fatty infiltration of the RV free wall can be visible on cardiac MRI. Fat has increased intensity in T1-weighted images. However, it may be difficult to differentiate intramyocardial fat and the epicardial fat that is commonly seen adjacent to the normal heart. Also, the sub-tricuspid region may be difficult to distinguish from the atrioventricular sulcus, which is rich in fat. Cardiac MRI can visualize the extreme thinning and akinesis of the RV free wall. However, the normal RV free wall may be about 3 mm thick, making the test less sensitive. ### Angiography[edit] Right ventricular angiography is considered the gold standard for the diagnosis of ACM. Findings consistent with ACM are an akinetic or dyskinetic bulging localized to the infundibular, apical, and subtricuspid regions of the RV. The specificity is 90%; however, the test is observer dependent. ### Biopsy[edit] Transvenous biopsy of the right ventricle can be highly specific for ACM, but it has low sensitivity. False positives include other conditions with fatty infiltration of the ventricle, such as chronic alcohol abuse and Duchenne/Becker muscular dystrophy. False negatives are common, however, because the disease progresses typically from the epicardium to the endocardium (with the biopsy sample coming from the endocardium), and the segmental nature of the disease. Also, due to the paper-thin right ventricular free wall that is common in this disease process, most biopsy samples are taken from the ventricular septum, which is commonly not involved in the disease process. A biopsy sample that is consistent with ACM would have > 3% fat, >40% fibrous tissue, and <45% myocytes. A post mortem histological demonstration of full thickness substitution of the RV myocardium by fatty or fibro-fatty tissue is consistent with ACM. ### Genetic testing[edit] ACM is an autosomal dominant trait with reduced penetrance. Approximately 40–50% of ACM patients have a mutation identified in one of several genes encoding components of the desmosome, which can help confirm a diagnosis of ACM.[27] Since ACM is an autosomal dominant trait, children of an ACM patient have a 50% chance of inheriting the disease-causing mutation. Whenever a mutation is identified by genetic testing, family-specific genetic testing can be used to differentiate between relatives who are at-risk for the disease and those who are not. ACM genetic testing is clinically available.[28] ### Diagnostic criteria[edit] There is no pathognomonic feature of ACM. The diagnosis of ACM is based on a combination of major and minor criteria. To make a diagnosis of ACM requires either 2 major criteria or 1 major and 2 minor criteria or 4 minor criteria.[29] Major criteria * Right ventricular dysfunction * Severe dilatation and reduction of RV ejection fraction with little or no LV impairment * Localized RV aneurysms * Severe segmental dilatation of the RV * Tissue characterization * Fibrofatty replacement of myocardium on endomyocardial biopsy * Electrocardiographical abnormalities * Epsilon waves in V1 – V3 * Localized prolongation (>110 ms) of QRS in V1 – V3 * Inverted T waves in V1 -V3 in an individual over 12 years old, in the absence of a right bundle branch block (RBBB) * Ventricular tachycardia with a left bundle branch block (LBBB) morphology, with superior axis * Family history * Familial disease confirmed either clinically or on autopsy or surgery Minor criteria * Right ventricular dysfunction * Mild global RV dilatation and/or reduced ejection fraction with normal LV. * Mild segmental dilatation of the RV * Regional RV hypokinesis * Tissue characterization * Electrocardiographical abnormalities * Late potentials on signal averaged EKG. * Ventricular tachycardia with a left bundle branch block (LBBB) morphology, with inferior or unknown axis * Frequent PVCs (> 500 PVCs / 24 hours) ## Management[edit] The goal of management of ACM is to decrease the incidence of sudden cardiac death. This raises a clinical dilemma: How to prophylactically treat the asymptomatic patient who was diagnosed during family screening. A certain subgroup of individuals with ACM are considered at high risk for sudden cardiac death. Associated characteristics include: * Young age * Competitive sports activity * Malignant familial history * Extensive RV disease with decreased right ventricular ejection fraction. * Left ventricular involvement * Syncope * Episode of ventricular arrhythmia Management options include pharmacological, surgical, catheter ablation, and placement of an implantable cardioverter-defibrillator. Prior to the decision of the treatment option, programmed electrical stimulation in the electrophysiology laboratory may be performed for additional prognostic information. Goals of programmed stimulation include: * Assessment of the disease's arrhythmogenic potential * Evaluate the hemodynamic consequences of sustained VT * Determine whether the VT can be interrupted via antitachycardia pacing. Regardless of the management option chosen, the individual is typically advised to undergo lifestyle modification, including avoidance of strenuous exercise, cardiac stimulants (i.e.: caffeine, nicotine, pseudoephedrine) and alcohol. Regarding physical activity and exercise, ARVC patients, as well as gene carriers of pathogenic ARVC-associated desmosomal mutations, should not participate in competitive sports. These patients should be advised to limit their exercise programmes to leisure-time activities and remain under clinical surveillance.[30] ### Medications[edit] Pharmacologic management of ACM involves arrhythmia suppression and prevention of thrombus formation. Sotalol, a beta blocker and a class III antiarrhythmic agent, is the most effective antiarrhythmic agent in ACM. Other antiarrhythmic agents used include amiodarone and conventional beta blockers (i.e.: metoprolol). If antiarrhythmic agents are used, their efficacy should be guided by series ambulatory holter monitoring, to show a reduction in arrhythmic events. While angiotensin converting enzyme inhibitors (ACE Inhibitors) are well known for slowing progression in other cardiomyopathies, they have not been proven to be helpful in ACM. Individuals with decreased RV ejection fraction with dyskinetic portions of the right ventricle may benefit from long term anticoagulation with warfarin to prevent thrombus formation and subsequent pulmonary embolism. ### Catheter ablation[edit] Catheter ablation may be used to treat intractable ventricular tachycardia. It has a 60–90% success rate.[31] Unfortunately, due to the progressive nature of the disease, recurrence is common (60% recurrence rate), with the creation of new arrhythmogenic foci. Indications for catheter ablation include drug-refractory VT and frequent recurrence of VT after ICD placement, causing frequent discharges of the ICD. ### Implantable cardioverter-defibrillator[edit] An ICD is the most effective prevention against sudden cardiac death. Due to the prohibitive cost of ICDs, they are not routinely placed in all individuals with ACM. Indications for ICD placement in the setting of ACM include: * Cardiac arrest due to VT or VF * Symptomatic VT that is not inducible during programmed stimulation * Failed programmed stimulation-guided drug therapy * Severe RV involvement with poor tolerance of VT * Sudden death of immediate family member Since ICDs are typically placed via a transvenous approach into the right ventricle, there are complications associated with ICD placement and follow-up. Due to the extreme thinning of the RV free wall, it is possible to perforate the RV during implantation, potentially causing pericardial tamponade. Because of this, every attempt is made at placing the defibrillator lead on the ventricular septum. After a successful implantation, the progressive nature of the disease may lead to fibro-fatty replacement of the myocardium at the site of lead placement. This may lead to undersensing of the individual's electrical activity (potentially causing inability to sense VT or VF), and inability to pace the ventricle. ### Heart transplant[edit] Heart transplant may be performed in ACM. It may be indicated if the arrhythmias associated with the disease are uncontrollable or if there is severe bi-ventricular heart failure that is not manageable with pharmacological therapy. ### Family screening[edit] All first degree family members of the affected individual should be screened for ACM. This is used to establish the pattern of inheritance. Screening should begin during the teenage years unless otherwise indicated. Screening tests include: * Echocardiogram * EKG * Signal averaged EKG * Holter monitoring * Cardiac MRI * Exercise stress test ## Prognosis[edit] There is a long asymptomatic lead-time in individuals with ACM. While this is a genetically transmitted disease, individuals in their teens may not have any characteristics of ACM on screening tests. Many individuals have symptoms associated with ventricular tachycardia, such as palpitations, light-headedness, or syncope. Others may have symptoms and signs related to right ventricular failure, such as lower extremity edema, or liver congestion with elevated hepatic enzymes. ACM is a progressive disease. Over time, the right ventricle becomes more involved, leading to right ventricular failure. The right ventricle will fail before there is left ventricular dysfunction. However, by the time the individual has signs of overt right ventricular failure, there will be histological involvement of the left ventricle. Eventually, the left ventricle will also become involved, leading to bi-ventricular failure. Signs and symptoms of left ventricular failure may become evident, including congestive heart failure, atrial fibrillation, and an increased incidence of thromboembolic events. ## Epidemiology[edit] The prevalence of ACM is about 1/10,000 in the general population in the United States, although some studies have suggested that it may be as common as 1/1,000. Recently, 1/200 were found to be carriers of mutations that predispose to ACM.[32] Based on these findings and other evidence, it is thought that in most patients, additional factors such as other genes, athletic lifestyle, exposure to certain viruses, etc. may be required for a patient to eventually develop signs and symptoms of ACM.[33] It accounts for up to 17% of all sudden cardiac deaths in the young. In Italy, the prevalence is 40/10,000, making it the most common cause of sudden cardiac death in the young population.[34] ## Notable cases[edit] * Columbus Crew midfielder Kirk Urso collapsed out with friends on August 5, 2012 and was pronounced dead an hour later. An autopsy later revealed the disease to be the likely culprit.[35][36] * Sevilla FC and Spanish international left wing-back Antonio Puerta died from the condition, at the age of 22, on 28 August 2007, three days after suffering several cardiac arrests, while disputing a La Liga game against Getafe CF.[37][38] * Englishman Matt Gadsby also died from the condition after collapsing on the pitch on 9 September 2006, while playing for Hinckley United in a Conference North game against Harrogate Town.[39][40] * Suzanne Crough, an American child actress best known for her role on The Partridge Family, died suddenly from the condition in 2015 at age 52.[41] * James Taylor English international cricketer, retired April 2016.[42] * Krissy Taylor, an American model, died on July 2, 1995 in the family home in Florida. Her official cause of death was cardiac arrhythmia and severe asthma, the latter of which she had never been diagnosed with. Her family had independent experts examine tissue samples of her heart muscle and they concluded that the most likely cause of death was a missed diagnosis of ACM. * Jordan Boyd (1997-2013), Canadian junior hockey player. He was posthumously diagnosed with the ailment after passing away from a collapse from training camp in 2013.[43] ## See also[edit] * Woolly hair nevus * List of conditions caused by problems with junctional proteins ## References[edit] 1. ^ Pilichou, Kalliopi; Thiene, Gaetano; Bauce, Barbara; Rigato, Ilaria; Lazzarini, Elisabetta; Migliore, Federico; Perazzolo Marra, Martina; Rizzo, Stefania; Zorzi, Alessandro; Daliento, Luciano; Corrado, Domenico; Basso, Cristina (2 April 2016). "Arrhythmogenic cardiomyopathy". Orphanet Journal of Rare Diseases. 11 (1): 33. doi:10.1186/s13023-016-0407-1. PMC 4818879. PMID 27038780. 2. ^ Freedberg IM, Fitzpatrick TB (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. ISBN 978-0-07-138076-8. 3. ^ James WD, Berger TG, Elston DM, Odom RB (2006). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. ISBN 978-0-7216-2921-6. 4. ^ a b c Corrado, Domenico; Basso, Cristina; Judge, Daniel P. (2017-09-15). "Arrhythmogenic Cardiomyopathy". Circulation Research. 121 (7): 784–802. doi:10.1161/CIRCRESAHA.117.309345. ISSN 1524-4571. PMC 4818879. PMID 28912183. 5. ^ Corrado, Domenico; Link, Mark S.; Calkins, Hugh (2017-01-05). "Arrhythmogenic Right Ventricular Cardiomyopathy". The New England Journal of Medicine. 376 (1): 61–72. doi:10.1056/NEJMra1509267. ISSN 1533-4406. PMID 28052233. 6. ^ Cox MG, van der Zwaag PA, van der Werf C, van der Smagt JJ, Noorman M, Bhuiyan ZA, Wiesfeld AC, Volders PG, van Langen IM, Atsma DE, Dooijes D, van den Wijngaard A, Houweling AC, Jongbloed JD, Jordaens L, Cramer MJ, Doevendans PA, de Bakker JM, Wilde AA, van Tintelen JP, Hauer RN (June 2011). "Arrhythmogenic right ventricular dysplasia/cardiomyopathy: pathogenic desmosome mutations in index-patients predict outcome of family screening: Dutch arrhythmogenic right ventricular dysplasia/cardiomyopathy genotype-phenotype follow-up study". Circulation. 123 (23): 2690–700. doi:10.1161/circulationaha.110.988287. PMID 21606396. 7. ^ Fressart V, Duthoit G, Donal E, Probst V, Deharo JC, Chevalier P, Klug D, Dubourg O, Delacretaz E, Cosnay P, Scanu P, Extramiana F, Keller D, Hidden-Lucet F, Simon F, Bessirard V, Roux-Buisson N, Hebert JL, Azarine A, Casset-Senon D, Rouzet F, Lecarpentier Y, Fontaine G, Coirault C, Frank R, Hainque B, Charron P (June 2010). "Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice". Europace. 12 (6): 861–8. doi:10.1093/europace/euq104. PMID 20400443. 8. ^ Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H (December 2010). "De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy". Human Molecular Genetics. 19 (23): 4595–607. doi:10.1093/hmg/ddq387. PMID 20829228. 9. ^ Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S, Šarić T, Klauke B, Gummert J, Anselmetti D, Heilemann M, Nienhaus GU, Milting H (May 2012). "Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants". The Journal of Biological Chemistry. 287 (19): 16047–57. doi:10.1074/jbc.M111.313841. PMC 3346104. PMID 22403400. 10. ^ Beffagna G, Occhi G, Nava A, Vitiello L, Ditadi A, Basso C, Bauce B, Carraro G, Thiene G, Towbin JA, Danieli GA, Rampazzo A (February 2005). "Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1". Cardiovascular Research. 65 (2): 366–73. doi:10.1016/j.cardiores.2004.10.005. PMID 15639475. 11. ^ Milting H, Lukas N, Klauke B, Körfer R, Perrot A, Osterziel KJ, Vogt J, Peters S, Thieleczek R, Varsányi M (August 2006). "Composite polymorphisms in the ryanodine receptor 2 gene associated with arrhythmogenic right ventricular cardiomyopathy". Cardiovascular Research. 71 (3): 496–505. doi:10.1016/j.cardiores.2006.04.004. PMID 16769042. 12. ^ Merner ND, Hodgkinson KA, Haywood AF, Connors S, French VM, Drenckhahn JD, Kupprion C, Ramadanova K, Thierfelder L, McKenna W, Gallagher B, Morris-Larkin L, Bassett AS, Parfrey PS, Young TL (April 2008). "Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene". American Journal of Human Genetics. 82 (4): 809–21. doi:10.1016/j.ajhg.2008.01.010. PMC 2427209. PMID 18313022. 13. ^ Christensen AH, Andersen CB, Tybjaerg-Hansen A, Haunso S, Svendsen JH (September 2011). "Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy". Clinical Genetics. 80 (3): 256–64. doi:10.1111/j.1399-0004.2011.01623.x. PMID 21214875. 14. ^ Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H (December 2010). "De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy". Human Molecular Genetics. 19 (23): 4595–607. doi:10.1093/hmg/ddq387. PMID 20829228. 15. ^ Bermúdez-Jiménez FJ, Carriel V, Brodehl A, Alaminos M, Campos A, Schirmer I, Milting H, Abril BÁ, Álvarez M, López-Fernández S, García-Giustiniani D, Monserrat L, Tercedor L, Jiménez-Jáimez J (April 2018). "Novel Desmin Mutation p.Glu401Asp Impairs Filament Formation, Disrupts Cell Membrane Integrity, and Causes Severe Arrhythmogenic Left Ventricular Cardiomyopathy/Dysplasia". Circulation. 137 (15): 1595–1610. doi:10.1161/CIRCULATIONAHA.117.028719. PMID 29212896. 16. ^ Bauce B, Basso C, Rampazzo A, Beffagna G, Daliento L, Frigo G, Malacrida S, Settimo L, Danieli G, Thiene G, Nava A (August 2005). "Clinical profile of four families with arrhythmogenic right ventricular cardiomyopathy caused by dominant desmoplakin mutations". European Heart Journal. 26 (16): 1666–75. doi:10.1093/eurheartj/ehi341. PMID 15941723. 17. ^ Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse-Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E, Thierfelder L (November 2004). "Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy". Nature Genetics. 36 (11): 1162–4. doi:10.1038/ng1461. PMID 15489853. 18. ^ Pilichou K, Nava A, Basso C, Beffagna G, Bauce B, Lorenzon A, Frigo G, Vettori A, Valente M, Towbin J, Thiene G, Danieli GA, Rampazzo A (March 2006). "Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy". Circulation. 113 (9): 1171–9. doi:10.1161/CIRCULATIONAHA.105.583674. PMID 16505173. 19. ^ Awad MM, Dalal D, Cho E, Amat-Alarcon N, James C, Tichnell C, Tucker A, Russell SD, Bluemke DA, Dietz HC, Calkins H, Judge DP (July 2006). "DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy". American Journal of Human Genetics. 79 (1): 136–42. doi:10.1086/504393. PMC 1474134. PMID 16773573. 20. ^ Heuser A, Plovie ER, Ellinor PT, Grossmann KS, Shin JT, Wichter T, Basson CT, Lerman BB, Sasse-Klaassen S, Thierfelder L, MacRae CA, Gerull B (December 2006). "Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy". American Journal of Human Genetics. 79 (6): 1081–8. doi:10.1086/509044. PMC 1698714. PMID 17186466. 21. ^ Syrris P, Ward D, Evans A, Asimaki A, Gandjbakhch E, Sen-Chowdhry S, McKenna WJ (November 2006). "Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2". American Journal of Human Genetics. 79 (5): 978–84. doi:10.1086/509122. PMC 1698574. PMID 17033975. 22. ^ Antoniades L, Tsatsopoulou A, Anastasakis A, Syrris P, Asimaki A, Panagiotakos D, Zambartas C, Stefanadis C, McKenna WJ, Protonotarios N (September 2006). "Arrhythmogenic right ventricular cardiomyopathy caused by deletions in plakophilin-2 and plakoglobin (Naxos disease) in families from Greece and Cyprus: genotype-phenotype relations, diagnostic features and prognosis". European Heart Journal. 27 (18): 2208–16. doi:10.1093/eurheartj/ehl184. PMID 16893920. 23. ^ Asimaki A, Syrris P, Wichter T, Matthias P, Saffitz JE, McKenna WJ (November 2007). "A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy". American Journal of Human Genetics. 81 (5): 964–73. doi:10.1086/521633. PMC 2265660. PMID 17924338. 24. ^ Brodehl A, Rezazadeh S, Williams T, Munsie NM, Liedtke D, Oh T, Ferrier R, Shen Y, Jones SJ, Stiegler AL, Boggon TJ, Duff HJ, Friedman JM, Gibson WT, Childs SJ, Gerull B (February 2019). "Mutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy". Translational Research. 208: 15–29. doi:10.1016/j.trsl.2019.02.004. PMC 7412573. PMID 30802431. 25. ^ Forleo C, Carmosino M, Resta N, Rampazzo A, Valecce R, Sorrentino S, Iacoviello M, Pisani F, Procino G, Gerbino A, Scardapane A, Simone C, Calore M, Torretta S, Svelto M, Favale S (2015). "Clinical and functional characterization of a novel mutation in lamin a/c gene in a multigenerational family with arrhythmogenic cardiac laminopathy". PLOS ONE. 10 (4): e0121723. Bibcode:2015PLoSO..1021723F. doi:10.1371/journal.pone.0121723. PMC 4383583. PMID 25837155. 26. ^ Mazzanti, Andrea; Ng, Kevin; Faragli, Alessandro; Maragna, Riccardo; Chiodaroli, Elena; Orphanou, Nicoletta; Monteforte, Nicola; Memmi, Mirella; Gambelli, Patrick (December 2016). "Arrhythmogenic Right Ventricular Cardiomyopathy". Journal of the American College of Cardiology. 68 (23): 2540–2550. doi:10.1016/j.jacc.2016.09.951. PMID 27931611. 27. ^ Sen-Chowdhry S, Syrris P, McKenna WJ (November 2007). "Role of genetic analysis in the management of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy". Journal of the American College of Cardiology. 50 (19): 1813–21. doi:10.1016/j.jacc.2007.08.008. PMID 17980246. 28. ^ Overview of ARVD/C Genetic Testing 29. ^ Marcus, Frank I. (2010). "Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Proposed Modification of the Task Force Criteria". Circulation. 30. ^ Pelliccia, A (2019). "Recommendations for participation in competitive and leisure time sport in athletes with cardiomyopathies,myocarditis, and pericarditis: position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology (EAPC)". European Heart Journal. 40: 19–33. 31. ^ Fontaine G, Tonet J, Gallais Y, Lascault G, Hidden-Lucet F, Aouate P, Halimi F, Poulain F, Johnson N, Charfeddine H, Frank R (November 2000). "Ventricular tachycardia catheter ablation in arrhythmogenic right ventricular dysplasia: a 16-year experience". Current Cardiology Reports. 2 (6): 498–506. doi:10.1007/s11886-000-0034-1. PMID 11203287. 32. ^ Lahtinen AM, Lehtonen E, Marjamaa A, Kaartinen M, Heliö T, Porthan K, Oikarinen L, Toivonen L, Swan H, Jula A, Peltonen L, Palotie A, Salomaa V, Kontula K (August 2011). "Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy". Heart Rhythm. 8 (8): 1214–21. doi:10.1016/j.hrthm.2011.03.015. PMID 21397041. 33. ^ Jain R. Athletic status and arrhythmogenic right ventricular dysplasia/cardiomyopathy: From physiological observations to pathological explanation. Hypothesis 2010, 8(1): e2. – See more at: http://www.hypothesisjournal.com/?p=844#sthash.aB859Jm2.dpuf 34. ^ Corrado D, Fontaine G, Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. Need for an International Registry. Circulation. 2000; 101: e101-e106 35. ^ Jardy A. "Crew midfielder Kirk Urso, 22, dies after being rushed to hospital from bar". The Columbus Dispatch. The Dispatch Printing Company. Retrieved 21 September 2012. 36. ^ Jardy A. "Coroner: Crew's Urso died of a preexisting heart condition". The Columbus Dispatch. The Dispatch Printing Company. Retrieved 21 September 2012. 37. ^ "Sevilla star suffers heart attack". BBC Sport. 2007-08-25. Retrieved 2007-08-25. 38. ^ Sevilla star dies after collapse 39. ^ "Cause of Death". Cardiac Inherited Disease Group. Archived from the original on 2006-08-18. Retrieved 2006-10-31. 40. ^ "Shock at star player's death". icBirmingham.co.uk. 11 September 2006. Retrieved 2007-11-26. 41. ^ Suzanne Crough died of rare heart ailment, coroner says, msn.com; accessed October 27, 2015. 42. ^ "James Taylor: England & Nottinghamshire batsman forced to retire". BBC Sport. 2016-04-12. Retrieved 2016-05-15. 43. ^ The life and career of Jordan Boyd \| NHL Home Team Heroes, retrieved 2019-10-14 ## External links[edit] Classification D * ICD-10: I42.8 * OMIM: 107970 * MeSH: D019571 * DiseasesDB: 29750 External resources * Patient UK: Arrhythmogenic cardiomyopathy Wikimedia Commons has media related to Arrhythmogenic right ventricular dysplasia. * GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant * OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever * v * t * e Cytoskeletal defects Microfilaments Myofilament Actin * Hypertrophic cardiomyopathy 11 * Dilated cardiomyopathy 1AA * DFNA20 * Nemaline myopathy 3 Myosin * Elejalde syndrome * Hypertrophic cardiomyopathy 1, 8, 10 * Usher syndrome 1B * Freeman–Sheldon syndrome * DFN A3, 4, 11, 17, 22; B2, 30, 37, 48 * May–Hegglin anomaly Troponin * Hypertrophic cardiomyopathy 7, 2 * Nemaline myopathy 4, 5 Tropomyosin * Hypertrophic cardiomyopathy 3 * Nemaline myopathy 1 Titin * Hypertrophic cardiomyopathy 9 Other * Fibrillin * Marfan syndrome * Weill–Marchesani syndrome * Filamin * FG syndrome 2 * Boomerang dysplasia * Larsen syndrome * Terminal osseous dysplasia with pigmentary defects IF 1/2 * Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1 * Striate palmoplantar keratoderma 3 * Epidermolytic hyperkeratosis * IHCM * KRT2E (Ichthyosis bullosa of Siemens) * KRT3 (Meesmann juvenile epithelial corneal dystrophy) * KRT4 (White sponge nevus) * KRT5 (Epidermolysis bullosa simplex) * KRT8 (Familial cirrhosis) * KRT10 (Epidermolytic hyperkeratosis) * KRT12 (Meesmann juvenile epithelial corneal dystrophy) * KRT13 (White sponge nevus) * KRT14 (Epidermolysis bullosa simplex) * KRT17 (Steatocystoma multiplex) * KRT18 (Familial cirrhosis) * KRT81/KRT83/KRT86 (Monilethrix) * Naegeli–Franceschetti–Jadassohn syndrome * Reticular pigmented anomaly of the flexures 3 * Desmin: Desmin-related myofibrillar myopathy * Dilated cardiomyopathy 1I * GFAP: Alexander disease * Peripherin: Amyotrophic lateral sclerosis 4 * Neurofilament: Parkinson's disease * Charcot–Marie–Tooth disease 1F, 2E * Amyotrophic lateral sclerosis 5 * Laminopathy: LMNA * Mandibuloacral dysplasia * Dunnigan Familial partial lipodystrophy * Emery–Dreifuss muscular dystrophy 2 * Limb-girdle muscular dystrophy 1B * Charcot–Marie–Tooth disease 2B1 * LMNB * Barraquer–Simons syndrome * LEMD3 * Buschke–Ollendorff syndrome * Osteopoikilosis * LBR * Pelger–Huet anomaly * Hydrops-ectopic calcification-moth-eaten skeletal dysplasia Microtubules Kinesin * Charcot–Marie–Tooth disease 2A * Hereditary spastic paraplegia 10 Dynein * Primary ciliary dyskinesia * Short rib-polydactyly syndrome 3 * Asphyxiating thoracic dysplasia 3 Other * Tauopathy * Cavernous venous malformation Membrane * Spectrin: Spinocerebellar ataxia 5 * Hereditary spherocytosis 2, 3 * Hereditary elliptocytosis 2, 3 Ankyrin: Long QT syndrome 4 * Hereditary spherocytosis 1 Catenin * APC * Gardner's syndrome * Familial adenomatous polyposis * plakoglobin (Naxos syndrome) * GAN (Giant axonal neuropathy) Other * desmoplakin: Striate palmoplantar keratoderma 2 * Carvajal syndrome * Arrhythmogenic right ventricular dysplasia 8 * plectin: Epidermolysis bullosa simplex with muscular dystrophy * Epidermolysis bullosa simplex of Ogna * plakophilin: Skin fragility syndrome * Arrhythmogenic right ventricular dysplasia 9 * centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II) Related topics: Cytoskeletal proteins * v * t * e Cell membrane protein disorders (other than Cell surface receptor, enzymes, and cytoskeleton) Arrestin * Oguchi disease 1 Myelin * Pelizaeus–Merzbacher disease * Dejerine–Sottas disease * Charcot–Marie–Tooth disease 1B, 2J Pulmonary surfactant * Surfactant metabolism dysfunction 1, 2 Cell adhesion molecule IgSF CAM: * OFC7 Cadherin: * DSG1 * Striate palmoplantar keratoderma 1 * DSG2 * Arrhythmogenic right ventricular dysplasia 10 * DSG4 * LAH1 * DSC2 * Arrhythmogenic right ventricular dysplasia 11 Integrin: * cell surface receptor deficiencies Tetraspanin * TSPAN7 * X-Linked mental retardation 58 * TSPAN12 * Familial exudative vitreoretinopathy 5 Other * KIND1 * Kindler syndrome * HFE * HFE hereditary haemochromatosis * DYSF * Distal muscular dystrophy * Limb-girdle muscular dystrophy 2B See also other cell membrane proteins * v * t * e Diseases of ion channels Calcium channel Voltage-gated * CACNA1A * Familial hemiplegic migraine 1 * Episodic ataxia 2 * Spinocerebellar ataxia type-6 * CACNA1C * Timothy syndrome * Brugada syndrome 3 * Long QT syndrome 8 * CACNA1F * Ocular albinism 2 * CSNB2A * CACNA1S * Hypokalemic periodic paralysis 1 * Thyrotoxic periodic paralysis 1 * CACNB2 * Brugada syndrome 4 Ligand gated * RYR1 * Malignant hyperthermia * Central core disease * RYR2 * CPVT1 * ARVD2 Sodium channel Voltage-gated * SCN1A * Familial hemiplegic migraine 3 * GEFS+ 2 * Febrile seizure 3A * SCN1B * Brugada syndrome 6 * GEFS+ 1 * SCN4A * Hypokalemic periodic paralysis 2 * Hyperkalemic periodic paralysis * Paramyotonia congenita * Potassium-aggravated myotonia * SCN4B * Long QT syndrome 10 * SCN5A * Brugada syndrome 1 * Long QT syndrome 3 * SCN9A * Erythromelalgia * Febrile seizure 3B * Paroxysmal extreme pain disorder * Congenital insensitivity to pain Constitutively active * SCNN1B/SCNN1G * Liddle's syndrome * SCNN1A/SCNN1B/SCNN1G * Pseudohypoaldosteronism 1AR Potassium channel Voltage-gated * KCNA1 * Episodic ataxia 1 * KCNA5 * Familial atrial fibrillation 7 * KCNC3 * Spinocerebellar ataxia type-13 * KCNE1 * Jervell and Lange-Nielsen syndrome * Long QT syndrome 5 * KCNE2 * Long QT syndrome 6 * KCNE3 * Brugada syndrome 5 * KCNH2 * Short QT syndrome * KCNQ1 * Jervell and Lange-Nielsen syndrome * Romano–Ward syndrome * Short QT syndrome * Long QT syndrome 1 * Familial atrial fibrillation 3 * KCNQ2 * BFNS1 Inward-rectifier * KCNJ1 * Bartter syndrome 2 * KCNJ2 * Andersen–Tawil syndrome * Long QT syndrome 7 * Short QT syndrome * KCNJ11 * TNDM3 * KCNJ18 * Thyrotoxic periodic paralysis 2 Chloride channel * CFTR * Cystic fibrosis * Congenital absence of the vas deferens * CLCN1 * Thomsen disease * Myotonia congenita * CLCN5 * Dent's disease * CLCN7 * Osteopetrosis A2, B4 * BEST1 * Vitelliform macular dystrophy * CLCNKB * Bartter syndrome 3 TRP channel * TRPC6 * FSGS2 * TRPML1 * Mucolipidosis type IV Connexin * GJA1 * Oculodentodigital dysplasia * Hallermann–Streiff syndrome * Hypoplastic left heart syndrome * GJB1 * Charcot–Marie–Tooth disease X1 * GJB2 * Keratitis–ichthyosis–deafness syndrome * Ichthyosis hystrix * Bart–Pumphrey syndrome * Vohwinkel syndrome) * GJB3/GJB4 * Erythrokeratodermia variabilis * Progressive symmetric erythrokeratodermia * GJB6 * Clouston's hidrotic ectodermal dysplasia Porin * AQP2 * Nephrogenic diabetes insipidus 2 See also: ion channels [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Arrhythmogenic cardiomyopathy	c0349788	26,655	wikipedia	https://en.wikipedia.org/wiki/Arrhythmogenic_cardiomyopathy	2021-01-18T18:52:00	{"gard": ["5847"], "mesh": ["D019571"], "umls": ["C0349788"], "orphanet": ["247", "217656"], "wikidata": ["Q2555727"]}
Piebaldism is a rare congenital pigmentation skin disorder characterized by the presence of hypopigmented and depigmented skin areas (leukoderma) on various parts of the body, preferentially on the forehead, chest, abdomen, upper arms, and lower extremities, that are associated with a white forelock (poliosis), and in some cases with hypopigmented and depigmented eyebrows and eyelashes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Piebaldism	c0080024	26,656	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2884	2021-01-23T17:08:35	{"gard": ["4344"], "mesh": ["D016116"], "omim": ["172800"], "umls": ["C0080024"], "icd-10": ["E70.3"]}
Solitary fibrous tumor (SFT) represents a diverse group of ubiquitous rare spindle cell neoplasms that may be benign or malignant and that most frequently arises from the pleura and peritoneum and rarely from other sites such as head and neck, liver and skeletal muscle. SFT may be clinically asymptomatic or may present with enlarging mass, compressive effects depending on the site involved and rarely with paraneoplastic manifestations (osteoarthropathy or hypoglycemia). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Solitary fibrous tumor/hemangiopericytoma	c0018922	26,657	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2126	2021-01-23T17:08:28	{"mesh": ["D006393"], "omim": ["234820"], "umls": ["C0018922", "C1266119"], "icd-10": ["D21.9"], "synonyms": ["SFT/HPC"]}
A rare benign vascular tumor characterized by rapid growth after birth (followed by spontaneous partial regression over the course of years), potentially leading to life-threatening airway obstruction due to the subglottic location. Patients present with respiratory symptoms including biphasic stridor, recurrent croup, cyanosis, apnea, and sternal and intercostal retractions. The tumor may be accompanied by cutaneous hemangiomata, especially in the lower facial ("beard") distribution. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Laryngotracheal angioma	c3839574	26,658	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137935	2021-01-23T18:19:31	{"icd-10": ["D18.0"]}
A number sign (#) is used with this entry because autosomal recessive spastic paraplegia-11 (SPG11) is caused by homozygous or compound heterozygous mutation in the gene encoding spatacsin (SPG11; 610844) on chromosome 15q21. Biallelic mutation in the SPG11 gene can also cause autosomal recessive juvenile-onset amyotrophic lateral sclerosis-5 (ALS5; 602099) and autosomal recessive Charcot-Marie-Tooth disease type 2X (CMT2X; 616668), different neurodegenerative disorders with overlapping features. Description Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity. For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800). Clinical Features Nakamura et al. (1995) reported 2 families with autosomal recessive hereditary spastic paraplegia, mental impairment, and thin corpus callosum. In the first family, 3 affected brothers had onset in the second decade of gait disturbance resulting in wheelchair use by age 21 years. All 3 patients had an IQ less than 60. Other features included lower limb spasticity, slight ataxia, and mild sensory impairment. Three sisters from a second family, in which the parents were first cousins, had similar features to the affected brothers in the first family. Brain CT and MRI of 4 patients showed mild frontal and temporal cortical atrophy, mild ventricular dilatation, and widening of the frontal longitudinal fissure. All patients had a markedly thin corpus callosum which was not consistent with a degenerative process and was distinct from congenital agenesis (ACC; 217990) and partial agenesis (e.g., 304100) of the corpus callosum. Peripheral nerve biopsies showed decreased numbers of myelinated fibers, axonal degeneration, and abnormal Schwann cell inclusions. Ueda et al. (1998) reported 2 Japanese sibs with SPG11 who showed thalamic glucose hypometabolism on positron emission tomography (PET) scan. Winner et al. (2004) reported 2 German sisters with SPG11. The more severely affected sister had onset at age 24 years of a slowly progressive spastic paraplegia with increasing urinary urge incontinence and slow cognitive decline. Both sisters were obese, whereas no other family members were overweight. Serial MRIs showed a tendency toward progressive atrophy of the rostral corpus callosum, as well as symmetric white matter lesions. Transcranial stimulation showed a lack of transcallosal inhibition, and PET scan showed cortical and thalamic hypometabolism that decreased further within 4 years. Combined axonal loss and demyelinating sensory neuropathy were also present. No mutations were identified in the SLC12A6 gene (604878), which is mutated in agenesis of the corpus callosum with peripheral neuropathy (ACCPN; 218000). Casali et al. (2004) reported 18 patients from 12 Italian families with HSP-TCC; 2 of the families were consanguineous. The clinical phenotype was homogeneous, with gait difficulties beginning at a median age of 13 years (range 4 to 20 years) and progressing to loss of ambulation within approximately 10 years. Neurologic features included spasticity, pyramidal signs, hyperreflexia, and severe mental deterioration. MRI studies showed thin corpus callosum in all patients and periventricular white matter changes in 15 of 18 patients. Lossos et al. (2006) reported 2 consanguineous Arab-Israeli families in which 2 sibs in each family had autosomal recessive HSP-TCC. All patients had onset of clinical symptoms during the second decade of life, with cognitive decline preceding gait disturbance by 2 to 5 years. Cardinal signs included pseudobulbar dysarthria, spastic paraparesis with lower limb hyperreflexia, upper limb hyperreflexia, extensor plantar responses, and distal amyotrophy. Brain imaging of 1 affected sib from each family showed thin corpus callosum, white matter abnormalities, and mild frontal atrophy. Two of 3 patients examined had mild axonal peripheral neuropathy. Two affected sibs in 1 family were obese. Stevanin et al. (2007) reviewed the features of autosomal recessive hereditary spastic paraplegia with thin corpus callosum (ARHSP-TCC). Cognitive impairment is first noticed in childhood and progresses insidiously to severe functional disability of a frontal type over a period of 10-20 years (Nakamura et al., 1995; Winner et al., 2004). Some affected individuals develop a pseudobulbar involvement, with dysarthria, dysphagia, and upper limb spasticity, associated with bladder dysfunction and signs of predominantly axonal, motor, or sensorimotor peripheral neuropathy. PET scan shows cortical and thalamic glucose hypometabolism. MRI shows thin corpus callosum that predominates in the rostral third, with hyperintensities in periventricular white matter and cerebral cortical atrophy predominating in the frontal region. Del Bo et al. (2007) reported 27-year-old Italian opposite-sex dizygotic twins with autosomal recessive SPG11. The sibs had onset of ataxia and cognitive impairment at ages 12 and 15 years, respectively. The disorder progressed rapidly, leading to spastic paraplegia, dysarthria, and peripheral neuropathy. Both were wheelchair-bound in their early twenties. Brain MRI showed thin corpus callosum and cortical atrophy in both sibs. Both parents were healthy and came from the same small town in Sicily but denied consanguinity. Genetic analysis identified a homozygous mutation in the SPG11 gene (733delAT; 610844.0004). Hehr et al. (2007) reported clinical details of 18 patients from 9 families with genetically confirmed SPG11. Several of the families had previously been reported by Olmez et al. (2006). The mean age at onset of walking impairment was 16 years (range, 8 to 31). Patients had predominantly lower limb paresis with proximal spasticity and hyperreflexia with extensor plantar responses. The gait was slow, spastic, and slightly ataxic. Dysarthria was noted in 85% of patients, and amyotrophy of the hypothenar and thenar muscles was commonly present. General mental impairment of varying degrees was present in 83%, and was associated with hypometabolism of the frontal cortex and thalamus on PET scan. MRI performed in at least 1 member of each family showed rostral atrophy of the corpus callosum and supratentorial white matter changes. Peripheral nerve biopsy showed hypomyelination of large fibers and loss of unmyelinated fibers, consistent with a clinical picture of mixed axonal and demyelinating polyneuropathy. Evidence also suggested disturbed axonal transport. The long-term course of 1 patient followed for 10 years showed progression of the disorder. Hehr et al. (2007) concluded that the disease process in SPG11 affects the corticospinal tract, major corticocortical connections via the corpus callosum, and the peripheral nervous system, and likely involves impaired axonal transport. Samaranch et al. (2008) reported 4 Spanish patients with SPG11 confirmed by genetic analysis. All had some degree of mental retardation and a thin corpus callosum on brain imaging. The 3 older individuals had spastic paraparesis since late childhood and decreased brain metabolism on PET studies, predominantly in the thalamus and paracentral cortex of the hemispheres. Samaranch et al. (2008) postulated that the thalamic dysfunction may contribute to impaired attention. ### Clinical Variability Crimella et al. (2009) identified homozygous or compound heterozygous mutations in the SPG11 gene in 4 (40%) of 10 patients with SPG and thin corpus callosum and in 3 (8.5%) of 35 patients with SPG without thin corpus callosum. The molecular findings were consistent with a loss-of-function mechanism. Orlen et al. (2009) reported 5 patients from 4 unrelated families with 5 truncating mutations in the SPG11 gene (see, e.g., 610844.0007-610844.0009). Two patients had delayed psychomotor development, 2 had onset at ages 3 and 4 years, respectively, and 1 had onset at age 14 years. Four patients were wheelchair-bound in the third or fourth decades; the fifth patient was only 14 at the time of the study and had a milder phenotype overall. The 4 older patients (ages 29 to 48) had lower limb spasticity, hyperreflexia with extensor plantar responses, sphincter disturbances, amyotrophy of the hands or calves, thin corpus callosum, cerebral atrophy, and periventricular white matter changes. All patients had some degree of cognitive dysfunction or mental retardation. Three were obese. An unusual finding in the 4 older patients was progressive central retinal degeneration, which was reminiscent of the phenotype for Kjellin syndrome (SPG15; 270700). Orlen et al. (2009) concluded that central retinal degeneration may be a previously unrecognized late-onset feature of this disorder. Mapping Martinez Murillo et al. (1999) performed genetic linkage analysis in 8 recessive familial spastic paraparesis families from America and Europe. The known recessive SPG loci, SPG5A, SPG7 (607259), as well as X-linked types of spastic paraplegia, SPG1 (303350) and SPG2 (312920), were excluded in 7 families; 1 family showed data consistent with linkage to the chromosome 8 locus. The other families showed positive lod scores for markers on 15q. The maximum multipoint combined lod score for non-chromosome 8 families was 3.14 for markers D15S1007, D15S971, D15S118, and D15S1012, at a distance of 6.41 cM from the marker D15S1007, in a region between D15S971 and D15S118. The data indicated a new locus for autosomal recessive familial spastic paraparesis on 15q13-q15, and the authors suggested that this may be a common form. Two of the 7 families linked to chromosome 15q had a complicated form of SPG with attenuation of the corpus callosum and mental deterioration; 3 families had SPG and pes cavus, but no abnormalities of the corpus callosum, and 2 families had a pure form of HSP. In 10 of 13 Japanese families with complicated HSP with mental impairment and thin corpus callosum, Shibasaki et al. (2000) found linkage to chromosome 15q13-q15 (maximum multipoint lod score of 9.68 at a position 1.2 cM telomeric from D15S994 to D15S659). Casali et al. (2004) demonstrated linkage to 15q13-q15 in 5 of 12 Italian families with HSP-TCC (maximum cumulative lod score of 3.35 at marker D15S659). Haplotype analysis excluded a founder effect. The absence of strong linkage to the SPG11 locus in 7 families indicated genetic heterogeneity. By linkage and haplotype analysis of 2 consanguineous Arab-Israeli families with SPG and thin corpus callosum, Lossos et al. (2006) refined the candidate SPG11 locus to a 13-Mb (17-cM) interval on chromosome 15q13-q15 between markers D15S971 and D15S143 (maximum multipoint lod scores of 3.1 and 2.5 for the 2 families, respectively). A third consanguineous Arab-Israeli family with a similar phenotype was excluded from the SPG11 locus, indicating genetic heterogeneity. Stevanin et al. (2006) reported 6 Mediterranean families with autosomal recessive HSP-TCC showing linkage to the SPG11 locus (positive lod scores at marker D15S659). Haplotype reconstruction allowed refinement of the locus to a 6-cM interval. Genetic analysis excluded mutations in the MAP1A (600178) and SEMA6D (609295) genes in the index patients from 5 families showing linkage to SPG11. Linkage to the SPG11 locus was excluded in 4 additional families with HSP-TCC, indicating genetic heterogeneity. Stevanin et al. (2007) genotyped 12 families with ARHSP-TCC using 34 microsatellite markers in the candidate interval for SPG11 and the adjacent and overlapping loci for SPG21 (248900) and agenesis of corpus callosum with polyneuropathy (218000). Maximal positive multipoint lod scores ranging from 0.60 to 3.85, which corresponded to the maximal expected values in the pedigrees, were obtained in 10 families in the SPG11 interval. The combined multipoint lod score reached the value of 17.32 for these families. Linkage was not conclusive in the 2 remaining kindreds. Haplotype reconstructions in 2 consanguineous families with strong evidence for linkage to SPG11 further restricted the region most likely to contain the responsible gene to a 3.2-cM homozygous region between D15S778 and D15S659. This interval contains approximately 40 genes. Molecular Genetics Stevanin et al. (2007) analyzed 18 genes in the 3.2-cM SPG11 candidate interval by direct sequencing of all exons and their splicing sites, and identified 10 mutations in the KIAA1840 gene (610844) in 11 families. The KIAA1840 gene, encoding spatacsin, is expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus, and pineal gland. The mutations were either nonsense or insertions or deletions leading to a frameshift, suggesting a loss-of-function mechanism. All mutations were in the homozygous state except in 2 kindreds, in which affected individuals were compound heterozygous. Only 2 mutations were found in more than 1 pedigree: R2034X (604360.0001) in 3 consanguineous North African kindreds, and a 5-bp deletion in exon 3 (604360.0002) in 2 Portuguese families. The SPG11 gene appears to be the one most frequently responsible for ARHSP-TCC. Only a single family (8%) in the cohort studied by Stevanin et al. (2007) did not have a mutation in SPG11, indicating that there is at least one other responsible gene. On the other hand, whether the SPG11 gene accounts for other clinical phenotypes of ARHSP remained to be determined. Spastic paraplegias are believed to result from a dying back of exons. Mitochondrial metabolism, endosomal and trans-Golgi trafficking and axonal transport have been implicated in several HSPs (Crosby and Proukakis, 2002). Although the function of spatacsin remains unknown, the experimental evidence that it is expressed in all tissues and is highly conserved among species suggests that it has an essential biologic function. The possible presence of at least one transmembrane domain suggested that spatacsin may be a receptor or transporter. In 18 patients from 9 unrelated families with SPG11, Hehr et al. (2007) identified 11 different mutations, including 10 novel mutations, in the SPG11 gene (see, e.g., 610844.0005-610844.0006) in the homozygous or compound heterozygous state. Four of the families were consanguineous, including 3 Turkish families initially reported by Olmez et al. (2006). Mutations were distributed throughout the entire spatacsin gene without obvious clustering. Bauer et al. (2009) used high-resolution comparative genomic hybridization (HRCGH) to identify deletions in the SPG11 gene in 3 patients with SPG11 in whom only 1 mutant SPG11 allele had been identified by gene sequencing. HRCGH analysis suggested heterozygous genomic deletion in all 3 patients; however, quantitative PCR confirmed an 8.23-kb deletion in only 1 patient. The 8.23-kb deletion resulted in loss of exons 31 to 34 and was also found in the proband's affected sister and their unaffected father. The clinical features in the brother and sister did not differ from those of patients with point mutations. Population Genetics Boukhris et al. (2009) identified a molecular basis for hereditary spastic paraplegia in 13 (34.2%) of 38 unrelated families from southern Tunisia with the disorder. The most common forms of SPG were SPG11 in 7 (18.4%) families and SPG15 (270700) in 4 (10.5%) families. SPG4 (182601) and SPG5 (270800) were present in 1 family each. INHERITANCE \- Autosomal recessive GROWTH Weight \- Obesity HEAD & NECK Eyes \- Nystagmus, gaze-evoked \- Pigmented macular degeneration, adult-onset \- Retinal degeneration, adult-onset \- Decreased visual acuity, adult-onset GENITOURINARY Bladder \- Urinary urgency \- Urinary incontinence \- Sphincter disturbances SKELETAL Feet \- Pes cavus MUSCLE, SOFT TISSUES \- Amyotrophy \- Muscle atrophy, neurogenic \- Atrophy of the thenar and hypothenar muscles NEUROLOGIC Central Nervous System \- Lower limb spasticity \- Lower limb weakness \- Walking on tiptoes \- Stiffness while walking \- Spastic gait \- Ataxia \- Hyperreflexia \- Extensor plantar responses \- Pyramidal signs \- Knee and ankle clonus \- Degeneration of the lateral corticospinal tracts \- Dysarthria \- Dysphagia \- Learning disability (early in life) \- Severe cognitive deficits (develop later) \- Mental retardation (develops later) \- Thin corpus callosum \- Agenesis of the corpus callosum \- Cortical atrophy \- Periventricular white matter changes Peripheral Nervous System \- Peripheral motor and sensory neuropathy, distal \- Decreased vibratory sense in the lower limbs \- Nerve biopsy shows loss of myelinated fibers MISCELLANEOUS \- Onset usually in early adolescence \- Adult onset has been reported (age 50 years) \- Childhood onset has been reported \- Progressive disorder \- Loss of ambulation within 10 years of onset \- Some patients do not have thin corpus callosum \- Several forms of autosomal recessive spastic paraplegia (see 270800 ) MOLECULAR BASIS \- Caused by mutation in the spatacsin gene (SPG11, 610844.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SPASTIC PARAPLEGIA 11, AUTOSOMAL RECESSIVE	c1858479	26,659	omim	https://www.omim.org/entry/604360	2019-09-22T16:12:11	{"doid": ["0110764"], "mesh": ["C537483"], "omim": ["604360"], "orphanet": ["2822"], "synonyms": ["Alternative titles", "SPASTIC PARAPLEGIA, AUTOSOMAL RECESSIVE, WITH MENTAL IMPAIRMENT AND THIN CORPUS CALLOSUM", "SPASTIC PARAPLEGIA, AUTOSOMAL RECESSIVE, COMPLICATED, WITH THIN CORPUS CALLOSUM", "HSP-TCC"], "genereviews": ["NBK1210"]}
A rare inherited neurodegenerative disorder characterized by rapidly progressive early-onset parkinsonism, central hypoventilation, weight loss, insomnia and depression. ## Epidemiology The prevalence is unknown. It has been described in 53 cases from 11 families to date in Canada, U.S., U.K., France, Turkey and Japan. ## Clinical description Perry syndrome has a mean age of onset of 48 years (range 35-61) and presents with parkinsonism (akinetic-rigid and rather symmetric), psychiatric changes manifesting as depression, lethargy, withdrawal, apathy, and changes in character, as well as sleep difficulties. The usual duration of Perry syndrome is about 5 years, with severe weight loss and central hypoventilation being seen late in the disease course. Marked autonomic dysfunction was reported in one family from Japan. Patients are often bedridden or wheelchair bound as motor impairment may be severe at a later stage of the disease. ## Etiology Perry syndrome is caused by mutations (five identified to date) in exon 2 of the dynactin DCTN1 gene coding for p150glued, the major subunit of the dynactin protein complex. Mutations in this gene alter the binding affinity of dynactin for microtubules and consequently this leads to the impairment of this important transport protein. Nigral neurons seem to be more affected by the dysfunction of this protein, explaining their increased cell death and the distinct pathology seen in Perry syndrome. ## Diagnostic methods Diagnosis is based on clinical findings of early-onset parkinsonism combined with depression, weight loss and hypoventilation and is confirmed by a molecular genetic test finding a mutation in the DCTN1 gene. Major histological findings consist of neuronal loss and TAR DNA-binding protein (TDP-43)-positive pathology in the substantia nigra and locus coeruleus, without Lewy bodies. Sleep studies should be performed to detect hypoventilation. ## Differential diagnosis The main differential diagnoses are other forms of familial early-onset parkinsonism (in particular those associated with mutations in the PARK2, PINK1, PARK7 and LRRK2 genes) as well as frontotemporal dementia (see these terms). ## Antenatal diagnosis Antenatal diagnosis is possible in laboratories that offer custom prenatal testing for families with a known DCTN1 mutation. ## Genetic counseling Perry syndrome is inherited in an autosomal dominant manner with full penetrance and children of a parent with the disease have a 50% risk of also having the mutation and developing the disease. Pre-symptomatic diagnosis can be offered to at-risk individuals. ## Management and treatment There is no cure for Perry syndrome. Symptomatic treatment requires a multidisciplinary team. Dopaminergic therapy is given to patients to help with parkinsonism, usually using levodopa / carbidopa. Response to levodopa can be erratic or absent but large doses (>2g) have been successful in reducing symptoms in several patients. Patients with hypoventilation require ventilator support (invasive or non-invasive), particularly at night. Respiratory function should be monitored continuously. Psychiatric follow-up along with antidepressant drugs are needed to manage depression and prevent suicide. Weight should be monitored and a high caloric diet should be implemented when weight loss is present. With worsening symptoms hospitalization and major medical assistance is often required. ## Prognosis Perry syndrome progresses rapidly and the prognosis is poor. Death is due to respiratory insufficiency or suicide or, in some cases, can be sudden and unexplained. Ventilation assistance may prolong survival with an acceptable quality of life. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Perry syndrome	c1868594	26,660	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=178509	2021-01-23T17:54:59	{"gard": ["10453"], "mesh": ["C566822"], "omim": ["168605"], "umls": ["C1868594"], "synonyms": ["Parkinsonism with alveolar hypoventilation and mental depression"]}
Mesial temporal lobe epilepsy with hippocampal sclerosis is a rare epilepsy syndrome defined by seizures originating in limbic areas of the mesial temporal lobe, particularly in the hippocampus, amygdala, and in the parahippocampal gyrus and its connections, and hippocampal sclerosis, usually unilateral or assymetric. It is frequently associated with an initial precipitating event, such as febrile seizures, hypoxia, intracranial infection or head trauma, most often occurring in the first five years of life, followed by a latent period without seizures. Typical seizures consist of a characteristic aura that is frequently a rising epigastric sensation associated with emotional disturbances, illusions, and autonomic symptoms (widened pupils, palpitations), progressive impairment of consciousness, oro-alimentary automatisms (lip smacking, chewing, licking, tooth grinding), behavioral arrest, head deviation, dystonic postures, hand and verbal automatisms. Seizures are followed by postictal dysfunction. Initially, seizures are easily controlled with antiepileptic drugs, later they frequently become refractory and associated with progressive behavioral changes and memory deficits. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mesial temporal lobe epilepsy with hippocampal sclerosis	None	26,661	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99701	2021-01-23T17:39:58	{"synonyms": ["MTLE-HS"]}
Creatine transporter defect SpecialtyMedical genetics Creatine Transporter Deficiency (CTD) is an inborn error of creatine metabolism in which creatine is not properly transported to the brain and muscles due to defective creatine transporters. CTD is an X-linked disorder caused by mutation in SLC6A8. SLC6A8 is located at Xq28.[1] Hemizygous males with CTD express speech and behavior abnormalities, intellectual disabilities, development delay, seizures, and autistic behavior. Heterozygous females with CTD generally express fewer, less severe symptoms.[1][2][3] CTD is one of three different types of cerebral creatine deficiency (CCD). The other two types of CCD are guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT) deficiency. Clinical presentation of CTD is similar to that of GAMT and AGAT deficiency.[4][1] CTD was first identified in 2001 with the presence of a hemizygous nonsense change in SLC6A8 in a male patient.[1] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 References * 7 External links ## Signs and symptoms[edit] Generally, the majority of individuals with creatine transporter defect express the following symptoms with varying levels of severity: developmental delay and regression, mental retardation, and abnormalities in expressive and cognitive speech.[5] However, several studies have shown a wider variety of symptoms including, but not limited to attention deficit and hyperactivity with impulsivity, myopathy, hypotonia, semantic-pragmatic language disorder, oral dyspraxia, extrapyramidal movement disorder, constipation, absent speech development, seizures, and epilepsy.[6][2][3][7] Furthermore, symptoms can significantly vary between hemizygous males and heterozygous females, although, symptoms are generally more severe in hemizygous males. Hemizygous males more commonly express seizures, growth deficiency, severe mental retardation, and severe expressive language impairment.[2][3] Heterozygous females more commonly express mild intellectual disability, impairments to confrontational naming and verbal memory, and learning and behavior problems.[6][2][8] ## Genetics[edit] CTD is caused by pathogenic variants in SLC6A8, located at Xq28. SLC6A8 contains 13 exons and spreads across 8.5 kb of genomic DNA (gDNA).[9] The presence of hemizygous variants in males and heterozygous variants in females in SLC6A8 provides evidence that CTD is inherited in an X-linked recessive manner. This usually results in hemizygous males having severe symptoms, while heterozygous female carriers tend to have less severe and more varying symptoms.[7][8] ## Mechanism[edit] The creatine phosphate system is needed for the storage and transmission of phosphate-bound energy in the brain and muscle. The brain and muscle have particularly high metabolic demands, therefore, making creatine a necessary molecule in ATP homeostasis.[10][11] In regard to the brain, in order for creatine to reach the brain, it must first pass through the blood–brain barrier (BBB). The BBB separates blood from brain interstitial fluid and is, therefore, able to regulate the transfer of nutrients to the brain from the blood. In order to pass through the BBB, creatine utilizes creatine transporter (CRT). When present at the BBB, CRT mediates the passage of creatine from the blood to the brain. When being transported from the blood to the brain, creatine has to constantly move against the creatine concentration gradient that is present at the border between the brain and circulating blood.[12] ## Diagnosis[edit] The diagnosis of CTD is usually suspected based on the clinical presentation of intellectual disability, abnormalities in cognitive and expressive speech, and developmental delay. Furthermore, a family history of X-linked intellectual disability, developmental coordination disorder, and seizures is strongly suggestive.[13] Initial screening of CTD involves obtaining a urine sample and measuring the ratio of creatine to creatinine. If the ratio of creatine to creatinine is greater than 1.5, then the presence of CTD is highly likely. This is because a large ratio indicates a high amount of creatine in the urine.[7][14] This, in turn, indicates inadequate transport of creatine into the brain and muscle. However, the urine screening test often fails in diagnosing heterozygous females. Studies have demonstrated that as a group heterozygous females have significantly decreased cerebral creatine concentration, but that individual heterozygous females often have normal creatine concentrations found in their urine. Therefore, urine screening tests are unreliable as a standard test for diagnosing CTD, particularly in females.[8] A more reliable and sophisticated manner of testing for cerebral creatine concentrations is through in vivo proton magnetic resonance spectroscopy (1H MRS). In vivo 1H MRS uses proton signals to determine the concentration of specific metabolites. This method of testing is more reliable because it provides a fairly accurate measurement of the amount of creatine inside the brain. Similar to urine testing, a drawback of using 1H MRS as a test for CTD is that the results of the test could be attributed to any of the cerebral creatine deficiencies.[14] The most accurate and reliable method of testing for CTD is through DNA sequence analysis of SLC6A8. DNA analysis of SLC6A8 allows the identification of the location and type of variant causing the cerebral creatine deficiency. Furthermore, DNA analysis of SLC6A8 is able to prove that a cerebral creatine deficiency is due to CTD and not GAMT or AGAT deficiency.[4][7][8] ## Treatment[edit] CTD is difficult to treat because the actual transporter responsible for transporting creatine to the brain and muscles is defective. Affected individuals have sufficient amounts of creatine, however it cannot get to the tissues where it is needed. Studies in which oral creatine monohydrate supplements were given to patients with CTD found that patients did not respond to treatment. However, similar studies conducted in which patients that had GAMT or AGAT deficiency were given oral creatine monohydrate supplements found that patient’s clinical symptoms improved. Patients with CTD are unresponsive to oral creatine monohydrate supplements because regardless of the amount of creatine they ingest, the creatine transporter is still defective, and therefore creatine is incapable of being transported across the BBB.[14][15] Given the major role that the BBB has in the transport of creatine to the brain and unresponsiveness of oral creatine monohydrate supplements in CTD patients, future research will focus on working with the BBB to deliver creatine supplements.[12] However, given the limited number of patients that have been identified with CTD, future treatment strategies must be more effective and efficient when recognizing individuals with CTD.[1][14] ## References[edit] 1. ^ a b c d e Salomons, G. S.; Dooren, S. J. M. Van; Verhoeven, N. M.; Marsden, D.; Schwartz, C.; Cecil, K. M.; DeGrauw, T. J.; Jakobs, C. (2003). "X-linked creatine transporter defect: An overview". Journal of Inherited Metabolic Disease. 26 (2–3): 309–318. doi:10.1023/A:1024405821638. ISSN 0141-8955. PMID 12889669. S2CID 7062586. 2. ^ a b c d Hahn, Kimberly A.; Salomons, Gajja S.; Tackels-Horne, Darci; Wood, Tim C.; Taylor, Harold A.; Schroer, Richard J.; Lubs, Herbert A.; Jakobs, Cornelis; Olson, Rick L. (2002). "X-Linked Mental Retardation with Seizures and Carrier Manifestations Is Caused by a Mutation in the Creatine-Transporter Gene (SLC6A8) Located in Xq28". The American Journal of Human Genetics. 70 (5): 1349–1356. doi:10.1086/340092. PMC 447610. PMID 11898126. 3. ^ a b c Anselm, I. M.; Alkuraya, F. S.; Salomons, G. S.; Jakobs, C.; Fulton, A. B.; Mazumdar, M.; Rivkin, M.; Frye, R.; Poussaint, T. Young (2006). "X-linked creatine transporter defect: A report on two unrelated boys with a severe clinical phenotype". Journal of Inherited Metabolic Disease. 29 (1): 214–219. doi:10.1007/s10545-006-0123-4. ISSN 0141-8955. PMC 2393549. PMID 16601897. 4. ^ a b "OMIM Entry - # 300352 - CEREBRAL CREATINE DEFICIENCY SYNDROME 1; CCDS1". www.omim.org. Retrieved 2016-11-27. 5. ^ Schulze, Andreas (2003-01-01). "Creatine deficiency syndromes". In Clark, Joseph F. (ed.). Guanidino Compounds in Biology and Medicine. Molecular and Cellular Biochemistry. Springer US. pp. 143–150. doi:10.1007/978-1-4615-0247-0_22. ISBN 9781461349853. 6. ^ a b deGrauw, Ton J.; Cecil, Kim M.; Byars, Anna W.; Salomons, Gajja S.; Ball, William S.; Jakobs, Cornelis (2003-01-01). Clark, Joseph F. (ed.). Guanidino Compounds in Biology and Medicine. Molecular and Cellular Biochemistry. Springer US. pp. 45–48. doi:10.1007/978-1-4615-0247-0_6. ISBN 9781461349853. 7. ^ a b c d Mancini, G.m.s.; Catsman-Berrevoets, C.e.; de Coo, I.f.m.; Aarsen, F.k.; Kamphoven, J.h.j.; Huijmans, J.g.; Duran, M.; van der Knaap, M.s.; Jakobs, C. (2005-01-30). "Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X-linked mental retardation in two unrelated Dutch families". American Journal of Medical Genetics Part A. 132A (3): 288–295. doi:10.1002/ajmg.a.30473. ISSN 1552-4833. PMID 15690373. 8. ^ a b c d van de Kamp, Jm; Mancini, Gms; Pouwels, Pjw; Betsalel, Ot; van Dooren, Sjm; de Koning, I; Steenweg, Me; Jakobs, C; van der Knaap, Ms (2011-03-01). "Clinical features and X-inactivation in females heterozygous for creatine transporter defect". Clinical Genetics. 79 (3): 264–272. doi:10.1111/j.1399-0004.2010.01460.x. ISSN 1399-0004. PMID 20528887. 9. ^ Sandoval, Natalia; Bauer, David; Brenner, Volker; Coy, Johannes F.; Drescher, Bernd; Kioschis, Petra; Korn, Bernd; Nyakatura, Gerald; Poustka, Annemarie (1996-07-15). "The Genomic Organization of a Human Creatine Transporter (CRTR) Gene Located in Xq28". Genomics. 35 (2): 383–385. doi:10.1006/geno.1996.0373. PMID 8661155. 10. ^ Snow, Rodney J.; Murphy, Robyn M. (2001). "Creatine and the creatine transporter: A review". Molecular and Cellular Biochemistry. 224 (1–2): 169–181. doi:10.1023/A:1011908606819. ISSN 0300-8177. PMID 11693194. S2CID 28502746. 11. ^ Stöckler, Sylvia; Hanefeld, Folker; Frahm, Jens (1996). "Creatine replacement therapy in guanidineoacetate methyltransferase deficiency, a novel inborn error of metabolism". The Lancet. 348 (9030): 789–790. doi:10.1016/s0140-6736(96)04116-5. PMID 8813986. 12. ^ a b Ohtsuki, Sumio; Tachikawa, Masanori; Takanaga, Hitomi; Shimizu, Hidemi; Watanabe, Masahiko; Hosoya, Ken-ichi; Terasaki, Tetsuya (2002-11-01). "The Blood–Brain Barrier Creatine Transporter is a Major Pathway for Supplying Creatine to the Brain". Journal of Cerebral Blood Flow & Metabolism. 22 (11): 1327–1335. doi:10.1097/01.WCB.0000033966.83623.7D. ISSN 0271-678X. PMID 12439290. 13. ^ Leuzzi, Vincenzo; Mastrangelo, Mario; Battini, Roberta; Cioni, Giovanni (2013-02-01). "Inborn errors of creatine metabolism and epilepsy". Epilepsia. 54 (2): 217–227. doi:10.1111/epi.12020. ISSN 1528-1167. PMID 23157605. 14. ^ a b c d Stromberger, C.; Bodamer, O. A.; Stöckler-Ipsiroglu, S. (2003). "Clinical characteristics and diagnostic clues in inborn errors of creatine metabolism". Journal of Inherited Metabolic Disease. 26 (2–3): 299–308. doi:10.1023/A:1024453704800. ISSN 0141-8955. PMID 12889668. S2CID 24963392. 15. ^ Wyss, Markus; Schulze, Andreas (2002-06-18). "Health implications of creatine: can oral creatine supplementation protect against neurological and atherosclerotic disease?". Neuroscience. 112 (2): 243–260. doi:10.1016/S0306-4522(02)00088-X. PMID 12044443. S2CID 24582378. ## External links[edit] Classification D * ICD-10: E72.9 * OMIM: 300532 * MeSH: C535598 * DiseasesDB: 34691 External resources * GeneReviews: Cerebral creatine deficiencies [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Creatine transporter defect	c1845862	26,662	wikipedia	https://en.wikipedia.org/wiki/Creatine_transporter_defect	2021-01-18T18:51:13	{"gard": ["1608"], "mesh": ["C535598"], "umls": ["C1845862"], "orphanet": ["52503"], "wikidata": ["Q17084842"]}
Linear porokeratosis is a rare skin condition characterized by streaks of reddish-brown patches surrounded by a ridge-like border. The patches usually develop in infants or young children, but they sometimes develop in adults. Patches may be on one area of the body (localized) or on multiple areas (generalized). They usually develop in a pattern over the skin known as the "lines of Blaschko," and most commonly occur on the arms or trunk. Some people experience itching or pain where the patches occur. Linear porokeratosis is thought be a form of disseminated superficial actinic porokeratosis (DSAP). Researchers think that people with linear porokeratosis may have one inherited mutation in a gene that causes DSAP. It is thought that a second mutation in that gene is acquired (a somatic mutation), occurring in only some cell lines. This may cause the presence of streaks of patches, rather than more widespread patches. Treatment options depend on each person's symptoms. There are no specific recommendations for treatment because no randomized clinical trials have been done. Options may include topical therapies, oral retinoids, cryotherapy, electrodessication, and surgery. Linear porokeratosis can progress to skin cancer (squamous cell and basal cell carcinoma), so sun protection and watching for changes within patches are recommended. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Linear porokeratosis	c0302319	26,663	gard	https://rarediseases.info.nih.gov/diseases/9515/linear-porokeratosis	2021-01-18T17:59:22	{"mesh": ["D017499"], "umls": ["C0302319"], "synonyms": ["Congenital facial linear porokeratosis (type)"]}
## Summary ### Clinical characteristics. Autosomal dominant polycystic kidney disease (ADPKD) is generally a late-onset multisystem disorder characterized by bilateral renal cysts, liver cysts, and an increased risk of intracranial aneurysms. Other manifestations include: cysts in the pancreas, seminal vesicles, and arachnoid membrane; dilatation of the aortic root and dissection of the thoracic aorta; mitral valve prolapse; and abdominal wall hernias. Renal manifestations include hypertension, renal pain, and renal insufficiency. Approximately 50% of individuals with ADPKD have end-stage renal disease (ESRD) by age 60 years. The prevalence of liver cysts increases with age and occasionally results in clinically significant severe polycystic liver disease (PLD). Overall the prevalence of intracranial aneurysms is fivefold higher than in the general population and further increased in those with a positive family history of aneurysms or subarachnoid hemorrhage. There is substantial variability in the severity of renal disease and other extrarenal manifestations even within the same family. ### Diagnosis/testing. The diagnosis of ADPKD is established in a proband with age-specific renal imaging criteria and an affected first-degree relative with ADPKD or identification of a heterozygous pathogenic variant in PKD1, PKD2, GANAB, or DNAJB11. ### Management. Treatment of manifestations: Vasopressin V2 receptor antagonists (e.g., tolvaptan) to slow disease progression. Treatment for hypertension may include ACE inhibitors or angiotensin II receptor blockers and diet modification. Conservative treatment of flank pain includes nonopioid agents, tricyclic antidepressants, narcotic analgesics, and splanchnic nerve blockade. More aggressive treatments include cyst decompression with cyst aspiration and sclerosis, laparoscopic or surgical cyst fenestration, renal denervation, and nephrectomy. Cyst hemorrhage and/or gross hematuria is usually self-limiting. Treatment of nephrolithiasis is standard. Treatment of cyst infections is difficult, with a high failure rate. Therapeutic agents of choice may include trimethoprim-sulfamethoxazole, fluoroquinolones, clindamycin, vancomycin, and metronidazole. The diagnosis of malignancy requires a high index of suspicion. Therapeutic interventions aimed at slowing the progression of ESRD in ADPKD include control of hypertension and hyperlipidemia, dietary protein restriction, control of acidosis, and prevention of hyperphosphatemia. Most individuals with PLD have no symptoms and require no treatment, but rare severe cases may require surgical resection or even liver transplantation. The mainstay of therapy for ruptured or symptomatic intracranial aneurysm is surgical clipping of the ruptured aneurysm at its neck; however, for some individuals, endovascular treatment with detachable platinum coils may be indicated. Thoracic aortic replacement is indicated when the aortic root diameter exceeds established size. Prevention of secondary manifestations (lifestyle and therapeutic factors that may modulate disease): Maintain appropriate blood pressure and urine osmolarity; low osmolar intake (e.g., moderate sodium and protein); increase hydration by moderate water intake; maintain sodium bicarbonate ≥22 mEq/L; moderate dietary phosphorus intake; moderate caloric intake to maintain normal BMI; low-impact exercise; lipid control; tolvaptan therapy. Surveillance: Early blood pressure monitoring starting in childhood; MRI screening for intracranial aneurysms in those determined to be at high risk; screening echocardiography in those with a heart murmur and those with a family history of a first-degree relative with a thoracic aortic dissection. Agents/circumstances to avoid: Long-term administration of nephrotoxic agents, high levels of caffeine, use of estrogens and possibly progestogens by individuals with severe PLD, smoking, and obesity. Evaluation of relatives at risk: Testing of adult relatives at risk permits early detection and treatment of complications and associated disorders. Pregnancy management: Pregnant women with ADPKD should be monitored for the development of hypertension, urinary tract infections, oligohydramnios, and preeclampsia; the fetus should be monitored for intrauterine fetal growth restriction, oligohydramnios, and fetal kidney anomalies including cysts, enlarged size, and atypical echogenicity. ### Genetic counseling. ADPKD is inherited in an autosomal dominant manner. About 95% of individuals with ADPKD have an affected parent, but at least 10% of families can be traced to a de novo pathogenic variant. Each child of an affected individual has a 50% chance of inheriting the pathogenic variant. Once the pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for ADPKD are possible. ## Diagnosis Diagnostic criteria for autosomal dominant polycystic kidney disease (ADPKD) are discussed in the executive summary of the KDIGO Controversies Conference [Chapman et al 2015]. ### Suggestive Findings ADPKD should be suspected in individuals with the following: * Multiple bilateral renal cysts and the absence of manifestations suggestive of a different renal cystic disease * Cysts in other organs, especially the liver, but also seminal vesicles, pancreas, and arachnoid membrane * Enlargement of the kidneys or liver on physical examination * Hypertension in an individual younger than age 35 years * An intracranial aneurysm * A family history of ADPKD ### Establishing the Diagnosis The diagnosis of ADPKD is established in a proband with ANY of the following: * Age-specific ultrasound criteria and an affected first-degree relative with ADPKD * Age-specific MRI criteria and an affected first-degree relative with ADPKD * Identification of a heterozygous pathogenic variant in one of the genes listed in Table 3 #### Age-Specific Ultrasound Criteria Age-specific ultrasound criteria in an individual with an affected first-degree relative [Pei et al 2009]: * The presence of three or more (unilateral or bilateral) renal cysts in an individual age 15-39 years * The presence of two or more cysts in each kidney in an individual age 40-59 years * Large echogenic kidneys without distinct macroscopic cysts in an infant/child at 50% risk for ADPKD Note: (1) The positive predictive value of these criteria is described as 100%, regardless of (a) whether the disorder is PKD1\- or PKD2-related ADPKD and (b) the age of the individual at the time of initial evaluation (see Table 1). Note that there are other genetic causes of renal cysts in addition to pathogenic variants in PKD1 or PKD2 (Table 3, Table 5). (2) The sensitivity is low (Table 1; 81.7%-95.5%), particularly in families with a pathogenic variant in PKD2 (69.5%-94.9%). A low sensitivity is likely true for families with a nontruncating PKD1 pathogenic variant (does not truncate or shorten the protein product, polycystin-1), and for pathogenic variants in GANAB or DNAJB11, which are typically associated with mild cystic disease (Table 3). In these situations, a significant number of affected individuals may not be diagnosed, which may pose a problem when exclusion of the diagnosis is critical (see Excluding the Diagnosis). ### Table 1. Ultrasound Criteria for Diagnosis of ADPKD in Individuals at 50% Risk for ADPKD Based on Family History View in own window AgePKD1PKD2Unknown ADPKD Genotype 15-30 yrs≥3 cysts 1 PPV = 100% SEN = 94.3%≥3 cysts 1 PPV = 100% SEN = 69.5%≥3 cysts 1 PPV = 100% SEN = 81.7% 30-39 yrs≥3 cysts 1 PPV = 100% SEN = 96.6%≥3 cysts 1 PPV = 100% SEN = 94.9%≥3 cysts 1 PPV = 100% SEN = 95.5% 40-59 yrs≥2 cysts in each kidney PPV = 100% SEN = 92.6%≥2 cysts in each kidney PPV = 100% SEN = 88.8%≥2 cysts in each kidney PPV = 100% SEN = 90% Derived from Pei et al [2009]. All values presented are mean estimates. PPV = positive predictive value; SEN = sensitivity 1\. Unilateral or bilateral Age-specific MRI criteria are particularly useful when ultrasound results are equivocal [Pei et al 2015]. For individuals ages 16-40 years who are at 50% risk for ADPKD because they have an affected first-degree relative, the presence of more than ten cysts is sufficient for a diagnosis of ADPKD. Note: These criteria may also be more appropriate to use when employing a modern, high-resolution ultrasound scanner that can detect cysts as small as 1-2 mm. #### Excluding the Diagnosis The absence of renal cysts by ultrasound examination virtually excludes a diagnosis of ADPKD caused by a truncating PKD1 pathogenic variant, which predicts a truncated polycystin-1, in an at-risk person age 15-30 years (negative predictive value [NPV] = 99.1%) or older (NPV = 100%). However, absence of renal cysts does not exclude the diagnosis in persons younger than age 40 years who are at risk for ADPKD caused by incompletely penetrant, nontruncating PKD1 variants or pathogenic variants in other ADPKD-related genes associated with milder disease. A normal renal ultrasound does not exclude ADPKD with certainty in an at-risk individual younger than age 30 years (see Table 2). Ultrasound criteria used to exclude an at-risk relative as a potential living-related kidney donor are shown in Table 2. MRI or contrast-enhanced CT examination, which has much higher sensitivity than ultrasound to detect cysts and is routinely performed in most transplantation centers to define the donor kidney anatomy, provides further assurance for the exclusion of the diagnosis if cysts are absent (see Age-specific MRI criteria). When evaluating at-risk individuals in the same age group as living-related donors, fewer than five cysts is considered sufficient for exclusion of the disease. When the family-specific pathogenic variant has not been identified: * Ultrasound examination showing normal kidneys in an individual age 30-39 years or no more than one renal cyst in an individual age 40 years or older has a negative predictive value of 100%. * The family history of renal disease severity can be used as a rough guide to predict the severity of disease in other family members (see Genotype-Phenotype Correlations). ### Table 2. Ultrasound Criteria That Exclude an Individual at 50% Risk for ADPKD from Being a Kidney Donor View in own window AgePKD1PKD2Unknown ADPKD Genotype 15-30 years≥1 cyst NPV = 99.1% SPEC = 97.6%≥1 cyst NPV = 83.5% SPEC = 96.6%≥1 cyst NPV = 90.8% SPEC = 97% 30-39 years≥1 cyst NPV = 100% SPEC = 96%≥1 cyst NPV = 96.8% SPEC = 93.8%≥1 cyst NPV = 98.3% SPEC = 94.8% 40-59 years≥2 cysts NPV = 100% SPEC = 98.4%≥2 cysts NPV = 100% SPEC = 97.8%≥2 cysts NPV = 100% SPEC = 98.2% Derived from Pei et al [2009]. All values presented are mean estimates. NPV = negative predictive value; SPEC = specificity #### Molecular Genetic Testing Testing approaches can include a multigene panel or concurrent gene testing. Option 1 (recommended) A multigene panel that includes PKD1, PKD2, GANAB, DNAJB11, and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) Multigene panels using next-generation sequencing should be carefully designed to maximize identification of a PKD1 pathogenic variant, which is complicated by several highly homologous pseudogenes [Trujillano et al 2014, Eisenberger et al 2015]. (2) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (3) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (4) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (5) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. Option 2 Concurrent gene testing. Sequence analysis and deletion/duplication analysis of PKD1 and PKD2 can be performed concurrently. Note: Sequence analysis should be designed to maximize identification of a PKD1 pathogenic variant, which is complicated by several highly homologous pseudogenes [Trujillano et al 2014, Eisenberger et al 2015]. ### Table 3. Molecular Genetic Testing Used in ADPKD View in own window Gene 1Proportion of ADPKD Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 2 Detectable by Method Sequence analysis 3Gene-targeted deletion/duplication analysis 4 PKD1~78%~97% 5~3% PKD2~15%~97% 5~3% GANAB~0.3%7/7Unknown, none reported 6 DNAJB11~0.1%7/7Unknown, none reported 6 Unknown~7%NA 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Due to the segmental duplication of PKD1, such analysis may require specific methods that detect large rearrangements, such as multiplex ligation-dependent probe amplification (MLPA) [Consugar et al 2008, Cornec-Le Gall et al 2013] or chromosomal microarray (CMA) that includes this gene/chromosome segment. 5\. Rossetti et al [2007], Audrézet et al [2012], Cornec-Le Gall et al [2016], Heyer et al [2016] 6\. No data on detection rate of gene-targeted deletion/duplication analysis are available. ## Clinical Characteristics ### Clinical Description #### Renal Manifestations Although all individuals with autosomal dominant polycystic kidney disease (ADPKD) develop cysts within the kidneys, there is substantial variability in severity of renal disease and other manifestations of the disease, even within the same family. Poor prognostic factors include: diagnosis before age 30 years [Gabow 1996]; first episode of hematuria before age 30 years; onset of hypertension before age 35 years [Cornec-Le Gall et al 2016]; hyperlipidemia and high body mass index (BMI) [Nowak et al 2018]; high urine sodium excretion [Torres et al 2017a]; lower renal blood flow; lower serum HDL cholesterol [Torres et al 2011a]; large total kidney volume (TKV) [Chapman et al 2012, Irazabal et al 2015]; and the presence of a truncating PKD1 variant [Cornec-Le Gall et al 2013, Heyer et al 2016]. The lower incidence of end-stage renal disease (ESRD) in affected females compared to affected males suggests that ADPKD is a more severe disease in males. Analysis of a population of individuals with PKD1-related ADPKD from the French Genkyst cohort showed poorer renal survival in males than females (mean age at onset of ESRD was 58.1 years for males and 59.5 years for females) [Cornec-Le Gall et al 2013]. Heyer et al [2016] showed lower estimated glomerular filtration rate (eGFR) and larger height-adjusted TKV (htTKV) in males compared to females in the total HALT PKD study population and in individuals with PKD1-related ADPKD. Males with PKD2-related ADPKD also had lower eGFR. Males with truncating PKD1 variants, onset of hypertension before age 35 years, and/or a urologic event before age 35 years were the most severely affected [Cornec-Le Gall et al 2016]. Cyst development and growth. The renal manifestations of ADPKD include renal function abnormalities, hypertension, renal pain, and renal insufficiency. These manifestations are directly related to the development and enlargement of renal cysts. A study by the Consortium of Imaging Studies to Assess the Progression of Polycystic Kidney Disease (CRISP) of 241 non-azotemic affected individuals followed prospectively with annual MRI examinations showed that TKV and cyst volumes increased exponentially. At baseline, TKV was 1,060 ± 642 mL; the mean increase over three years was 204 mL, or 5.3% per year. The baseline TKV predicted the subsequent rate of increase in renal volume, meaning that the larger the kidney, the faster the rate of renal enlargement over time. Declining glomerular filtration rate (GFR) was observed in persons with baseline TKV above 1,500 mL [Grantham et al 2006]. Kidney size has been shown to be a strong predictor of subsequent decline in renal function with an htTKV of ≥600 mL/m showing a high predictive value for the individual to develop renal insufficiency within eight years [Chapman et al 2012]. Compartmentalizing age-adjusted htTKV into five classes based on htTKV/age has also shown that this strongly predicts decline in renal function and ESRD. A model including htTKV (that can be estimated using renal dimensions and the ellipsoid equation), age, and eGFR (available via an online app) has good predictive value in estimating future eGFR [Irazabal et al 2015]. Individuals with PKD1-related ADPKD often have significantly larger kidneys with more cysts than individuals with PKD2-related ADPKD. However, the rates of cystic growth are not different, indicating that PKD1-related ADPKD is more severe because more cysts develop earlier, not because they grow faster [Harris et al 2006]. Occasionally, enlarged and echogenic kidneys with or without renal cysts are detected prenatally in a fetus at risk for ADPKD [Zerres et al 1993]. The prognosis in these individuals is often more favorable than expected given the large kidney size with a decrease in volume and no decline in renal function commonly seen, at least during childhood. However, ESRD develops earlier than is typically seen in adult-onset disease [Fick et al 1993, Zerres et al 1993]. Biallelic PKD1 or PKD2 pathogenic variants have been reported in individuals with very early-onset ADPKD (see Genotype-Phenotype Correlations) [Cornec-Le Gall et al 2018]. Renal function abnormalities. Reduction in urinary concentrating capacity and excretion of ammonia occur early in individuals with ADPKD. The reduction of urinary excretion of ammonia in the presence of metabolic stresses (e.g., dietary indiscretions) may contribute to the development of uric acid and calcium oxalate stones, which, in association with low urine pH values and hypocitric aciduria, occur with increased frequency in individuals with ADPKD. Studies suggest that the urinary concentrating defect and elevated serum concentration of vasopressin may contribute to cystogenesis [Nagao et al 2006]. They may also contribute to the glomerular hyperfiltration seen in children and young adults, development of hypertension, and progression of chronic kidney disease [Torres 2005]. Plasma copeptin concentration (a marker of endogenous vasopressin levels) has been associated with various markers of disease severity (positively with TKV and albuminuria and negatively with GFR and effective renal blood flow) in a cross-sectional analysis of people with ADPKD [Meijer et al 2011]. Plasma copeptin concentration has also been associated with the change in TKV during follow up in the CRISP study [Boertien et al 2013]. A decline in renal function, detected as a rise in serum creatinine, is generally seen only later in the course of disease, typically about a dozen years before ESRD. However, once kidney function starts to deteriorate, GFR has been observed to decline rapidly (~4-6 mL/min/yr) [Klahr et al 1995]. The severity of the kidney disease may influence the timing and rate of decline. Another early functional abnormality is a reduction in renal blood flow, which can be detected in young individuals (when systolic and diastolic blood pressures are still normal) and precedes the development of hypertension [Torres et al 2007b]. Hypertension usually develops before any decline in GFR. It is characterized by the following: * An increase in renal vascular resistance and filtration fraction * Normal or high peripheral plasma renin activity * Resetting of the pressure-natriuresis relationship * Salt sensitivity * Normal or increased extracellular fluid volume, plasma volume, and cardiac output * Partial correction of renal hemodynamics and sodium handling by converting enzyme inhibition Hypertension is often diagnosed much later than when it first occurs in individuals with ADPKD. Twenty-four-hour monitoring of ambulatory blood pressure of children or young adults may reveal elevated blood pressure, attenuated decrease in nocturnal blood pressure, and exaggerated blood pressure response during exercise, which may be accompanied by left ventricular hypertrophy and diastolic dysfunction [Seeman et al 2003]. Monitoring of blood pressure in children at risk for ADPKD is recommended [Massella et al 2018]. Early detection and treatment of hypertension in ADPKD is important because cardiovascular disease is the main cause of death. Uncontrolled high blood pressure increases the risk for: * Proteinuria, hematuria, and a faster decline of renal function; * Morbidity and mortality from valvular heart disease and aneurysms; * Fetal and maternal complications during pregnancy. Renal pain. Pain is a common manifestation of ADPKD [Bajwa et al 2004]. Potential etiologies include: cyst hemorrhage, nephrolithiasis, cyst infection, and, rarely, tumor. Discomfort, ranging from a sensation of fullness to severe pain, can also result from renal enlargement and distortion by cysts. Gross hematuria can occur in association with complications such as cyst hemorrhage and nephrolithiasis or as an isolated event. Passage of clots can also be a source of pain. Cyst hemorrhage can be accompanied by fever, possibly caused by cyst infection. Most often, the pain is self-limited and resolves within two to seven days. Rarely, pain may be caused by retroperitoneal bleeding that may be severe and require transfusion. Nephrolithiasis. The prevalence of renal stone disease in individuals with ADPKD is approximately 20% [Torres et al 1993]. The majority of stones are composed of uric acid and/or calcium oxalate. Urinary stasis thought to be secondary to distorted renal anatomy and metabolic factors plays a role in the pathogenesis [Torres et al 2007a]. Postulated factors predisposing to the development of renal stone disease in ADPKD include: decreased ammonia excretion, low urinary pH, and low urinary citrate concentration. However, these factors occur with the same frequency in individuals with ADPKD with and without a history of nephrolithiasis [Nishiura et al 2009]. Urinary tract infection and cyst infection. In the past, the incidence of urinary tract infection may have been overestimated in individuals with ADPKD because of the frequent occurrence of sterile pyuria. As in the general population, females experience urinary tract infections more frequently than males; the majority of infections are caused by E coli and other enterobacteriaceae. Retrograde infection from the bladder may lead to pyelonephritis or cyst infection. Renal cyst infections account for approximately 9% of hospitalizations in individuals with ADPKD [Sallée et al 2009]. Renal cell carcinoma (RCC) does not occur more frequently in individuals with ADPKD than in the general population. However, when RCC develops in individuals with ADPKD, it has a different biologic behavior, including: earlier age of presentation; frequent constitutional symptoms; and a higher proportion of sarcomatoid, bilateral, multicentric, and metastatic tumors. Males and females with ADPKD are equally likely to develop RCC. A solid mass on ultrasound; speckled calcifications on CT examination; and contrast enhancement, tumor thrombus, and regional lymphadenopathies on CT or MRI examination should raise suspicion for a carcinoma. An increased risk for RCC in individuals with ADPKD who are on dialysis for ESRD can be explained by the increased incidence of RCC with advanced kidney disease [Hajj et al 2009, Nishimura et al 2009]. A retrospective study of 40,821 Medicare primary renal transplant recipients transplanted from January 1, 2000 to July 31, 2005 (excluding those with pre-transplant nephrectomy), demonstrated that acquired renal cystic disease pre-transplant, but not ADPKD, was associated with post-transplant RCC. When age and other co-variants were taken into consideration, the rate of all cancers in individuals with ADPKD after kidney transplantation was reported to be lower than in kidney transplant recipients who did not have ADPKD [Wetmore et al 2014]. Other. Massive renal enlargement can cause complications resulting from compression of local structures, such as inferior vena cava compression and gastric outlet obstruction (mainly caused by cysts of the right kidney). Renal failure. Approximately 50% of individuals with ADPKD have ESRD by age 60 years. Mechanisms accounting for the decline in renal function include: compression of the normal renal parenchyma by expanding cysts, vascular sclerosis, interstitial inflammation and fibrosis, and apoptosis of the tubular epithelial cells. The CRISP study [Grantham et al 2006] confirmed a strong relationship with renal enlargement and showed that kidney and cyst volumes are the strongest predictors of renal functional decline. CRISP also found that renal blood flow (or vascular resistance) is an independent predictor of renal function decline [Torres et al 2007b]. This points to the importance of vascular remodeling in the progression of the disease and may account for reports in which the decline of renal function appears to be out of proportion to the severity of the cystic disease. Angiotensin II, transforming growth factor-β, and reactive oxygen species may contribute to the vascular lesions and interstitial fibrosis by stimulating the synthesis of chemokines, extracellular matrix, and metalloproteinase inhibitors. Other factors including heavy use of analgesics may contribute to kidney disease progression in some individuals. #### Extrarenal Manifestations Polycystic liver disease (PLD) is the most common extrarenal manifestation of ADPKD. Hepatic cysts are rare in children. The frequency of hepatic cysts increases with age and may have been underestimated by ultrasound and CT studies. Their prevalence by MRI in the CRISP study is 58% in participants age 15-24 years, 85% in those age 25-34 years, and 94% in those age 35-46 years [Bae et al 2006]. PLD develops at a younger age in women than men and is more severe in women who have had multiple pregnancies. After menopause, the size of liver cysts increased in women who received estrogen replacement therapy, suggesting that estrogens have an important effect on the progression of PLD [Everson & Taylor 2005]. Analysis of liver volumes and liver cyst volumes in 534 individuals with ADPKD in the HALT PKD study showed an increase in parenchymal volume and a correlation between the severity of PLD and biochemical and hematologic features, in addition to reduced quality of life [Hogan et al 2015]. Analysis of individuals with severe PLD, defined as a height-adjusted total liver volume of 1.8 liters, showed no difference in frequency among those with truncating PKD1 variants, nontruncating PKD1 variants, and PKD2 pathogenic variants, suggesting that other factors are primarily responsible for the severity of PLD [Chebib et al 2016]. This study also showed that severe PLD often regressed in females after menopause. Liver cysts are usually asymptomatic and never cause liver failure. Symptoms, when they occur, are caused by the mass effect of the cysts, the development of complications, or rare associations. Mass effects include: abdominal distention and pain, early satiety, dyspnea, and low back pain. Liver cysts can also cause extrinsic compression of the inferior vena cava (IVC), hepatic veins, or bile ducts [Torres 2007]. The liver cyst epithelia produce and secrete carbohydrate antigen 19-9 (CA19-9), a tumor marker for gastrointestinal cancers. The concentration of CA19-9 is increased in the serum of individuals with PLD and markedly elevated in hepatic cyst fluid. Serum CA19-9 levels correlate with polycystic liver volume [Waanders et al 2009, Kanaan et al 2010]. Complications of PLD include cyst hemorrhage, infection, or rupture. Hemorrhagic cysts may cause fever and masquerade as cholecystitis or cyst infection. Usually cyst infections are monomicrobial, are caused by enterobacteriaceae, and present with localized pain or tenderness, fever, leukocytosis, elevated erythrocyte sedimentation rate, and high serum concentration of alkaline phosphatase and CA19-9. Elevations of CA19-9, however, can also be observed in other conditions causing abdominal pain and fever, such as acute cholangitis or diverticulitis. CT and MRI examination are helpful in the diagnosis of cyst infection but have low specificity. On CT examination, the following have been associated with infection: fluid-debris levels within cysts, cyst wall thickening, intracystic gas bubbles, and heterogeneous or increased density. Indium-labeled white blood cell scans are more specific but not always conclusive. 18F-fluorodeoxyglucose positron emission tomography examination is the most sensitive technique for diagnosis of infected cysts [Bleeker-Rovers et al 2003]. The rupture of a hepatic cyst can cause acute abdominal pain and ascites. Other liver disease * Dilatation of biliary ducts may be associated with episodes of cholangitis. * Congenital hepatic fibrosis is rarely seen in individuals with ADPKD. * Cholangiocarcinoma is infrequently associated with ADPKD. * Adenomas of the ampulla of Vater have been rarely reported. Pancreatic lesions * Pancreatic cysts occur in approximately 8% of individuals with ADPKD. They are usually less prominent than those observed in von Hippel-Lindau syndrome (see Table 5). They are almost always asymptomatic, and rarely associated with recurrent pancreatitis [Başar et al 2006]. * Intraductal papillary mucinous tumors have been reported with increased frequency, but their prevalence and prognosis in ADPKD are uncertain [Naitoh et al 2005]. * An association between ADPKD and pancreatic carcinomas was reported [Sakurai et al 2001]; however, this may represent a chance association of two common disorders. Cysts in other organs * Seminal vesicle cysts, present in 40% of males, rarely result in infertility. Defective sperm motility is another cause of male infertility in ADPKD [Torra et al 2008]. * Arachnoid membrane cysts, present in 8% of affected individuals [Danaci et al 1998], are usually asymptomatic, but may increase the risk for subdural hematomas [Wijdicks et al 2000]. * Spinal meningeal diverticula may occur with increased frequency and individuals may present with intracranial hypotension secondary to cerebrospinal fluid leak [Schievink & Torres 1997]. * Ovarian cysts are not associated with ADPKD [Stamm et al 1999, Heinonen et al 2002]. Vascular and cardiac manifestations. The most important non-cystic manifestations of ADPKD include: intracranial and other arterial aneurysms and, more rarely, dolichoectasias, dilatation of the aortic root, dissection of the thoracic aorta and cervicocephalic arteries, abnormalities of the cardiac valves, and, possibly, coronary artery aneurysms [Pirson et al 2002]. Evidence of familial clustering of thoracic aortic dissections in ADPKD also exists. Intracranial aneurysms occur in approximately 10% of individuals with ADPKD [Pirson et al 2002]. The prevalence is higher in those individuals with a positive family history of intracranial or subarachnoid hemorrhage (22%) than in those without such a family history (6%). The majority of intracranial aneurysms are asymptomatic. Focal findings, such as cranial nerve palsy or seizure, may result from compression of local structures by an enlarging aneurysm. The mean age of rupture of intracranial aneurysms is lower in individuals with ADPKD than in the general population (39 years vs 51 years). The risk of rupture of asymptomatic intracranial aneurysms depends on the history of rupture from a different site [International Study of Unruptured Intracranial Aneurysms Investigators 1998]. In the absence of a history of rupture from a different site, the risk for rupture is as follows: * 0.05% per year for aneurysms <10 mm in diameter * ~1% per year for aneurysms 10-24 mm * 6% within one year for aneurysms ≥25 mm In the presence of a history of rupture from a different site, the risk of rupture is 0.5%-1% per year regardless of size. The risk of rupture of symptomatic aneurysms is higher – approximately 4% per year. Intracranial aneurysm rupture confers a 35% to 55% risk for combined severe morbidity and mortality at three months [Inagawa 2001]. At the time of rupture of an aneurysm, most individuals have normal renal function; and up to 30% have normal blood pressure. Follow-up studies of individuals with ADPKD with intracranial aneurysms found a moderate risk for the development of new aneurysms or enlargement of an existing one in previously symptomatic individuals and a low risk of enlargement of asymptomatic aneurysms detected by presymptomatic screening [Belz et al 2003, Gibbs et al 2004, Irazabal et al 2011]. Individuals with ADPKD may be at increased risk for vasospasm and transient ischemic complications following cerebral angiography. They may also be at increased risk for central retinal arterial and venous occlusions, possibly as a result of enhanced vasoconstriction to adrenergic stimulation and arterial wall remodeling [Qian et al 2007b]. Mitral valve prolapse, the most common valvular abnormality in ADPKD, has been demonstrated by echocardiography in up to 25% of affected individuals. Aortic insufficiency may occur in association with dilatation of the aortic root. Although these lesions may progress with time, they rarely require valve replacement. Screening echocardiography is not indicated unless a murmur is detected on examination. Several studies have shown increased left ventricular mass, left ventricular diastolic dysfunction, endothelial dysfunction, increased carotid intima-media thickness, and exaggerated blood pressure response during exercise even in young normotensive individuals with ADPKD with well-preserved renal function. Even normotensive individuals with ADPKD may show significant biventricular diastolic dysfunction, suggesting cardiac involvement early in the course of the disease [Martinez-Vea et al 2004, Oflaz et al 2005]. The clinical significance of this finding remains to be determined. A study of 543 affected individuals with GFR >60 mL/min per 1.73 m2, short duration of hypertension, and prior use of angiotensin-converting enzyme inhibitors / angiotensin receptor blockers who underwent cardiac MRI found a very low prevalence of left ventricular hypertrophy, possibly due to early blood pressure intervention [Perrone et al 2011]. Pericardial effusion occurs with an increased frequency in individuals with ADPKD, possibly because of increased compliance of the parietal pericardium. These effusions are generally well tolerated and clinically inconsequential. In the absence of known predisposing factors, extensive investigative and/or therapeutic interventions for silent pericardial effusion in persons with ADPKD are not indicated [Qian et al 2007a]. Recent studies have suggested that individuals with ADPKD may be predisposed to idiopathic dilated and hypertrophic obstructed cardiomyopathy, and left ventricular non-compaction [Paavola et al 2013, Chebib et al 2017]. Diverticular disease. Colonic diverticulosis and diverticulitis are more common in individuals with ESRD associated with ADPKD than in those with other renal diseases [Sharp et al 1999, Lederman et al 2000]. Whether this increased risk extends to persons with ADPKD prior to development of ESRD is uncertain. Extracolonic diverticular disease may also occur with increased frequency and become clinically significant in a minority of affected individuals [Kumar et al 2006]. #### Mosaicism Variable disease presentation in a family and apparent de novo disease can be due to mosaicism. Four families with ADPKD in which an individual has been found to have a somatic and/or germline PKD1 pathogenic variant have been described [Connor et al 2008, Consugar et al 2008, Reiterová et al 2013, Tan et al 2015]. The disease phenotype in these families is variable, ranging from similar to other non-mosaic affected family members, to much milder disease, presumably reflecting the level of the pathogenic variant in the kidneys. A recent study of individuals with ADPKD without a family history found germline mosaicism in two families and somatic mosaicism in one [Iliuta et al 2017]. ### Phenotype Correlations by Gene PKD1. Pathogenic variants in PKD1 are associated with more severe disease with an earlier age at diagnosis and mean age of onset of ESRD than in PKD2-related ADPKD (58.1 years for PKD1; 79.7 years for PKD2) [Hateboer et al 1999, Cornec-Le Gall et al 2013]. Most individuals with fully penetrant pathogenic variants in PKD1 experience renal failure by age 70 years; more than 50% of individuals with pathogenic variants in PKD2 have adequate renal function at that age. GANAB. Pathogenic variants cause mild cystic kidney disease, usually without a decline in renal function, with the majority of affected individuals having liver cysts [Porath et al 2016]. However, some affected individuals have a phenotype of autosomal dominant polycystic liver disease (ADPLD) with severe liver cystic disease and few renal cysts [Porath et al 2016, Besse et al 2017, Besse et al 2018]. DNAJB11. The phenotype is quite consistent and results in the development of small, bilateral kidney cysts, usually without renal enlargement. In older individuals the kidneys become fibrotic and renal insufficiency often develops; ESRD is noted in seven individuals between ages 59 and 89 years [Cornec-Le Gall et al 2018]. The renal insufficiency without renal enlargement shows some characteristics of autosomal dominant tubulointerstitial kidney disease (ADTKD). Liver cysts are sometimes present. ### Genotype-Phenotype Correlations PKD1. The average age at onset of ESRD in affected individuals with truncating PKD1 variants is 55.6 years compared to 67.9 years for those with nontruncating PKD1 variants, suggesting that a significant proportion of in-frame changes are likely hypomorphic (i.e., resulting in partial loss of gene function, which is manifested as a reduced level of functional protein) [Cornec-Le Gall et al 2013, Hwang et al 2016]. More detailed bioinformatic analysis divided nontruncating PKD1 pathogenic variants into two mutation strength groups (MSG), with nonconservative substitutions at well-conserved sites in orthologs and domains (MSG2) found to have similar severity to truncating PKD1 pathogenic variants in terms of eGFR and htTKV [Heyer et al 2016]. Therefore, it is likely that approximately 50% of missense and other in-frame changes are fully penetrant pathogenic variants [Harris & Hopp 2013]. However, a group of variants with more conservative substitutions at less well-conserved sites (MSG3) was found to be hypomorphic by analysis of eGFR and htTKV. Family studies have identified incompletely penetrant nontruncating PKD1 variants that are associated with less severe disease [Rossetti et al 2009, Pei et al 2012]. One such well-studied PKD1 variant, p.Arg3277Cys, causes just a few cysts or no evidence of disease in heterozygotes [Rossetti et al 2009]. These hypomorphic alleles often result in a reduced level of functional protein. Thus the phenotype depends on whether a hypomorphic allele occurs in isolation or in combination with other PKD1 and/or PKD2 pathogenic variants (see Biallelic PKD1\- and PKD2-related ADPKD). PKD2. Recently, truncating PKD2 pathogenic variants were found to be associated with more severe disease with lower eGFR than nontruncating pathogenic variants [Cornec-Le Gall et al 2017]. Biallelic PKD1\- or PKD2-related ADPKD. Fully penetrant (i.e., non-hypomorphic) biallelic pathogenic variants in either PKD1 or PKD2 in humans are predicted to be incompatible with live birth, consistent with Pkd1 or Pkd2 knockout mice that develop fetal cystic kidneys and are embryonic lethal [Lu et al 1997, Wu et al 2000]. However, biallelic pathogenic variants where at least one variant is hypomorphic can be compatible with life. Rossetti et al [2009] reported two families with individuals homozygous for PKD1 pathogenic variants, including p.Arg3277Cys. A hypomorphic allele in trans configuration with a typical disease-causing allele can also explain some cases of in utero-onset ADPKD [Zerres et al 1993, Rossetti et al 2009, Bergmann et al 2011, Audrézet et al 2016]. Biallelic pathogenic variants in which both are hypomorphic alleles can also result in early-onset disease with an apparently negative family history, and therefore can be mistaken for ARPKD [Vujic et al 2010]. Neonatal-onset ADPKD has also been associated with homozygosity of a hypomorphic PKD2 allele, which arose by uniparental disomy [Losekoot et al 2012]. Digenic ADPKD. Individuals with pathogenic variants in both PKD1 and PKD2 have been described. Two individuals in one family were double heterozygotes for a pathogenic variant in both PKD1 and PKD2 and developed more severe renal disease than was reported in heterozygous relatives [Pei et al 2001]. It has been suggested that early-onset PKD may be caused by a heterozygous pathogenic variant in both PKD1 and HNF1B (digenic inheritance) [Bergmann et al 2011]. Variants in HNF1B are associated with ADTKD (see Table 5). ### Penetrance Penetrance in ADPKD is age and genotype dependent. The penetrance of multiple bilateral renal cysts in older adults is close to 100%. However, because the disease is progressive, few cysts may be evident during childhood or young adulthood, especially in individuals with nontruncating PKD1 pathogenic variants or pathogenic variants in PKD2, GANAB, or DNAJB11. ### Nomenclature A term for ADPKD that is no longer in use is "adult polycystic kidney disease" (APKD). ### Prevalence ADPKD is the most common potentially lethal single-gene disorder. Its prevalence at birth is approximately 1:1,000; and it affects approximately 300,000 persons in the United States. ## Differential Diagnosis In the absence of a family history of PKD and/or in the presence of atypical presentations, benign simple cysts (see Table 4) and other cystic diseases should be considered in the differential diagnosis. Studies of potential kidney donors using contrast-enhanced CT, which detects smaller cysts (1-2 mm), showed that from age 19 to 49 years, 39%, 22%, 7.9%, and 1.6% had at least one cyst ≥2 mm, ≥5 mm, ≥10 mm, and ≥20 mm in diameter, respectively, while from age 50 to 75 years, 63%, 43%, 22%, and 7.8% had at least one cyst ≥2 mm, ≥5 mm, ≥10 mm, and ≥20 mm in diameter, respectively [Rule et al 2012]. ### Table 4. Prevalence of Simple Renal Cysts in Unaffected Individuals on Ultrasound Examination View in own window Age in YearsSimple Renal Cysts 1Bilateral Renal Cysts 2 15-290%\-- 30-491.7%1% 50-6911.5%4% ≥7022.1%9% Ravine et al [1993] 1\. ≥1 renal cyst 2\. ≥1 cyst in each kidney The conditions in Table 5 can be confused with ADPKD. ### Table 5. Disorders to Consider in the Differential Diagnosis of ADPKD View in own window DisorderGene(s)MOIClinical Features of Differential Diagnosis Disorder Overlapping w/ADPKDDistinguishing from ADPKD AD tubulointerstitial kidney disease (type 5 maturity-onset diabetes of the young)HNF1BADCystic renal disease * Diabetes * Pancreatic disease * ↑ liver enzymes * Hypomagnesemia * Congenital renal & urinary tract anomalies AR polycystic kidney diseasePKHD1ARBilateral renal cystic disease * Majority present in neonatal period * Pulmonary hypoplasia * Early-onset renal failure * Liver fibrosis rather than cysts * TKV ↓over time (rather than ↑) AD polycystic liver disease 1 (OMIM PS174050)ALG8 GANAB LRP5 PRKCSH SEC63 SEC61BAD * Liver cysts * Occasional kidney cysts * Predominant phenotype is liver disease w/very mild kidney disease if present. * Note an overlap between ADPKD & ADPLD w/GANAB pathogenic variants causing either disease. AD tubulointerstitial kidney disease, UMOD-relatedUMODADRenal cysts * Kidney function ↓ w/out ↑ in TKV * No liver cysts * Gout AD tubulointerstitial kidney disease, MUC1-relatedMUC1ADRenal cysts * Kidney function ↓ w/out ↑ in TKV * No liver cysts Familial juvenile hyperuricemic nephropathy type 4 (OMIM 617056)SEC61A1ADRenal cysts * Kidney function ↓ w/out ↑ in TKV * No liver cysts Tuberous sclerosis complexTSC1 TSC2ADRenal cysts * Renal angiomyolipomas * Skin & brain manifestations * Rhabdomyomas * Lymphangioleiomyomatosis Von Hippel-Lindau syndromeVHLAD * Renal cysts * Pancreatic cysts * Hemangioblastomas * Pheochromocytoma * Neuroendocrine tumors Oral-facial-digital syndrome type 1OFD1XLRenal cysts in affected females * Hyperplastic frenula * Cleft tongue * Cleft lip or palate * Malpositioned teeth * Broad nasal root w/hypoplasia of nasal alae & malar bone & digital abnormalities * X-linked inheritance; usually male lethal during gestation Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (see COL4A1-Related Disorders)COL4A1ADRenal cysts * Hematuria * Muscle cramps or ↑ CPK * Tortuosity of retinal artery * Brain small-vessel disease Hajdu-Cheney syndrome (OMIM 102500)NOTCH2ADRenal enlargement w/cortical & medullary cysts * Short stature * Midfacial flattening w/proptosis * Receding chin * Hirsutism * Acroosteolysis of terminal phalanges * Basilar invagination of the skull Localized renal cystic diseaseNANAHistologic appearance strongly resembling advanced ADPKD * Cystic degeneration of a portion of 1 kidney * Non-progressive * Nonfamilial Acquired renal cystic diseaseNANARenal cystsCysts develop after ESRD onset. AD = autosomal dominant; AR = autosomal recessive; CPK = creatinine phosphokinase; ESRD = end-stage renal disease; MOI = mode of inheritance; NA = not applicable; XL = X-linked 1\. Porath et al [2016], Besse et al [2017], Besse et al [2018] See Polycystic Kidney disease: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with autosomal dominant polycystic kidney disease (ADPKD), the following evaluations are recommended if they have not already been completed: * Renal ultrasound examination (if CT or MRI examination is unavailable) to determine the severity of disease and provide an estimate of size and distribution of cysts and kidney size * CT or MRI examination of the abdomen with and without contrast enhancement, which is more sensitive and allows better quantification of the disease severity to help determine the extent of cystic disease in the kidneys and liver, as well as to estimate the prognosis. CT, but not MRI, can detect stones and parenchymal calcifications. CT or MR angiography (MRA) can be used when visualization of the renal arteries is necessary. MRI can be used when administration of iodinated contrast material is contraindicated. * Blood pressure examination to detect hypertension. When "white coat" hypertension (i.e., blood pressure that is elevated when measured in the clinic, but normal when measured outside of the clinic) is suspected, ambulatory blood pressure monitoring is appropriate. * Measurement of blood lipid concentrations because hyperlipidemia is a correctable risk factor for progressive renal disease, including ADPKD * Urine studies to detect the presence of microalbuminuria or proteinuria, which in the presence of severe renal cystic disease indicates an increased likelihood of disease progression and mandates strict control of the blood pressure * Echocardiography in persons with heart murmurs or systolic clicks possibly resulting from valvular heart disease, mitral valve prolapse, or congenital cardiac abnormalities * Echocardiography or cardiac MRI to screen persons at high risk because of a family history of thoracic aortic dissections * Head MRA or CT angiography to screen persons at high risk because of a family history of intracranial aneurysms. Note: Screening for intracranial aneurysms in individuals without a family history of intracranial aneurysms is not recommended [Irazabal et al 2011]. * Consultation with a clinical geneticist and/or genetic counselor if the nephrologist is not an expert in inherited disorders ### Treatment of Manifestations Treatment guidelines formulated at the ADPKD KDIGO conference are summarized in Chapman et al [2015]. Current therapy for ADPKD is directed toward reducing morbidity and mortality from the renal and extrarenal complications of the disease, although specific treatments are becoming available. #### Vasopressin V2 Receptor Antagonists Studies have shown that modulation of cAMP levels by targeting the vasopressin V2 receptor can dramatically inhibit cyst development in animal models of nephronophthisis, ARPKD, and ADPKD [Gattone et al 2003, Torres et al 2004, Wang et al 2005, Wang et al 2008]. A Phase II open-label clinical trial [Higashihara et al 2011] and a Phase III global randomized double-blind placebo-controlled trial with a vasopressin V2 receptor antagonist (tolvaptan) have been completed [Torres 2008, Torres et al 2011b, Torres et al 2012]. The Phase III trial, which extended over three years, included 1,445 affected individuals with preserved renal function but large kidney volumes. The increase in kidney volume in the treated group was 2.8% per year compared to 5.5% in the untreated group. Use of tolvaptan was also associated with a slower decline in kidney function. There were fewer kidney-related adverse events in the treated group but more aquaresis, and reversible elevations in liver enzyme levels occurred in approximately 5% of individuals on tolvaptan. These elevations met Hy's law criteria denoting a 10% risk of liver failure. Recently a one-year Phase III global randomized double-blind placebo-controlled trial of tolvaptan in 1,370 affected individuals with renal insufficiency has been completed [Torres et al 2017b]. Individuals were either 18-55 years with an eGFR of 25-65 mL/min/1.73 m2 or 56-65 years with an eGFR of 25-44 mL/min/1.73 m2. The change in eGFR was -2.34 mL/min/1.73 m2 in the treated group compared to -3.61 mL/min/1.73 m2 in the control group (p<0.001). As previously, elevations in liver enzymes were found in approximately 5% of treated subjects; elevations reversed on withdrawal from tolvaptan. No cases met Hy's law criteria likely because of more frequent monitoring of liver enzymes and earlier discontinuation of tolvaptan. Tolvaptan has been approved for clinical use in persons with ADPKD in Japan, Canada, Europe, and the US. Various guidelines have been generated for guiding the administration of tolvaptan, focusing on selecting individuals with rapidly progressive disease that is likely to result in ESRD [Gansevoort et al 2016, Soroka et al 2017]. Factors considered for identifying rapidly progressive ADPKD are TKV/age, rate of change of TKV, eGFR/age, rate of decline of eGFR, genotype, and family history. #### Hypertension The antihypertensive agent(s) of choice in ADPKD have not been clearly established. However, because of the role of the renin angiotensin system in the pathogenesis of hypertension in ADPKD, ACE inhibitors and angiotensin II receptor antagonists may be superior to other agents in individuals with preserved renal function. ACE inhibitors and angiotensin II receptor blockers increase renal blood flow, have a low side-effect profile, and may reduce vascular smooth muscle proliferation and development of atherosclerosis: * The administration of ACE inhibitors, but not the administration of calcium channel blockers, has been shown to reduce microalbuminuria in individuals with ADPKD [Ecder & Schrier 2001]. * In a non-randomized study, the administration of ACE inhibitors without diuretics was found to result in a lower rate of decline in glomerular filtration rate (GFR) and less proteinuria than the administration of a diuretic without an ACE inhibitor for similar control of blood pressure [Ecder & Schrier 2001]. However, another study found no renal protective effect of an ACE inhibitor over a β-blocker [van Dijk et al 2003]; another study found that although more rigorous blood pressure control did not preserve renal function, it did lead to a greater decrease in left ventricular mass [Schrier et al 2002]. * A long-term follow up of the Modification of Diet in Renal Disease (MDRD) Study that involved protein restriction and low blood pressure targets showed that individuals with ADPKD randomized to the low blood pressure target (mean arterial pressure [MAP] <92 mmHg) experienced significantly less ESRD and combined ESRD/death than those randomized to the usual blood pressure target (MAP <107 mmHg) [Sarnak et al 2005]. * The HALT PKD trial did not show a benefit of the addition of an angiotensin II receptor blocker (ARB) to an ACE inhibitor in preservation of renal function [Torres et al 2014]. However, in the same trial, a lower blood pressure target (95-110/60-75 mm Hg) compared to the standard target (120-130/70-80 mm Hg) in younger affected individuals with preserved renal function was associated with a slower increase in kidney volume but no overall change in the decline in renal function, as measured by eGFR [Schrier et al 2014]. #### Flank Pain After excluding causes of flank pain that may require intervention, such as infection, stone, or tumor, an initial conservative approach to pain management is recommended: * Nonopioid agents are preferred and care should be taken to avoid long-term administration of nephrotoxic agents such as combination analgesic and nonsteroidal anti-inflammatory drugs. * Tricyclic antidepressants are helpful, as in all chronic pain syndromes, and are well tolerated. * Narcotic analgesics should be reserved for the management of acute episodes, as chronic use can lead to physical and psychological dependence. * Splanchnic nerve blockade with local anesthetics or steroids can result in pain relief beyond the duration of the local anesthetic. When conservative measures fail, therapy can be directed toward cyst decompression with cyst aspiration and sclerosis: * Cyst aspiration, under ultrasound or CT guidance, is a relatively simple procedure carried out routinely by interventional radiologists. Complications from aspiration of centrally located cysts are more common, and the morbidity of the procedure is proportional to the number of cysts treated. Cyst aspiration can help to establish causality between a cyst and the presence of pain, but seldom provides long-lasting relief because of fluid reaccumulation. * Sclerosing agents, such as 95% ethanol or acidic solutions of minocycline, are commonly used to prevent the reaccumulation of cyst fluid. Good results have been obtained with 95% ethanol, achieving a success rate of 90% in benign renal cysts. Minor complications include: microhematuria, localized pain, transient fever, and systemic absorption of the alcohol. More serious complications such as pneumothorax, perirenal hematoma, arteriovenous fistula, urinoma, and infection are rare. In individuals with many cysts contributing to pain, laparoscopic or surgical cyst fenestration through lumbotomy or flank incision, renal denervation, and (in those who have reached ESRD) nephrectomy may be of benefit: * Surgical decompression was effective in 80% to 90% of individuals for one year; 62% to 77% had sustained pain relief for longer than two years. Surgical intervention neither accelerates the decline in renal function nor preserves remaining renal function. * Laparoscopic fenestration has been shown to be as effective as open surgical fenestration in short-term follow up for individuals with limited disease and has a shorter, less complicated recovery period than open surgery. * Renal denervation via a thoracoscopic approach was successful in one affected individual [Chapuis et al 2004] and percutaneous transluminal catheter-based denervation was effective in a small number of individuals [Shetty et al 2013, Casteleijn et al 2014]. * Laparoscopic and retroperitonoscopic nephrectomy and arterial embolization have been used in individuals with ADPKD who have ESRD [Ubara et al 1999, Dunn et al 2000]. * Hand-assisted laparoscopic nephrectomy may be preferable to standard laparoscopic nephrectomy because of shorter operating time and lower morbidity [Lee & Clayman 2004]. #### Cyst Hemorrhage and Gross Hematuria Cyst hemorrhage and gross hematuria are usually self limited and respond well to conservative management with bed rest, analgesics, and adequate hydration to prevent development of obstructing clots. Rarely, episodes of bleeding are severe with extensive subcapsular or retroperitoneal hematoma, significant drop in hematocrit, and hemodynamic instability. These individuals require hospitalization, transfusion, and investigation by CT or angiography. In individuals with unusually severe or persistent hemorrhage, segmental arterial embolization can be successful. If not, surgery may be required to control bleeding. Some reports suggest a role for tranexamic acid in the treatment of life-threatening hematuria [Hulme & Wylie 2015]. Gross hematuria persisting more than one week or developing for the first time in an individual older than age 50 years requires thorough investigation. #### Nephrolithiasis Small uric acid stones can be missed on nephrotomography and are best detected by CT. CT should be obtained before and after the administration of contrast material to confirm the localization within the collecting system and to differentiate calculi from parenchymal calcifications. Dual absorption CT now facilitates the differentiation of uric acid stones from calcium-containing stones. Excretory urography detects precaliceal tubular ectasia in 15% of individuals with ADPKD. The treatment of nephrolithiasis in individuals with ADPKD is the same as that for individuals without ADPKD: * High fluid intake and potassium citrate are the treatment of choice in uric acid lithiasis, hypocitric calcium oxalate nephrolithiasis, and distal acidification defects. * Medical dissolution of uric acid stones can usually be achieved by a program of high fluid intake, urine alkalinization (to maintain a pH of 6-6.5), and administration of allopurinol. * Extracorporeal shock-wave lithotripsy and percutaneous nephrostolithotomy can be successful in individuals with ADPKD without excessive complications [Umbreit et al 2010]. #### Cyst Infection If cyst infection is suspected, diagnostic imaging should be undertaken to assist in the diagnosis: * CT and MRI are sensitive for detecting complicated cysts and provide anatomic definition, but the findings are not specific for infection. * Nuclear imaging, especially indium-labeled white cell scanning, is useful, but false negative and false positive results are possible. * 18F-fluorodeoxyglucose positron emission tomography scanning is the most sensitive method to detect an infected cyst, but it is expensive, not readily available, and may not be reimbursed by insurance companies [Sallée et al 2009]. In the appropriate clinical setting of fever, flank pain, and suggestive diagnostic imaging, cyst aspiration under ultrasound or CT guidance should be undertaken to culture the organism and assist in selection of antimicrobial therapy, particularly if blood and urine cultures are negative [Torres et al 2007a]. Cyst infection is often difficult to treat. It has a high treatment failure rate despite prolonged therapy with an antibiotic to which the organism is susceptible. Treatment failure results from the inability of certain antibiotics to penetrate the cyst epithelium successfully and achieve therapeutic concentrations within the cyst. The epithelium that lines gradient cysts has functional and ultrastructural characteristics of the distal tubule epithelium. Penetration is via tight junctions, allowing only lipid-soluble agent access. Non-gradient cysts, which are more common, allow solute access via diffusion. However, kinetic studies indicate that water-soluble agents penetrate non-gradient cysts slowly and irregularly, resulting in unreliable drug concentrations within the cysts. Lipophilic agents have been shown to penetrate both gradient and non-gradient cysts equally and reliably and have a pKa that allows for favorable electrochemical gradients into acidic cyst fluids. Therapeutic agents of choice include trimethoprim-sulfamethoxazole and fluoroquinolones. Clindamycin, vancomycin, and metronidazole are also able to penetrate cysts well. Chloramphenicol has shown therapeutic efficacy in otherwise refractory disease. If fever persists after one to two weeks of appropriate antimicrobial therapy, percutaneous or surgical drainage of infected cysts should be undertaken. If fever recurs after discontinuation of antibiotics, complicating features such as obstruction, perinephric abscess, or stones should be considered and treated appropriately. If complicating features are not identified, the course of previously effective therapy should be extended; several months may be required to completely eradicate the infection. #### End-Stage Renal Disease (ESRD) Actuarial data indicate that individuals with ADPKD do better on dialysis than individuals with ESRD from other causes. Females appear to do better than males. The reason for this improved outcome is unclear but may relate to better-maintained hemoglobin levels through higher endogenous erythropoietin production. Rarely, hemodialysis can be complicated by intradialytic hypotension if the inferior vena cava is compressed by a medially located renal cyst. Despite renal size, peritoneal dialysis can usually be performed in individuals with ADPKD; although these individuals are at increased risk for inguinal and umbilical hernias, which require surgical repair. Following transplantation, there is no difference in patient or graft survival between individuals with ADPKD and those with ESRD caused by other conditions, and complications are no greater than in the general population. Complications directly related to ADPKD are rare. One study has suggested an increased risk for thromboembolic complications [Jacquet et al 2011]. Whether individuals with ADPKD are at increased risk for new-onset diabetes mellitus after transplantation is questionable [Ruderman et al 2012]. Nephrectomy of the native kidneys is reserved for affected individuals with a history of infected cysts, frequent bleeding, severe hypertension, or massive renal enlargement. There is no consensus on the optimal timing of nephrectomy; whether nephrectomy is performed before, at, or following transplantation depends to some extent on the indication for the nephrectomy and other considerations [Lucas et al 2010, Kirkman et al 2011]. Hand-assisted laparoscopic nephrectomy is increasingly being used [Lee & Clayman 2004]. #### Polycystic Liver Disease (PLD) Most individuals with PLD have no symptoms and require no treatment. The treatment of symptomatic disease includes the avoidance of estrogens and caffeine and the use of H2 blockers or proton pump inhibitors for symptomatic relief. Severe symptoms may require percutaneous aspiration and sclerosis, laparoscopic fenestration, combined hepatic resection and cyst fenestration, liver transplantation, or selective hepatic artery embolization. Any of these interventions should be tailored to the individual [Torres 2007, Drenth et al 2010]. * Cyst aspiration and sclerosis with alcohol or minocyline is the treatment of choice for symptoms caused by one or a small number of dominant cysts. Before instillation of the sclerosing agent, a contrast medium is injected into the cyst to evaluate for communication with the bile ducts. The success rate of this procedure (70% after a single treatment and an additional 20% after repeated treatment) is inversely correlated with the size of the cyst(s). * Laparoscopic fenestration of hepatic cysts, a less commonly performed procedure, is complicated by transient ascites in 40% of individuals; and the results are often short-lived. Thus, laparoscopic cyst fenestration is indicated only for the treatment of disproportionally large cysts as an alternative to percutaneous sclerosis. * Neither percutaneous sclerosis nor laparoscopic fenestration is helpful in individuals with large polycystic livers with many small- and medium-sized cysts. In most individuals, part of the liver is spared, allowing treatment by combined hepatic resection and cyst fenestration. Because the surgery and recovery can be difficult, with complications such as transient ascites and bile leaks and a perioperative mortality of 2.5%, it should be performed only in specialized centers [Schnelldorfer et al 2009]. The surgery has good long-term results in individuals with severe PLD and is often preferable to liver transplantation, which is reserved for individuals for whom liver resection is not feasible or in whom liver function is impaired. * Because individuals with severe PLD have mostly normal liver function, their MELD (model for end-stage liver disease) scores are low, placing them at a disadvantage for organ allocation. For highly selected individuals in this group, caval-sparing hepatectomy and subsequent living donor liver transplantation could provide a potential alternative [Mekeel et al 2008]. * Selective hepatic artery embolization can be considered for highly symptomatic individuals who are not candidates for surgery [Takei et al 2007]. #### Intracranial Aneurysm Ruptured or symptomatic. The mainstay of therapy is surgical clipping of the ruptured aneurysm at its neck. Asymptomatic. Those aneurysms measuring ≤5.0 mm in diameter and diagnosed by presymptomatic screening can be observed and followed initially at yearly intervals. If the size increases, surgery is indicated. The management of aneurysms 6.0-9.0 mm in size remains controversial. Surgical intervention is usually indicated for aneurysms >10.0 mm in diameter. For individuals with high surgical risk or with technically difficult-to-manage lesions, endovascular treatment with detachable platinum coils may be indicated. Endovascular treatment appears to be associated with fewer complications than clipping, but the long-term efficacy of this method is as yet unproven [Pirson et al 2002]. #### Aortic Dissection When the aortic root diameter reaches 55-60 mm, replacement of the aorta is indicated. Guidelines for management of thoracic aortic disease have been published [Hiratzka et al 2010]. Management of aortic dissection requires coordinated input from a multidisciplinary team including a cardiologist and cardiothoracic and vascular surgeons. ### Prevention of Secondary Manifestations Additional interventions aimed at slowing the progression of ESRD in ADPKD include control of hypertension and hyperlipidemia, dietary protein restriction, control of acidosis, and prevention of hyperphosphatemia. The Modification of Diet in Renal Disease (MDRD) trial showed only a slight (borderline significant) beneficial effect of a very low protein diet when introduced at a late state of the disease (GFR 13-55 mL/min per 1.73 m2). In the CRISP study body mass indices ≥30 kg/m2 have been associated with faster increase in kidney volume and decline in glomerular filtration rate [Nowak et al 2018]. Animal studies have shown a possible benefit of caloric restriction in an ADPKD model [Warner et al 2016]. As indicated above (see Hypertension), a lower blood pressure target (95-110/60-75 mm Hg) compared to the standard target (120-130/70-80 mm Hg) in younger affected individuals with preserved renal function was associated with a slower increase in kidney volume in the HALT PKD study [Schrier et al 2014]. * Blood pressure control (goal ≤110/75 mmHg if 18-50 years old and eGFR >60 mL/min; otherwise ≤130/85 mmHg) * Maintainance of UOsm at ≤280 mOsm/kg by moderately enhancing hydration spread out over 24 hours (during the day, at bedtime, and at night if waking up) * Low osmolar intake: moderate sodium (2-3 g/d) and protein (0.8-1 g/kg of ideal body weight) restriction * Maintainance of serum bicarbonate at ≥22 mEq/L; moderate dietary phosphorus intake (800 mg/d) * Moderation of caloric intake; normal BMI; low-impact exercise * Lipid control; low threshold to start statins (aim for LDL ≤100 mg/dL) * Consideration of disease-modifying treatment (at present tolvaptan is the only one approved) in individuals at risk for rapidly progressive disease (see Treatment of Manifestations) ### Surveillance Guidance on surveillance is provided in Chapman et al [2015]. Early detection of hypertension. Children with a family history of ADPKD should have their blood pressure monitored beginning at age five years, with an interval of three years in individuals in whom blood pressure is normal. The diagnosis of hypertension is made when systolic or diastolic BP is at or above the 95th percentile for age, height, and gender. Intracranial aneurysms. Screening is usually not recommended since most intracranial aneurysms found by screening asymptomatic individuals are small, have a low risk of rupture, and require no treatment [Irazabal et al 2011, Chapman et al 2015], although dissenting opinions have been published [Rozenfeld et al 2014]. Indications for screening in affected individuals with a good life expectancy include a family history of intracranial aneurysms or subarachnoid hemorrhage, previous rupture of an aneurysm, preparation for elective surgery with potential hemodynamic instability, high-risk occupations such as airplane pilot, and significant anxiety on the part of the individual despite adequate risk information. MRA is the diagnostic imaging modality of choice for presymptomatic screening because it is noninvasive and does not require intravenous contrast material. Because only one of 76 individuals with an initial negative study had a new intracranial aneurysm after a mean follow up of 9.8 years, rescreening after an interval of ten years has been suggested as a reasonable approach [Schrier et al 2004]. Aortic dissection. Until more information becomes available, it is reasonable to screen first-degree adult relatives of individuals with thoracic aortic dissection using either echocardiography or chest MRI examination every two to three years. If aortic root dilatation is found, referral to a cardiologist is indicated. Surveillance for renal cell carcinoma, cardiac valvular abnormalities, and colon diverticulosis is not indicated in individuals with ADPKD who do not have suggestive signs or symptoms of these complications. ### Agents/Circumstances to Avoid Avoid the following: * Long-term administration of nephrotoxic agents (e.g., combination analgesics, NSAIDs) * Caffeine in large amounts; there is no evidence that low or moderate use of caffeinated beverages accelerates the progression of ADPKD. * Use of estrogens and possibly progestogens in individuals with severe polycystic liver disease * Smoking * Obesity ### Evaluation of Relatives at Risk It is appropriate to clarify the clinical/genetic status of apparently asymptomatic at-risk adult (age ≥18 years) relatives of an affected individual in order to: * Allow those found to be affected to become better educated about ADPKD; * Permit early detection and treatment of complications and associated disorders; * Reassure those found to be unaffected; * Start treatment, where appropriate. Evaluations of at-risk relatives include the following: * Imaging with abdominal ultrasound, CT, or MRI examination * Molecular genetic testing if the ADPKD-related pathogenic variant in the family is known. For families with a known pathogenic variant, molecular genetic testing may provide clarification if findings on imaging are equivocal. Note: (1) Appropriate counseling prior to imaging or molecular testing, including a discussion of the possible impact on insurability and employability, is most important. (2) At present, there is no indication for testing of asymptomatic children. This may change in the future, if and when effective therapies for children are developed. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management The literature on pregnancy and PKD is limited. * Pregnant women with ADPKD should be monitored closely for the development of hypertension and urinary tract infections. * Pregnant women who develop hypertension during pregnancy or who have impaired renal function are at increased risk and should be monitored closely for the development of preeclampsia, intrauterine fetal growth restriction, and oligohydramnios. * A second-trimester prenatal sonographic examination is indicated if either parent has ADPKD to assess fetal kidney size and echogenicity, presence of fetal kidney cysts, and amniotic fluid volume [Vora et al 2008]. ### Therapies Under Investigation Significant advances in the understanding of the genetics of ADPKD and the mechanisms of cyst growth have revealed additional likely targets for therapeutic intervention. Somatostatin analogs. Octreotide, a long-acting form of somatostatin, has been shown to slow the enlargement of polycystic kidneys and livers in an animal model of PKD [Masyuk et al 2007] and of polycystic kidneys and liver in a small randomized, placebo-controlled, crossover study [Ruggenenti et al 2005, Caroli et al 2010]. Two randomized, placebo-controlled trials of octreotide and lanreotide for polycystic kidney and liver disease have shown that the administration of these somatostatin analogs causes a moderate but significant reduction in liver volume and decreases the growth velocity of polycystic kidneys compared to placebo [van Keimpema et al 2009, Hogan et al 2010]. A randomized, three-year, single-blind, placebo-controlled trial of octreotide long-acting release (LAR) in 75 affected individuals (38 of whom received octreotide-LAR and 37 of whom received placebo) was completed in Italy [Caroli et al 2013]. The numeric increase in kidney and liver size was significantly smaller in the treated group after one year; after three years, the size of the organs was smaller in the treated group vs the untreated group, but the difference was no longer statistically significant for either organ. A larger and longer randomized study is presently under way [Meijer et al 2014] to determine whether these drugs can be administered safely to persons with ADPKD and/or polycystic liver disease and whether they are efficacious. Studies of tolvaptan and the somatostatin analog pasireotide in a Pkd1 mouse model showed an additive effect of the combined treatment [Hopp et al 2015]. mTOR inhibitors. The results of clinical trials of mTOR inhibitors for ADPKD have been mostly disappointing. These studies have shown either no effect on TKV or eGFR [Serra et al 2010], an association with a slower rate of increase in TKV but a faster rate of decline in eGFR [Walz et al 2010], or a faster decline in GFR and increase in TKV [Ruggenenti et al 2016]. Clinical trials of mTOR inhibitors have also been accompanied by significant drug toxicity [Serra et al 2010, Walz et al 2010, Ruggenenti et al 2016]. Because the intended dosage was limited by toxicity of the drug, the blood levels achieved may not have been enough to effectively inhibit mTOR activity in the kidney [Canaud et al 2010]. Tyrosine kinase inhibitors. A Phase II clinical trial of the Src inhibitor bosutinib showed a slower rate of increase in TKV and no difference in decline in eGFR in the treated group [Tesar et al 2017]. However, there was a high level of dropout from the study with significant adverse events, especially with a higher dose of the compound. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Polycystic Kidney Disease, Autosomal Dominant	c0085413	26,664	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1246/	2021-01-18T21:03:36	{"mesh": ["D016891"], "synonyms": ["ADPKD"]}
A number sign (#) is used with this entry because of evidence that branchiooculofacial syndrome (BOFS) is caused by heterozygous mutation in the TFAP2A gene (107580) on chromosome 6p24. Description Branchiooculofacial syndrome (BOFS) is characterized by branchial cleft sinus defects, ocular anomalies such as microphthalmia and lacrimal duct obstruction, a dysmorphic facial appearance including cleft or pseudocleft lip/palate, and autosomal dominant inheritance. Although anomalies of the external and middle ear frequently cause conductive hearing loss in BOFS, severe to profound sensorineural hearing loss due to inner ear anomalies has rarely been reported (summary by Tekin et al., 2009). See also chromosome 6pter-p24 deletion syndrome (612582) for a similar phenotype. The deletion region lies telomeric to the TFAP2A gene. Clinical Features Lee et al. (1982) described a 38-year-old woman and her 8-year-old son who had low birth weight for dates and retarded postnatal growth, bilateral branchial cleft sinuses, congenital strabismus, obstructed nasolacrimal ducts, broad nasal bridge, protruding upper lip, and carp mouth. Graying of the mother's hair occurred at age 18. Intelligence was normal. The same disorder may have been reported by Hall et al. (1983) and Fujimoto et al. (1987). Hall et al. (1983) described 2 unrelated children (1 male, 1 female) with hemangiomatous branchial clefts and pseudocleft of the upper lip (resembling a surgically repaired cleft or a fused cleft). They found reports of 2 additional patients who, they suspected, also represented sporadic cases of this syndrome. In several persons in 3 families, Fujimoto et al. (1987) observed an autosomal dominant disorder of abnormal upper lip, which resembled a poorly repaired median cleft lip, malformed nose with broad bridge and flattened tip, lacrimal duct obstruction, malformed ears, and branchial cleft sinuses and/or linear skin lesions behind the ears. In each of the 3 families an affected parent had at least 1 affected child, and father-to-son transmission was observed in 1. Other anomalies included coloboma, microphthalmia, auricular pits, lip pits, highly arched palate, dental anomalies, and subcutaneous cysts of the scalp. Premature graying of hair occurred in affected adults. The abnormality of the upper lip might be described as an unusually broad and prominent philtrum. Mazzone et al. (1992) reported a patient who, in addition to typical features of BOFS, had partial agenesis of the cerebellar vermis. Lin et al. (1992) concluded that the father and son reported by Legius et al. (1990) had the BOF syndrome and that this additional finding of male-to-male transmission confirmed autosomal dominant inheritance. Fielding and Fryer (1992) described 2 sibs with this syndrome, each of whom also had orbital hemangiomatous cysts. Both parents were clinically normal and unrelated. Thus this may have represented an autosomal recessive form of the disorder or germline mosaicism for the dominant gene. Schmerler et al. (1992) reviewed the development of an affected child over a 12-year period of observation. Normal intelligence, regular class placement, hypernasal speech, and continued growth along the 3rd centile were noted. The infant had been referred at the age of 5 months for evaluation of his facial appearance and 'burn-like' lesions behind both ears. McCool and Weaver (1994) observed the BOF syndrome in a mother and her son who lacked the ocular and branchial abnormalities but had bilateral supraauricular sinuses and hearing loss. The son had bilateral cleft lip and right alveolar cleft; the mother had asymmetric nostrils and upper lip. The supraauricular sinuses were thought to represent persistence of the otic vesicle sinus tract. Lin et al. (1995) described 15 new cases of the BOF syndrome and reviewed previously reported cases (28 with typical and 5 with atypical manifestations) in detail. Postauricular cervical branchial defects were found in 40 of 43 patients, and supraauricular defects were found in 6. Pathologic findings of the excised branchial defects showed thymic remnants in several cases. Colobomata were found in 16 of 35 patients, cataracts in 8 of 33, deafness in 14 of 38, scalp cysts in 4 of 38, and premature graying of hair in 9 of 38. Pseudoclefts were observed in 23 patients, and cleft lip and/or palate in 20. Urologic examination of 19 patients revealed kidney abnormalities (agenesis, cysts, hydronephrosis) in 7. Autosomal dominant inheritance of the BOF syndrome is supported by a 3-generation German family, 2 instances of father-to-son transmission, and 7 other parent-offspring families (Fujimoto et al., 1987; Lin et al., 1995). Richardson et al. (1996) described a boy with cleft lip and palate, microphthalmos, colobomata of optic nerves and irides, and cystic dysplasia of the left kidney. His mother had similar ocular abnormalities (plus polycoria), obstruction of nasolacrimal ducts, bifid nasal tip, abnormal philtrum, hypodontia, and premature graying of the hair. His maternal grandmother had the same facial defects and nasolacrimal duct obstruction, but normal eyes. The spectrum of abnormalities in this family fits the BOF syndrome, although cervical hemangiomata or branchial sinuses were not found in affected persons in this family. McGaughran (2001) described a 1-year-old male with BOF syndrome together with preaxial polydactyly and a white forelock at birth. The author stated that this was only the second case in which preaxial polydactyly had been described in the branchiooculofacial syndrome. Demirci et al. (2005) reported the ocular manifestations of BOF syndrome in a 10-year-old girl who had undergone excision of an orbital dermoid cyst and branchial cleft fistula at age 4 years. At age 10, she had sinus tracts on each side of the nose, connecting the lacrimal sac to the skin. In addition, she had an iris pigment epithelial cyst in one eye and a combined hamartoma of the retina and retinal pigment epithelium in the other. Although BOF syndrome and branchiootorenal (BOR) syndrome (113650) are sufficiently distinctive that they should not be confused, both can be associated with nasolacrimal duct stenosis, deafness, prehelical pits, malformed pinna, and renal anomalies. Furthermore, Legius et al. (1990) reported father and son with features of both conditions. In light of these issues, Lin et al. (2000) performed a mutation search of the EYA1 gene in 5 BOF syndrome patients and found no EYA1 mutations, suggesting that BOF syndrome is not allelic to the BOR syndrome. Lin et al. (2000) emphasized that the unusual areas of thin, erythematous wrinkled skin of the neck or infra/supraauricular region of BOF syndrome differ from the discrete cervical pits, cysts, and fistulas of the BOR syndrome. Tekin et al. (2009) reported a 4-year-old Turkish girl who was diagnosed with bilateral profound sensorineural hearing loss at 1 year of age, in whom temporal bone CT scan revealed bilateral cochlear dysplasia, enlarged vestibule, and enlarged vestibular aqueduct; she underwent cochlear implantation. In addition, she was diagnosed with right multicystic dysplastic kidney and underwent unilateral nephrectomy. At 4 years of age, she had dolichocephaly, broad nasal bridge, upslanting palpebral fissures, bilateral pseudoclefts on philtrum, low-set posteriorly rotated ears, bilateral scars from skin defects in the supraauricular region, 2 pits in the suprasternal notch, and bilateral accessory nipples. Ophthalmologic examination was normal. Stoetzel et al. (2009) studied a 3-generation family in which the proband, his father, and his paternal grandmother had BOFS and a heterozygous missense mutation in the TFAP2A gene. CT scan of the temporal bone in the affected individuals showed consistent stenosis of the round window, stenosis of the oval window, malformations of the stapes, hypoplasia of the long process of the incus, normal cochlea, and normal internal auditory meatus. Stoetzel et al. (2009) noted that major differences on CT scan between BOFS and BOR syndrome, particularly of the cochlea and internal auditory meatus canals, which are generally normal in BOFS but always abnormal in BOR syndrome, could help distinguish the 2 phenotypes. Titheradge et al. (2015) described a 3-generation family in which 4 members, the proband and her brother, mother, and daughter, displayed variable severity of BOFS. The proband and her mother had typical features of the disorder, but the proband also had preaxial polydactyly, sensorineural hearing loss, and dental anomalies. Her 2-year-old daughter was mildly affected with only typical facies, right-sided cleft lip and left-sided pseudocleft lip. All 3 were found to have a heterozygous mutation in the TFAP2A gene. The proband's brother, who was not sequenced, died at 6 hours of life. He had multiple congenital anomalies including contractures of the hands, large low-set ears, left anophthalmia, and left-sided cleft lip. Autopsy revealed agenesis of the right kidney and ureter, dysplastic left kidney with narrowing of the left ureter, and secondary lung hypoplasia. Cytogenetics Davies et al. (1999) reported a child with microphthalmia and corneal clouding and a number of other dysmorphic features, including hypertelorism, micrognathia, dysplastic ears, thin limbs, and congenital cardiac defects. This child had an interstitial deletion of chromosome 6p25-p24 that did not include the FOXC1 gene (601090) but did include the TFAP2A gene. Davies et al. (1999) suggested that there is an additional locus within chromosome 6p25-p24 involved in anterior eye chamber development and that AP2-alpha is a candidate gene. Molecular Genetics Milunsky et al. (2008) performed genomewide microarray analysis in a mother and son with BOF syndrome and detected a 3.2-Mb deletion at chromosome 6p24.3. Sequencing of candidate genes in that region in 4 additional unrelated BOFS patients, 2 of whom had previously been studied by Lin et al. (2000), revealed 4 different de novo missense mutations in a conserved region of the TFAP2A gene (see, e.g., 107580.0001 and 107580.0002) that were not found in more than 300 controls. Milunsky et al. (2008) noted that although the affected mother and son did not have overt cleft lip and palate, the boy did have an abnormally short philtrum and bilaterally notched vermilion-mucosa border, which are on the spectrum of microform cleft lip in BOFS. The authors stated that their 'patient 5' was the first BOFS patient to be reported with medulloblastoma. Gestri et al. (2009) sequenced the TFAP2A gene in 37 patients with developmental eye defects plus variable defects associated with BOFS and identified 2 heterozygous mutations in 2 patients (107580.0003 and 107580.0004, respectively). In addition, multiplex ligation-dependent probe amplification (MPLA) revealed a heterozygous deletion on chromosome 6p24.3, encompassing TFAP2A and an adjacent predicted gene, C6ORF218, in 2 sibs and their father from the family previously reported by Fielding and Fryer (1992). The father, who was originally described as unaffected, was found to exhibit mild, classic features of BOFS, including prominent philtrum, bilateral 2/3 partial syndactyly of the toes, bilateral malformed pinnae, and premature aging changes. He also showed subtle ocular changes, with normal anterior segments bilaterally but a dysplastic right optic disc with an unusual vessel pattern and mild dysplasia of the left disc. In a 4-year-old Turkish girl with profound bilateral sensorineural hearing loss and features of BOFS, Tekin et al. (2009) identified a heterozygous deletion/insertion mutation in the TFAP2A gene (107580.0005). In 2 families with BOFS, 1 of which was originally reported by Lin et al. (1995), and 3 sporadic patients with BOFS, Reiber et al. (2010) identified heterozygous mutations in the TFAP2A gene (see, e.g., 107580.0001 and 107580.0006-107580.0007). Reiber et al. (2010) stated that 1 of the sporadic patients studied by Reiber et al. (2010) designated patient 'SP2,' had been previously reported by Bennaceur et al. (1998) as 'patient 2.' Patient SP2 was not blind and did not have severe deafness, but did display severe mental retardation. Reiber et al. (2010) suggested that her developmental disability, which was not due to a dual sensory handicap of blindness and deafness, might be part of the spectrum of BOFS. INHERITANCE \- Autosomal dominant GROWTH Other \- Prenatal growth deficiency (27%) \- Postnatal growth deficiency (50%) HEAD & NECK Head \- Microcephaly Face \- Micrognathia \- Small forehead Ears \- Low-set ears \- Posteriorly rotated ears \- Hypoplastic superior helix \- Microtia \- Posterior auricular pit \- Preauricular pit \- Overfolded ears \- Supraauricular sinuses \- Conductive hearing loss Eyes \- Lacrimal sac fistula \- Orbital dermoid cyst \- Iris pigment epithelial cyst \- Combined hamartoma of the retina and retinal pigment epithelium \- Upslanting palpebral fissures \- Telecanthus \- Hypertelorism \- Ptosis \- Lacrimal duct obstruction \- Iris coloboma \- Retinal coloboma \- Microphthalmia \- Anophthalmia \- Myopia \- Cataract \- Strabismus Nose \- Broad nasal tip \- Divided nasal tip \- Depressed nasal bridge \- Short nasal septum Mouth \- Pseudocleft \- Incomplete/complete cleft lip \- Cleft palate \- Lip pits Teeth \- Dental abnormalities Neck \- Branchial anomalies CHEST Breasts \- Widely spaced nipples \- Supernumerary nipples GENITOURINARY Kidneys \- Renal agenesis \- Cystic kidney SKELETAL Skull \- Malar hypoplasia \- Mastoid hypoplasia with absence of air cells \- Fusion of middle ear ossicles Spine \- Kyphosis \- Lordosis Hands \- Polydactyly \- Clinodactyly \- Single transverse palmar crease \- Hypoplastic thumbs SKIN, NAILS, & HAIR Skin \- Aplasia cutis congenita \- Subcutaneous scalp cysts \- Hemangiomatous branchial clefts (extend along sternocleidomastoid muscle) \- Single transverse palmar crease Nails \- Hypoplastic fingernails Hair \- Premature graying of hair NEUROLOGIC Central Nervous System \- Mild mental retardation \- Agenesis of cerebellar vermis VOICE \- Hypernasal speech IMMUNOLOGY \- Ectopic thymus MISCELLANEOUS \- Normal intelligence in majority MOLECULAR BASIS \- Caused by mutation in the transcription factor AP2-alpha gene (TFAP2A, 107580.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	BRANCHIOOCULOFACIAL SYNDROME	c0376524	26,665	omim	https://www.omim.org/entry/113620	2019-09-22T16:43:57	{"doid": ["0050691"], "mesh": ["D019280"], "omim": ["113620"], "orphanet": ["1297"], "synonyms": ["Alternative titles", "BOF SYNDROME", "BRANCHIAL CLEFTS WITH CHARACTERISTIC FACIES, GROWTH RETARDATION, IMPERFORATE NASOLACRIMAL DUCT, AND PREMATURE AGING", "HEMANGIOMATOUS BRANCHIAL CLEFTS-LIP PSEUDOCLEFT SYNDROME", "LIP PSEUDOCLEFT-HEMANGIOMATOUS BRANCHIAL CYST SYNDROME"], "genereviews": ["NBK1378", "NBK55063"]}
Xia-Gibbs syndrome is a neurological disorder characterized by weak muscle tone (hypotonia), mild to severe intellectual disability and delayed development. Expressive language skills (vocabulary and the production of speech) are particularly affected; children with this condition usually do not speak their first word, a milestone typically achieved within the first year, until age two or later, and some never learn to talk. Development of motor skills, such as crawling and walking, can also be delayed. Other signs and symptoms of Xia-Gibbs syndrome vary among affected individuals. Additional neurological features include poor coordination and balance (ataxia) and seizures. Feeding problems and sleep abnormalities can also occur in people with the condition, and many affected individuals experience short pauses in breathing while they sleep (obstructive sleep apnea). In some people with Xia-Gibbs syndrome, imaging tests of the brain show abnormalities in the brain's structure. For example, the tissue connecting the left and right halves of the brain (the corpus callosum) can be abnormally thin. Xia-Gibbs syndrome can also affect physical development. Growth is usually impaired, and many affected individuals are shorter than their peers. Side-to-side curvature of the spine (scoliosis) is also a common feature. Some people with Xia-Gibbs syndrome have unusual facial features, such as a broad forehead, low-set ears or ears that stick out, widely space eyes (hypertelorism), eye openings that slant up or down (upslanting palpebral fissures or downslanting palpebral fissures), a flat bridge of the nose, or a thin upper lip. Other, less-common abnormalities involving the bones and skin include premature fusion of certain skull bones (craniosynostosis), unusually loose (lax) joints, and loose skin. Behavior problems can also occur in Xia-Gibbs syndrome. Some affected individuals have features of autism spectrum disorder, which is characterized by impaired communication and social interactions, or of attention-deficit/hyperactivity disorder (ADHD). Other problems can include aggression, anxiety, poor impulse control, and self-injury. ## Frequency Xia-Gibbs syndrome is thought to be a rare disorder, although its prevalence is unknown. Doctors believe the condition is underdiagnosed, because many people with intellectual disability never have genetic testing to determine the underlying cause. ## Causes Xia-Gibbs syndrome is caused by mutations in a gene called AHDC1. This gene provides instructions for making a protein with an unknown function. Researchers suspect that the protein may be able to attach (bind) to DNA and control the activity of other genes. Most of the AHDC1 gene mutations involved in Xia-Gibbs syndrome lead to production of abnormally short AHDC1 proteins. The effects of these changes in cells are unclear. The shortened proteins may be quickly broken down or be unable to function. Or, the abnormal proteins may interfere with the function of AHDC1 proteins produced from the normal copy of the gene. Researchers suspect that a reduction in the amount of functional AHDC1 protein impairs normal brain development, leading to intellectual disability, speech problems, and other neurological features of Xia-Gibbs syndrome. Abnormal development of other body systems caused by a shortage of AHDC1 protein may account for additional signs and symptoms of the condition. ### Learn more about the gene associated with Xia-Gibbs syndrome * AHDC1 ## Inheritance Pattern Xia-Gibbs syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The condition results from new (de novo) mutations in the gene that occur either during the formation of reproductive cells (eggs or sperm) in an affected individual’s parent or in early embryonic development. Affected individuals have no history of the disorder in their family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Xia-Gibbs syndrome	c4014419	26,666	medlineplus	https://medlineplus.gov/genetics/condition/xia-gibbs-syndrome/	2021-01-27T08:24:39	{"gard": ["13409"], "omim": ["615829"], "synonyms": []}
Enteroaggregative E. coli strain EAEC 042 aggregates during infection of Hep-2 cells. Enteroaggregative Escherichia coli (EAEC or EAggEC) are a pathotype of Escherichia coli which cause acute and chronic diarrhea in both the developed and developing world.[1][2] They may also cause urinary tract infections.[2] EAEC are defined by their "stacked-brick" pattern of adhesion to the human laryngeal epithelial cell line HEp-2.[3] The pathogenesis of EAEC involves the aggregation of and adherence of the bacteria to the intestinal mucosa, where they elaborate enterotoxins and cytotoxins that damage host cells and induce inflammation that results in diarrhea. EAEC is now recognized as an emerging enteric pathogen. In particular, EAEC are reported as the second most common cause of traveler's diarrhea, second only to Enterotoxigenic E. coli, and a common cause of diarrhea amongst pediatric populations.[4][5] It has also been associated with chronic infections in the latter, as well as in immunocompromised hosts, such as HIV-infected individuals.[6] Awareness of EAEC was increased by a serious outbreak in Germany during 2011, causing over 5000 cases and at least 50 fatalities. The pathogen responsible was found to be an EAEC O104:H4 strain which was lysogenized by a Shiga toxin encoding phage (typically associated with Shiga toxin-producing Escherichia coli, which often encode the adhesin intimin).[7][8] The putative cause of the outbreak were sprouted fenugreek seeds.[9] Strains of EAEC are highly genetically heterogeneous, and the identification of virulence factors important for pathogenesis has proven difficult.[10] Many EAEC encode a transcriptional factor named aggR (aggregative regulator), part of the AraC family of transcription activators. AggR regulates many plasmid, as well chromosomally encoded, virulence factors, that include genes implicated in aggregative adherence fimbriae biogenesis and toxin production. Several toxins have been linked to EAEC virulence, including ShET1 (Shigella enterotoxin 1), Pet (plasmid‐encoded toxin), and EAST-1. However, further studies of these factors have failed to elucidate their role in pathogenesis.[11] ## Contents * 1 Classification * 2 Symptoms and Causes * 3 Treatment * 4 Pathogenesis * 5 History * 6 References ## Classification[edit] Developing Countries in 2007 Diarrhea is still an important disease burden worldwide. It causes considerable childhood mortality in the developing world and is correlated with morbidity (or of relating to disease) and substation health care costs in industrialized countries. The cause of infectious diarrhea is diarrheagenic Escheriachia coli (DEC) group. Subgroups of diarrheagenic Escheriachia coli (DEC) are the following: enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC), enterotoxigenic E.coli (ETEC), Shiga toxin-producing E. coli (STEC) and Enteroaggregative E. coli (EAEC).[2] E. coli is a bacteria that is found in the intestines, its mostly harmless, but some strains of bacteria can cause illness and infection, ## Symptoms and Causes[edit] Enteroaggregative Escheichia coli (EAEC) is a type of strain from E.coli. E.coli causes intestinal infections, some intestinal infections include diarrhea, fever and abdominal pain. Most severe cases can lead to bloody diarrhea, dehydration or even kidney failure. People with weakened immune systems, young children, older adults and pregnant women are at increased risks for developing these complications. Symptoms of intestinal infection usually begin between 8 and 52 hours after you have been infected with E.coli,[2] this is the incubation period. The incubation period is the time between catching an infection and symptoms appearing.[12] Symptoms: * abdominal cramping, pain or tenderness * watery or mucoidy diarrhea * nausea and vomiting, in some people Bloody diarrhea has only been observed in children, and only rarely.[2] On the other hand, the STEC-EAEC hybrid strain identified in the 2011 Germany outbreak caused bloody diarrhea.[13] The bacteria that causes the infection can enter your body in numerous ways * contaminated water - Human and animal feces may pollute ground and surface water, including streams, lakes, rivers, and water used to water or irrigate crops. Although public water systems use chlorine and other chemicals to kill such organisms like E. coli, some outbreaks have been linked to contaminated water supplies. * contaminated food - most common way to get a E.coli infection is by eating contaminated food such as ground beef, unpasteurized milk and fresh produce. * improper food handling - by consuming raw food, or not cooking the food properly, especially meats and poultry. It can also be transmitted by not cleaning your cooking utensils properly, causing cross contamination. * person to person - E.coli can be easily transmitted from person to person, especially when infected children and adults don't wash their hands properly. ## Treatment[edit] Ciprofloxacin structure Antibiotics is a type of medicine that is used to destroy or inhibit the growth of microorganisms.[14] Studies have suggested that fluoroquinolone, especially ciprofloxacin, may be the most effective antibiotic when treating Enteroaggregative E.coli (EAEC) infections, patients treated with ciprofloxacin had significant reductions in duration of diarrhea. Unfortunately resistance toward ciprofloxacin in Enteroaggregative E.coli (EAEC) strains has been reported in several studies. The illness caused by the strain of E.coli cannot be treated to cure the infection, relieve symptoms or prevent complications. For most people treatments include, rest and the intake of fluids. For patients with profuse diarrhea or vomit should be rehydrated by drinking much water or by drinking rehydration solutions such as Rehydralyte or Pedialyte.[15] ## Pathogenesis[edit] E. coli fimbriae EAEC is transmitted through the fecal-oral route and primarily contaminated by food and water.[16] EAEC has been associated with many symptoms such as diarrhea in some individuals and intestinal colonization in others.[17] Because many strains of EAEC have been identified, it is difficult to identify the mechanism of its pathogenesis. Most candidate virulence genes are not always connected with disease.[10] The model of EAEC pathogenesis comprises three stages: Stage 1 is the attachment of the intestinal mucosa by (AAF) aggregative adherence fimbriae and other adhering projections, Stage 2 an increase in mucus that covers EAEC on its surface of enterocytes is found; Stage 3 evocation of an inflammatory response, mucosal toxicity, and intestinal secretion as well as a release of toxins exist. Stage One: Aggregative adherence factors (AAF) are responsible for the adhesion to the intestinal mucosa. AAF are made up of three fimbriae encoded by the pAA plasmid; aag aafA agg-3. aggA is in charge of aggregative phenotype and human erythrocyte haemagglutination of EAEC. aafA allows EAEC to adhere to the intestinal mucosa. agg-3 serves as an adhesion. MAP, three-membrane associated proteins, are essential in the EAEC adherence to haemagglutination of animal cells.[10] Stage two: After AAF factors in stage 1, adherence to the mucosa is characterized by the presence a biofilm. The production of biofilm is regulated by AggR and demands several genes. The loss of biofilm production and diffuse adherence pattern was reported in EAEC at a pH of 4.0. Many studies reveal that EAEC are capable of surviving in the mucus layer. This evidence can support why malnourished children who are infected with EAEC and live in poor conditions develop mucoid stools and prolonged diarrhea.[10] Stage Three: Cytotoxic effects are found in the release of toxins in EAEC as well as an elicitation of the inflammatory response, mucosal toxicity, and intestinal secretion. EAEC toxins are destructive to the intestinal villi and enterocytes. There are three toxins found in EAEC; plasmid encoded toxin (Pet), heat-stable toxin (EAST1), and Shigella enterotoxin 1 (ShET1).[10] ## History[edit] E. coli has been involved as agents of diarrheal disease since 1920. Enteroaggregative Escheichia coli (EAEC) was first found in 1987, in a child in Lima, Peru.[18] Since 1987, Enteroaggregative Escheichia coli (EAEC) has been recognized as agents of diarrhea in industrialized and developing countries. Enteroaggregative Escheichia coli (EAEC) is most commonly found in developing countries due to less developed industrial base and low human development (HDI) compared to other countries. India, Jamaica and Mexico are the most commonly risked countries. ## References[edit] 1. ^ Nataro, J. P.; Mai, V.; Johnson, J.; Blackwelder, W. C.; Heimer, R.; Tirrell, S.; Edberg, S. C.; Braden, C. R.; Morris, J. G. (2006-08-15). "Diarrheagenic Escherichia coli Infection in Baltimore, Maryland, and New Haven, Connecticut". Clinical Infectious Diseases. 43 (4): 402–407. doi:10.1086/505867. ISSN 1058-4838. PMID 16838226. Archived from the original on 2017-02-08. Retrieved 2017-02-03. 2. ^ a b c d e Jensen, Betina Hebbelstrup; Olsen, Katharina E. P.; Struve, Carsten; Krogfelt, Karen Angeliki; Petersen, Andreas Munk (2014). "Epidemiology and Clinical Manifestations of Enteroaggregative Escherichia coli". Clinical Microbiology Reviews. 27 (3): 614–630. doi:10.1128/CMR.00112-13. ISSN 0893-8512. PMC 4135892. PMID 24982324. 3. ^ Nataro, J. P.; Kaper, J. B.; Robins-Browne, R.; Prado, V.; Vial, P.; Levine, M. M. (1987-09-01). "Patterns of adherence of diarrheagenic Escherichia coli to HEp-2 cells". The Pediatric Infectious Disease Journal. 6 (9): 829–831. doi:10.1097/00006454-198709000-00008. ISSN 0891-3668. PMID 3313248. Archived from the original on 2018-01-26. Retrieved 2017-02-01. 4. ^ Huang, David B.; Mohanty, Alakananda; DuPont, Herbert L.; Okhuysen, Pablo C.; Chiang, Tom (2006-10-01). "A review of an emerging enteric pathogen: enteroaggregative Escherichia coli" (PDF). Journal of Medical Microbiology. 55 (Pt 10): 1303–1311. doi:10.1099/jmm.0.46674-0. ISSN 0022-2615. PMID 17005776. Archived (PDF) from the original on 2019-02-22. Retrieved 2019-11-22. 5. ^ Adachi JA, Jiang ZD, Mathewson JJ, Verenkar MP, Thompson S, Martinez-Sandoval F, Steffen R, Ericsson CD, DuPont HL (2001). "Enteroaggregative Escherichia coli as a Major Etiologic Agent in Traveler's Diarrhea in 3 Regions of the World" (PDF). Clin Infect Dis. 32 (12): 1706–9. doi:10.1086/320756. PMID 11360211. Archived (PDF) from the original on 2017-02-03. Retrieved 2017-02-03. 6. ^ Huang, D. B.; et al. (2006). "A review of an emerging enteric pathogen: enteroaggregative Escherichia coli" (PDF). Journal of Medical Microbiology. 55 (10): 1303–1311. doi:10.1099/jmm.0.46674-0. PMID 17005776. Archived (PDF) from the original on 2019-02-22. Retrieved 2019-11-22. 7. ^ Kalita, Anjana; Hu, Jia; Torres, Alfredo G. (2014). "Recent advances in adherence and invasion of pathogenic Escherichia coli". Current Opinion in Infectious Diseases. 27 (5): 459–464. doi:10.1097/QCO.0000000000000092. ISSN 0951-7375. PMC 4169667. PMID 25023740. 8. ^ Nadia Boisen; Angela R. Melton-Celsa; Flemming Scheutz; Alison D. O'Brien; James P. Nataro (2015). "Shiga toxin 2a and Enteroaggregative Escherichia coli—a deadly combination". Gut Microbes. 6 (4): 272–278. doi:10.1080/19490976.2015.1054591. PMC 4615819. PMID 26039753. 9. ^ "Outbreak of Escherichia coli O104:H4 Infections Associated with Sprout Consumption — Europe and North America, May–July 2011". www.cdc.gov. Archived from the original on 2017-01-18. Retrieved 2017-02-01. 10. ^ a b c d e Jenkins C (2018). "Enteroaggregative Escherichia coli". Current Topics in Microbiology and Immunology. 416: 27–50. doi:10.1007/82_2018_105. ISBN 978-3-319-99663-9. PMID 30232602. 11. ^ Ruan, Xiaosai; Crupper, Scott S.; Schultz, Bruce D.; Robertson, Donald C.; Zhang, Weiping (2012-08-15). "Escherichia coli Expressing EAST1 Toxin Did Not Cause an Increase of cAMP or cGMP Levels in Cells, and No Diarrhea in 5-Day Old Gnotobiotic Pigs". PLOS One. 7 (8): e43203. Bibcode:2012PLoSO...743203R. doi:10.1371/journal.pone.0043203. ISSN 1932-6203. PMC 3419656. PMID 22905235. 12. ^ "What are the incubation periods for infections?". 2018-06-26. Archived from the original on 2019-11-10. 13. ^ Kampmeier S, Berger M, Mellmann A, Karch H, Berger P (2018). "The 2011 German Enterohemorrhagic Escherichia Coli O104:H4 Outbreak-The Danger Is Still Out There". Current Topics in Microbiology and Immunology. 416: 117–148. doi:10.1007/82_2018_107. ISBN 978-3-319-99663-9. PMID 30062592. 14. ^ "What Are Antibiotics?". WebMD. Archived from the original on 2019-10-29. Retrieved 2019-11-12. 15. ^ "E. coli - treatments and diagnosis". Mayo Clinic. Archived from the original on 2019-11-12. Retrieved 2019-11-12. 16. ^ Nataro, James P.; Steiner, Theodore (2002), "Enteroaggregative and Diffusely Adherent Escherichia Coli", Escherichia Coli, Elsevier, pp. 189–207, doi:10.1016/b978-012220751-8/50007-0, ISBN 9780122207518 17. ^ Kaur, P.; Chakraborti, A.; Asea, A. (2010). "Enteroaggregative Escherichia coli : An Emerging Enteric Food Borne Pathogen". Interdisciplinary Perspectives on Infectious Diseases. 2010: 254159. doi:10.1155/2010/254159. ISSN 1687-708X. PMC 2837894. PMID 20300577. 18. ^ Nataro, J. P.; Kaper, J. B.; Robins-Browne, R.; Prado, V.; Vial, P.; Levine, M. M. (September 1987). "Patterns of adherence of diarrheagenic Escherichia coli to HEp-2 cells". The Pediatric Infectious Disease Journal. 6 (9): 829–831. doi:10.1097/00006454-198709000-00008. ISSN 0891-3668. PMID 3313248. * v * t * e Escherichia coli Outbreaks * 1993 Jack in the Box * 1996 Odwalla * 2000 Walkerton * 2005 South Wales (O157) * 2006 North American (spinach; O157:H7) * 2006 North American (multiple; O157:H7) * 2009 United Kingdom * 2011 Germany (O104:H4) * 2015 United States Genes * CPS operon * DnaG * Fis * FNR regulon * OmpT * RecBCD * RpoE * RpoF * RpoN * RpoS Strains * Enterohemorrhagic * Enteroinvasive * Enterotoxigenic * O104:H21 * O104:H4 * O121 * O157:H7 * Verotoxin-producing Related * Aerobactin * Coliform index * Long-term evolution experiment * EcoCyc * Enteroaggregative * Molecular biology * Hok/sok system * LacUV5 * Min System * Pathogenic * EnvZ/OmpR * Rho factor * T4 rII system * Theodor Escherich [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Enteroaggregative Escherichia coli	None	26,667	wikipedia	https://en.wikipedia.org/wiki/Enteroaggregative_Escherichia_coli	2021-01-18T19:05:29	{"umls": ["CL541237"], "wikidata": ["Q1344595"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Cataract-microcornea syndrome" – news · newspapers · books · scholar · JSTOR (October 2015) (Learn how and when to remove this template message) Cataract-microcornea syndrome Other namesMicrocornea cataract syndrome[1] Cataract-microcornea syndrome is inherited in an autosomal dominant manner[2] The cataract-microcornea syndrome is the association of congenital cataract and microcornea. ## Contents * 1 Genetics * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Genetics[edit] Mutations in ABCA3 were found to be associated to this syndrome.[3] ## Diagnosis[edit] This section is empty. You can help by adding to it. (September 2017) ## Treatment[edit] This section is empty. You can help by adding to it. (September 2017) ## References[edit] 1. ^ "Cataract microcornea syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 18 October 2019. 2. ^ "OMIM Entry - # 116200 - CATARACT 1, MULTIPLE TYPES; CTRCT1". omim.org. Retrieved 1 September 2017. 3. ^ Chen, P; Dai, Y; Wu, X; Wang, Y; Sun, S; Xiao, J; Zhang, Q; Guan, L; Zhao, X; Hao, X; Wu, R; Xie, L (2014). "Mutations in the ABCA3 gene are associated with cataract-microcornea syndrome". Investigative Ophthalmology & Visual Science. 55 (12): 8031–43. doi:10.1167/iovs.14-14098. PMID 25406294. ## External links[edit] Classification D * ICD-10: Q13.8 * OMIM: 116150 * MeSH: C538287 External resources * Orphanet: 1377 This article about an ophthalmic disease is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Cataract-microcornea syndrome	c1861829	26,668	wikipedia	https://en.wikipedia.org/wiki/Cataract-microcornea_syndrome	2021-01-18T18:28:17	{"gard": ["1155"], "mesh": ["C538287"], "umls": ["C1861829"], "orphanet": ["1377"], "wikidata": ["Q18589315"]}
A number sign (#) is used with this entry because long QT syndrome-2 (LQT2) is caused by heterozygous mutation in the HERG gene (KCNH2; 152427) on chromosome 7q36. Digenic inheritance has also been reported; see MOLECULAR GENETICS. There is evidence that mutation in the KCR1 gene (ALG10B; 603313) on chromosome 12q12 confers reduced susceptibility to acquired long QT syndrome-2. Description Congenital long QT syndrome is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncope, seizure, or sudden death (Jongbloed et al., 1999). For a discussion of genetic heterogeneity of long QT syndrome, see LQT1 (192500). Mapping Jiang et al. (1994) found linkage to D7S483 at chromosome 7q35-q36 in 9 families with the long QT syndrome; the combined lod score was 19.41 at theta = 0.001. Curran et al. (1995) showed that the KCNH2 gene mapped to the same YAC as D7S505, a polymorphic marker tightly linked to LQT2. They found no recombination events using linkage analysis with polymorphisms within KCNH2 for linkage studies of chromosome 7-linked LQT. Pathogenesis Curran et al. (1995) noted that 2 hypotheses for LQT had previously been proposed. One suggested that a predominance of left autonomic innervation caused abnormal cardiac repolarization and arrhythmias. This hypothesis was supported by the finding that arrhythmias can be induced in dogs by removal of the right stellate ganglion. In addition, anecdotal evidence suggested that some LQT patients are effectively treated by beta-adrenergic blocking agents and by left stellate ganglionectomy. The second hypothesis for LQT-related arrhythmias suggested that mutations in cardiac-specific ion channel genes (or genes that modulate cardiac ion channels) cause delayed myocellular repolarization. Delayed myocellular repolarization could promote reactivation of L-type Ca(2+) channels, resulting in secondary depolarizations. These secondary depolarizations are the likely cellular mechanism of torsade de pointes arrhythmias. This hypothesis is supported by the observation that pharmacologic block of potassium channels can induce QT prolongation and repolarization-related arrhythmias in human and animal models. The discovery that one form of LQT results from mutations in a cardiac potassium channel gene supported the myocellular hypothesis. In a surrogate model of LQT2, Akar et al. (2002) investigated a mechanism by which dysfunction at the molecular level may provide the electrical substrate for the life-threatening arrhythmia torsade de pointes. The authors used the novel approach of transmural optical imaging in a canine wedge preparation to determine the spatial organization of repolarization and arrhythmogenesis. They demonstrated islands of midmyocardial cells (M cells) with increased refractoriness, producing steep spatial gradients of repolarization that were directly responsible for conduction block and self-sustained intramural reentrant circuits. These data highlighted a central role for M cells in the development of reentrant torsade de pointes in LQT2. Roden and Viswanathan (2005) reviewed the genetics of acquired long QT syndrome and discussed the structural features of the HERG channel that render it more vulnerable to blockade by drugs: the presence of multiple aromatic residues oriented to face the permeation pore, which provide high-affinity binding sites for a wide range of compounds; and the absence of a pair of proline residues in the S6 helix that forms part of the pore, resulting in an unkinked S6 helix in the HERG channel that is hypothesized to increase access to the binding site. Itzhaki et al. (2011) reported the development of a patient/disease-specific human induced pluripotent stem cell (iPSC) line from a patient with long QT syndrome-2 that was due to an A614V missense mutation in the KCNH2 gene (152427.0026). The generated iPSCs were coaxed to differentiate into the cardiac lineage. Detailed whole-cell patch-clamp and extracellular multielectrode recordings revealed significant prolongation of the action-potential duration in LQTS human iPSC-derived cardiomyocytes when compared to healthy control cells. Voltage-clamp studies confirmed that this action potential duration prolongation stems from a significant reduction of the cardiac potassium current I(Kr). Importantly, LQTS-derived cells also showed marked arrhythmogenicity, characterized by early-after depolarizations and triggered arrhythmias. Itzhaki et al. (2011) then used the LQTS human iPSC-derived cardiac tissue model to evaluate the potency of existing and novel pharmacologic agents that may either aggravate (potassium-channel blockers) or ameliorate (calcium-channel blockers, K(ATP)-channel openers, and late sodium-channel blockers) the disease phenotype. Itzhaki et al. (2011) concluded that their study illustrated the ability of human iPSC technology to model the abnormal functional phenotype of an inherited cardiac disorder and to identify potential new therapeutic agents. Inheritance Although inheritance of the long QT syndrome is autosomal dominant, female predominance has often been observed and has sometimes been attributed to an increased susceptibility to cardiac arrhythmias in women. Imboden et al. (2006) demonstrated distortion in the transmission of the mutant alleles in both LQT1 and LQT2. They investigated the distribution of mutant alleles in 484 nuclear families with LQT1 (192500) and 169 nuclear families with LQT2, all with fully genotyped offspring. Classic mendelian inheritance ratios were not observed in the offspring of either female carriers of LQT1 or male and female carriers of LQT2. Among the 1,534 descendants, the proportion of genetically affected offspring was significantly greater than that expected according to mendelian inheritance: 870 were carriers of a mutation (57%), and 664 were noncarriers (43%) (p less than 0.001). Among the 870 carriers, the allele for the long QT syndrome was transmitted more often to female offspring (55%) than to male offspring (45%) (p = 0.005). Increased maternal transmission of the long QT syndrome mutation to daughters was also observed, possibly contributing to the excess of female patients with autosomal dominant long QT syndrome. Clinical Management Defective protein trafficking is a possible consequence of gene mutation. Trafficking-defective mutant HERG proteins are characterized by a reduced delayed rectifier potassium current and give rise to LQT2. High-affinity HERG channel-blocking drugs can result in pharmacologic rescue of this current. Rajamani et al. (2002) studied the electrophysiologic consequences of pharmacologic mutant HERG blockade using 2 blocking agents. One compound, fexofenadine, rescued the electrophysiologic defect without complete channel blockade, suggesting that this might be a useful treatment for some LQT2 patients. Molecular Genetics Curran et al. (1995) performed single-strand conformation polymorphism and DNA sequence analyses and detected HERG mutations in 6 LQT families, including 2 intragenic deletions, 1 splice-donor mutation, and 3 missense mutations. In 1 kindred, the mutation arose de novo. Northern blot analyses showed that HERG is highly expressed in the heart. The data were interpreted as indicating that mutation in the HERG gene is responsible for LQT2. Zhou et al. (1998) used electrophysiologic, biochemical, and immunohistochemical methods to study the molecular mechanisms of HERG channel dysfunction caused by LQT2 mutations. They found that some mutations, e.g., tyr611 to his and val822 to met (152427.0005), caused defects in biosynthetic processing of HERG channels with the protein retained in the endoplasmic reticulum (ER). Other mutations, e.g., ile593 to arg (152427.0004) and gly628 to ser (152427.0008), were processed similarly to wildtype HERG protein, but these mutations did not produce functional channels. In contrast, the thr474-to-ile mutation expressed HERG current but with altered gating properties. These findings suggested that the loss of HERG channel function in LQT2 mutations is caused by multiple mechanisms including abnormal channel processing, the generation of nonfunctional channels, and altered channel gating. Priori et al. (1999) identified 9 families, each with a 'sporadic' case of LQTS, i.e., only the proband was diagnosed clinically as being affected by LQTS. Six probands were symptomatic for syncope, 2 were asymptomatic with QT prolongation found on routine examination, and 1 was asymptomatic but showed QT prolongation when examined following her brother's sudden death while swimming. Five had mutations in HERG (4 missense, 1 nonsense) and 4 had missense mutations in KCNQ1 (607542). Four of the mutations were de novo; in the remaining families at least 1 silent gene carrier was found, allowing estimation of penetrance at 25%. This contrasted greatly with the prevailing view that LQTS gene mutations may have penetrances of 90% or more. This study highlighted the importance of detecting such silent gene carriers since they are at risk of developing torsade de pointes if exposed to drugs that block potassium channels. Further, the authors stated, carrier status cannot be reliably excluded on clinical grounds alone. In a Dutch family with long QT syndrome in which affected members carried an A558P mutation in the KCNH2 gene in heterozygosity (152427.0025), Amin et al. (2008) described fever-induced QT prolongation and demonstrated that the A558P mutation is trafficking-deficient, that it has a dominant-negative effect in coassembly with wildtype subunits, and that its current density fails to increase with increasing temperature to the same extent as wildtype channels. ### Digenic Inheritance Tester et al. (2005) analyzed 5 LQTS-associated cardiac channel genes in 541 consecutive unrelated patients with LQT syndrome (average QTc, 482 ms). In 272 (50%) patients, they identified 211 different pathogenic mutations, including 88 in KCNQ1, 89 in KCNH2, 32 in SCN5A, and 1 each in KCNE1 and KCNE2. Mutations considered pathogenic were absent in more than 1,400 reference alleles. Among the mutation-positive patients, 29 (11%) had 2 LQTS-causing mutations, of which 16 (8%) were in 2 different LQTS genes (biallelic digenic). Tester et al. (2005) noted that patients with multiple mutations were younger at diagnosis, but they did not discern any genotype/phenotype correlations associated with location or type of mutation. In 44 unrelated patients with LQT syndrome, Millat et al. (2006) used DHLP chromatography to analyze the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes for mutations and SNPs. Most of the patients (84%) showed a complex molecular pattern, with an identified mutation associated with 1 or more SNPs located in several LQTS genes; 4 of the patients also had a second mutation in a different LQTS gene (biallelic digenic inheritance; see, e.g., 152427.0020 and 152427.0022-152427.0023). ### Susceptibility to Acquired Long QT Syndrome 2 Although many commonly used drugs block I(Kr), in certain individuals drugs evoke a paradoxical life-threatening cardiac rhythm disturbance, known as acquired long QT syndrome. Although acquired long QT syndrome is a leading cause of drug withdrawal according to the US Food and Drug Administration, DNA sequencing in patients with acquired long QT syndrome revealed HERG mutations only in rare cases (see 152427.0014), suggesting that HERG modulators are often responsible. By using C. elegans, Petersen et al. (2004) developed in vivo behavior assays that identified candidate modulators of Unc103, the worm HERG ortholog. By using RNA interference methods, they showed that worm homologs of 2 HERG-interacting proteins, hyperkinetic and Kcr1, modify Unc103 function. In patients with drug-induced cardiac repolarization defects, sequencing of the KCR1 gene (ALG10; 603313) revealed an ile447-to-val substitution (I447V; 603313.0001) that occurred at a reduced frequency (1.1%) relative to a matched control population (7.0%), suggesting that I447V may confer reduced susceptibility to acquired long QT syndrome. The clinical result was supported by in vitro studies of sensitivity of HERG to dofetilide by using coexpression of HERG with wildtype and I447V KCR1 cDNAs. ### Reviews A comprehensive review of the genetic and molecular bases of long QT syndromes was provided by Priori et al. (1999, 1999). Genotype/Phenotype Correlations In a large collaborative study, Zareba et al. (1998) determined the influence of genotype on phenotype of the long QT syndrome; 112 persons had mutations at the LQT1 locus, 72 had mutations at the LQT2 locus, and 62 had mutations at the LQT3 (603830) locus. The frequency of cardiac events (syncope, aborted cardiac arrest, or sudden death) was highest with mutations at the LQT1 locus (63%) or the LQT2 locus (46%) than among subjects with mutations at the LQT3 locus (18%). The cumulative mortality through the age of 40 among members of 3 groups of families studied was similar; however, the likelihood of dying during a cardiac event was significantly higher among families with mutations at the LQT3 locus (20%) than among those with mutations at the LQT1 locus (4%) or the LQT2 locus (4%). Moss et al. (2002) investigated the clinical features and prognostic implications of mutations involving the pore and nonpore regions of the HERG channel in LQT2. Forty-four different mutations in this gene were identified in 201 subjects, with 14 localized to the pore region (amino acid residues 550 through 650). A total of 35 individuals had mutations in the pore region and 166 in nonpore regions. Those with pore mutations had a markedly increased risk for arrhythmia-associated cardiac events (syncope, cardiac arrest, or sudden death) compared with those with nonpore mutations. Animal Model Through homologous recombination in mouse embryonic stem cells, Lees-Miller et al. (2003) eliminated the ERG1 B potassium channel transcript while the ERG1 A transcript remained. Heterologous expression of ERG1 isoforms had previously indicated that the deactivation time course of ERG1 B is 10-fold more rapid than that of ERG1 A. In day 18 fetal +/+ myocytes, I(Kr) exhibited 2 time constants of deactivation, whereas in age-matched ERG1 B -/- mice the rapid component was absent. In adult ERG1 B -/- myocytes no I(Kr) was detected. Electrocardiogram intervals were similar in 6 of 21 +/+ and -/- mice; however, adult -/- mice manifested abrupt spontaneous episodes of sinus brachycardia. This phenomenon was never observed in +/+ mice. Thus, ERG1 B appears to be necessary for I(Kr) expression in the surface membrane of adult myocytes. Lees-Miller et al. (2003) concluded that knockout of ERG1 B predisposes mice to episodic sinus brachycardia. In a porcine model of postmyocardial infarction ventricular tachycardia, Sasano et al. (2006) demonstrated that focal gene transfer of the dominant-negative mutant G628S (152427.0008) to the infarct scar border zone resulted in complete elimination of ventricular arrhythmia inducibility, showing that gene transfer can eliminate cardiac tachyarrhythmias in a clinically relevant disease model. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Prolonged QT interval on EKG \- Syncope \- Sudden cardiac death \- Ventricular fibrillation \- Torsade de pointes MISCELLANEOUS \- Association of cardiac events with exercise \- Genetic heterogeneity (see LQT1 192500 ) \- Patients with a more severe phenotype have been reported with mutations in more than 1 LQTS-related gene \- GEI (gene-environment interaction) - association of cardiac events with drug administration MOLECULAR BASIS \- Caused by mutation in the potassium voltage-gated channel, subfamily H, member 2 gene or human ether-a-go-go related gene (KCNH2, 152427.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	LONG QT SYNDROME 2	c1141890	26,669	omim	https://www.omim.org/entry/613688	2019-09-22T15:57:50	{"doid": ["0110645"], "omim": ["613688"], "orphanet": ["768", "101016"], "genereviews": ["NBK1129"]}
A number sign (#) is used with this entry because of evidence that Marshall syndrome (MRSHS) is caused by heterozygous mutation in the COL11A1 gene (120280) on chromosome 1p21. Stickler syndrome type II (604841) is an allelic disorder with overlapping features. Clinical Features Marshall (1958) reported 4 generations of a family in which 7 members had (1) nasal defect and facies characteristic of anhidrotic ectodermal dysplasia; (2) congenital and juvenile cataracts; (3) myopia and fluid vitreous; (4) spontaneous, sudden maturation and absorption of congenital cataract; (5) luxation of cataract and (6) congenital hearing loss. Deficiency in sweating was minimal. The transmission was dominant. Marshall (1958) emphasized the ectodermal abnormalities, including defects in sweating and dental structures in the family he reported, which had 7 affected members in 3 generations. Shanske et al. (1997) found reports of 7 subsequently reported families, seemingly with the same disorder; they added an eighth family with 6 affected individuals in 4 generations. The affected individuals had ectodermal dysplasia and ocular hypertelorism, features not shared by Stickler syndrome (see 108300), Wagner syndrome (143200), or Weissenbacher-Zweymuller syndrome (WZS; 184840), all of which are conditions often confused with Marshall syndrome. The proposita of the African American family had sparse scalp hair and sparse eyebrows and lashes, but her teeth, nails, and sweating were normal. Craniofacial surgery was performed for hypertelorism. Her 2 brothers were also affected and had craniofacial surgery. Ruppert et al. (1970) described father and daughter with features like those in Marshall's family, namely saddle nose, myopia, and deafness and, in the father, cataracts. Cohen et al. (1971) described a father and 2 sons and 2 daughters with myopia, hyaloideoretinal degeneration, retinal detachment, flat face from maxillary hypoplasia, and in the father and 2 of his children, submucous cleft palate. Families that the authors felt had the same disorder also included those reported by Delaney et al. (1963) and Frandsen (1966). Retinal detachment with complicating cataract and cleft palate occurred in multiple members of a family reported by Delaney et al. (1963). Two brothers reported as Pierre Robin syndrome (see 261800) with eye complications by Smith and Stowe (1961) and by Smith (1969) probably had this condition or the Stickler syndrome. Zellweger et al. (1974) considered Marshall syndrome a distinct entity. They provided a report of the third recorded family, the others being those of Marshall (1958) and Ruppert et al. (1970). Cohen (1974) wrote that 'it is time to put an end to the so-called Marshall syndrome.' Yet the book of which he was a co-author (Gorlin et al., 1976) listed and discussed it as a distinct entity. Cohen (1974) thought the reported families in fact had Stickler syndrome. O'Donnell et al. (1976) insisted that the Marshall syndrome is distinct from the Stickler syndrome because of the rarity of cleft palate in the former and of deafness in the latter. They found calcification of the falx cerebri and meninges in a case, as well as platyspondyly. Winter et al. (1983) described families demonstrating nosologic overlap among Weissenbacher-Zweymuller syndrome, Stickler syndrome, and Marshall syndrome. Three unrelated children with neonatal radiologic characteristics of the Weissenbacher-Zweymuller syndrome, including small mandible, midface hypoplasia, cleft palate, and dumbbell-shaped femora, subsequently developed Marshall syndrome. The first patient was found at age 3 months to have high myopia, extensive vitreous detachments and thin peripheral retina, as well as moderate hearing loss. The second patient had a small VSD that closed spontaneously. He had nerve deafness but no eye abnormality was detected at age 2 years. The third patient had both sensorineural deafness and severe myopia. His father and 1 of 2 sisters were also affected. Winter et al. (1983) interpreted the findings in the father of patient 3 as consistent with Stickler syndrome and concluded that Marshall, WZS, and Stickler syndromes are manifestations of the identical mutation. They also noted the phenotypic overlap with Nance-Insley syndrome (OSMEDB; 215150). The distinctness of the Stickler and Marshall syndromes was strongly supported by the work of Ayme and Preus (1984) who surveyed published reports on the 2 syndromes. A set of 18 patients with clinical description, photographs, and radiographs was used to tabulate a list of 53 signs. Cluster analysis using these signs demonstrated 2 groups of patients. An index score based on the 20 most discriminating signs was applied to other reported patients with confirmation of the authors' diagnosis. Ayme and Preus (1984) concluded, therefore, that there is 'no objective reason to consider that these two syndromes are not separate dominant disorders with variable expressivity.' They suggested that the facies differ. Patients with the Marshall syndrome have a flat or retracted midface whereas those with the Stickler syndrome have a flat mala which is often erroneously described as a flat midface. Marshall syndrome patients have a thick calvaria, abnormal frontal sinuses, and intracranial calcifications. The eyeballs appear large, possibly because of a shallow orbit. Opitz and Lowry (1987) stated: 'We have the strong impression that the Marshall syndrome is different from the Stickler syndrome in spite of clinical overlap.' Stratton et al. (1991) reported Marshall syndrome in mother and daughter; the daughter also had the Pierre Robin sequence. The mother was 147 cm tall. Profile photograph showed flat facies with short nose and upturned tip and nares. She wore bilateral hearing aids and had high-grade myopia. There was mild brachycephaly with an area of occipital cutis aplasia, which had been present since birth. Studies of the COL2A1 gene (120140) showed no gross rearrangement. Griffith et al. (1998) described a large kindred with Marshall syndrome in which 9 affected members of the family, in 3 generations, were available for study. Features of Marshall syndrome included a markedly short nose with flat root, depression of the nasal bridge, anteverted nostrils, and retracted midface. Four of the affected persons had cleft palate and recurrent otitis media, which also were associated with Pierre Robin sequence in 1 individual. Four other affected individuals had bifid uvula. No dental anomalies were observed. Affected individuals had myopia and cataracts, which became apparent during the first decade of life and were located in subcapsular, cortical, nuclear, zonular, or anterior axial embryonic sites. Fluid vitreous humor was present in all affected individuals undergoing cataract surgery. Sensorineural hearing loss was noted as early as 3 years of age, with gradual progression to moderate or severe levels by late adulthood. Other features included short stature relative to unaffected family members and stocky build. Also observed was symptomatic osteoarthritis beginning in the fourth or fifth decades and affecting the knees and lumbosacral spine, as well as mild hypotrichosis and hypohidrosis in some affected family members. Radiologic findings included hypoplasia of the maxilla, nasal bones, and frontal sinuses, calvarial thickening and intracranial calcifications, and narrowed joint spaces, with osteophytic degeneration in the hips and knees. Shanske et al. (1998) suggested that the family reported by Griffith et al. (1998) suffered from Stickler syndrome, not Marshall syndrome. Shanske et al. (1997) reported a family in which 6 members in 4 generations were affected with Marshall syndrome. From a review of the literature, they attempted to distinguish the Stickler and Marshall syndromes. In both disorders, ophthalmologic abnormalities including high myopia, as well as midfacial hypoplasia, micrognathia with or without palatal clefting, and nonspecific skeletal abnormalities have been reported. In spite of these overlaps, each of the disorders has distinctive features. Striking ocular hypertelorism and abnormalities of ectodermal derivatives had been reported only in Marshall syndrome. The phenotype described by Griffith et al. (1998) included only 'mild' orbital hypertelorism and no evidence of ectodermal derivative abnormalities. Shanske et al. (1998) suggested, therefore, that the family reported by Griffith et al. (1998) most likely did not have Marshall syndrome but had the subset of Stickler syndrome in families associated with COL11A1 mutations. Warman et al. (1998) vigorously defended the diagnosis of Marshall syndrome in the family they reported (Griffith et al., 1998). They argued that a comparison of the principal findings reported by Marshall (1958) with the findings in their family revealed high concordance, whereas comparison with the patients reported by Shanske et al. (1997) showed low concordance. Marshall's patients and their patients all had congenital or juvenile cataracts and fluid vitreous; none of the patients described by Shanske et al. (1997) had these conditions. Marshall's patients and their patients all had significant hearing loss; none of the patients described by Shanske et al. (1997) had hearing loss. Marshall's patients had 'ample and normal hair,' as did their patients; the patients described by Shanske et al. (1997) all had 'sparse' hair or a 'paucity of hair.' Two of Marshall's patients were studied radiographically; each had nasal bones that were 'small, short, and far back of their normal position.' These patients also had 'prominence of the frontal bossae,' which served to 'accentuate the flatness or depression of the bridge of the nose,' and 'thickening of the outer table of the skull and absent frontal sinuses.' In their report (Griffith et al., 1998), a patient photograph and cranial CT scan were included that showed nearly identical features. In contrast, the patients described by Shanske et al. (1997) had 'significant frontal recession' and normal skeletal surveys. Warman et al. (1998) pointed out that although the presence of ectodermal abnormalities in the patients of Marshall (1958) had been emphasized, e.g., sparse hair, eyebrows, and eyelashes, the patients, in fact, did not have these; instead, Marshall (1958) thought that his patients had an altered ability to sweat. When comparing his patients with a 32-year-old female control, Marshall (1958) observed that sweat production was 'diminished, perhaps 25% below normal.' Molecular Genetics In affected members in a large kindred with Marshall syndrome in which linkage analysis had mapped the phenotype to the 1p21 region, Griffith et al. (1998) demonstrated a splice-donor site mutation in the COL11A1 gene (120280.0002). The results demonstrated allelism of Marshall syndrome with a subset of Stickler syndrome families associated with COL11A1 mutations. Both Stickler syndrome and Marshall syndrome are dominantly inherited chondrodysplasias characterized by midfacial hypoplasia, high myopia, and sensorineural hearing deficit. Since the characteristics of these syndromes overlap, it has been argued whether they are distinct entities or different manifestations of a single syndrome. Several mutations causing Stickler syndrome had been found in the COL2A1 gene (see, e.g., 120140.0005) and 1 mutation causing Stickler syndrome (120280.0001) and 1 causing Marshall syndrome (120280.0002) had been detected in the COL11A1 gene. By screening patients with Stickler syndrome, Stickler-like syndrome, or Marshall syndrome, Annunen et al. (1999) identified 23 novel mutations of the COL11A1 gene. Genotypic-phenotypic comparisons revealed an association between the Marshall syndrome phenotype and the splicing mutations of the 54-bp exons in the C-terminal region of the COL11A1 gene. Null-allele mutations in the COL2A1 gene led to the typical phenotype of Stickler syndrome. Some patients, however, presented with phenotypes of both Marshall and Stickler syndromes (120280.0003). Majava et al. (2007) analyzed 44 patients with a phenotype suggestive of Stickler syndrome or Marshall syndrome who were negative for mutations in the COL2A1 gene, and they identified mutations in COL11A1 in 10 patients (see, e.g., 120280.0002 and 120280.0006). Four of the 10 mutation-positive patients were diagnosed with Marshall syndrome, but the remaining 6 showed an overlapping Marshall/Stickler phenotype. Majava et al. (2007) concluded that heterozygous COL11A1 mutations can result in either Marshall syndrome or Stickler syndrome, and also in phenotypes that are difficult to classify with respect to the 2 disorders. A type I vitreous anomaly was diagnosed in a patient with a mutation in COL11A1 (120280.0006), suggesting that the vitreous phenotype does not always allow prediction of the defective gene in Stickler and Marshall syndromes. Ala-Kokko and Shanske (2009) reported a 3-year-old boy with Marshall syndrome in whom they identified heterozygosity for a splice site mutation in the COL11A1 gene (120280.0012). Mosaicism for the same mutation was demonstrated in his mildly affected mother and believed to be the cause of her less severe manifestations. Ala-Kokko and Shanske (2009) stated that this was the first report of mosaicism in Marshall syndrome. Nomenclature Note that the designation 'Marshall syndrome' has sometimes been used for the Marshall-Smith syndrome; see 602535. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Face \- Flat midface \- Micrognathia \- Long philtrum Ears \- Sensorineural hearing loss \- Low-set ears Eyes \- Myopia \- Congenital cataracts \- Esotropia \- Retinal detachment \- Glaucoma \- Lens dislocation \- Vitreoretinal degeneration \- Hypertelorism \- Epicanthal folds Nose \- Short, depressed nose \- Flat nasal bridge \- Anteverted nares Mouth \- Thick lips \- Cleft palate \- Robin sequence Teeth \- Prominent, protruding upper incisors SKELETAL Skull \- Calvarial thickening \- Absent frontal sinuses \- Falx, tentorial, and meningeal calcifications Spine \- Mild platyspondyly Pelvis \- Small iliac bones \- Coxa valga Limbs \- Small, irregular distal femoral epiphyses \- Small, irregular proximal tibial epiphyses \- Outward radial bowing \- Outward ulnar bowing Hands \- Wide tufts of distal phalanges MISCELLANEOUS \- Stickler syndrome ( 108300 ) and Marshall syndrome share several characteristics such as midface hypoplasia, high myopia, and sensorineural hearing loss \- Marshall syndrome is allelic to Stickler syndrome, type 2 ( 604841 ) MOLECULAR BASIS \- Caused by mutation in the collagen XI, alpha-1 polypeptide gene (COL11A1, 120280.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MARSHALL SYNDROME	c0265235	26,670	omim	https://www.omim.org/entry/154780	2019-09-22T16:38:32	{"mesh": ["C536025"], "omim": ["154780"], "orphanet": ["560"]}
Pulmonary valve agenesis-tetralogy of Fallot-absence of ductus arteriosus syndrome is a rare congenital heart malformation characterized by a tetralogy of Fallot (pulmonary stenosis, overriding aorta, ventricular septal defect and right ventricular hypertrophy), complete absence or rudimentary pulmonary valve that is both stenotic and regurgitant and an absence of the ductus arteriosus. It presents prenatally with cardiomegaly, polyhydramnios, fetal heart failure, hydrops fetalis and fetal demise or postnatally with cyanosis and respiratory failure due to bronchomalacia secondary to bronchial compression from dilated pulmonary arteries. It is frequently associated with 22q11 deletion. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Pulmonary valve agenesis-tetralogy of Fallot-absence of ductus arteriosus syndrome	None	26,671	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101206	2021-01-23T18:56:08	{"icd-10": ["Q22.2"], "synonyms": ["APV/ADA, Fallot type", "Absence of pulmonary valve-Fallot tetralogy-absence of ductus arteriosus syndrome", "PVA/ADA, Fallot type"]}
Ataxia telangiectasia (A-T) is rare condition that affects the nervous system, the immune system, and many other parts of the body. Signs and symptoms of the condition usually begin in early childhood, often before age 5. The condition is typically characterized by cerebellar ataxia (uncoordinated muscle movements), oculomotor apraxia, telangiectasias, choreoathetosis (uncontrollable movements of the limbs), a weakened immune system with frequent infections, and an increased risk of cancers such as leukemia and lymphoma. A-T is caused by changes (mutations) in the ATM gene and is inherited in an autosomal recessive manner. Treatment is supportive and based on the signs and symptoms present in each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Ataxia telangiectasia	c0004135	26,672	gard	https://rarediseases.info.nih.gov/diseases/5862/ataxia-telangiectasia	2021-01-18T18:02:01	{"mesh": ["D001260"], "omim": ["208900"], "orphanet": ["100"], "synonyms": ["AT", "Louis-Bar syndrome", "Cerebello-oculocutaneous telangiectasia", "Immunodeficiency with ataxia telangiectasia"]}
A number sign (#) is used with this entry because GLUT1 deficiency syndrome-2 (GLUT1DS2), also known as paroxysmal exercise-induced dyskinesia (PED) with or without epilepsy and/or hemolytic anemia and as dystonia-18 (DYT18), is caused by heterozygous mutation in the SLC2A1 gene (138140), which encodes the GLUT1 transporter, on chromosome 1p34. Allelic disorders with overlapping features include GLUT1 deficiency syndrome-1 (GLUT1DS1; 606777), dystonia-9 (DYT9; 601042), and idiopathic generalized epilepsy-12 (EIG12; 614847). Description GLUT1 deficiency syndrome-2 is an autosomal dominant disorder characterized primarily by onset in childhood of paroxysmal exercise-induced dyskinesia. The dyskinesia involves transient abnormal involuntary movements, such as dystonia and choreoathetosis, induced by exercise or exertion, and affecting the exercised limbs. Some patients may also have epilepsy, most commonly childhood absence epilepsy, with an average onset of about 2 to 3 years. Mild mental retardation may also occur. One family has been reported with the additional feature of hemolytic anemia (Weber et al., 2008). GLUT1 deficiency syndrome-2 shows wide clinical variability both within and between affected families. The disorder, which results from a defect in the GLUT1 glucose transporter causing decreased glucose concentration in the central nervous system, is part of a spectrum of neurologic phenotypes resulting from GLUT1 deficiency. GLUT1 deficiency syndrome-1 (606777) represents the more severe end of the phenotypic spectrum. Correct diagnosis of GLUT1 deficiency is important because a ketogenic diet often results in marked clinical improvement in motor and seizure symptoms (reviews by Pascual et al., 2004 and Brockmann, 2009). Clinical Features Plant et al. (1984) reported a mother and daughter with exercise-induced paroxysmal dystonia. The mother first developed involuntary movements of the legs after walking at age 8 years. Involvement of the upper limbs sometimes occurred with stress or continuous writing. The attacks could also be elicited with other stimuli, including passive movement and vibration. The patient's daughter was similarly affected. Margari et al. (2000) reported a family in which 6 members had paroxysmal exertion-induced dyskinesia with onset in childhood. Other precipitating factors included fasting and stress. The attacks were characterized by involuntary flexing and extending movements and alternately twisting movements of the upper and lower limbs lasting between 10 and 40 minutes. All patients also had absence seizures or partial complex seizures, which spontaneously resolved with age. One patient had generalized tonic-clonic seizures. Some had mild learning disabilities and irritable behavior with aggressive or impulsive outbursts. The dyskinesias showed decreased frequency with age. Detailed neurophysiologic studies suggested hyperexcitability at the muscular and brain cell membrane levels, and Margari et al. (2000) postulated a defect in an ion channel. Munchau et al. (2000) reported a family in which 4 members had paroxysmal exercise-induced dystonia with a mean age at onset of 12 years (range, 9-15 years). Attacks of PED in affected members were predominantly dystonic and lasted between 15 and 30 minutes. They were consistently precipitated by walking but could also occur after other exercise. Three patients also had migraine without aura. Overweg-Plandsoen et al. (2003) reported a 6-year-old boy with delayed psychomotor development, moderate mental retardation, horizontal nystagmus, dysarthria, limb ataxia, hyperreflexia, and dystonic posturing of the limbs. He had never had seizures. The motor activity and coordination fluctuated throughout the day, which was unrelated to food intake. Laboratory studies showed hypoglycorrhachia and low CSF lactate. Genetic analysis identified a de novo heterozygous mutation in the GLUT1 gene (N34I; 138140.0011). A ketogenic diet helped with the motor symptoms. Wang et al. (2005) reported 3 patients with an atypical phenotype of GLUT1 deficiency syndrome without infantile seizures. Two had a phenotype consistent with that reported in a child by Overweg-Plandsoen et al. (2003): all had mental retardation, dysarthria, dystonia, and ataxia, but no seizures. The third patient with an atypical phenotype reported by Wang et al. (2005) had choreoathetosis, dystonia, paroxysmal episodes of blinking, and abnormal head and eye movements, which ceased at age 3 years. He also had hypotonia, dysarthria, and developmental delay. Biochemical analysis showed that all patients had decreased CSF glucose and decreased glucose uptake into erythrocytes compared to controls. Kamm et al. (2007) reported a German family in which 4 individuals spanning 3 generations had paroxysmal exercise-induced dystonia, 2 of whom also had clinical seizures. Onset of PED ranged from 2 to 10 years and affected the legs. One woman had generalized seizures during pregnancy at age 22 years, and a boy had onset of frequent absence seizures at age 3.5 years. EEG studies showed abnormalities in all 4 patients, even those without seizures, as well as in 2 unaffected family members. EEG findings were variable, and included synchronous and hypersynchronous spike-wave complexes, sharp waves, and rhythmic theta- and delta-activity. Two individuals had speech and developmental delay, and 1 had migraine with visual aura. Joshi et al. (2008) reported a 13-year-old boy with a history of ataxia since early childhood who was diagnosed with GLUT1 deficiency syndrome after onset of epilepsy at age 11 years. He had delayed psychomotor development, early-onset ataxia, and hyperreflexia. He first developed a seizure disorder at age 11 years, with staring spells, head jerking, eye rolling, and loss of tone, which progressed to absence, myoclonic, and atonic seizures. His cognitive and motor skills deteriorated during this period. EEG showed moderate background slowing. Laboratory studies showed decreased CSF glucose and lactate, consistent with GLUT1 deficiency syndrome. Genetic analysis identified a heterozygous mutation in the SLC2A1 gene (R93W; 138140.0013). A ketogenic diet resulted in complete seizure control with motor and cognitive improvement. Zorzi et al. (2008) reported 3 unrelated Italian females with GLUT1 deficiency associated with paroxysmal movement disorders diagnosed in early adulthood. None had a positive family history. All had global developmental delay noted in infancy, and 2 had seizures beginning in the first 6 months of life (myoclonic absence and complex partial seizures, respectively). All had microcephaly, dysarthria, spasticity, and moderate mental retardation. Paroxysmal movements included myoclonic jerks, stiffening, and dystonic posturing. Two had exercise-induced dystonia, 1 with choreoathetosis. Zorzi et al. (2008) noted that the abnormal movements were consistent with paroxysmal dyskinesia, thus expanding the phenotype associated with GLUT1 deficiency. Suls et al. (2008) reported a 5-generation Belgian family segregating paroxysmal exercise-induced dyskinesia and epilepsy. Three additional smaller unrelated families with a similar phenotype were also observed. Of the 22 affected individuals from all families, 19 (76%) had a history of PED and 14 (56%) had a history of epilepsy; 11 (44%) had a history of both. Three SLC2A1 mutation carriers were asymptomatic, indicating reduced penetrance. The median age at onset of PED was 8 years (range, 3-30), and all patients had involvement of the legs. Precipitating factors included exertion (89%), particularly prolonged brisk walking, stress (39%), starvation (28%) and sleep deprivation (6%). All patients had involvement of the legs: 9 (50%) reported involuntary movements suggestive of choreoathetosis alone, 3 (17%) of dystonia, and 6 (33%) of both. Choreoathetosis was described as uncontrollable rapid movements, and dystonia as stiffening and cramps. PED made walking impossible and caused falls in some individuals. The 14 mutation carriers with epilepsy had a median age at onset of 2 years (range, 0-19). The seizure types could be classified as absence (64%), generalized tonic-clonic seizures without focal onset (50%), and complex and simple partial seizures (14%). Most patients had seizure remission with antiepileptic drug treatment. Most mutation carriers were of average intelligence or had mild mental retardation. Four patients underwent formal neuropsychologic testing and had a median IQ of 65 (45-79). EEG studies were often normal (43%), but some showed interictal generalized epileptic discharges (29%) and/or background slowing (5-10%). The mean CSF glucose level was 44 mg/dl (range, 34-64) and the mean CSF:plasma glucose was 0.52 (range, 0.47-0.60), indicating a mild decrease compared to controls. PET studies suggested that disordered glucose metabolism in the corticostriate pathways plays a role in PED, and that disordered glucose metabolism in the frontal lobes plays a role in epilepsy. Three patients were successfully treated with a ketogenic diet. Most patients reported that PED and epilepsy became less severe when they grew older. The findings indicated that both PED without epilepsy and PED with epilepsy can be caused by mutations in the SLC2A1 gene. Suls et al. (2008) suggested that attacks of PED may be caused by reduced glucose transport across the blood-brain barrier, possibly when the energy demand of the brain overcomes its supply after prolonged periods of exercise. Rotstein et al. (2009) reported a 10-year-old boy with GLUT1 deficiency syndrome who presented at age 2 years with onset of episodic ataxia and slurred speech associated with unilateral muscle weakness. Laboratory studies showed significantly decreased CSF glucose levels. He showed gradual cognitive decline, progressive microcephaly, and ataxia during childhood. Studies in patient erythrocytes showed about a 50% decrease in glucose uptake compared to controls. Genetic analysis identified a de novo heterozygous R93W mutation in the SLC2A1 gene (138140.0013). Rotstein et al. (2009) noted that the phenotype in this patient was reminiscent of alternating hemiplegia of childhood (104290). Perez-Duenas et al. (2009) reported a 7-year-old girl with GLUT1 deficiency syndrome-2. She had delayed psychomotor development from infancy, and presented at age 5 years with episodic flaccidity and loss of ambulation. The episodes continued and were accompanied by gait ataxia, dysarthria, dyskinesias, and choreic movements. Milder features included action tremor, upper limb dysmetria, and ataxia. Brain MRI showed moderately severe supratentorial cortico-subcortical atrophy, and EEG showed mild diffuse slowing. CSF glucose was decreased. Institution of a ketogenic diet resulted in clinical improvement of the movement disorder and increased brain growth, although cognitive skills did not improve. Genetic analysis identified a heterozygous de novo mutation in the SLC2A1 gene (138140.0017). Roubergue et al. (2011) reported a 20-year-old girl with GLUT1 deficiency syndrome-2, confirmed by genetic analysis, who presented at age 11 years with action tremor and a 'jerky' voice. She had learning disabilities, history of a single seizure at age 10.5, hyperreflexia, unstable tandem walk, and foot PED. By age 20, the tremor had improved and PED was stable. The patient's mother, who also carried the mutation, had a similar phenotype, with tremor, PED, 'jerky' voice, unstable tandem gait, and hyperreflexia. EMG in both patients showed an irregular 6- to 8.5-Hz postural hand tremor without myoclonus; CSF analysis in the daughter showed mild glycorrhachia. Family history revealed that the maternal grandmother and great-grandmother of the proband had hand tremor, foot PED, and 'jerky' speech. Both patients refused treatment with medication or a ketogenic diet. In a literature review, Roubergue et al. (2011) found that about 6% of patients with GLUT1 mutations, including their patients, had action tremor. Most patients with tremor had additional mild neurologic disorders, such as learning disabilities, seizures, cerebellar symptoms, and paroxysmal dystonia. The report indicated that dystonic tremor can be a presenting symptom of mild GLUT1 deficiency. Thouin and Crompton (2016) reported a 19-year-old man with GLUT1DS2 confirmed by genetic analysis. He was referred for refractory childhood absence epilepsy with onset of absence seizures at age 3; the seizures sometimes occurred up to 30 times a day and were precipitated by hunger. He also had poor fine motor skills, developmental dyspraxia, and poor school performance. He had a history of paroxysmal exercise-induced dyskinesia, manifest as loss of control of his legs and frequent falls after prolonged walking. EEG during fasting was abnormal, with irregular 1- to 4-Hz slow waves and 4- to 6-Hz high amplitude sharp waves. After eating, the EEG was normal. CSF glucose was at the low-normal range. There was no family history of a similar disorder. Thouin and Crompton (2016) noted the phenotypic variability of GLUT1 deficiency syndromes and emphasized the importance of clinical clues for diagnosis, including early-onset absence seizures and paroxysmal exercise-induced dyskinesia, because symptoms of the disorder may respond to a ketogenic diet. ### Clinical Variability Weber et al. (2008) reported a 3-generation family in which 4 members had childhood onset of episodic involuntary exertion-induced dystonic, choreoathetotic, and ballistic movements associated with macrocytic hemolytic anemia with reticulocytosis. One woman reported less frequent symptoms since the age of 35, which disappeared completely after the age of 45. Neuropsychologic evaluation revealed slight deficits in attention concerning complex tasks and verbal memory in the 2 adults, mild developmental delay in 1 child, and decreased cognitive function with an IQ of 77 in the second child. The 2 younger patients developed seizures in infancy and childhood, respectively, that were more frequent in the morning before breakfast and improved after carbohydrate intake. Ketogenic diets were beneficial in the younger patients. Electron microscopy of the patients' red cells showed echinocytes, and erythrocytes of all affected individuals had increased sodium and decreased potassium. CSF revealed glucose levels at or below the lower limit of normal. Mullen et al. (2010) reported significant intrafamilial clinical variability of GLUT1 deficiency syndrome in 2 unrelated families, one with 9 mutation carriers spanning 2 generations and the other with 6 mutation carriers spanning 2 generations. Of 15 patients with SLC2A1 mutations, 12 had epilepsy, most commonly absence epilepsy, with onset between ages 3 and 34 years. Eight patients had idiopathic generalized epilepsies with absence seizures, 2 had myoclonic-astatic epilepsy, and 2 had focal epilepsy. Seven patients had subtle paroxysmal exertional dyskinesia as the only manifestation, and 2 mutation carriers were unaffected. Only 3 of 15 patients had mild intellectual disabilities. Mullen et al. (2010) emphasized the phenotypic overlap with common forms of idiopathic generalized epilepsy (see EIG12, 614847). Inheritance The transmission pattern of paroxysmal exercise-induced dyskinesia in the family reported by Munchau et al. (2000) was consistent with autosomal dominant inheritance with reduced penetrance. Molecular Genetics In affected members of the families reported by Margari et al. (2000) and Munchau et al. (2000), Weber et al. (2008) identified 2 different heterozygous mutations in the SLC2A1 gene (138140.0009 and 138140.0010, respectively). Two additional families with PED did not have SLC2A1 mutations, suggesting genetic heterogeneity. In affected members of a large Belgian family segregating PED and epilepsy, Suls et al. (2008) identified a heterozygous missense mutation in the GLUT1 gene (S95I; 138140.0012). In affected members of a family with PED and hemolytic anemia, Weber et al. (2008) identified a deletion in the SLC2A1 gene (138140.0008). Weber et al. (2008) concluded that the dyskinesias resulted from an exertion-induced energy deficit causing episodic dysfunction in the basal ganglia. The hemolysis was demonstrated in vitro to result from alterations in intracellular electrolytes caused by a cation leak through mutant SLC2A1. Schneider et al. (2009) identified 2 different de novo heterozygous mutations in the GLUT1 gene (see, e.g., 138140.0015) in 2 of 10 unrelated Caucasian patients with paroxysmal exercise-induced dyskinesias. One of the patients had childhood onset of absence epilepsy. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Dyskinesia, limb, exertion-induced \- Dystonia, limb, exercise-induced \- Flaccidity, episodic \- Choreoathetosis \- Ataxia, mild \- Tremor, action \- Dystonic tremor \- Dystonic vocal tremor \- Seizures, particularly absence (in some patients) \- EEG abnormalities \- Generalized spike wave discharges \- Generalized slowing \- Delayed psychomotor development \- Cognitive impairment \- Decreased CSF glucose \- Migraine headache (less common) \- Cerebral atrophy Behavioral Psychiatric Manifestations \- Irritability (in 1 family) HEMATOLOGY \- Macrocytic hemolytic anemia, appears in infancy (in 1 family) \- Echinocytes \- Reticulocytosis \- Erythrocytes have defects in cation permeability LABORATORY ABNORMALITIES \- Hypoglycorrhachia (low glucose in CSF) \- Low-to-normal CSF lactate \- Increased serum bilirubin due to hemolysis MISCELLANEOUS \- Onset in childhood \- Highly variable phenotype \- Favorable response to a ketogenic diet \- Incomplete penetrance \- Allelic disorder to GLUT1 deficiency syndrome 1 ( 606777 ) MOLECULAR BASIS \- Caused by mutation in the solute carrier family 2 (facilitated glucose transporter), member 1 gene (SLC2A1, 138140.0008) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	GLUT1 DEFICIENCY SYNDROME 2	c1842534	26,673	omim	https://www.omim.org/entry/612126	2019-09-22T16:02:18	{"doid": ["0090045"], "mesh": ["C564288"], "omim": ["612126"], "orphanet": ["98811"], "synonyms": ["Alternative titles", "PAROXYSMAL EXERCISE-INDUCED DYSKINESIA WITH OR WITHOUT EPILEPSY AND/OR HEMOLYTIC ANEMIA", "PED WITH OR WITHOUT EPILEPSY AND/OR HEMOLYTIC ANEMIA", "PAROXYSMAL EXERTION-INDUCED DYSTONIA WITH OR WITHOUT EPILEPSY AND/OR HEMOLYTIC ANEMIA", "DYSTONIA 18"], "genereviews": ["NBK1430"]}
Dust pneumonia A Dust Bowl-era dust storm in Texas (1935) SpecialtyPulmonology Dust pneumonia describes disorders caused by excessive exposure to dust storms, particularly during the Dust Bowl in the United States.[1] A form of pneumonia, dust pneumonia results when the lungs are filled with dust, inflaming the alveoli.[citation needed] Symptoms of dust pneumonia include high fever, chest pain, difficulty in breathing, and coughing. With dust pneumonia, dust settles all the way into the alveoli of the lungs, stopping the cilia from moving and preventing the lungs from ever clearing themselves.[citation needed] People who had dust pneumonia often died.[1] There are no official death rates published for the Great Plains in the 1930s. In 1935, dozens of people died in Kansas from dust pneumonia.[1] Red Cross volunteers made and distributed thousands of dust masks, although some farmers and other people in the affected areas refused to wear them.[1] ## In popular culture[edit] Dust pneumonia was featured in the work of several musicians and artists of the day, such as Woody Guthrie's song "Dust Pneumonia Blues".[2] ## See also[edit] * Silicosis – Pneumoconiosis caused by inhalation of silica, quartz or slate particles * Dust storm * Pneumonitis ## References[edit] 1. ^ a b c d Worster, Donald (2004-09-16). Dust Bowl: The Southern Plains in the 1930s. OUP USA. pp. 20–21. ISBN 9780195174885. 2. ^ Butler, Martin (2007). Voices of the down and out: The dust bowl migration and the great depression in the songs of Woody Guthrie. Heidelberg: Winter. p. 67. ISBN 9783825353674. OCLC 191828843. This article about a medical condition affecting the respiratory system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Dust pneumonia	None	26,674	wikipedia	https://en.wikipedia.org/wiki/Dust_pneumonia	2021-01-18T18:45:17	{"wikidata": ["Q5317031"]}
A rare germ cell tumor characterized by composition of two or more malignant germ cell components, the most common combination being dysgerminoma and yolk sac tumor. The tumors typically occur between childhood and young adulthood. They are usually located in the gonads, occasionally also in other regions. Clinical presentation corresponds to the individual germ cell components and the tumor location; manifestations may include abdominal pain, abdominal mass, and menstrual disorder in females, and a testicular mass in males. The most important prognostic factor is tumor stage. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mixed germ cell tumor	c0334524	26,675	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=180234	2021-01-23T17:17:07	{"umls": ["C0334524"]}
Subependymomas are slow-growing brain tumors that are usually benign. They are most often found in the fourth or lateral ventricles in the brain, but may occur in the spine. Symptoms depend on the tumor location. Some people do not have symptoms, while others may have headaches, changes in vision, and/or difficulty with balance. These symptoms are thought to be due to obstruction of cerebral spinal fluid (CSF) due to the tumor's location. Most subependymomas are benign with a low recurrence rate. However, a few progress to anaplastic ependymoma (a faster growing tumor). The cause of subependymomas is not well understood. Surgery to remove the tumor is often curative. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Subependymoma	c0206725	26,676	gard	https://rarediseases.info.nih.gov/diseases/10070/subependymoma	2021-01-18T17:57:28	{"mesh": ["D018315"], "omim": ["137800"], "umls": ["C0206725"], "orphanet": ["251639"], "synonyms": ["Subependymal astrocytoma (formerly)"]}
## Summary ### Clinical characteristics. Arrhythmogenic right ventricular cardiomyopathy (ARVC) – previously referred to as arrhythmogenic right ventricular dysplasia (ARVD) – is characterized by progressive fibrofatty replacement of the myocardium that predisposes to ventricular tachycardia and sudden death in young individuals and athletes. It primarily affects the right ventricle, and it may also involve the left ventricle. The presentation of disease is highly variable even within families, and some affected individuals may not meet established clinical criteria. The mean age at diagnosis is 31 years (±13; range: 4-64 years). ### Diagnosis/testing. The diagnosis of ARVC is made using a combination of noninvasive and invasive tests to evaluate cardiac structure and rhythm. The common genetic causes known to be associated with ARVC are: DSC2, DSG2, DSP, JUP, PKP2, and TMEM43. Less common genetic causes include CTNNA3, DES, LMNA, PLN, RYR2, TGFB3, and TTN. A subset of these 13 genes encode components of the desmosome. ### Management. Treatment of manifestations: Management is individualized and focused on prevention of syncope, cardiac arrest, and sudden death through use of antiarrhythmic medication and an implantable cardioverter-defibrillator. Heart transplantation is considered when ARVC has progressed to right or left ventricular heart failure, although severe diffuse biventricular involvement simulating dilated cardiomyopathy and requiring heart transplantation appears to be rare. Agents/circumstances to avoid: Regular, vigorous athletic activity including competitive athletics should be discouraged because of the strain caused on the right heart and its promotion of ARVC and associated arrhythmias. Evaluation of relatives at risk: Molecular genetic testing of at-risk relatives in families in which the pathogenic variant is known; those with the family-specific pathogenic variant warrant annual clinical screening of cardiac function and rhythm between ages ten and 50 years. If genetic testing has not been performed or did not identify a pathogenic variant in an affected family member, clinical screening for cardiac involvement is recommended for asymptomatic at-risk first-degree relatives every three to five years after age ten years. ### Genetic counseling. ARVC is typically inherited in an autosomal dominant manner. A proband with autosomal dominant ARVC may have the disorder as a result of a de novo pathogenic variant. The proportion of cases caused by a de novo variant is unknown. Each child of an individual with autosomal dominant ARVC has a 50% chance of inheriting the pathogenic variant. ARVC may also be inherited in a digenic manner (i.e., a single allele of two different genes has a pathogenic variant). Prenatal diagnosis for pregnancies at increased risk is possible if the pathogenic variant(s) have been identified in the family. ## Diagnosis ARVC is a primary cardiomyopathy that is most commonly diagnosed after an individual presents with arrhythmia findings. Diagnostic criteria were initially proposed by an international task force [McKenna et al 1994], and were revised by Marcus et al [2010]. Diagnostic criteria rely on a combination of ECG and signal averaged ECGs, imaging studies that include 2D echocardiography, cardiac MRI or RV angiography, and arrhythmia presence documented by telemetric monitoring, genetic testing, and family history. ### Suggestive Findings Arrhythmogenic right ventricular cardiomyopathy (ARVC) should be suspected in individuals with any of the following findings: * Syncope * Palpitations * Sudden cardiac death * Abnormal ECG * Abnormal right ventricle seen through cardiac imaging Diagnostic criteria for ARVC, initially proposed by an international task force [McKenna et al 1994], were revised by Marcus et al [2010] (see full text) to incorporate new knowledge and technology to improve diagnostic sensitivity while maintaining diagnostic specificity. Individuals are classified as having a definite, borderline, or possible diagnosis of ARVC based on the number of major and/or minor diagnostic criteria present (see Establishing the Diagnosis). #### Imaging Findings: Global and/or Regional Cardiac Dysfunction and Structural Alterations Major * By 2D echo * Regional right ventricular (RV) akinesia, dyskinesia, or aneurysm; AND * ONE of the following (end diastole): * PLAX (parasternal long axis) RVOT (right ventricular outflow tract) ≥32 mm; corrected for body surface area (PLAX/BSA) ≥19 mm/m2 * PSAX (parasternal short axis) RVOT ≥36 mm; corrected for BSA ≥21 mm/m2 * Fractional area change ≤33% * By MRI * Regional RV akinesia or dyskinesia or dyssynchronous RV contraction; AND * ONE of the following: * Ratio of RV end-diastolic volume to BSA ≥110mL/m2 (male) or ≥100 mL/m2 (female) * RV ejection fraction ≤40% * By right ventricular angiography. Regional RV akinesia, dyskinesia or aneurysm Minor * By 2D echo * Regional right ventricular akinesia or dyskinesia; AND * ONE of the following (end diastole): * PLAX RVOT ≥29 to <32 mm; corrected for BSA ≥16 to <19 mm/m2 * PSAX RVOT ≥32 to <36 mm; corrected for BSA ≥18 to <21 mm/m2 * Fractional area change >33% to ≤40% * By MRI * Regional RV akinesia or dyskinesia or dyssynchronous RV contraction; AND * ONE of the following: * Ratio of RV end-diastolic volume to BSA ≥100 to <110 mL/m2 (male) or ≥90 to <100 mL/m2 (female) * RV ejection fraction >40% to ≤45% #### Endomyocardial Biopsy or Autopsy Findings Major. Residual myocytes lower than 60% by morphometric analysis (or <50% if estimated), with fibrous replacement of the RV free wall myocardium in at least one sample, with or without fatty replacement of tissue Minor. Residual myocytes 60% to 75% by morphometric analysis (or 50%-65% if estimated), with fibrous replacement of the RV free wall myocardium in at least one sample, with or without fatty replacement of tissue #### ECG Findings Repolarization abnormalities * Major. Inverted T waves in right precordial leads (V1, V2, and V3) or beyond in individuals age >14 years (in the absence of complete right bundle branch block QRS ≥120 ms) * Minor * Inverted T waves in leads V1 and V2 in individuals age >14 years (in absence of complete right bundle branch block) or in V4, V5, or V6 * Inverted T waves in leads V1, V2, V3, and V4 in individuals age >14 years in the presence of complete right bundle branch block Depolarization/conduction abnormalities * Major. Epsilon waves (reproducible low-amplitude signals between end of QRS complex to onset of the T wave) in the right precordial leads (V1 to V3) * Minor * Late potential by signal-averaged ECG in at least one of three parameters in the absence of a QRS duration of ≥110 ms on the standard ECG * Filtered QRS duration (fQRS) ≥114 ms * Duration of terminal QRS <40 uV (low amplitude signal duration) ≥38 ms * Root-mean-square voltage of terminal 40 ms ≤20 uV * Terminal activation duration of QRS >55 ms measured from the nadir of the S wave to the end of the QRS, including R', in V1, V2, or V3 in the absence of complete right bundle branch block Arrhythmias * Major. Nonsustained or sustained ventricular tachycardia of left bundle branch morphology with superior axis (negative or indeterminate QRS in leads II, III, and aVF and positive in lead aVL) * Minor * Nonsustained or sustained ventricular tachycardia of RV outflow configuration, left bundle branch block morphology with inferior axis (positive QRS in leads II, III, and aVF and negative in lead aVL) or of unknown axis * >500 ventricular extrasystoles per 24 hours (Holter) #### Family History Major * ARVC confirmed in a first-degree relative who meets current task force criteria [Marcus et al 2010] * ARVC confirmed pathologically at autopsy or surgery in a first-degree relative * Identification of a pathogenic variant categorized as associated or probably associated with ARVC in the individual under evaluation Minor * History of ARVC in a first-degree relative in whom it is not possible or practical to determine whether the family member meets current task force criteria [Marcus et al 2010] * Premature sudden death (age <35 years) due to suspected ARVC in a first-degree relative * ARVC confirmed pathologically or by current task force criteria in second-degree relative ### Establishing the Diagnosis The diagnosis of ARVC is established in a proband with the following findings from different categories (see Suggestive Findings): • Two major criteria; OR • One major AND two minor criteria; OR • Four minor criteria In the task force criteria, a heterozygous pathogenic variant in one of the genes listed in Table 1a or Table 1b detected by molecular genetic testing is considered a major criterion. Molecular genetic testing approaches can include use of a multigene panel and more comprehensive genomic testing: * A multigene panel that includes DSC2, DSG2, DSP, JUP, PKP2, and TMEM43 and other genes of interest (see Differential Diagnosis) is recommended as the primary test for the proband. Other genes to include on the panel are CTNNA3, DES, LMNA, PLN, RYR2, TGFB3, and TTN. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered. Alternatively, broader cardiomyopathy gene panels can be considered as first-line testing since there is phenotypic and genotypic overlap with dilated, hypertrophic, and left ventricular noncompaction cardiomyopathies. A broader cardiomyopathy panel can also be considered as an intermediate test prior to using comprehensive genomic testing. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. Note: With the expansion of gene panel testing for ARVC, individuals with two pathogenic variants may be found (digenic/biallelic inheritance). The estimate of digenic/biallelic inheritance varies from 4% to 47% [Xu et al 2010, Bao et al 2013, Rigato et al 2013, Bhonsale et al 2015, Groeneweg et al 2015]. In most studies, digenic/biallelic carriers have a more severe arrhythmia phenotype. See Genotype/Phenotype Correlations. ### Table 1a. Molecular Genetic Testing Used in Arrhythmogenic Right Ventricular Cardiomyopathy: Most Common Genetic Causes View in own window Gene 1Proportion of ARVC Attributed to Pathogenic Variants in This Gene 2Proportion of Pathogenic Variants 3 Detectable by Method Sequence analysis 4Gene-targeted deletion/duplication analysis 5 DSC21%-2%>90% 6Unknown 7 DSG25%-26%>90% 6Unknown 7 DSP2%-39%>90% 60%-8% 8 JUP0.5%-2%>90% 6Unknown 7 PKP234%-74%>80% 611.7% TMEM43Rare>90% 6Unknown 7 Unknown 9NA Pathogenic variants of any one of the genes listed in this table account for ≥1% of ARVC; genes are listed in alphabetic order. 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. From Jacob et al [2012], a comprehensive overview of all published studies to date to yield overall population prevalence of the gene in which pathogenic variants are identified 3\. See Molecular Genetics for information on allelic variants detected in this gene. 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Bao et al [2013], Rigato et al [2013], Groeneweg et al [2015], Lazzarini et al [2015]. The proportion of ARVC attributed to specific genes varied by cohort studied, suggesting that the relative contribution of the different genes associated with ARVC may differ based on ethnicity and also on the medical care setting at the time of diagnosis (since the criteria for diagnosis of ARVC and for genetic testing may differ). 7\. No data on detection rate of gene-targeted deletion/duplication analysis are available. 8\. Groeneweg et al [2015], Lazzarini et al [2015] 9\. Evidence for additional locus heterogeneity includes as-yet undetermined loci/genes as well as the following loci for which no genes have yet been identified: ARVD3 (14q12-q22) [Severini et al 1996], ARVD4 (2q32.1-q32.3) [Rampazzo et al 1997], ARVD6 (10p14-p12) [Li et al 2000, Matolweni et al 2006]. ### Table 1b. Molecular Genetics of Arrhythmogenic Right Ventricular Cardiomyopathy: Less Common Genetic Causes View in own window Gene 1, 2Reference CTNNA3van Hengel et al [2013] DESKlauke et al [2010], Otten et al [2010], Hedberg et al [2012], Lorenzon et al [2013] LMNAQuarta et al [2012], Forleo et al [2015] PLNvan der Zwaag et al [2012] RYR2Roux-Buisson et al [2014] TGFB3Beffagna et al [2005] TTNTaylor et al [2011], Brun et al [2014] Pathogenic variants of any one of the genes listed in this table are reported in only a few families (i.e., <1% of ARVC) and the syndromes associated with these genes may overlap with the broader disorder, arrhythmogenic cardiomyopathy. Genes are listed in alphabetic order. 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. Click here (pdf) for further information on some of the genes included in the table. Note: (1) Molecular genetic testing should be considered in individuals who are suspected of having ARVC based on international task force criteria [Marcus et al 2010], but who do not meet criteria for a definite clinical diagnosis. For some of these individuals, identification of a pathogenic variant in one of the ARVC-related genes fulfills the remaining criteria (see Suggestive Findings). Borderline diagnosis of ARVC: * One major AND one minor criterion; OR * Three minor criteria from different categories Possible diagnosis of ARVC: One major criterion; OR * Two minor criteria from different categories (2) The overall yield of genetic testing for all available genes in probands who meet the revised task force criteria [Marcus et al 2010] approximates 50% [Quarta et al 2011]. Thus, if molecular genetic testing does not identify a pathogenic variant in an individual who meets diagnostic criteria, the clinical diagnosis of ARVC is unchanged. ### Beyond the Diagnostic Criteria: Additional Information Note: The phenotype of ARVC is widely variable and some affected individuals may not meet the specific criteria [McKenna et al 1994, Marcus et al 2010]; however, such individuals may still be at risk for cardiovascular events including arrhythmias and, therefore, warrant continuing care by a cardiologist. Additional considerations regarding the noninvasive and invasive tests of cardiac structure and rhythm are outlined here (pdf). ## Clinical Characteristics ### Clinical Description Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a myocardial disorder affecting the right ventricle and in some cases also the left ventricle. ARVC is progressive and characterized by fibrofatty replacement of the myocardium, predisposing to ventricular tachycardia and sudden death in young individuals [Marcus et al 1982, Thiene et al 1988, Corrado et al 1998, Fontaine et al 1998]. The disease often affects the right ventricular apex, the base of the right ventricle, and the right ventricle outflow tract. The arrhythmias in ARVC most frequently arise from the right ventricle and have left bundle branch block morphology. Pathology in ARVC may also extend to involve the left ventricle [Horimoto et al 2000, Hamid et al 2002]. Cardiac MRI studies have identified regional left ventricular dysfunction in individuals with ARVC [Sen-Chowdhry et al 2006, Jain et al 2010]. Delayed enhancement may also be seen in the left ventricle [Marra et al 2012]. Presentation. The most common presenting symptoms are heart palpitations, syncope, and death. As expected, probands / index cases have a more severe presentation. See Penetrance. Age at diagnosis and survival. ARVC typically presents in adults, although it may be seen in children during the second decade. Two long-term studies following individuals with ARVC suggest that survival is greater than 72% after six years of follow up. In ARVC overall, cardiac mortality and need for transplant are less than 5% [Bhonsale et al 2015, Groeneweg et al 2015]. Gender differences. Males are more likely to present as probands with ARVC, although females constituted nearly half of a large cohort (45%) [Bhonsale et al 2015]. In a multivariate analysis of indviduals with genetically confirmed ARVC, male sex was more likely to associate with arrhythmia events [Protonotarios et al 2016]. Progression. The four described stages of ARVC [Dalal et al 2006]: 1. Concealed phase (no clinical manifestations of ARVC, but potential risk of sudden cardiac death) 2. An overt electrical disorder (characterized by symptomatic arrhythmias) 3. Right ventricular failure 4. A biventricular pump failure (resembling dilated cardiomyopathy) [Dalal et al 2006] Left ventricle involvement can occur at any of the above stages [Sen-Chowdhry et al 2007]. Symptomatic arrhythmia. Symptomatic arrhythmias include palpitations, syncope, and presyncope attributable to ventricular ectopy or sustained or nonsustained ventricular tachycardia. Arrhythmia and sudden death. The principal characteristic of arrhythmogenic cardiomyopathies is the tendency for ventricular arrhythmia and sudden death in the absence of overt ventricular dysfunction. The increased risk for sudden death in ARVC is thought to relate to sudden ventricular arrhythmias. Studies that have investigated the propensity to arrhythmia in ARVC include the following: * Bhonsale et al [2015] evaluated 541 individuals (220 probands and 321 family members); 53% were asymptomatic at the time of first evaluation. Twenty-five percent presented with sustained ventricular tachycardia; this included 54% of probands versus 4% of family members. The median age range at symptom onset was 30 years (range 10-84 years). Of the overall cohort, 30% had spontaneous sustained VT over the follow up of six years. * Rigato et al [2013] examined a cohort of 113 individuals of whom 84% had a single desmosomal gene variant and 16% had compound heterozygous or digenic inheritance. Over an observation period that averaged 39 years, 16% had major arrhythmic events. Specific risk factors for having events were male sex and having multiple genetic variants. * Groeneweg et al [2015] reviewed the outcomes in a cohort of 439 individuals who met task force criteria and 562 family members. Over a median follow-up interval of seven years, 72% of living probands experienced sustained ventricular arrhythmias. Of family members of probands who carried pathogenic variants, 11% experienced ventricular arrhythmias over the follow-up interval. * Protonotarios et al [2016] followed 105 individuals with desmosomal gene variants finding that males were more likely to have an arrhythmic event than females. Furthermore, 41% experienced a primary arrhythmic event by age 29 (range 21-46 years). Of note, definitive diagnosis by task force criteria in the presence of a desmosomal variant showed a 57% positive and 100% negative predictive value for the occurrence of an arrhythmic event. Cardiomyopathy. The cohort of individuals with ARVC followed by Bhonsale et al [2015] had an overall incidence of left ventricular dysfunction of 14% over the follow-up interval, with 5% experiencing heart failure. ### Genotype-Phenotype Correlations Few genotype-phenotype correlations have emerged correlating specific ARVC genotypes to clinical outcomes. One observation is that DSP variants are more likely to be associated with left ventricular dysfunction [López-Ayala et al 2014, Bhonsale et al 2015]. A second observation is that having more than one variant increases propensity to arrhythmias and progression to cardiomyopathy [Bao et al 2013, Rigato et al 2013, Bhonsale et al 2015, Groeneweg et al 2015]. It has also been suggested that PKP2 pathogenic variants are more likely to be associated with ventricular tachycardia [Bao et al 2013]. ### Penetrance Probands are more likely to have ventricular arrhythmias than their family members [Groeneweg et al 2015]. Of family members with a pathogenic variant, 324 of 385 were asymptomatic, and of these 324 asymptomatic subjects, 221 (68%) did not meet task force criteria. Therefore, penetrance for ventricular arrhythmias appears to be relatively low in this disorder. ### Nomenclature Arrhythmogenic right ventricular cardiomyopathy (ARVC) has had numerous names, including Uhl anomaly and right ventricular dysplasia. Until 1996, ARVC was called arrhythmogenic right ventricular dysplasia (ARVD) [Richardson et al 1996]. Currently the term "ARVC" is favored. ### Prevalence The prevalence of ARVC is estimated at 1:1,000 to 1:1,250 in the general population [Peters 2006]. The prevalence of ARVC is greater in certain regions; in Italy and Greece (Island of Naxos), it can be as high as 0.4%-0.8% [Thiene & Basso 2001]. ## Differential Diagnosis ARVC and anterior polar cataract (APC). A single family with ARVC and subscapular cataract, a rare hereditary form of lens opacity, has been described [Frances et al 1997]. The proband and his sister both had ARVC and APC. The gene responsible for APC previously was linked to 14q24qter. Parents of the sibs were second cousins (OMIM 115650). DES. Pathogenic variants in DES have been associated with: * The phenotype of skeletal myopathy, dilated cardiomyopathy, and ARVC (per the 1994 ARVC diagnostic criteria) in families [van Tintelen et al 2009, Otten et al 2010]; * Skeletal myopathy (OMIM PS601419) or dilated cardiomyopathy with or without cardiac conduction defects; * Both myopathy and cardiomyopathy with or without cardiac conduction defects [Goldfarb et al 1998, Dalakas et al 2000]. It is unknown at this point whether unique DES variants cause the ARVC phenotype; however, pathogenic variants in the DES regions encoding both the head and tail of desmin have been identified as causative of ARVC in association with desminopathy [van Tintelen et al 2009, Otten et al 2010]. Cardiomyopathy. Many forms of cardiomyopathy may mimic aspects of ARVC. Cardiomyopathies may arise from genetic, toxic, or immunologic insults. Clinical testing may be useful to distinguish cardiomyopathy from ARVC. See Dilated Cardiomyopathy Overview. Active myocarditis. Inflammation of the myocardium defines acute myocarditis. Myocarditis may arise from viral or other pathogen exposure as well as toxic or immunologic insult. Clinical testing may be useful to distinguish myocarditis from ARVC. Coronary artery disease and myocardial infarction. Coronary artery disease, or atherosclerotic narrowing of the coronary arteries, may lead to acute or chronic ischemic conditions that may mimic aspects of ARVC. Clinical testing may be useful to distinguish these from ARVC. Right ventricular outflow tract tachycardia (RVOT) is a clinical arrhythmia condition that is not typically associated with structural heart disease as is seen in ARVC. ECG and cardiac imaging may be useful to distinguish these disorders. Brugada syndrome is characterized by ST segment abnormalities in leads V1-V3 on the ECG and a high risk of ventricular arrhythmias and sudden death. Considerable clinical overlap may be present. One discriminating factor: the right ventricular dilation and fibrofatty infiltration characteristic of ARVC is rarely seen in Brugada syndrome. Sarcoidosis. The fibrofatty infiltration of the heart characteristic of ARVC may resemble noncaseating granulomas seen on MRI in cardiac sarcoidosis [Dechering et al 2013]. Intense exercise. ARVC is present in 4%-22% of athletes with sudden cardiac death [Corrado et al 2003, Maron et al 2009]. There is some debate over whether high-intensity endurance exercise promotes the manifestation of ARVC. La Gerche et al [2010] studied athletes with a history of arrhythmias of right ventricular origin to determine if they met the 1994 task force criteria [McKenna et al 1994]. Sequence analysis of five genes that encode desmosomal proteins (DSC2, DSG2, DSP, JUP, and PKP2) revealed lower than expected variant rates, particularly in athletes performing the most exercise. More recently, a study of individuals with ARVC found that a history of intense exercise (e.g., endurance running) resulted in an earlier age of onset of ARVC [James et al 2013]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC), the following evaluations are recommended if not performed at the time of diagnosis: * ECG * Echocardiogram and/or MRI, depending on the expertise of the imaging center * Noninvasive monitoring. Cardiac rhythm can be monitored noninvasively through Holter or event monitoring, and this is an effective means of detecting ventricular ectopy including nonsustained ventricular tachycardia. Implantable loop recorders can also be used in individuals with ARVC for whom arrhythmia risks are not clear. Signal-averaged ECGs may also be useful [Philips & Cheng 2016]. * Electrophysiology study to assess the risk for ventricular arrhythmias and the appropriateness of device insertion (e.g., an implantable cardioverter defibrillator). A cardiac catheter ablation of tissue causing abnormal rhythms can be performed during the electrophysiology study; however, ablation may not be effective long-term in individuals with ARVC because of the multiple sites of primary ventricular tachycardias. ### Treatment of Manifestations Affected individuals should be monitored by a cardiologist who is knowledgeable about ARVC. Management of individuals with ARVC is complicated by its variable course and the limited specificity of clinical findings to predict arrhythmia risk. Management should be individualized and based on the specific results of detailed clinical and genetic investigation. * Management is focused on prevention of syncope, cardiac arrest, and sudden death (see Prevention of Primary Manifestations). * Beta blockers are considered first line therapy. Although their efficacy has not been shown in a randomized, prospective clinical trial, beta blockers are recommended [Yancy et al 2013, Corrado et al 2015]. * Amiodarone may also be effective [Corrado et al 2015]. * The mainstay of arrhythmia prevention relies on device insertion and management. Risk-benefit analysis for device insertion and management should be balanced against clinical risk stratification for arrhythmias. Education regarding sudden death risk to affected adults and parents of affected children is an important aspect of management. Physical exercise ‒ specifically regular, intense exercise ‒ is thought to promote ARVC and its associated arrhythmias. Therefore, those with fully diagnosed ARVC are usually recommended to reduce or eliminate prolonged exercise and participation in competitive sports [James et al 2013]. Supporting this idea that intense exercise hastens the onset of ARVC, Ruwald et al [2015] reported that a history of participation in competitive sports was associated with an earlier age of onset. These findings support the notion that intense exercise can induce ARVC even in the absence of an identifiable genetic predisposition. Heart transplantation is considered when ARVC has progressed to right or left ventricular heart failure. Severe diffuse biventricular involvement simulating dilated cardiomyopathy and requiring heart transplantation appears to be rare. ### Prevention of Primary Manifestations Prospective randomized trials have not been conducted in ARVC for the prevention of arrhythmias. Management relies on personalized recommendations based on clinical assessment. Implantable cardioverter-defibrillators (ICDs). Observational studies support that ICD placement is effective in reducing the risk for sudden cardiac death in ARVC. ICD placement should be considered in anyone with a clinical diagnosis of ARVC. Corrado et al [2010] reported results of ICD implantation in 106 individuals with ARVC who met task force criteria. Device placement was based on the presence of arrhythmia risk factor defined as syncope, family history of sudden death, nonsustained ventricular tachycardia, and whether ventricular tachycardia or fibrillation was inducible in an electrophysiology done at the time of device implant. Over the follow-up interval of 58 months, 24% of subjects had an appropriate ICD discharge. Syncope was found to predict appropriate ICD discharge. The advisability of placing an ICD for primary prevention remains a question of debate [Zorzi et al 2016]. The ACC/AHA (American College of Cardiology / American Heart Association) and European Society of Cardiology (ESC) guidelines, which are based on experience and previously published reports, recommend as a Class I indication (i.e., procedure/treatment should be performed) ICD implantation for prevention of sudden cardiac death in individuals with documented sustained ventricular tachycardia or ventricular fibrillation who have a reasonable expectation of survival with good functional status for more than one year. Class II indications (i.e., it is reasonable to perform procedure/treatment) for ICD implantation include extensive disease (e.g., left ventricular involvement), family members with sudden death, or undiagnosed syncope when ventricular fibrillation or ventricular tachycardia cannot be excluded as the cause of syncope while the individual was on optimal medical therapy [Tracy et al 2013, Priori et al 2015]. ### Surveillance Screening for degree of cardiac involvement in persons diagnosed with ARVC is essential to ascertain severity and disease progression over time. Screening recommendations: * ECG, annually or more frequently depending on symptoms * Echocardiogram, annually or more frequently depending on symptoms * Holter monitoring, event monitoring, implantable loop recorder * Exercise stress testing * Cardiac MRI, with frequency depending on symptoms and findings ### Agents/Circumstances to Avoid Individuals with ARVC are discouraged from participating in vigorous athletic activity, including competitive athletics, because of the strain caused on the right heart [Corrado et al 2015]. ### Evaluation of Relatives at Risk It is appropriate to offer molecular genetic testing to relatives at risk for ARVC (even those age <18 years) if the pathogenic variant(s) have been identified in an affected family member so that morbidity and mortality can be reduced by early diagnosis and treatment. Predictive testing should be offered in the context of formal genetic counseling. Note: The initial molecular testing in the proband should encompass ARVC-related genes as a gene panel because of the high rate of digenic heterozygosity (a heterozygous pathogenic variant in two different genes) and to increase the yield of genetic testing [Barahona-Dussault et al 2010, Bauce et al 2010, Christensen et al 2010, Xu et al 2010, Nakajima et al 2012]. Once one (or more) family-specific variant(s) have been identified, targeted variant testing is performed in relatives. Guidelines exist for screening for cardiac involvement in asymptomatic first-degree relatives at risk for ARVC [Hershberger et al 2009, Charron et al 2010]: * If the family-specific pathogenic variant has been identified in the asymptomatic at-risk relative, screening for cardiac involvement is recommended yearly between ages ten and 50 years. * If genetic testing has not been performed or did not identify a pathogenic variant in an affected family member, screening for cardiac involvement is recommended for asymptomatic at-risk first-degree relatives every three to five years after age ten years. Screening for cardiac involvement comprises the following [Hershberger et al 2009, Charron et al 2010]: * Medical history with attention to heart failure symptoms, arrhythmia, presyncope, and syncope * ECG, with consideration of signal-averaged electrocardiogram * Echocardiogram * Holter monitoring * Cardiac MRI At-risk first-degree relatives with any abnormal clinical screening tests for cardiac involvement should be considered for repeat clinical screening in one year [Hershberger et al 2009]. Children younger than age ten are not usually screened, as ARVC features are not usually seen in children before this age. See Hamilton & Fidler [2009] for a review of screening for ARVC in the young. A recent MRI study of ARVC in the young suggested that MRI increases sensitivity but that it was still unusual, even with this more sensitive modality, to see ARVC in children before age ten years [Etoom et al 2015]. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Case reports describe successful outcomes in women with ARVC who are pregnant and give birth [Agir et al 2014, Cozzolino et al 2014]. Specific guidelines for managing ARVC in pregnancy have not been developed, but affected individuals need to be monitored by a multidisciplinary team. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Arrhythmogenic Right Ventricular Cardiomyopathy	c0349788	26,677	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1131/	2021-01-18T21:42:47	{"mesh": ["D019571"], "synonyms": ["ARVC", "ARVD"]}
Orthostatic purpura Other namesStasis purpura SpecialtyDermatology Orthostatic purpura is a skin condition that results from prolonged standing or even sitting with the legs lowered (as in a bus, airplane, or train), which produced edema and a purpuric eruption on the lower extremities.[1]:827 ## See also[edit] * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Orthostatic purpura	c0343087	26,678	wikipedia	https://en.wikipedia.org/wiki/Orthostatic_purpura	2021-01-18T19:01:46	{"umls": ["C0343087"], "wikidata": ["Q7104928"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant familial hypercholesterolemia-3 (FHCL3) is caused by heterozygous gain-of-function mutation in the PCSK9 gene (607786) on chromosome 1p32. Low density lipoprotein cholesterol level quantitative trait locus-1 (LDLCQ1) is associated with heterozygous loss-of-function mutation in the PCSK9 gene. Description Familial hypercholesterolemia-3 (FHCL3) is an autosomal dominant disorder of lipid metabolism characterized by a selective increase of low density lipoprotein particles in plasma, giving rise to tendon and skin xanthomas, arcus corneae, and coronary artery disease (summary by Varret et al., 1999). For a general description and a discussion of genetic heterogeneity of hypercholesterolemia, see 143890. Varret et al. (1999) reported a large 3-generation French family (HC2) in which 7 individuals had hypercholesterolemia. All affected members had levels of total cholesterol above the 97th percentile when compared with age- and sex-matched French individuals. The proband was a 36-year-old woman, ascertained at age 17 years with 3.32 g/l total cholesterol, 2.36 g/l LDL-C, 0.48 g/l HDL-C, 0.61 g/l triglycerides, and arcus corneae. Her sister, aged 40 years, was ascertained at age 20 years with similar lipid levels, arcus corneae, tendon xanthomas, and xanthelasmas. Haddad et al. (1999) reported a large Utah kindred (K1173) segregating hypercholesterolemia. In this pedigree, the LDL levels (mean, 237 +/-70) were similar to those of familial hypercholesterolemia pedigrees with mutations in the LDL receptor gene (FHCL1; 606945), and penetrance was complete even at young ages. Triglyceride levels were significantly lower than in FHCL1 pedigrees, but mean age and body mass index were also lower. There were no differences in the frequency of tendon xanthomas or coronary artery disease. Inheritance The transmission pattern of hyercholesterolemia in the French family reported by Varret et al. (1999) was consistent with autosomal dominant inheritance. Mapping Varret et al. (1999) identified a large French pedigree and 12 additional Caucasian families with autosomal dominant hypercholesterolemia in which linkage to both the LDLR gene (606945) and the APOB gene (107730) was excluded, implicating a new locus, which they designated FH3. A lod score of 3.13 at a recombination fraction of 0.0 was obtained at markers D1S2892 and D1S2722. Varret et al. (1999) localized the FH3 locus to a 9-cM interval at 1p34.1-p32. Heterogeneity tests indicated linkage to FH3 in approximately 27% of these non-LDLR/non-APOB autosomal dominant hypercholesterolemia families, implying the existence of yet a fourth locus. Hunt et al. (2000) found that familial hypercholesterolemia in a Utah kindred (K1173), previously described by Haddad et al. (1999), mapped to 1p32. Hunt et al. (2000) mapped the disorder to a region of approximately 17 cM between markers D1S2130 and D1S1596. This region appeared to overlap the region found to be linked to severe hypercholesterolemia in French and Spanish families by Varret et al. (1999). By expansion of the K1173 pedigree and increased marker density within the region of interest, Timms et al. (2004) narrowed the linked region. They also identified additional families sharing the same microsatellite haplotype. Whereas all haplotype carriers in the K1173 kindred were affected, the haplotype carriers within the newly identified families were unaffected, suggesting that the causal mutation had occurred after divergence of these pedigrees from a common ancestor. Molecular Genetics Abifadel et al. (2003) carried out positional cloning using the French family (HC92) in which linkage was originally identified by Varret et al. (1999) and 23 French families in which involvement of LDLR (606945) and APOB (107730) had been excluded as the site of causative mutations. The critical region was found to contain 41 genes, including PCSK9 (607786). They identified PCSK9 mutations (607786.0001 and 607786.0002) in 3 French families with hypercholesterolemia. By mutation screening of genes in the chromosome 1p32 region in patients with familial hypercholesterolemia from the Utah pedigree (K1173) studied by Haddad et al. (1999) and Hunt et al. (2000), Timms et al. (2004) identified a D374Y (607786.0003) mutation in the PCSK9 gene. In 3 of 64 African American subjects with low plasma levels of low density lipoprotein cholesterol (LDLCQ1), Cohen et al. (2005) identified a nonsense mutation (Y142X; 607786.0004) in the PCSK9 gene. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Arcus corneae CARDIOVASCULAR Heart \- Coronary artery disease SKIN, NAILS, & HAIR Skin \- Xanthelasmas \- Tendinous xanthomata LABORATORY ABNORMALITIES \- High total cholesterol High LD cholesterol MISCELLANEOUS \- Elevated cholesterol levels evident before age 20 MOLECULAR BASIS \- Caused by mutation in the proprotein convertase, subtilisin/kexin-type, 9 gene (PCSK9, 607786.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HYPERCHOLESTEROLEMIA, FAMILIAL, 3	c1863551	26,679	omim	https://www.omim.org/entry/603776	2019-09-22T16:12:46	{"mesh": ["C566337"], "omim": ["603776"], "synonyms": ["Alternative titles", "HYPERCHOLESTEROLEMIA, AUTOSOMAL DOMINANT, 3", "FH3"], "genereviews": ["NBK174884"]}
Neuronal ceroid lipofuscinosis 7 (CLN7-NCL) is a rare condition that affects the nervous system. Signs and symptoms of the condition generally develop in early childhood (average age 5 years) and may include loss of muscle coordination (ataxia), seizures that do not respond to medications, muscle twitches (myoclonus), visual impairment, and developmental regression (the loss of previously acquired skills). CLN7-NCL is caused by changes (mutations) in the MFSD8 gene and is inherited in an autosomal recessive manner. Treatment options are limited to therapies that can help relieve some of the symptoms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Neuronal ceroid lipofuscinosis 7	c1838571	26,680	gard	https://rarediseases.info.nih.gov/diseases/1220/neuronal-ceroid-lipofuscinosis-7	2021-01-18T17:58:43	{"mesh": ["C563989"], "omim": ["610951"], "umls": ["C1838571"], "orphanet": ["228366"], "synonyms": ["CLN7", "CLN7 disease, late infantile ", "CLN7 disease"]}
Clonorchiasis Differential symptoms of parasite infection by raw fish: Clonorchis sinensis (a trematode/fluke), Anisakis (a nematode/roundworm) and Diphyllobothrium a (cestode/tapeworm),[1] all have gastrointestinal, but otherwise distinct, symptoms.[2][3][4][5] SpecialtyInfectious disease, medical parasitology Clonorchiasis is an infectious disease caused by the Chinese liver fluke (Clonorchis sinensis) and two related species. Clonorchiasis is a known risk factor for the development of cholangiocarcinoma, a neoplasm of the biliary system. Symptoms of opisthorchiasis caused by Opisthorchis viverrini and by O. felineus are indistinguishable from clonorchiasis caused by Clonorchis sinensis,[6] so the disease by these three parasites should be referred as clonorchiasis.[6] ## Contents * 1 Cause * 2 Diagnosis * 3 References * 4 External links ## Cause[edit] Clonorchiasis sinensis is a trematode (fluke) which is part of the phylum Platyhelminthes. It is a hermaphroditic fluke that requires two intermediate hosts. The parasitic worm is as long as 10 to 25mm and lives in the bile ducts of the liver. The eggs of the worms are passed through fecal matter which are then ingested by mollusks. One becomes infected by eating undercooked, smoked, pickled salted freshwater fish. Freshwater fish are a second intermediate host for the parasitic worm. They become infected when the larvae (cercaria) of the worm penetrates the flesh of the fish. The water snail is the first intermediate host in which a miracidium (an embryonated egg discharged in stool) goes through its developmental stages (sporocyst, rediae and cercariae). Clonorchiasis is endemic in the Far East, especially in Korea, Japan, Taiwan, and Southern China. Clonorchiasis has been reported in non endemic areas (including the United States). In such cases, the infection follows the ingestion of imported, undercooked or pickled freshwater fish containing metacercariae.[7] ## Diagnosis[edit] Adult C. sinensis worms can inhabit the bile ducts of humans for 20–25 years without any clear clinical symptoms. This, in addition to the nonspecific symptoms infected persons may develop, can lead to missed diagnoses.[citation needed] Patients are diagnosed when C. sinensis eggs are found in stools. The formalin-ether concentration technique (FECT) method of stool examination is most effective at diagnosing light cases of infection, while the Kato-Katz (KK) method is more suitable for the diagnosing of persons with clonorchiasis. Serological methods that use enzyme-linked immunosorbent assay (ELISA) can help differentiate the eggs of C. sinensis from other flukes.[8] ## References[edit] 1. ^ WaiSays: About Consuming Raw Fish Retrieved on April 14, 2009 2. ^ For Chlonorchiasis: Public Health Agency of Canada – Clonorchis sinensis – Material Safety Data Sheets (MSDS) Retrieved on April 14, 2009 3. ^ For Anisakiasis: WrongDiagnosis: Symptoms of Anisakiasis Retrieved on April 14, 2009 4. ^ For Diphyllobothrium: MedlinePlus > Diphyllobothriasis Updated by: Arnold L. Lentnek, MD. Retrieved on April 14, 2009 5. ^ For symptoms of diphyllobothrium due to vitamin B12-deficiency University of Maryland Medical Center > Megaloblastic (Pernicious) Anemia Retrieved on April 14, 2009 6. ^ a b King, Sandie; Scholz, Tomáš (2001). "Trematodes of the family Opisthorchiidae: A minireview". The Korean Journal of Parasitology. 39 (3): 209–21. doi:10.3347/kjp.2001.39.3.209. PMC 2721069. PMID 11590910.. 7. ^ "Clonorchiasis". CDC – DPDx. Archived from the original on 2013-02-16. 8. ^ Tang, Ze-Li; et al. (6 Jul 2016). "Current status and perspectives of Clonorchis sinensis and clonorchiasis: epidemiology, pathogenesis, omics, prevention and control". Infectious Diseases of Poverty. 5 (5): 71. doi:10.1186/s40249-016-0166-1. PMC 4933995. PMID 27384714. ## External links[edit] Classification D * ICD-10: B66.1 * ICD-9-CM: 121.1 * MeSH: D003003 * DiseasesDB: 29302 External resources * Patient UK: Clonorchiasis * v * t * e Parasitic disease caused by helminthiases Flatworm/ platyhelminth infection Fluke/trematode (Trematode infection) Blood fluke * Schistosoma mansoni / S. japonicum / S. mekongi / S. haematobium / S. intercalatum * Schistosomiasis * Trichobilharzia regenti * Swimmer's itch Liver fluke * Clonorchis sinensis * Clonorchiasis * Dicrocoelium dendriticum / D. hospes * Dicrocoeliasis * Fasciola hepatica / F. gigantica * Fasciolosis * Opisthorchis viverrini / O. felineus * Opisthorchiasis Lung fluke * Paragonimus westermani / P. kellicotti * Paragonimiasis Intestinal fluke * Fasciolopsis buski * Fasciolopsiasis * Metagonimus yokogawai * Metagonimiasis * Heterophyes heterophyes * Heterophyiasis Cestoda (Tapeworm infection) Cyclophyllidea * Echinococcus granulosus / E. multilocularis * Echinococcosis * Taenia saginata / T. asiatica / T. solium (pork) * Taeniasis / Cysticercosis * Hymenolepis nana / H. diminuta * Hymenolepiasis Pseudophyllidea * Diphyllobothrium latum * Diphyllobothriasis * Spirometra erinaceieuropaei * Sparganosis * Diphyllobothrium mansonoides * Sparganosis Roundworm/ Nematode infection Secernentea Spiruria Camallanida * Dracunculus medinensis * Dracunculiasis Spirurida Filarioidea (Filariasis) * Onchocerca volvulus * Onchocerciasis * Loa loa * Loa loa filariasis * Mansonella * Mansonelliasis * Dirofilaria repens * D. immitis * Dirofilariasis * Wuchereria bancrofti / Brugia malayi / \|B. timori * Lymphatic filariasis Thelazioidea * Gnathostoma spinigerum / G. hispidum * Gnathostomiasis * Thelazia * Thelaziasis Spiruroidea * Gongylonema Strongylida (hookworm) * Hookworm infection * Ancylostoma duodenale / A. braziliense * Ancylostomiasis / Cutaneous larva migrans * Necator americanus * Necatoriasis * Angiostrongylus cantonensis * Angiostrongyliasis * Metastrongylus * Metastrongylosis Ascaridida * Ascaris lumbricoides * Ascariasis * Anisakis * Anisakiasis * Toxocara canis / T. cati * Visceral larva migrans / Toxocariasis * Baylisascaris * Dioctophyme renale * Dioctophymosis * Parascaris equorum Rhabditida * Strongyloides stercoralis * Strongyloidiasis * Trichostrongylus spp. * Trichostrongyliasis * Halicephalobus gingivalis Oxyurida * Enterobius vermicularis * Enterobiasis Adenophorea * Trichinella spiralis * Trichinosis * Trichuris trichiura (Trichuriasis / Whipworm) * Capillaria philippinensis * Intestinal capillariasis * C. hepatica [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Clonorchiasis	c0009021	26,681	wikipedia	https://en.wikipedia.org/wiki/Clonorchiasis	2021-01-18T18:40:27	{"mesh": ["D003003"], "umls": ["C0009021"], "wikidata": ["Q1102300"]}
## Description Female pelvic floor disorders, including pelvic organ prolapse (POP), urinary incontinence, and stress urinary incontinence, affect over one-third of adult women (Bump and Norton, 1998). These disorders are characterized by weakening of the tissues supporting and anchoring the pelvic organs, which can affect both structure and function of the vagina, uterus, bladder, anus, and intestines. Clinical Features Yip and Kirsner (1983) described a 69-year-old woman who developed vaginal prolapse at age 29 for which vaginal hysterectomy was performed, and rectal prolapse at age 57 for which Dolorme operation was performed at age 62. At age 67, she had recurrence of rectal prolapse and later fecal incontinence, seemingly from loss of control of her anal sphincter. Vaginal prolapse had occurred also in her mother and daughter but no other examples of rectal prolapse were known in the family. The possibility that this represents a manifestation of a form of the Ehlers-Danlos syndrome comes to mind (VAM). Pathogenesis Connell et al. (2008) found that the uterosacral ligaments of 18 women with pelvic organ prolapse showed approximately 75-fold and 17-fold lower expression of HOXA11 (142958) and collagen III (COL3A1; 120180), respectively, compared to controls. In addition, MMP2 (120360) was increased 2-fold in patient tissue. Histologic examination showed more loosely organized collagen architecture in the ligaments from patients with prolapse. In vitro studies on murine embryonic fibroblasts showed that Hoxa11 increased collagen III expression and decreased Mmp2 expression. The findings were consistent with a pathway of extracellular matrix metabolism involving HOX11A, COL3A1, and MMP2. Connell et al. (2008) concluded that HOXA11 is essential for the development of the uterosacral ligaments, and suggested that women with pelvic organ prolapse may have weakened connective tissue due to changes in this signaling pathway. Population Genetics Ethnic and racial variations in the incidence of female pelvic floor disorders support the role of genetic factors. Women of European and Hispanic descent may be at greater risk compared to women of Asian, African, and Native American ethnicity. Dietz (2003) concluded that Asian women have significantly less pelvic organ mobility, both antepartum and postpartum, as opposed to women of Caucasian ancestry. Inheritance Chiaffarino et al. (1999) in several studies reported that among women with POP, approximately 30% show a familial occurrence. The risk factors for POP are multifactorial (Nikolova et al., 2007). Vaginal parity, increased infant birth weight, episiotomy, extended second stage of labor, previous surgery, obesity, age, hormonal status, smoking, and constipation have all been reported to contribute to increased risk of POP. However, environmental factors alone fail to fully explain the genesis and progression of the disorder. Severe female pelvic floor disorders have been observed on occasion in nulliparous women with minimal risk factors; furthermore, most multiparous women do not develop symptoms. Mapping Nikolova et al. (2007) described a family in which 7 women in 3 generations, including a set of identical twins, suffered from pelvic organ prolapse from a very young age. A genomewide linkage scan identified 10 regions with a lod score of 1.5, the maximum possible for this family. Candidate genes within these regions were analyzed for expression in vaginal tissue by RT-PCR. Of the genes confirmed to be expressed, LAMC1 (150290) was further evaluated by sequencing and SNP genotyping. One such SNP, rs10911193, for which a rare T variant was segregating with the condition in this family, was present at a frequency of 4.9% in the general population and 22% among probands from a cohort of families with early-onset familial pelvic organ prolapse. The SNP was located in the promoter region of LAMC1. Animal Model Connell et al. (2008) found that Hoxa11-null mice had no detectable uterosacral ligaments. GU \- Vaginal prolapse GI \- Rectal prolapse \- Late fecal incontinence Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PELVIC ORGAN PROLAPSE, SUSCEPTIBILITY TO	c2752090	26,682	omim	https://www.omim.org/entry/176780	2019-09-22T16:35:41	{"omim": ["176780"], "synonyms": ["Alternative titles", "PROLAPSE OF VAGINA AND RECTUM", "RECTAL PROLAPSE", "VAGINAL PROLAPSE"]}
Ameloblastoma is a rare, noncancerous (benign) tumor that typically develops in the jaw near the molars. It originates in the cells that form the enamel that protects your teeth. The condition most often occurs in adults in their 30s and 40s, though it can occur at any age. In many cases, the first sign is painless swelling in the jaw. While it can be very aggressive, these tumors are rarely found outside of the jaw. Treatment is complete surgical removal of the affected tissue. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Ameloblastoma	c0002448	26,683	gard	https://rarediseases.info.nih.gov/diseases/5747/ameloblastoma	2021-01-18T18:02:10	{"mesh": ["D000564"], "synonyms": ["Adenoameloblastoma"]}
A number sign (#) is used with this entry because X-linked reducing body myopathy-1 with late childhood or adult onset (RBMX1B) is caused by mutation in the FHL1 gene (300163) on chromosome Xq26. Description Reducing-body myopathy (RBM) is a rare myopathy characterized pathologically by the presence of intracytoplasmic inclusion bodies strongly stained by menadione-linked alpha-glycerophosphate dehydrogenase (MAG) in the absence of substrate, alpha-glycerophosphate. The term 'reducing body' refers to the reducing activity of the inclusions to nitroblue tetrazolium (NBT) in the absence of substrate. This condition is also commonly associated with rimmed vacuoles and cytoplasmic bodies. The clinical features of RBM are variable; a severe form has onset in infancy or early childhood and results in severe disability or early death (RBMX1A; 300717), and a less severe form has onset in late childhood or adulthood (RBMX1B) (summary by Liewluck et al., 2007 and Shalaby et al., 2009). Clinical Features Kiyomoto et al. (1995) described a 42-year-old woman with distal myopathy in whom skeletal muscle biopsy showed rimmed vacuoles and nitroblue tetrazolium reducing bodies in the cytoplasm. Goebel et al. (2001) reported a boy who developed decreased mobility of the spine and contractures at age 7. He had left-sided scoliosis and an inability to reduce physiologic cervical lordosis. Serum creatine kinase was increased. The disorder was rapidly progressive, leaving him wheelchair-bound at age 8. He developed progressive muscle weakness in the hips and shoulders and loss of deep tendon reflexes. His maternal grandmother developed slowly progressive weakness of the legs at age 50. Skeletal muscle biopsy of the boy showed fiber size variation, internal nuclei, multiple inclusion bodies, reducing bodies, and rimmed vacuoles. Some inclusion bodies reacted with anti-desmin and anti-ubiquitin. Electron microscopy showed 2 types of inclusion bodies: cytoplasmic with granular material at the core and fine filaments in the periphery, and reducing bodies with granular appearance. Goebel et al. (2001) classified this patient as having reducing body myopathy with cytoplasmic bodies, a 'mixed' congenital myopathy. Ohsawa et al. (2007) reported a boy, born of a Japanese father and Filipino mother, who developed lower limb weakness and frequent falls at age 10 years. He had proximal muscle weakness and atrophy, winging of the scapulae, lumbar lordosis, and spinal rigidity. He could walk on his toes but on not his heels; he had Gowers sign and decreased deep tendon reflexes. His mother developed foot drop at age 29 and became wheelchair-bound within 5 years. Both mother and son had increased serum creatine kinase. Skeletal muscle biopsy in both showed clusters of atrophic fibers containing reducing bodies that stained bright red with hematoxylin and eosin. In a detailed study of the muscle biopsies of the patients reported by Ohsawa et al. (2007), Liewluck et al. (2007) determined that the reducing bodies contained virtually all membrane-associated proteins tested, including those of nuclei, sarcoplasmic reticulum, Golgi apparatus, lysosome, and plasma membrane. Reducing bodies also had features of aggresomes, including positive immunoreactivity for ubiquitin and other chaperones, indicating activation of the unfolded protein response. Liewluck et al. (2007) concluded that accumulation of various misfolded membrane proteins could be a primary event in this disorder, which results in activation of the unfolded protein response and subsequent aggresome formation. Schessl et al. (2008) reported 2 unrelated boys with childhood-onset progressive muscle weakness associated with NBT-positive reducing bodies on skeletal muscle biopsy. One boy had onset at age 5 years, followed by loss of ambulation at age 8, and respiratory failure requiring ventilatory support at age 11. Dilated cardiomyopathy was detected at age 18. His mother began to have weakness in her early thirties and required a wheelchair in her forties. The second boy developed weakness and a rigid spine at age 10 years. This was followed by progressive weakness and contractures with loss of ambulation by age 16. His mother had proximal muscle weakness beginning in her mid-thirties. Both had normal cardiac examinations. Shalaby et al. (2008) reported a 16-year-old boy with late childhood onset of X-linked reducing body myopathy. He had been a good runner during childhood and was noted to have scoliosis at age 13 years. He then developed progressive walking and running difficulties. By age 16, he had difficulty in bending his body and in neck flexion, atrophy and weakness of the proximal muscles, and joint contractures. He was diagnosed with rigid spine syndrome. Serum creatine kinase was mildly elevated, and he had mild respiratory insufficiency. Skeletal muscle biopsy showed intracytoplasmic inclusions, rimmed vacuoles, and decreased protein levels of FHL1. Molecular Genetics In 2 unrelated boys with childhood-onset reducing body myopathy, Schessl et al. (2008) identified hemizygous mutations in the FHL1 gene (300163.0006 and 300163.0007, respectively). Both mutations affected the second LIM domain. Both mothers had a less severe phenotype and were heterozygous for the respective FHL1 mutations. In the mother and son reported by Ohsawa et al. (2007), Shalaby et al. (2009) identified a mutation in the FHL1 gene (300163.0009). in the second LIM domain. In a 16-year-old boy with late childhood onset of X-linked reducing body myopathy, Shalaby et al. (2008) identified an in-frame 9-bp deletion in the FHL1 gene affecting the second LIM domain (300163.0017). INHERITANCE \- X-linked HEAD & NECK Neck \- Short neck \- Hyperextended neck CARDIOVASCULAR Heart \- Dilated cardiomyopathy (less common) RESPIRATORY \- Respiratory insufficiency due to muscle weakness \- Most patients become ventilator-dependent CHEST Ribs Sternum Clavicles & Scapulae \- Winging of the scapulae SKELETAL \- Joint contractures Spine \- Rigid spine \- Decreased spinal mobility \- Cervical hyperextension \- Scoliosis \- Kyphosis \- Lordosis MUSCLE, SOFT TISSUES \- Muscle weakness, proximal, progressive \- Hyporeflexia \- Skeletal muscle biopsy shows reducing bodies \- Inclusions stain positively with nitroblue tetrazolium (NBT) \- Increased fiber size variation \- Cytoplasmic inclusion bodies \- Internal nuclei LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Onset in childhood (5 to 10 years) \- Frequent falls \- Loss of ambulation \- Rapidly progressive \- Female carriers may be less severely affected \- See also severe, early-onset form ( 300717 ) MOLECULAR BASIS \- Caused by mutation in the four-and-a-half LIM domains 1 gene ({FHL1, 300163.0006 ). ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	REDUCING BODY MYOPATHY, X-LINKED 1B, WITH LATE CHILDHOOD OR ADULT ONSET	c0270970	26,684	omim	https://www.omim.org/entry/300718	2019-09-22T16:19:47	{"doid": ["0080090"], "omim": ["300718"], "orphanet": ["97239"]}
A number sign (#) is used with this entry because of evidence that patterned macular dystrophy-2 (MDPT2) is caused by heterozygous mutation in the CTNNA1 gene (116805) on chromosome 5q31. Description Butterfly-shaped pigmentary macular dystrophy is an autosomal dominant eye disease characterized by bilateral accumulation of pigment in the macular area that resembles the wings of a butterfly (summary by van Lith-Verhoeven et al., 2003). For a general phenotypic description and a discussion of genetic heterogeneity of patterned macular dystrophy, see 169150. Clinical Features Deutman et al. (1970) described 4 of 5 brothers and the son of 1 of them with a peculiar, bilateral, butterfly-shaped pigment dystrophy of the fovea. Although electrooculogram indicated a diffuse abnormality of the retina, there was little or no impairment of vision. The disorder was characterized by abnormal pigment at the level of the retinal pigment epithelium (RPE). This material is yellow, white, or black, and often accumulates in an unusual configuration consisting of 3 to 5 'arms' or 'wings' that resemble the wings of a butterfly. The material can be detected in some patients in the second decade of life, but affected individuals most commonly become symptomatic in their late twenties or early thirties. Mapping Van Lith-Verhoeven et al. (2003) performed linkage studies in the Dutch family in which butterfly-shaped pigmentary macular dystrophy was first described (Deutman et al., 1970) and excluded involvement of 44 loci known to be involved in retinal dystrophies, the ROM1 gene (180721), and the RDS gene (PRPH2; 179605). Den Hollander et al. (2004) performed a genomewide linkage scan in this family and identified a novel locus for butterfly-shaped macular dystrophy on chromosome 5q21.2-q33.2 (maximum multipoint lod score of 4.05 between markers D5S433 and D5S410). The critical interval spans 46 cM (52 Mb) and contains the PDE6A gene (180071). Sequence analysis of PDE6A showed no pathologic mutation. Molecular Genetics In the large Dutch family with patterned macular dystrophy mapping to chromosome 5q21-q33, originally described by Deutman et al. (1970), Saksens et al. (2016) performed whole-exome sequencing and identified a heterozygous missense mutation in the CTNNA1 gene (L318S; 116805.0001). The mutation segregated fully with disease in the family and was not found in 162 ancestry-matched controls or in the Exome Variant Server database. Sequencing CTNNA1 in 93 unrelated individuals with butterfly-shaped pigment dystrophy and other pattern dystrophies identified 2 more missense mutations that segregated with disease: I431M (116805.0002) in a Dutch mother and son, and E307K (116805.0003) in a Belgian mother and daughter. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Butterfly-shaped foveal hyperpigmentation \- Pigmentation consists of closely packed pigment granules in the retina pigment epithelium (RPE) \- Butterfly surrounded by hypopigmentation (in some patients) \- Uneven distribution of macular yellow \- Diffuse pigment mottling in peripheral retina \- Bone spicule-like pigmentation in peripheral retina (in some patients) \- Decreased sensitivity of central visual field \- Defects in RPE seen on fluorescein angiography \- Drusen-like structures deforming parts of Bruch membrane \- Low to low-normal values seen on electrooculogram MISCELLANEOUS \- Onset of symptoms in third to fourth decade of life \- Pigmentation not always butterfly-shaped \- Variable severity between patients and between eyes (in some patients) MOLECULAR BASIS \- Caused by mutation in the alpha-1 catenin gene (CTNNA1, 116805.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MACULAR DYSTROPHY, PATTERNED, 2	c1837029	26,685	omim	https://www.omim.org/entry/608970	2019-09-22T16:06:53	{"doid": ["0060864"], "mesh": ["C536309"], "omim": ["608970"], "orphanet": ["99001"], "synonyms": ["Butterfly-shaped pattern dystrophy", "MACULAR DYSTROPHY, BUTTERFLY-SHAPED PIGMENTARY, 2", "Alternative titles", "Butterfly-shaped pigmentary macular dystrophy"]}
Begeer et al. (1991) described 2 sisters in their 50s who had mild mental retardation from birth and were born with congenital cataract for which surgery had been performed. Both sisters had onset of progressive sensorineural deafness in the third decade. They were of short stature (height, 1.55 m and 1.52 m). Ataxia, attributed mainly to impairment of the proprioceptive system, was present in both. Other signs of polyneuropathy included absent deep tendon reflexes and diminished sensation distally. Begeer et al. (1991) concluded that this syndrome is distinct from the ataxia-deafness-retardation syndrome (ADR syndrome; 208850) because of the presence of congenital cataract and the later onset of hearing loss and ataxia, which start in infancy in the ADR syndrome. Eyes \- Congenital cataract Growth \- Short stature Neuro \- Mild mental retardation \- Ataxia \- Proprioceptive loss \- Polyneuropathy \- Deep tendon reflexes absent \- Distal sensation loss Inheritance \- Autosomal recessive Ears \- Sensorineural deafness, late-onset ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CATARACT-ATAXIA-DEAFNESS-RETARDATION SYNDROME	c0796123	26,686	omim	https://www.omim.org/entry/212710	2019-09-22T16:30:03	{"mesh": ["C538283"], "omim": ["212710"], "orphanet": ["1368"], "synonyms": ["Alternative titles", "POLYNEUROPATHY-CATARACT-DEAFNESS SYNDROME"]}
Carpotarsal osteochondromatosis is a very rare primary bone dysplasia disorder characterized by abnormal bone proliferation and osteochondromas in the upper and lower limbs. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Carpotarsal osteochondromatosis	c1300233	26,687	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2767	2021-01-23T18:46:26	{"gard": ["1128"], "omim": ["127820"], "umls": ["C1300233"], "icd-10": ["D16.9"], "synonyms": ["Maroteaux-Le Merrer-Bensahel syndrome"]}
A number sign (#) is used with this entry because hypophosphatemic nephrolithiasis/osteoporosis-1 (NPHLOP1) is caused by heterozygous mutation in the SLC34A1 gene (182309) on chromosome 5q35. See also NPHLOP2 (612287), caused by mutation in the SLC9A3R1 gene (604990). Clinical Features Prie et al. (2002) reported 2 unrelated patients with hypophosphatemia and decreased renal phosphate absorption. The first patient was a 34-year-old man with recurrent urolithiasis. His maximal renal phosphate resorption, normalized for GFR, was decreased at 0.47 mmol/L. The second patient was a 64-year-old woman with bone demineralization. Her only daughter had a spinal deformity and a history of arm fractures. Both mother and daughter had decreased renal phosphate absorption at 0.58 and 0.67 mmol/L, respectively. Molecular Genetics In 2 of 20 unrelated probands with hypophosphatemic nephrolithiasis/osteoporosis, Prie et al. (2002) identified 2 different heterozygous mutations in the SLC34A1 gene (182309.0001 and 182309.0002). The study provided genetic evidence that heterozygous mutations in the SLC34A1 gene are involved in hypophosphatemia resulting from idiopathic renal phosphate loss, and that a defect in renal phosphate resorption contributes to the pathogenesis of urolithiasis and bone demineralization. Animal Model By targeted mutagenesis, Beck et al. (1998) generated mice deficient in the Npt2 (Slc34a1) gene. They found that homozygous mutants (Npt2 -/-) exhibited increased urinary P(i) excretion, hypophosphatemia, an appropriate elevation in the serum concentration of 1,25-dihydroxyvitamin D with attendant hypercalcemia, hypercalciuria and decreased serum parathyroid hormone levels, and increased serum alkaline phosphatase activity. The biochemical features were typical of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH; 241530), a mendelian disorder of renal P(i) resorption. However, unlike HHRH patients, Npt2 -/- mice did not have rickets or osteomalacia. At weaning, Npt2 -/- mice had poorly developed trabecular bones and retarded secondary ossification, but with increasing age there was a dramatic reversal and eventual overcompensation of the skeletal phenotype. The findings demonstrated that Npt2 is a major regulator of P(i) homeostasis and is necessary for normal skeletal development. INHERITANCE \- Autosomal dominant GENITOURINARY Kidneys \- Nephrolithiasis \- Renal phosphate wasting SKELETAL \- Osteopenia \- Osteoporosis \- Increased susceptibility to fractures Spine \- Spinal deformity LABORATORY ABNORMALITIES \- Hypophosphatemia \- Hyperphosphaturia \- Hypercalciuria \- Increased serum 1,25-dihydroxyvitamin D MOLECULAR BASIS \- Caused by mutation in the solute carrier family 34 (sodium/phosphate cotransporter), member 1 gene (SLC34A1, 182309.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	NEPHROLITHIASIS/OSTEOPOROSIS, HYPOPHOSPHATEMIC, 1	c2676786	26,688	omim	https://www.omim.org/entry/612286	2019-09-22T16:01:57	{"doid": ["0080077"], "mesh": ["C567363"], "omim": ["612286"], "orphanet": ["244305"], "synonyms": []}
A rare vascular tumor characterized by a poorly circumscribed, infiltrative nodular lesion with vascular differentiation, centered in the dermis and subcutis. The tumor is composed of histologically benign, intermediate, and malignant components. Typical is an admixture of different components which include epithelioid and retiform hemangioendothelioma, spindle cell hemangioma, angiosarcoma-like areas, and benign vascular lesions. Predilection sites are the distal extremities. Many patients have a history of lymphedema. Local recurrence is frequent, while metastasis is rare. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Composite hemangioendothelioma	c1304513	26,689	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=458758	2021-01-23T17:12:16	{"icd-10": ["D18.0"]}
Axonotmesis of the nerve Axonotmesis is an injury to the peripheral nerve of one of the extremities of the body. The axons and their myelin sheath are damaged in this kind of injury, but the endoneurium, perineurium and epineurium remain intact. Motor and sensory functions distal to the point of injury are completely lost over time leading to Wallerian degeneration due to ischemia, or loss of blood supply. Axonotmesis is usually the result of a more severe crush or contusion than neurapraxia.[1] Axonotmesis mainly follows a stretch injury. These stretch injuries can either dislocate joints or fracture a limb, due to which peripheral nerves are severed. If the sharp pain from the exposed axon of the nerve is not observed, one can identify a nerve injury from abnormal sensations in their limb. A doctor may ask for a nerve conduction velocity (NCV) test to completely diagnose the issue. If diagnosed as nerve injury, electromyography performed after 3 to 4 weeks shows signs of denervations and fibrillations, or irregular connections and contractions of muscles.[2] ## Contents * 1 Injury classification * 1.1 Sunderland's Stage II Classification[4][5] * 1.2 Sunderland's Stage III Classification * 1.3 Sunderland's Stage IV Classification * 2 Assessment * 3 EMG and NCV findings * 3.1 Changes in EMG * 3.2 Changes in NCV (nerve conduction velocity) * 4 Treatment * 5 Prognosis * 6 See also * 7 References ## Injury classification[edit] There are two kinds of nerve injury classifications:[3] Seddon Sunderland Neurapraxia Grade I Axonotmesis Grade II Axonotmesis Grade III Axonotmesis Grade IV Neurotmesis Grade V ### Sunderland's Stage II Classification[4][5][edit] * Endoneurial tube remains intact * Emergence of Wallerian degeneration * Can be detected with Tinel's sign ### Sunderland's Stage III Classification[edit] * Endoneurial tube is damaged * Perineurium remains intact * Scarring occurs * Intrafascicular fibrosis occurs due to edema ### Sunderland's Stage IV Classification[edit] * Perineurium is damaged * Epineurium remains intact * Neuroma could occur * Surgery is required for treatment ## Assessment[edit] A nerve contains sensory fibers, motor fibers, or both. Sensory fibers lesions cause the sensory problems below to the site of injury. Motor fibers injuries may involve lower motor neurons, sympathetic fibers, and or both. Assessment items include: * Sensory fibers that send sensory information to the central nervous system. * Motor fibers that allow movement of skeletal muscle. * Sympathetic fibers that innervate the skin and blood vessels of the four extremities. In assessment, sensory-motor defects may be mild, moderate, or severe. Damage to motor fibers results in paralysis of the muscles. Nervous plexus injuries create more signs and symptoms from sensory-motor problems (such as brachial plexus injuries). In these cases, the prognosis depends on the amount of damage and the degree of functional impairment. ## EMG and NCV findings[edit] ### Changes in EMG[edit] Electromyography (EMG) is a medical test performed to evaluate and record the electrical activity (electromyogram) produced by skeletal muscles using an instrument called electromyograph. In axonotmesis, EMG changes (2 to 3 weeks after injury) in the denervated muscles include: 1. Fibrillation potentials (FP) 2. Positive sharp waves ### Changes in NCV (nerve conduction velocity)[edit] EMG test is often performed together with another test called nerve conduction study, which measures the conducting function of nerves. NCV study shows loss of nerve conduction in the distal segment (3 to 4 days after injury). According to NCV study, in axonotmesis there is an absence of distal sensory-motor responses. ## Treatment[edit] Schwann cells provide the nerve with protection through the production of Nerve Growth Factors, and because these cells are intact this kind of nerve injury can be cured and normal feeling and sensations can be restored. Surgery can be done in order to help the nerve heal. The surgery will help with nerve regeneration, providing guidance to the nerve sprouts on where to attach on the proximal side of the injury. Damaged nerve axons can reattach themselves after surgery.[3] Treatment of axonotmesis also consists of: * Physical therapy or Occupational Therapy. Physical or Occupational therapy aims include: * Pain relief * Maintain range of motion * Reducing muscular atrophy * Patient education * Use of assistive devices (Orthotic needs) ## Prognosis[edit] The prognosis is usually good in terms of recovery. Rate of recovery depends on the distance from the site of injury, and axonal regeneration can go up to 1 inch per month. Complete recovery can take anywhere from 6 months to a year[6] ## See also[edit] * Seddon's classification * Neurapraxia * Neurotmesis * Nerve fiber * Nerve * Neuroregeneration * Connective tissue in the peripheral nervous system * Wallerian degeneration * Peripheral nerve injury * Nerve injury ## References[edit] 1. ^ Saidoff, David C.; McDonough, Andrew (2002). Critical Pathways in Therapeutic Intervention. Missouri: Mosby Inc. p. 262. ISBN 0-323-00105-X. 2. ^ "Nerve Injury (Neuropraxia, Axonotmesis, Neurotmesis) and Healing \| Healthhype.com". www.healthhype.com. Retrieved 2017-05-03. 3. ^ a b Menorca, Ron M. G.; Fussell, Theron S.; Elfar, John C. (2017-05-05). "Peripheral Nerve Trauma: Mechanisms of Injury and Recovery". Hand clinics. 29 (3): 317–330. doi:10.1016/j.hcl.2013.04.002. ISSN 0749-0712. PMC 4408553. PMID 23895713. 4. ^ Prince, Jim McMorran, Damian Crowther, Stew McMorran, Steve Youngmin, Ian Wacogne, Jon Pleat, Clive. "Sunderland classification of nerve injuries - General Practice Notebook". www.gpnotebook.co.uk. Retrieved 2017-05-05. 5. ^ Goubier, Jean-Noel (2015). Nerve and Nerve Injuries, 1st Edition. Vol 2: Pain, Treatment, Injury, Disease and Future Directions. London: Academic Press. p. 604. ISBN 9780128026533. 6. ^ Otto D. Payton & Richard P. Di Fabio et al. Manual of physical therapy. Churchill Livingstone Inc. Page 24. ISBN 0-443-08499-8 * v * t * e Neurotrauma Traumatic brain injury * Intracranial hemorrhage * Intra-axial * Intraparenchymal hemorrhage * Intraventricular hemorrhage * Extra-axial * Subdural hematoma * Epidural hematoma * Subarachnoid hemorrhage * Brain herniation * Cerebral contusion * Cerebral laceration * Concussion * Post-concussion syndrome * Second-impact syndrome * Dementia pugilistica * Chronic traumatic encephalopathy * Diffuse axonal injury * Abusive head trauma * Penetrating head injury Spinal cord injury * Anterior spinal artery syndrome * Brown-Séquard syndrome * Cauda equina syndrome * Central cord syndrome * Paraplegia * Posterior cord syndrome * Spinal cord injury without radiographic abnormality * Tetraplegia (Quadriplegia) Peripheral nerves * Nerve injury * Peripheral nerve injury * classification * Wallerian degeneration * Injury of accessory nerve * Brachial plexus injury * Traumatic neuroma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Axonotmesis	c0476201	26,690	wikipedia	https://en.wikipedia.org/wiki/Axonotmesis	2021-01-18T19:06:17	{"mesh": ["D020196"], "umls": ["C0476201"], "wikidata": ["Q792612"]}
A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by a late onset with severe sensory loss (paresthesia and hypoesthesia) associated with distal weakness, mainly of the legs, and absent or reduced deep tendon reflexes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Autosomal dominant Charcot-Marie-Tooth disease type 2I	c3888087	26,691	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99942	2021-01-23T17:30:09	{"gard": ["9197"], "mesh": ["C535416"], "omim": ["607677"], "umls": ["C3888087"], "icd-10": ["G60.0"], "synonyms": ["CMT2I"]}
## Clinical Features Stratakis et al. (2001) reported a family with acromegaloid features but normal growth hormone (139250) secretion. The proband was born at term with length and weight above 95th centile (60 cm and 5018 g, respectively). He had a submucosal cleft palate and a diaphragmatic hernia, which was surgically repaired. He developed sleep apnea as a child but had otherwise normal health and cognitive development. He completed puberty normally. On presentation at 14 years and 3 months of age, height and weight were above 95th centile, and acromegaloid facies and body habitus were observed. He had normal tooth spacing and no acral enlargement. Examination of the tongue, thyroid, heart, and abdomen was normal. Oral glucose tolerance test, thyrotropin-releasing hormone (613879) stimulation test, 24-hour growth hormone profile, and IGF1 (147440) levels were normal. Pituitary MRI, echocardiogram, and renal ultrasonography were normal. The bone age was advanced. Radiologic imaging of the skull and skin biopsy ruled out the diagnosis of pachydermoperiostosis (167100). The proband's mother, 1 sister, and an uncle who had died from complications of sleep apnea had palatal clefts, overgrowth, and acromegaloid features of variable severity. Cytogenetics The proband in the family reported by Stratakis et al. (2001) had a pericentric inversion of chromosome 11 with breakpoints at p15.3 and q23.3 (46,XY,inv(11)(p15.3;q23.3)). The mother and sister had the same pericentric inversion, while the father and 2 unaffected sisters had normal karyotypes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	ACROMEGALOID FEATURES, OVERGROWTH, CLEFT PALATE, AND HERNIA	c1853757	26,692	omim	https://www.omim.org/entry/606049	2019-09-22T16:10:46	{"mesh": ["C535656"], "omim": ["606049"], "synonyms": ["Alternative titles", "AOCH"]}
A number sign (#) is used with this entry because autosomal recessive cutis laxa type IB is caused by homozygous or compound heterozygous mutation in the EFEMP2 gene (604633), also known as FBLN4, on chromosome 11q13. Description Autosomal recessive cutis laxa type IB (ARCL1B) is characterized by the presence of severe systemic connective tissue abnormalities, including emphysema, cardiopulmonary insufficiency, birth fractures, arachnodactyly, and fragility of blood vessels. All symptoms refer to disturbed elastic fiber formation (summary by Hoyer et al., 2009). For a complete phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100). Clinical Features Ades et al. (1996) reported 4 unrelated children, 3 boys and 1 girl, with congenital abnormalities of the great vessels, comprising either single or multiple arterial aneurysms, aortic and/or arterial dilation, and/or vessel tortuosity. The authors noted that each child had a distinct phenotype, but all had in common the rare finding of aneurysms of the aorta and main pulmonary artery. Progression of these abnormalities was clearly evident in the female patient, who had diffuse vessel irregularity and tortuosity involving intraabdominal, intracranial, and extracranial arteries. She presented within the first 2 months of life with airway compression, aneurysm of the ascending aorta with dilatation of the proximal aortic arch and innominate artery, massive dilatation of the pulmonary trunk beyond the pulmonary valve, proximal pulmonary arterial stenosis, and moderate pulmonary regurgitation. After surgical repair of the aortic and pulmonary trunk aneurysms at 2.5 months of age, recurrent episodes of life-threatening respiratory obstruction developed at age 7 months, at which time she was found to have a massive recurrence of aneurysm of the ascending aorta and innominate artery, requiring reoperation at 8 months of age. Cineangiography at 39 months of age showed redundant aortic arch with significant dilation of the pulmonary trunk and proximal right and left branches and a mildly tortuous abdominal aorta with tortuosity and dilation of the major abdominal arteries. Ultrasonography at 4.5 years of age showed marked tortuosity and mild fusiform dilatation of the right common carotid artery, with less marked tortuosity of the left common carotid. Cerebral angiography at 5.5 years showed extreme tortuosity and dilatation of intra- and extracranial arteries. Other features in this patient included prominent eyes, bulbous nasal tip, prominent premaxilla, highly arched palate, micrognathia, generalized mild joint hypermobility, and velvety smooth skin with normal scarring. Histologic examination of tissue from the aorta and pulmonary artery showed a marked disruption of elastic fibers with an increase in deposition of interstitial glycosaminoglycans and marked thickening of the arterial intima. Large elastic fibers were markedly reduced in number and small elastic fibers were highly irregular in distribution. Analysis of dermal fibroblasts from this patient demonstrated that the proportion of collagen forming mature crosslinks was within the normal range, as was the kinetics of crosslink formation. Baspinar et al. (2005) studied a 3-year-old boy referred for evaluation of a widened mediastinum discovered on routine chest x-ray. The boy had unusually flattened facies with a prominent forehead, depressed nasal bridge, hypertelorism, narrow nostrils, high-arched palate, pectus excavatum, and moderate hypermobility of the joints. CT of the chest revealed a dilated aortic arch; transthoracic echocardiography demonstrated an aneurysmal dilation of the ascending aorta and a high aortic arch with a kink at the isthmus level. The diameters of the aortic valve, aortic root at the sinus Valsalva level, and the ascending aorta were 1.07 cm, 2.8 cm, and 4.3 cm, respectively. Aortography showed an elongated aorta with 2 acute curves, at the arcus aorta and at the diaphragmatic level. Although the boy was asymptomatic, he was placed on beta blocker therapy due to the risk of spontaneous rupture of the ascending aorta. Baspinar et al. (2005) noted that the facial dysmorphism and multiple joint dislocations were suggestive of Larsen syndrome (150250). Hucthagowder et al. (2006) described a patient with cutis laxa and severe systemic connective tissue abnormalities. The patient, the child of unaffected nonconsanguineous parents of Iraqi descent, was born with multiple fractures at gestational age 36 weeks, after an uneventful pregnancy, although oligohydramnios was reported. Examination at age 9 months revealed generalized cutis laxa with soft, velvety, and transparent skin. Additional observations included hypotonia, emphysema, generalized arterial tortuosity, inguinal and diaphragmatic hernia, joint laxity, and pectus excavatum. Diaphragmatic plication was performed at the age of 10 months. During surgery, both arterial and venous tortuosity, emphysematous and hyperexpanded lungs, and an esophagus not fixed to the posterior chest were observed. The diaphragm contained very little muscle and mainly consisted of pleuroperitoneal membrane. Aortic root aneurysm was diagnosed at the age of 2 years. Dasouki et al. (2007) reported an infant girl with apparent arachnodactyly, mild cutis laxa, and severe systemic vascular abnormalities that were inoperable and incompatible with life; she died on day 27 of life. Autopsy findings included biventricular hypertrophy and right ventricle dilatation, aneurysmal dilation of the ascending aorta and main branches of pulmonary arteries with dissection of the wall, and intussusception-like telescoping of the inner arterial layer causing severe luminal narrowing of the main branches of the pulmonary arteries. Histopathologic examination of skin, aortic wall, and pulmonary artery revealed that elastic fibers in all 3 tissues were markedly decreased in density, fragmented, and shortened. Hoyer et al. (2009) reported the third case of cutis laxa due to FBLN4 mutation (604633.0004). The patient was an infant girl who was born of consanguineous Iraqi parents, from a pregnancy remarkable for fetal overgrowth and oligohydramnios, and who died immediately after birth with extreme bradycardia. She exhibited cutis laxa, arachnodactyly of hands and feet with contractures of the third to fifth fingers, medial rotation of feet, spina bifida of the os sacrum, microcephaly, and facial dysmorphism. Autopsy showed collapsed lungs with hypoplastic diaphragm and signs of cervical soft tissue bleeding due to vessel fragility. Histologic examination showed fragmentation of elastic fibers with formation of cystic cavities in the medial layer of the aorta and central lung vessels. Hoyer et al. (2009) stated that this case extended the phenotypic spectrum of FBLN4 mutations to include microcephaly, overgrowth, and arachnodactyly. ### ARCL1B, Mappila Type Kappanayil et al. (2012) reported 22 unrelated infants, members of the Mappila Muslim group from the northern coastal Malabar region of the southern Indian state of Kerala. Eight of these patients had a family history of consanguinity; 4 families had a history of infant death. Patients presented at a median age of 1.5 months with the typical aneurysmal dilatation, elongation, tortuosity, and narrowing of the aorta, pulmonary artery and their branches seen in other patients with ARC1B. The phenotype included a variable combination of cutis laxa (52%), long philtrum with thin vermilion (90%), micrognathia (43%), hypertelorism (57%), prominent eyes (43%), sagging cheeks (43%), long, slender digits (48%), and visible arterial pulsations (38%). Early death (at 4 months of age or less) occurred in 17 of 21 patients homozygous for the same mutation (see MOLECULAR GENETICS). Isthmic hypoplasia in 9 correlated with early death. Molecular Genetics Hucthagowder et al. (2006) described a child with cutis laxa caused by homozygosity for a missense mutation (604633.0001) in the EFEMP2 gene (FBLN4). Dasouki et al. (2007) identified compound heterozygosity for a missense mutation and a 4-bp duplication in the FBLN4 gene (604633.0002 and 604633.0003, respectively) in a patient with cutis laxa, arachnodactyly, and severe systemic vascular abnormalities. Analysis of the FBLN5 (604580) gene showed no mutations. The authors noted overlapping phenotypic similarities to the patient described by Hucthagowder et al. (2006). In the infant girl with cutis laxa reported by Hoyer et al. (2009), sequencing of the FBLN4 gene revealed a homozygous missense mutation in exon 7 (604633.0004). Renard et al. (2010) sequenced the FBLN4 gene in 17 patients with prominent cutis laxa but no major cardiovascular findings, who were known to be negative for mutation in the ELN (130160) and FBLN5 genes, but detected no FBLN4 mutations. Analysis of a second cohort of 22 patients who had mild skin involvement but significant cardiovascular features, including arterial tortuosity, stenosis, and aneurysms, and who had previously tested negative for mutation in the SLC2A10 (606145), FBN1 (134797), TGFBR1 (190181), and TGFBR2 (190182) genes, revealed homozygosity or compound heterozygosity for mutations in the FBLN4 gene in 3 patients (604633.0005-604633.0008), 2 of whom had previously been described (Ades et al., 1996; Baspinar et al., 2005). Renard et al. (2010) concluded that patients with recessive FBLN4 mutations are predominantly characterized by aortic aneurysms and arterial tortuosity and stenosis, and stated that these findings confirmed the important role of fibulin-4 in vascular elastic fiber assembly. Kappanayil et al. (2012) detected homozygosity for a missense mutation in exon 7 of the FBLN4 gene (604633.0009) in 21 of 22 infants from the Mappila community of southern India with characteristic arterial dilatation and tortuosity. One patient was compound heterozygous for this mutation and a de novo missense mutation on the paternal allele. Both mutations occurred in the same conserved calcium-binding EGF domain. Homozygosity was lethal in the majority; 17 of 21 died at a median age of 4 months. INHERITANCE \- Autosomal recessive GROWTH Other \- Fetal overgrowth (in some patients) HEAD & NECK Head \- Microcephaly (rare) Face \- Prominent forehead \- Prominent premaxilla \- Micrognathia Ears \- Dysplastic ears \- Low-set ears Eyes \- Prominent eyes \- Small palpebral fissures \- Downslanting palpebral fissures \- Hypertelorism, mild Nose \- Bulbous nasal tip (in some patients) \- Hooked nose (in some patients) \- Depressed nasal bridge (in some patients) Mouth \- High-arched palate CARDIOVASCULAR Heart \- Thickened myocardium (rare) \- Bradycardia (rare) Vascular \- Aortic aneurysm \- Pulmonary artery aneurysm \- Arterial aneurysms, multiple \- Arterial tortuosity, general \- Venous tortuosity \- Arterial stenoses, multiple \- Vascular fragility \- Vascularization increased in upper dermis RESPIRATORY Lung \- Emphysema CHEST Ribs Sternum Clavicles & Scapulae \- Pectus excavatum Diaphragm \- Hypoplastic diaphragm \- Diaphragmatic hernia GENITOURINARY External Genitalia (Male) \- Inguinal hernia SKELETAL \- Joint hypermobility, generalized \- Fractures at birth Hands \- Arachnodactyly \- Contractures of third to fifth fingers Feet \- Arachnodactyly SKIN, NAILS, & HAIR Skin \- Cutis laxa \- Velvety skin \- Normal scarring Skin Histology \- Collagen bundles smaller than normal \- Vascularization increased in upper dermis \- Underdeveloped elastic fibers, severe NEUROLOGIC Central Nervous System \- Hypotonia \- Brain hemorrhage PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios (in some patients) MISCELLANEOUS \- Relatively mild cutis laxa, associated with severe vascular abnormalities \- Massive aortic aneurysm can cause airway compression in affected infants MOLECULAR BASIS \- Caused by mutation in the EGF-containing fibulin-like extracellular matrix protein-2 gene (EFEMP2, 604633.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB	c0432336	26,693	omim	https://www.omim.org/entry/614437	2019-09-22T15:55:11	{"doid": ["0070133"], "omim": ["614437"], "orphanet": ["90349", "314718"], "genereviews": ["NBK54467"]}
A number sign (#) is used with this entry because low molecular weight proteinuria is caused by mutation in the chloride channel-5 gene (CLCN5; 300008) on chromosome Xp11.22. Description Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis is a form of X-linked hypercalciuric nephrocalcinosis, a group of disorders characterized by proximal renal tubular reabsorptive failure, hypercalciuria, nephrocalcinosis, and renal insufficiency. These disorders have also been referred to as the 'Dent disease complex' (Scheinman, 1998; Gambaro et al., 2004). For a general discussion of Dent disease, see 300009. Clinical Features Suzuki et al. (1985) identified 5 boys with asymptomatic proteinuria in a screening program of Japanese children. More than 50% of their urinary proteins were those with a molecular weight of less than 40 kD, defined by Suzuki et al. (1985) as low molecular weight (LMW) proteins, including lysozyme (153450) and beta-2-microglobulin (109700). Serum proteins with a molecular weight of less than 50 kD are freely filtered by the renal glomeruli, but the filtered proteins in normal persons are then almost completely reabsorbed at the proximal tubules. Thus, the patients appeared to have an impaired proximal tubular reabsorption of LMW proteins. Follow-up for 4 to 16 years found that 3 patients developed further evidence of tubular dysfunction, including glycosuria, hypophosphatemia, aminoaciduria, and increasing serum creatinine, indicating that it was a progressive disorder. In urine specimens from the patients reported by Suzuki et al. (1985), Murakami et al. (1987) also detected alpha-1-acid glycoprotein (orosomucoid; 138600), alpha-1-microglobulin (176870), and retinol-binding protein (180250), all of which have low molecular weights. Murakami and Kawakami (1990) reported a slight tendency toward shortening stature with increasing age in affected children. Renal biopsies showed focal changes, including focal glomerulosclerosis and focal tubular atrophy, in approximately one-third of patients. In studying first-degree relatives of 8 male patients with asymptomatic LMW proteinuria in 6 families, Kawakami et al. (1991) found elevated urinary levels of beta-2-microglobulin in 2 of 6 fathers and 2 of 6 mothers and in 4 of 12 other first-degree relatives. The authors concluded that the increased frequency in fathers argued against X-linked inheritance. Geary et al. (1985) described 3 patients in England, 2 boys and a girl, with possible asymptomatic LMW proteinuria, indicating that the disorder was not confined to Japan. Furuse et al. (1992) described 6 male patients with what they referred to as familial progressive renal tubulopathy but recognized as identical to familial low molecular weight proteinuria. The 6 patients belonged to 2 families in a single kindred: the propositus, his father, a paternal first cousin, 2 paternal uncles, and a maternal uncle. X-linked inheritance was thought to be most likely, but the possibility of autosomal dominant inheritance remained because of the occurrence of abnormality on both sides of the family. Furuse et al. (1992) suggested that the disorder may be progressive since older subjects showed more severe tubular dysfunction. All 6 had aminoaciduria and hypercalciuria, whereas glycosuria was present in 2 and phosphaturia in 4. Igarashi et al. (1995) found that patients with low molecular weight proteinuria tended to have hypercalciuric nephrocalcinosis without rickets or renal failure. Some children additionally demonstrated hematuria, glycosuria, amino aciduria, impaired urinary concentrating ability, and a mild decrease in creatinine clearance. Molecular Genetics In affected members of 4 unrelated Japanese kindreds with LMW proteinuria, Lloyd et al. (1997) identified 4 different mutations in the CLCN5 gene (300008.0001 and 300008.0008-300008.0010). Nakazato et al. (1997) identified mutations in the CLCN5 gene in affected members of 2 Japanese families with low molecular weight proteinuria. Akuta et al. (1997) identified mutations in the CLCN5 gene in 7 of 10 unrelated Japanese patients with low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis. They estimated that over 70% of Japanese patients with the disorder have mutations in the CLCN5 gene. INHERITANCE \- X-linked recessive GROWTH Height \- Short stature GENITOURINARY Kidneys \- Proximal renal tubule defect \- Nephrocalcinosis \- A subset of patients develop renal insufficiency with decreased creatinine clearance \- Renal biopsy shows focal tubular atrophy (in 33%) \- Focal glomerulosclerosis (in 33%) LABORATORY ABNORMALITIES \- Low-molecular-weight proteinuria \- Hypercalciuria \- Microscopic hematuria \- Glycosuria (less common) \- Aminoaciduria (less common) \- Hypophosphatemia (less common) MISCELLANEOUS \- Usually asymptomatic \- Slowly progressive disorder \- Part of 'Dent disease complex' (see 300009 ) MOLECULAR BASIS \- Caused by mutation in the chloride channel 5 gene (CLCN5, 300008.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PROTEINURIA, LOW MOLECULAR WEIGHT, WITH HYPERCALCIURIA AND NEPHROCALCINOSIS	c1839874	26,694	omim	https://www.omim.org/entry/308990	2019-09-22T16:17:55	{"mesh": ["C545036"], "omim": ["308990"], "orphanet": ["1652", "93622"]}
A number sign (#) is used with this entry because this form of Zellweger syndrome (PBD13A) is caused by homozygous mutation in the PEX14 gene (601791) on chromosome 1p36. Description Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group K (CGK) have mutations in the PEX14 gene. For information on the history of PBD complementation groups, see 214100. Clinical Features Shimozawa et al. (2004) studied a patient with Zellweger syndrome. At birth the patient showed typical craniofacial dysmorphia of Zellweger syndrome, including large open fontanels, high forehead, flat occiput, low/broad nasal bridge, and micrognathia, as well as neurologic abnormalities including hypotonia. Plasma analysis showed elevated very long chain fatty acids (VLCFA) and di- and trihydroxycholestanoic acid, and a normal phytanic acid level. Erythrocyte plasmalogens were undetectable. The patient died at 10 days of age. The Pakistani patient with Zellweger syndrome studied by Huybrechts et al. (2008) showed prolonged neonatal hyperbilirubinemia and presented at 3 months of age with icterus, axial hypotonia, and hepatomegaly. Dysmorphic features included slight dolichocephaly, triangular face, and large fontanel. Metabolic screening showed increased long chain fatty acids and hypoketotic dicarboxylic aciduria. Further studies showed severe hepatic parenchymatic destruction and cholestasis. His gaze fixed and followed normally, he had normal spontaneous movements in all limbs, but deep tendon reflexes were absent. Radiologic examination of the skeleton was normal. Ophthalmologic examination showed posterior embryotoxon. Metabolic screening at this age showed normal plasma amino acids, phytanic acid, pristanic acid, and C24:0 levels; increased C26:0 values, and decreased C22:0 and plasmalogen concentrations. Cerebral ultrasound and electroencephalography were normal, but brain magnetic resonance imaging (MRI) at 5 months and computed tomography (CT) at 13 months showed a polymicrogyria in the right frontal and parietal cortex and left Rolandic cortex, and bilateral zones of laminar heterotopia. An epileptic seizure (unresponsive, cyanosis) was suspected at age 13 months. At the age of 21 months, the patient had lost vision and showed generalized hypotonia, with no spontaneous movements anymore. The cholestasis had completely disappeared (normal bilirubin and alkaline phosphatase) but transaminases remained high. Plasma phytanic acid was at the upper limit of normal, and pristanic acid increased from the age of 14 months on. Plasmalogen content of erythrocytes remained low. Family history revealed that the mother had a mentally retarded sib and a sister with 3 children who all died before age 1 year. Molecular Genetics The patient with Zellweger syndrome studied by Shimozawa et al. (2004) carried a homozygous nonsense mutation in the PEX14 gene (601791.0001). Huybrechts et al. (2008) detected a 41-kb deletion in the PEX14 gene (601791.0002) in a patient with Zellweger syndrome. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Flat occiput \- Dolicocephaly Face \- High forehead \- Micrognathia \- Triangular face Eyes \- Icterus Nose \- Low, broad nasal bridge ABDOMEN Liver \- Hepatomegaly \- Cholestasis SKELETAL Skull \- Large fontanels \- Open fontanel SKIN, NAILS, & HAIR Skin \- Icterus NEUROLOGIC Central Nervous System \- Hypotonia LABORATORY ABNORMALITIES \- Elevated very long chain fatty acids (VLCFA) \- Normal phytanic acid level \- Elevated di- and trihydroxycholestanoic acid MISCELLANEOUS \- Based on detailed clinical information provided on 1 patient MOLECULAR BASIS \- Caused by mutation in the peroxisome biogenesis factor 14 gene (PEX14, 601791.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PEROXISOME BIOGENESIS DISORDER 13A (ZELLWEGER)	c0043459	26,695	omim	https://www.omim.org/entry/614887	2019-09-22T15:53:49	{"doid": ["0080487"], "mesh": ["D015211"], "omim": ["614887"], "orphanet": ["912"]}
A number sign (#) is used with this entry because of evidence that progressive myoclonic epilepsy-7 (EPM7) is caused by heterozygous mutation in the KCNC1 gene (176258) on chromosome 11p15. Description Progressive myoclonic epilepsy-7 is a neurologic disorder characterized by onset of severe progressive myoclonus and infrequent tonic-clonic seizures in the first or second decades of life. Most patients become wheelchair-bound; some patients may have cognitive decline (summary by Muona et al., 2015). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800). Clinical Features Muona et al. (2015) reported 13 unrelated patients with progressive myoclonic epilepsy. After normal development in early childhood, the patients presented between 6 and 14 years of age with progressive myoclonus, sometimes reported as tremor. One patient developed ataxia at an early age, but this was overshadowed by myoclonus. All patients also had infrequent tonic-clonic seizures. The movement disorder generally became disabling in adolescence, with most patients becoming wheelchair-bound. Some patients had learning disabilities or mild cognitive decline. Brain imaging was essentially normal, except for cerebellar atrophy in some patients. One of the probands had 3 affected family members, and the phenotype in this family was slightly milder compared to that in the other families. Muona et al. (2015) called this disorder 'myoclonic epilepsy with ataxia due to potassium channel mutation,' symbolized 'MEAK.' Inheritance Muona et al. (2015) found that progressive myoclonic epilepsy-7 occurred as a de novo event in 12 probands. One other proband was found to have an affected sib and 2 affected children who also carried the pathogenic mutation, consistent with autosomal dominant inheritance; however, peripheral blood DNA from both mutation-negative unaffected parents of the proband did not suggest mosaicism. Molecular Genetics In 13 unrelated patients with childhood-onset progressive myoclonic epilepsy-7, Muona et al. (2015) identified the same de novo heterozygous missense mutation in the KCNC1 gene (R320H; 176258.0001). The mutation was found in 11 (13%) of 84 patients who underwent exome sequencing and in 2 (7%) of 28 patients who underwent direct sequencing of the KCNC1 gene. In vitro functional expression studies showed that the mutation caused a loss of channel function with a dominant-negative effect. Muona et al. (2015) noted that KCNC1 is prominently expressed in inhibitory GABAergic interneurons in the central nervous system, and suggested that loss of these currents may contribute to myoclonus and seizures. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Normal early development \- Myoclonic epilepsy \- Myoclonus \- Tonic-clonic seizures \- Tremor \- Ataxia (in some patients) \- Learning disabilities (in some patients) \- Cognitive decline (in some patients) \- Cerebellar atrophy (in some patients) MISCELLANEOUS \- Onset between 6 and 14 years \- Progressive disorder \- Most mutations occur de novo \- Most patients become wheelchair-bound in adolescence MOLECULAR BASIS \- Caused by mutation in the voltage-gated potassium channel, Shaw-related subfamily, member 1 gene (KCNC1, 176258.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	EPILEPSY, PROGRESSIVE MYOCLONIC 7	c4015420	26,696	omim	https://www.omim.org/entry/616187	2019-09-22T15:49:43	{"omim": ["616187"], "orphanet": ["435438"], "synonyms": ["EPM7", "MEAK", "Myoclonus epilepsy and ataxia due to potassium channel mutation", "PME type 7", "Progressive myoclonic epilepsy due to KV3.1 deficiency", "Progressive myoclonus epilepsy type 7"]}
Rosenthal–Kloepfer syndrome Other namesFamilial pachydermoperiostosis SpecialtyDermatology Rosenthal–Kloepfer syndrome, is a cutaneous condition characterized by abnormal growth of bone and skin, coupled with clouding of the cornea.[1] It was described in 1962.[2] Another name for the condition is Acromegaly-cutis verticis gyrata-corneal leukoma syndrome. ## Contents * 1 Signs and Symptoms * 2 Cause * 3 Diagnosis * 4 See also * 5 References * 6 External links ## Signs and Symptoms[edit] Presenting symptoms include unilateral or bilateral opacification of the cornea, which progressively involves the whole structure. Visual disturbance secondary to corneal opacification is often the presenting symptom. Other symptoms include furrowing of the scalp, enlargement of the bony portion of the eyebrows, and disproportionately large hands.[3] ## Cause[edit] No gene mutation as has been associated with this disorder. Inheritance follows an autosomal dominant pattern. ## Diagnosis[edit] Radiographic imaging reveals thickening of bones, especially of the skull, and widening of the bones in the fingers.[4] ## See also[edit] * Amniotic band syndrome * List of cutaneous conditions ## References[edit] 1. ^ "Rosenthal-Kloepfer Syndrome \| Hereditary Ocular Diseases". disorders.eyes.arizona.edu. Retrieved 2018-02-27. 2. ^ ROSENTHAL JW, KLOEPFER HW (December 1962). "An acromegaloid, cutis verticis gyrata, corneal leukoma syndrome. A new medical entity". Arch. Ophthalmol. 68: 722–6. doi:10.1001/archopht.1962.00960030726004. PMID 13974983. Archived from the original on 2012-03-06. 3. ^ "Rosenthal-Kloepfer Syndrome \| Hereditary Ocular Diseases". disorders.eyes.arizona.edu. Retrieved 2018-02-27. 4. ^ "Rosenthal-Kloepfer Syndrome \| Hereditary Ocular Diseases". disorders.eyes.arizona.edu. Retrieved 2018-02-27. ## External links[edit] Classification D * OMIM: 102100 * MeSH: C535654 External resources * Orphanet: 964 This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Rosenthal–Kloepfer syndrome	c1321495	26,697	wikipedia	https://en.wikipedia.org/wiki/Rosenthal%E2%80%93Kloepfer_syndrome	2021-01-18T19:06:57	{"gard": ["500"], "mesh": ["C535654"], "umls": ["C1321495"], "orphanet": ["964"], "wikidata": ["Q7368611"]}
Eye injury A small piece of iron has lodged in the margin of the cornea SpecialtyOphthalmology, neurology Physical or chemical injuries of the eye can be a serious threat to vision if not treated appropriately and in a timely fashion. The most obvious presentation of ocular (eye) injuries is redness and pain of the affected eyes. This is not, however, universally true, as tiny metallic projectiles may cause neither symptom. Tiny metallic projectiles should be suspected when a patient reports metal on metal contact, such as with hammering a metal surface. Corneal foreign body is one of the most common preventable occupational hazard.[1] Intraocular foreign bodies do not cause pain because of the lack of nerve endings in the vitreous humour and retina that can transmit pain sensations. As such, general or emergency department doctors should refer cases involving the posterior segment of the eye or intraocular foreign bodies to an ophthalmologist. Ideally, ointment would not be used when referring to an ophthalmologist, since it diminishes the ability to carry out a thorough eye examination. Flicking sand, flying pieces of wood, metal, glass and stone are notorious for causing much of the eye trauma. Sporting balls such as cricket ball, lawn tennis ball, squash ball, shuttlecock, and other high speed flying objects can strike the eye. The eye is also susceptible to blunt trauma in a fistfight. Children’s games such as bow-and-arrows, bb guns and firecrackers can lead to eye trauma. Road traffic accidents (RTAs) with head and facial trauma may also have an eye injury - these are usually severe in nature with multiple lacerations, shards of glasses embedded in tissues, orbital fractures, severe hematoma and penetrating open-globe injuries with prolapse of eye contents. Other causes of intraocular trauma may arise from workplace tools or even common household implements,[2] including bottle-caps suddenly propelling at great force.[3] About 5.3 million cases of foreign bodies in the eyes occurred in 2013.[4] ## Contents * 1 Presentation * 1.1 Complications * 2 Diagnosis * 2.1 Classification * 2.2 Emergency * 2.3 Urgent * 2.4 Semi-urgent * 3 Management * 3.1 Irrigation * 3.2 Patching * 3.3 Suturing * 4 Recovery * 5 Epidemiology * 6 See also * 7 References ## Presentation[edit] ### Complications[edit] Multiple complications are known to occur following eye injury: corneal scarring, hyphema, iridodialysis, post-traumatic glaucoma, uveitis cataract, vitreous hemorrhage and retinal detachment. The complications risk is high with retinal tears, penetrating injuries and severe blunt trauma. ## Diagnosis[edit] The goal of investigation is the assessment of the severity of the ocular injury with an eye to implementing a management plan as soon as is required. The usual eye examination should be attempted, and may require a topical anesthetic in order to be tolerable. Many topical agents cause burning upon instillation. Proxymetacaine has been found to have the best tolerance.[5] Depending on the medical history and preliminary examination, the primary care physician should designate the eye injury as a true emergency, urgent or semi-urgent. ### Classification[edit] Eye injury by impact of small plastic body Based on the injury to the eyewall (outer fibrous coat of the eye consisting of cornea and sclera) * Closed globe injury: the eye globe is intact, but the seven rings of the eye have been classically described as affected by blunt trauma. Types include contusion and lamellar laceration * Open globe injury: there is a full thickness injury of the eye wall (cornea and sclera) It includes A) Globe rupture: caused by blunt trauma and is an inside-out injury. B) Globe laceration: a full-thickness wound caused by sharp objects. It includes 1)Penetrating trauma: the globe integrity is disrupted by a full-thickness entry wound and may be associated with prolapse of the internal contents of the eye. Such injuries are often referred to as a Globe fracture or a Globe rupture, although these can be incurred by blunt trauma as well. 2) Perforating trauma: the globe integrity is disrupted in two places due to an entrance and exit wound (through and through injury). This is a quite severe type of eye injury. Other types include * Blowout fracture of the orbit is caused by blunt trauma, classically described for fist or ball injury, leading to fracture of the floor or medial wall of the orbit due to sudden increased pressure on the orbital contents. * Muscular Entrapment Fracture of the orbital bones can lead to muscular entrapment limiting gaze in one direction. ### Emergency[edit] An emergency must be treated within minutes. This includes chemical burns of both the conjunctiva and cornea. ### Urgent[edit] An urgent case must be treated within hours. This includes penetrating globe injuries; corneal abrasions or corneal foreign bodies; hyphema (must be referred); eyelid lacerations that are deep, involve the lid margin or involve the lacrimal canaliculi; radiant energy burns such as arc eye (welder's burn) or snow blindness; or, rarely, traumatic optic neuropathy. ### Semi-urgent[edit] Semi-urgent cases must be managed within 1–2 days. They include orbital fractures and subconjunctival hemorrhages. ## Management[edit] ### Irrigation[edit] The first line of management for chemical injuries is usually copious irrigation of the eye with an isotonic saline or sterile water. In the cases of chemical burns, one should not try to buffer the solution, but instead dilute it with copious flushing. ### Patching[edit] Depending on the type of ocular injury, either a pressure patch or shield patch should be applied. Up until circa 1987, pressure patches were the preferred method of treatment for corneal abrasions in non-contact lens wearers; Multiple controlled studies conducted by accredited organizations such as the American Academy of Ophthalmology have shown that pressure patching is of little or no value in healing corneal abrasions and is actually detrimental to healing in some cases. A Cochrane Review found that patching simple corneal abrasions may not improve healing or reduce pain.[6] Pressure patching should never be used on an individual presenting with a corneal abrasion who has a history of contact lens wear. In this circumstance, a virulent infection caused by the bacterium Pseudomonas aeruginosa is at a clearly delineated increased risk for occurrence. These infections can cause blindness within 24 – 48 hours and there is a possibility that the infection can move into the peri-orbital socket, resulting in the need for evisceration of the eyeball. In rare cases, the infection can enter the brain and cause death to the patient. In cases of globe penetration, pressure patches should never be applied, and instead a shield patch should be applied that protects the eye without applying any pressure. If a shield patch is applied to one eye, the other eye should also be patched due to eye movement. If the uninjured eye moves, the injured eye will also move involuntarily possibly causing more damage. ### Suturing[edit] In cases of eyelid laceration, sutures may be a part of appropriate management by the primary care physician so long as the laceration does not threaten the canaliculi, is not deep, and does not affect the lid margins. ## Recovery[edit] Eating certain products and using special routines may help recovery.[citation needed] ## Epidemiology[edit] A recent study estimated that from 2002–2003 there were 27,152 injuries in the United States related to the wearing of eyeglasses.[7] The same study concluded that sports-related injuries due to eyeglasses wear were more common in those under the age of 18 and that fall-related injuries due to wearing eyeglasses were more common in those aged 65 and over.[7] Although eyeglasses-related injuries do occur, prescription eyeglasses and non-prescription sunglasses have been found to "offer measurable protection which results in a lower incidence of severe eye injuries to those wearing [them]".[8] ## See also[edit] * Black eye * Chemical eye injury * United States Eye Injury Registry * Wilderness medical emergencies ## References[edit] 1. ^ Onkar A. Commentary: Tackling the corneal foreign body. Indian J Ophthalmol 2020;68:57-8. 2. ^ Feist RM, Lim JI, Joondeph BC, Pflugfelder SC, Mieler WF, Ticho BH, Resnick K (Jan 1991). "Penetrating ocular injury from contaminated eating utensils". Archives of Ophthalmology. 109 (1): 23–30. PMID 1987951. 3. ^ Spang, S.; Höh, H.; Ruprecht, K. W. (February 1995). "[Eye injuries caused by opening or explosion of beverage bottles]". Der Ophthalmologe: Zeitschrift Der Deutschen Ophthalmologischen Gesellschaft. 92 (1): 35–37. ISSN 0941-293X. PMID 7719073. 4. ^ Global Burden of Disease Study 2013, Collaborators (22 August 2015). "Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 386 (9995): 743–800. doi:10.1016/s0140-6736(15)60692-4. PMC 4561509. PMID 26063472. 5. ^ "BestBets: Proxymetacaine is the local anaesthetic of choice for removal of corneal foreign bodies". 6. ^ Lim CH, Turner A, Lim BX (2016). "Patching for corneal abrasion". Cochrane Database Syst Rev. 7: CD004764. doi:10.1002/14651858.CD004764.pub3. PMC 6457868. PMID 27457359. 7. ^ a b Sinclair SA, Smith GA, Xiang H (Feb 2006). "Eyeglasses-related injuries treated in U.S. emergency departments in 2002-2003". Ophthalmic Epidemiol. 13 (1): 23–30. doi:10.1080/09286580500346645. PMID 16510343. 8. ^ May DR, Kuhn FP, Morris RE, Witherspoon CD, Danis RP, Matthews GP, Mann L (Feb 2000). "The epidemiology of serious eye injuries from the United States Eye Injury Registry". Graefes Arch Clin Exp Ophthalmol. 238 (2): 153–57. doi:10.1007/pl00007884. PMID 10766285. * v * t * e Nonmusculoskeletal injuries of head (head injury) and neck Intracranial * see neurotrauma Extracranial/ facial trauma eye: * Black eye * Eye injury * Corneal abrasion ear: * Perforated eardrum Either/both * Penetrating head injury [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Eye injury	c0015408	26,698	wikipedia	https://en.wikipedia.org/wiki/Eye_injury	2021-01-18T18:58:02	{"mesh": ["D005131"], "wikidata": ["Q2681162"]}
A rare, genetic, syndromic intellectual disability disorder characterized by non-progressive, congenital, marked, central hypotonia, severe psychomotor delay and intellectual disability, chronic constipation, distended abdomen, abnormal dermatoglyphics, delayed and dysharmonic skeletal maturation, and preponderance of type 2 larger-sized muscle fibers. Additional features include narrow and high-arched palate, prominent nasal root, long philtrum, and open mouth with drooling, as well as variably present cryptorchidism, hypertelorism, and tapered fingers. Seizures and/or an abnormal electroencephalograph may also be assoicated. There have been no further descriptions in the literature since 1994. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Qazi-Markouizos syndrome	c2931142	26,699	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3010	2021-01-23T18:16:22	{"gard": ["371"], "mesh": ["C536259"], "omim": ["600096"], "umls": ["C2931142"], "icd-10": ["Q87.8"], "synonyms": ["Dysharmonic skeletal maturation-muscular fiber disproportion syndrome"]}

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.