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For a phenotypic description and discussion of genetic heterogeneity of migraine headaches, see MGR1 (157300). Carlsson et al. (2002) reported a large Swedish family with migraine with or without aura in 30 individuals spanning 4 generations. Clinical characteristics of both types included nausea and vomiting, photophobia, phonophobia, and long duration (greater than 12 hours). Multipoint linkage analysis gave a maximum lod score of 5.78 at marker D6S452. Haplotype analysis restricted the disease locus to a 10-Mb region between flanking markers on chromosome 6p21.1-p12.2. The same migraine haplotype segregated in members with and without aura, suggesting that one or more genetic factors is involved in both migraine types in this family. Of 280 control chromosomes analyzed, none had the same allele as the disease haplotype. INHERITANCE \- Autosomal dominant ABDOMEN Gastrointestinal \- Nausea \- Vomiting NEUROLOGIC Central Nervous System \- Migraine with aura \- Migraine without aura \- Photophobia \- Phonophobia MISCELLANEOUS \- Long headache duration (greater than 12 hours) \- Variable frequency (weekly to yearly) \- Genetic heterogeneity, see MGR1, ( 157300 ) ▲ 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-hydroxybutyric 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	MIGRAINE WITH OR WITHOUT AURA, SUSCEPTIBILITY TO, 3	c1843782	24,600	omim	https://www.omim.org/entry/607498	2019-09-22T16:09:13	{"omim": ["607498"], "synonyms": ["Alternative titles", "MGR3"]}
A number sign (#) is used with this entry because ichthyosis prematurity syndrome (IPS) is caused by mutation in the FATP4 (SLC27A4; 604194) gene. Clinical Features Autosomal recessive congenital ichthyosis is a clinically and genetically heterogeneous group of inherited keratinization disorders. The rare subtype ichthyosis prematurity syndrome presents with complications at mid-trimester of pregnancy leading to prematurity, a thick caseous and desquamating skin, respiratory complications, and persistent eosinophilia. Skin features evolve into a flat follicular hyperkeratosis with atopy (Klar et al., 2004). Population Genetics IPS has a high prevalence in a small geographic region in middle Norway and adjacent Sweden (see Anton-Lamprecht, 1992 and Klar et al., 2004). Cases have been reported in other ethnic groups (see, e.g., Niemi et al., 1993 and Brusasco et al., 1997). Mapping Klar et al. (2004) performed genomewide linkage analysis in 16 families with ichthyosis prematurity syndrome from Norway and Sweden. Thirteen families had 1 or 2 affected members or had pairs of sibs with at least 1 affected; 3 families had 1 affected single child. A maximum multipoint lod score of 3.73 at theta = 0.0 was obtained with the short tandem repeat D9S778. A 12-cM region was defined by haplotype analysis and recombinant events at D9S250 and D9S63. This region was further refined by allelic association to a 1-Mb region at chromosome 9q33.3-q34.13 with no indication of genetic heterogeneity. Haplotype analysis suggested the presence of 2 founder mutations. In 28 affected and 22 healthy sibs from 22 unrelated Norwegian and Swedish families with ichthyosis prematurity syndrome, 13 of which had been previously studied by Klar et al. (2004), Melin et al. (2006) confirmed linkage to chromosome 9q33.3-q34.13 and refined the IPS haplotype to a 76-kb core region. Sequencing of DNA from 3 patients revealed no alterations in the exons or flanking intronic sequences of 4 candidate genes, TBC1D13 (616218), ENDOG (600440), C9ORF114, and CCBL1 (600547), and there were no significant differences in transcript levels between patients and controls for those genes. Based on the average length of the haplotype in IPS patients, the age of a founder mutation was calculated to be approximately 1,900 years. Klar et al. (2009) performed a homozygosity scan on a consanguineous family of North African origin in which several individuals had ichthyosis prematurity syndrome. Affected family members were found to be homozygous for a 76-kb genomic region on chromosome 9p that coincided with the IPS locus in the Scandinavian families. Pathogenesis Klar et al. (2009) observed abnormal distribution of lipids between epidermal layers in ichthyosis prematurity syndrome that is consistent with the expression pattern of FATP4 in normal epidermis, and suggested a defect in lipid homeostasis and skin barrier formation in IPS. Klar et al. (2009) also demonstrated that FATP4 deficiency in human fibroblasts is associated with reduced VLCFA-CoA synthetase activity and a reduced incorporation of VLCFA into neutral and polar lipids. Molecular Genetics Klar et al. (2009) performed sequence analysis of the FATP4 gene in a North African family, a Middle Eastern family, and 18 families of Scandinavian origin segregating IPS. They identified 7 different mutations. All affected members of the Scandinavian families were homozygous or compound heterozygous for a nonsense mutation (C168X; 604194.0001), indicating a founder effect. A splice site mutation (604194.0002) and a missense mutation (604194.0007) were identified in homozygosity in affected members of the North African and the Middle Eastern families, respectively. None of the mutations were found in 120 healthy control individuals. [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-hydroxybutyric 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	ICHTHYOSIS PREMATURITY SYNDROME	c1837610	24,601	omim	https://www.omim.org/entry/608649	2019-09-22T16:07:24	{"mesh": ["C536271"], "omim": ["608649"], "orphanet": ["88621"], "synonyms": ["Alternative titles", "ICHTHYOSIS CONGENITA IV"], "genereviews": ["NBK1420"]}
For a general discussion of hereditary prostate cancer, see 176807. Mapping Eeles et al. (2008) conducted a genomewide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at or before the age of 60 years or with a family history of disease, and 1,894 population-screened controls with a low prostate-specific antigen (PSA) concentration (less than 0.5 ng/ml). They analyzed these samples for 541,129 SNPs using the Illumina Infinium platform. Initial putative associations were confirmed using a further 3,268 cases and 3,366 controls. They identified 3 single-nucleotide polymorphisms (SNPs) on chromosome 19 that were significantly associated with prostate cancer. Of these, the most significantly associated (p = 1.5 x 10(-18)) was rs2735839. This SNP is located between KLK2 (147960), encoding prostatic kallikrein, and KLK3 (176820), encoding prostate-specific antigen (PSA), a serine protease that liquifies semen and is used as a serum marker in screening and disease progression. Following up on the paper by Eeles et al. (2008), Ahn et al. (2008) evaluated the association of 24 tag SNPs in the KLK region, including SNPs in KLK3 and nearby genes KLK1 (147910), KLK2, and KLK15 (610601), with prostate cancer risk in 1,172 prostate cancer cases and 1,157 controls in men of European ancestry from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, in which serum PSA was used in screening for this disease. Ahn et al. (2008) also examined the prostate cancer risk relationship for 12 of these tag SNPs in the KLK3 region in 4 independent studies from diverse populations including 4,020 prostate cancer cases and 4,028 controls, as a component of Cancer Genetic Markers of Susceptibility (CGEMS) GWAS. Ahn et al. (2008) found that none of the 24 tag SNPs in the KLK region showed strong evidence for association with prostate cancer in the PLCO study, and none of the SNPs in the KLK3 region were significant in the CGEMS combined analyses. However, 2 of the tag SNPs (rs1058205 and rs2735839), located in the 3-prime untranslated region of KLK3 and in high linkage disequilibrium (LD), along with 4 other variants upstream of the gene and several downstream in high LD, were strongly associated with serum PSA concentrations. Only rs2735839 remained significantly associated with PSA concentration when all these SNPs were simultaneously included in the multivariate model. When Ahn et al. (2008) preferentially limited the men in the control group in the PLCO Trial GWAS to those with PSA less than 0.5 ng/ml, prostate cancer risk associations were greater by more than 5-fold for some genotypes, even though the same SNPs showed no clear association when the full control group was used. KLK SNPs were not associated with prostate cancer risk in PLCO when only cases and controls with high PSA levels or only cases and controls with low PSA levels were compared. Ahn et al. (2008) concluded that SNPs in the KLK3 region were not associated with prostate cancer risk in their series of 5 case-control studies. Furthermore, with widespread use of PSA in clinical practice, even modest associations observed between KLK3 SNPs and prostate cancer risk in some epidemiologic studies may be due to PSA-directed differential identification of prostate cancer cases with particular KLK3-PSA profiles. Eeles et al. (2008) replied to the comments by Ahn et al. (2008) with a report of an analysis of rs2735839 in 13 further case-control studies as part of the PRACTICAL Consortium. The estimated per allele OR for prostate cancer associated with rs2735839 was 0.89 (95% CI = 0.83-0.95; p = 0.0007), very close to their original estimate. Eeles et al. (2008) also noted that when data from the 5 CGEMS studies were combined, the per allele OR was also remarkably similar (per allele OR = 0.90, 95% CI = 0.83-0.90, p = 0.01), although this was not formally significant using the 4-degree-of-freedom test given by Ahn et al. (2008). If the combined results from stage 2 of their initial study (Eeles et al., 2008), PRACTICAL, and CGEMS are combined, the overall evidence of association reached genomewide levels of significance (p less than 10(-8)). Molecular Genetics Hua et al. (2018) confirmed that homozygosity for the G allele of rs11672691 within the gene for the long noncoding RNA (lncRNA) PCAT19 (618192) on chromosome 19q13 was associated with poor prognosis after prostate cancer diagnosis. The authors determined that the promoter region of the PCAT19-short variant, which is in intron 3 of the PCAT-long variant, contains rs11672691. The SNP regulated expression of the 2 PCAT19 isoforms in a reciprocal manner, with the G risk allele associated with decreased abundance of PCAT19-short and increased abundance of PCAT19-long. The transcription factors NKX3.1 (602041) and YY1 (600013) preferentially bound the A nonrisk allele of rs11672691 of the PCAT19-short promoter region and promoted expression of PCAT19-short. In contrast, the G risk allele of rs11672691 decreased binding of NKX3.1 and YY1, resulting in weaker promoter activity but stronger enhancer activity that subsequently activated PCAT19-long. In vitro and in vivo analyses revealed that PCAT19-long increased cell proliferation and promoted prostate cancer progression. RNA pull-down assays showed that PCAT19-long interacted with the RNA-binding protein HNRNPAB (602688) to activate a subset of cell-cycle genes that promoted aggressive prostate cancer. Hua et al. (2018) concluded that the G risk allele of rs11672691 mediates a promoter-enhancer switching mechanism underlying both initiation and progression of aggressive prostate cancer. Gao et al. (2018) confirmed that the G risk allele of the intronic SNP rs11672691 within PCAT19 was associated with aggressive prostate cancer. Moreover, the G risk allele was associated with higher expression levels of PCAT19 and CEACAM21 (618191), and upregulation of PCAT19 and CEACAM21 correlated with prostate cancer development. The authors determined that the transcription factor HOXA2 (604685) directly bound an enhancer element encompassing rs11672691 and showed a preference for the G risk allele. Knockdown of PCAT19 led to reduced mRNA levels of CEACAM21, indicating that PCAT19 contributes to CEACAM21 regulation. Variation at rs11672691 also altered CEACAM21 promoter activity directly and contributed to HOXA2-mediated regulation of CEACAM21 expression. CRISPR/Cas9-mediated single-nucleotide editing in prostate cancer cells revealed direct effects of the G risk allele of rs11672691 on enhanced expression of PCAT19 and CEACAM21 and on prostate cancer proliferation and severity. [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-hydroxybutyric 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	PROSTATE CANCER, HEREDITARY, 15	c2931456	24,602	omim	https://www.omim.org/entry/611959	2019-09-22T16:02:34	{"doid": ["10283"], "mesh": ["C537243"], "omim": ["611959"], "orphanet": ["1331"]}
## Description Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, and dyspnea; bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test; serum IgE levels; atopy; and atopic dermatitis (Laitinen et al., 2001; Illig and Wjst, 2002; Pillai et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of asthma, see 600807. Mapping By genomewide linkage analysis of 364 families with asthma, Pillai et al. (2006) identified a region on chromosome 2p that was associated with susceptibility to bronchial hyperresponsiveness. BHR was defined as a positive response on a methacholine challenge test showing a 20% or greater reduction in forced expiratory volume at or below 8 mg/ml of methacholine. The patients with BHR included 184 informative sib pairs. Fine mapping yielded a multipoint lod score of 4.58 with a peak at the marker rs2063871 and flanked by rs737030 and rs920520. The 'strict asthma' phenotype, defined as 2 or more classic clinical asthma symptoms and a positive methacholine challenge test, also showed significant linkage to this region, yielding a lod score of 3.98. Pillai et al. (2006) noted that the candidate region overlapped with a locus for BHR on 2p at marker D2S2298 reported in a genomewide scan of 97 German families by Wjst et al. (1999) and Immervoll et al. (2001). [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-hydroxybutyric 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	ASTHMA-RELATED TRAITS, SUSCEPTIBILITY TO, 3	c1864959	24,603	omim	https://www.omim.org/entry/609958	2019-09-22T16:05:23	{"omim": ["609958"], "synonyms": ["Alternative titles", "ASRT3"]}
A number sign (#) is used with this entry because of evidence that some cases of hyperCKemia are caused by heterozygous mutation in the CAV3 gene (601253) on chromosome 3p25. Clinical Features The existence of a 'normal' high serum creatine phosphokinase (CPK) was discussed by Emery and Spikesman (1970) in the context of 'subclinical Duchenne muscular dystrophy.' Patients may describe muscle cramps with exertion, but there is no evidence of neuromuscular disease: muscle biopsy and exercise lactic acid production are normal. This familial trait can plague the physician and medical geneticist who are counseling a family with muscular dystrophy. In the course of studying exercise physiology, Michael Brook of St. Louis (Drachman, 1980) found that he, as well as a number of other normal physicians, developed markedly elevated CPK levels after bicycle ergometer exercise. Bertorini et al. (1980) described a man with carnitine palmitoyltransferase I deficiency (255120) who had no clinical difficulties until age 51 years. However, at age 46 he had been found to have elevated CPK for no apparent reason. Sunohara et al. (1984) studied 3 unrelated Japanese adult men with what the authors termed 'idiopathic hyperCKemia.' One was the father of a girl who had survived malignant hyperthermia (145600); his parents were first cousins and his mother, a sister, and a daughter of the sister also had high serum CK activity. Sensitivity to caffeine of muscles in vitro, as in malignant hyperthermia, was seen in this man and in one other. Frydman et al. (1995) described a 7-month-old boy with gross motor delay and failure to thrive who presented with rhabdomyolysis following an acute asthmatic episode. During hospitalization, the ECG changed from normal sinus rhythm to a type I Wolff-Parkinson-White pattern. Duchenne muscular dystrophy (DMD; 310200) was suspected based on elevated creatine kinase serum levels, muscle biopsy, and family history. The diagnosis was confirmed by molecular analyses which documented a deletion in the dystrophin gene (300377) in the propositus, and in an affected male cousin of his mother. 'Idiopathic' hyperCKemia was found in the propositus, his father, and 5 of his relatives. Frydman et al. (1995) suggested that the unusually early and severe manifestations of DMD in this patient may be related to the coincidental inheritance of a maternal DMD gene and of a paternal gene causing hyperCKemia. Diagnosis ### Differential Diagnosis Afifi (1998) pointed out that reports of idiopathic hyperCKemia had dramatically diminished since the discovery of dystrophin and its gene and the subsequent development of knowledge regarding the variable presentations of dystrophinopathies. About 75% of reported cases have been male. Clinical and/or histopathologic evidence of a neuromuscular disorder developed between 1 and 7 years after detection of hyperCKemia in about one-third of the cases. Diagnoses included distal myopathy, myoadenylate deaminase deficiency, polymyositis, mitochondrial myopathy, sarcoid myopathy, McArdle disease, central core disease, multicore disease, inclusion body myopathy, and Duchenne muscular dystrophy carrier status. Della Marca et al. (2009) reported 7 patients with severe myalgia in the lower limbs and hyperCKemia who were found to have severe restless legs syndrome with severe periodic limb movements in sleep (RLS; 102300). Treatment of RLS resulted in improved serum creatine kinase levels in 6 patient who underwent treatment. The authors concluded that some severe cases of RLS can result in increased serum CK, and discussed the possible overlap of the 2 disorders. Inheritance From study of 14 monozygotic twins and 14 dizygotic twins, Meltzer et al. (1978) found evidence of significant heritability of plasma CPK level. Molecular Genetics Carbone et al. (2000) identified a de novo recurrent sporadic mutation in the CAV3 gene (601253.0007) in 2 unrelated children with persistent elevated levels of serum creatine kinase (hyperCKemia) without muscle weakness. They concluded that their data indicate that partial caveolin-3 deficiency should be considered in the differential diagnosis of idiopathic hyperCKemia. Muscle \- Muscle cramps with exertion Lab \- Elevated serum CPK \- Normal muscle biopsy \- Normal exercise lactic acid production 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-hydroxybutyric 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	CREATINE PHOSPHOKINASE, ELEVATED SERUM	c0241005	24,604	omim	https://www.omim.org/entry/123320	2019-09-22T16:42:41	{"omim": ["123320"], "synonyms": ["Alternative titles", "CPK, ELEVATED SERUM", "HYPERCKEMIA, IDIOPATHIC"], "genereviews": ["NBK1385"]}
Fryns and Van den Berghe (1979) observed a kindred in which several persons had scalp defects and postaxial polydactyly type A. They raised the question of this being a single gene trait. One person had both, 4 had scalp defects only, and 3 had postaxial polydactyly only. Buttiens et al. (1985) reported a sporadic case. Limb \- Postaxial polydactyly type A Head \- Scalp defects 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-hydroxybutyric 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	SCALP DEFECTS AND POSTAXIAL POLYDACTYLY	c1867021	24,605	omim	https://www.omim.org/entry/181250	2019-09-22T16:35:00	{"mesh": ["C536622"], "omim": ["181250"], "orphanet": ["1003"]}
A number sign (#) is used with this entry because autosomal dominant deafness-41 (DFNA41) is caused by heterozygous mutation in the P2RX2 gene (600844) on chromosome 12q24. Description Autosomal dominant deafness-41 (DFNA41) is characterized by onset of progressive sensorineural hearing loss usually in the second decade. The hearing loss is severe and ultimately affects all frequencies. Exposure to noise exacerbates the hearing loss, particularly at high frequencies (summary by Yan et al., 2013). Clinical Features Blanton et al. (2002) reported a large Chinese family in which 30 members over 6 generations had nonsyndromic progressive sensorineural deafness involving all frequencies. The age at onset ranged from 12 to 20 years and was generally accompanied by high frequency tinnitus. Yan et al. (2005) provided follow-up of the family reported by Blanton et al. (2002) and reported an additional Chinese family with the same disorder. All had moderate to severe progressive sensorineural hearing loss with onset in the second decade with severe loss by age 20 years. Some patients in the second family showed increased thresholds at age 6 to 10 years, suggesting an even earlier onset. Those with occupational noise exposure early in life had more severe hearing loss at high frequencies compared to those without noise exposure. Imaging of the temporal bone in 1 patient showed no abnormalities. Faletra et al. (2014) reported a large Italian family with onset of progressive sensorineural hearing loss in the second decade. The hearing loss could be classified as mild to profound in almost all affected family members, mainly affecting medium to high frequencies (1,000 and 4,000 Hz). The severity of the disorder appeared to worsen with age. Imaging of the temporal bone showed no abnormalities. Inheritance The transmission pattern of DFNA41 in the family reported by Blanton et al. (2002) was consistent with autosomal dominant inheritance. Mapping In a large Chinese family with autosomal dominant nonsyndromic sensorineural deafness, Blanton et al. (2002) found linkage to a 15-cM region on chromosome 12q24.32-qter, proximal to marker D12S1609. A maximum 2-point lod score of 6.56 was obtained with D12S343. The authors noted that the locus, designated DFNA41, is distal to DFNA25 (605583), which is located at 12q21-q24. Yan et al. (2005) applied the transmission disequilibrium test to the large Chinese family reported by Blanton et al. (2002) and found an association between deafness and 2 SNPs (rs1566667 and rs1027557) within the DFNA41 region. Haplotype analysis revealed that affected individuals were heterozygous for a core haplotype, confirming location and autosomal dominant inheritance. Molecular analysis excluded several genes within the candidate region on chromosome 12q24.33. Molecular Genetics In affected members of 2 unrelated Chinese families with autosomal dominant deafness-41, Yan et al. (2013) identified a heterozygous missense mutation in the P2RX2 gene (V60L; 600844.0001). The mutation in the first family (Blanton et al., 2002) was found by whole-exome sequencing; the second family was 1 of 65 families in whom the P2RX2 gene was sequenced. In vitro functional expression studies showed that the V60L mutation caused a loss of channel function with a loss of inward current and macropore permeability. The findings provided a link between P2X2 receptor signaling in the cochlea and protection from noise and progressive hearing loss. Faletra et al. (2014) identified a heterozygous missense mutation in the P2RX2 gene (G353R; 600844.0002) in affected members of a large Italian family with DFNA41, confirming the findings of Yan et al. (2013) that mutations in this gene can cause progressive hearing loss. Animal Model Yan et al. (2013) found that P2rx2-null mice developed progressive hearing loss at about 19 to 23 weeks of age in the absence of noise exposure. At 17 months of age, mutant mice had significantly more severe age-related hearing loss compared to wildtype mice, and the hearing loss was due to loss of outer hair cell function in the mid-basal region of the cochlea. Histologic analysis of older mutant mice showed deterioration of the organ of Corti, loss of hair cells, loss of sensory epithelium, and loss of spiral ganglion neurons within the Rosenthal canal. Exposure to noise impaired hearing in both wildtype and mutant mice, but mutant mice showed more severe hearing loss at higher frequencies compared to wildtype mice after noise exposure. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, progressive sensorineural (most severe at high frequencies, but ultimately affecting all frequencies) \- Tinnitus MISCELLANEOUS \- Onset in second decade, but sometimes earlier \- Hearing loss is usually severe by age 20 years \- Noise exposure causes more severe hearing loss at high frequencies (2,000 to 8,000 Hz) MOLECULAR BASIS \- Caused by mutation in the purinergic receptor P2X, ligand-gated ion channel, 2 gene (P2RX2, 600844.0001 ) ▲ 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-hydroxybutyric 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	DEAFNESS, AUTOSOMAL DOMINANT 41	c1842371	24,606	omim	https://www.omim.org/entry/608224	2019-09-22T16:08:08	{"doid": ["0110567"], "mesh": ["C564272"], "omim": ["608224"], "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"]}
Desmoplastic infantile astrocytoma/ganglioglioma are mixed neuronal-glial tumors representing a histological spectrum of the same tumor. They are usually supratentorially located, large, cystic masses with a peripheral solid component, characterized by prominent desmoplastic stroma and pleomorphic populations of neoplastic cells with either astrocytic or ganglionic differentiation and poorly differentiated cells in variable proportions. They usually present in the first 18 months of age with rapid head growth, bulging anterior fontanel and bone structures over the tumor, signs of raised intracranial pressure (headache, vomiting, papilledema), focal neurological signs and sometimes seizures. [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-hydroxybutyric 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	Desmoplastic infantile astrocytoma/ganglioglioma	None	24,607	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251940	2021-01-23T18:44:45	{"synonyms": ["DIA/DIG"]}
## Summary ### Clinical characteristics. Hereditary sensory and autonomic neuropathy type II (HSAN2) is characterized by progressively reduced sensation to pain, temperature, and touch. Onset can be at birth and is often before puberty. The sensory deficit is predominantly distal with the lower limbs more severely affected than the upper limbs. Over time sensory function becomes severely reduced. Unnoticed injuries and neuropathic skin promote ulcerations and infections that result in spontaneous amputation of digits or the need for surgical amputation. Osteomyelitis is common. Painless fractures can complicate the disease. Autonomic disturbances are variable and can include hyperhidrosis, tonic pupils, and urinary incontinence in those with more advanced disease. ### Diagnosis/testing. Diagnosis is based on clinical findings and molecular genetic testing of WNK1 (previously HSN2) (type HSAN2A), RETREG1 (previously FAM134B, JK1) (type HSAN2B), KIF1A (type HSAN2C), and SCN9A (type HSAN2D), the only genes in which mutation is known to cause HSAN2. ### Management. Treatment of manifestations: Treatment is symptomatic and often involves a team including neurologists, orthopedic surgeons, and physiotherapists. Training in the care of the sensory-impaired limb, often in a diabetic clinic, is important and includes self-examination especially of the feet for any signs of trauma. To prevent osteomyelitis, and hence amputations, wounds require cleaning and protection along with antiseptic treatment. To prevent callous formation the skin of neuropathic limbs requires hydration and lipid-based unguents. Appropriate shoes and socks are recommended. Surveillance: The feet should be inspected daily for injuries or sources of wear. Annual follow up in centers with comprehensive care of diabetics and/or persons with Charcot-Marie-Tooth neuropathy is recommended. Agents/circumstances to avoid: Ill-fitting shoes or other sources of trauma to the feet or hands (e.g., use protective gloves when handling hot items when cooking). ### Genetic counseling. HSAN2, which includes HSAN2A, HSAN2B, HSAN2C, and HSAN2D, is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing of at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if the pathogenic variants in the family are known. ## Diagnosis ### Clinical Diagnosis The clinical diagnosis of hereditary sensory and autonomic neuropathy type II (HSAN2) is based on the presence of the following: * Congenital or early-onset (1st-2nd decade) sensory deficit * Sensory loss affecting all modalities * Ulcerations of hands/feet often requiring amputations * Acral mutilations * Painless fractures and neuropathic arthropathy in some * Varying degree of autonomic involvement: hyperhidrosis, urinary incontinence, and slow pupillary reaction to light. Note: Autonomic disturbances appear to be less prominent in HSAN2 than in the other autosomal recessive sensory neuropathies (HSAN3, HSAN4, HSAN5, HSAN6). * Family history consistent with autosomal recessive inheritance ### Testing Electrophysiology reveals the following: * Reduced/absent sensory nerve action potentials * Preserved or reduced motor nerve conduction velocities (NCV) * Variably reduced compound muscle action potentials (CMAP) Histopathology. Sural nerve biopsy shows signs of an axonal sensory neuropathy, pronounced absence of (small) myelinated fibers, and decreased unmyelinated fibers. Additionally, loss of large myelinated fibers may be seen in those with HSAN2D. #### Molecular Genetic Testing Genes. The four types of hereditary sensory and autonomic neuropathy type II (HSAN2) and associated genes: * HSAN2A. WNK1 (previously named HSN2, a gene symbol that is now retired). The previously designated HSN2 was first reported as a single-exon gene located in intron 8 of WNK1, with both genes transcribed from the same strand [Lafreniere et al 2004]. Subsequently, HSN2 was found to be an alternatively spliced exon present in a nervous system-specific isoform of WNK1 [Shekarabi et al 2008]. This exon, the so-called ‘HSN2’ exon, is exon 10 in the reference sequence of the nervous system-specific WNK1 isoform variant 4 (see Molecular Genetics for details). * HSAN2B. RETREG1 (previously FAM134B, JK1) * HSAN2C. KIF1A * HSAN2D. SCN9A ### Table 1. Molecular Genetic Testing Used in Hereditary Sensory and Autonomic Neuropathy Type II View in own window HSAN2 TypeGene 1Test MethodProportion of Probands with a Pathogenic Variant Detectable by This Method HSAN2AWNK1 2Sequence analysis 3, 4Unknown HSAN2BRETREG1 5 HSAN2CKIF1A HSAN2DSCN9A 1\. See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene. 2\. The pathogenic variants reported are (except for one) located in an alternatively-spliced nervous system-specific WNK1 transcript that is expressed in the cell body of sensory ganglia neurons and particularly in neuronal projections. Pathogenic variants in this nervous system-specific transcript, which includes the ‘HSN2’ exon, cause HSAN2A disease. This should be taken into account when performing molecular genetic testing. Because pathogenic variants in other exons of WNK1 may also contribute to the HSAN2A phenotype, sequence analysis of all known exons from genomic DNA may be necessary if only one pathogenic variant is found in the ‘HSN2’ exon. Note: Homozygous or compound heterozygous null alleles affecting all WNK1 isoforms are speculated to be embryonically lethal. 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\. To date, all WNK1, RETREG1, KIF1A, and SCN9A variants that cause HSAN2 are nonsense, frameshift, or splice site variants. Copy number variants in the genes have not been addressed in the current literature. 5\. HSAN2B has been confirmed in six families by RETREG1 sequence analysis. ### Testing Strategy To confirm/establish the diagnosis in a proband. The diagnosis of HSAN2 is established in individuals who meet clinical diagnostic criteria and who have biallelic pathogenic variants in either WNK1, RETREG1, KIF1A, or SCN9A. Molecular testing approaches can include serial single-gene testing, use of a multigene panel, and more comprehensive genomic testing. Serial single-gene testing is based on phenotype: * Sequence analysis of WNK1 and KIF1A may be considered first in individuals who do not have clinical autonomic dysfunction. Note: Due to the small number of affected individuals reported with HSAN2, presence or absence of autonomic dysfunction may not be a sufficient criterion to distinguish between HSAN2 subtypes. * Sequence analysis of RETREG1 may be considered first in affected individuals who have autonomic dysfunction with or without distal motor involvement. * Sequence analysis of SCN9A should be performed in those who have no pathogenic variant (or only one pathogenic variant) identified by sequence analysis of RETREG1, WNK1, and KIF1A. A multigene panel that includes WNK1, RETREG1, KIF1A, SCN9A, and other genes of interest (see Differential Diagnosis) may also be considered. 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 if serial single-gene testing (and/or use of a multigene panel) fails to confirm a diagnosis in an individual with features of HSAN2. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ## Clinical Characteristics ### Clinical Description The hereditary sensory and autonomic neuropathies present a genetically and clinically heterogeneous group of neurodegenerative disorders of the peripheral nervous system. The published clinical descriptions of hereditary sensory and autonomic neuropathy type II (HSAN2) are inconsistent, possibly in part as a result of reports that lack molecular genetic confirmation of the diagnosis. Clinically, WNK1-related HSAN (HSAN2A), RETREG1-related HSAN (HSAN2B) and KIF1A-related HSAN (HSAN2C) appear to be very similar but may actually be distinguishable as additional cases are described in the future. Autonomic dysfunction may be more pronounced in RETREG1-related neuropathy, and individuals with KIF1A-related HSAN also showed distal muscle weakness. SCN9A-related HSAN (HSAN2D) was reported only recently in two families [Yuan et al 2013]. Typically in molecularly confirmed HSAN2, the onset is in the first two decades (often before puberty). It is characterized by progressive numbness of the hands and feet, together with reduced sensation to pain, temperature, and touch. The sensory deficit is predominantly distal with the lower limbs more severely affected than the upper limbs. Over time sensory function becomes severely reduced. Neuropathic skin tends to produce excessive keratin and hyperkeratosis that may be forced down into the deeper layers of soft tissue and/or may crack, promoting ulcerations and infections that result in spontaneous amputation of digits or the need for surgical amputation. Osteomyelitis is common. Secondary muscle atrophy and Charcot joints may occur. Painless fractures can complicate the disease. Intellectual development is usually normal. Autonomic disturbances appear to be less pronounced than in the other autosomal recessive sensory neuropathies. Sweating and tearing are usually normal but hyperhidrosis is present in some cases. Tonic pupils are observed. With progression of the disease urinary incontinence is reported. ### Genotype-Phenotype Correlations No genotype-phenotype correlations are known. Inter- and intrafamilial phenotypic variability is reported. ### Nomenclature HSAN2 has also been reported as the following: * Morvan’s disease * Congenital sensory neuropathy * Neurogenic acroosteolysis * Hereditary sensory radicular neuropathy Dyck originally proposed five different HSAN types on the basis of clinical symptoms and nerve biopsy specimens [Dyck 1993]. This classification still stands after the molecular characterization of the subtypes, but additional genetic and phenotypic heterogeneity has been included [Verhoeven et al 2006], suggesting a need for a detailed classification based on the underlying gene defects [Rotthier et al 2012] ### Prevalence The worldwide prevalence of HSAN2 is unknown. For comparison, the overall prevalence of the closely related hereditary motor and sensory neuropathies (HMSN or Charcot-Marie-Tooth disease) is on the order of 30:100,000, and hereditary sensory and autonomic neuropathies (HSAN) occur with markedly lower frequency. Clustering of cases of HSAN2A in eastern Canada is the result of relatively common founder variants [Roddier et al 2005]. ## Differential Diagnosis Disorders accompanied by self-mutilating behavior resemble some aspects of the congenital forms of HSAN including Lesch-Nyhan syndrome or untreated phenylketonuria. Diabetic neuropathy shares some aspects of adult-onset HSAN. Confusion of HSAN with leprosy is reported in some cases. Clinical overlap is also observed between adult-onset HSAN and Charcot-Marie-Tooth Neuropathy (CMT). For example, CMT2J, caused by the p.Thr124Met pathogenic variant in MPZ, encoding myelin protein zero, is characterized by severe sensory loss, but no ulcerations [De Jonghe et al 1999]. CMT2B, caused by pathogenic variants in RAB7A, is characterized by distal muscle weakness and wasting as often the first and most prominent sign of the disease [Verhoeven et al 2003]. The disease is accompanied by sensory loss of all modalities with a high frequency of foot ulcers necessitating amputations. Nerve conduction velocity studies indicate a primarily axonal neuropathy. (See Charcot-Marie-Tooth Neuropathy Overview.) Hereditary sensory and autonomic neuropathy type I (HSAN1) is an autosomal dominant genetically heterogeneous disorder: * HSAN1A and HSAN1C (OMIM 613640) are caused by pathogenic variants in SPTLC1 (HSAN1A) [Bejaoui et al 2001, Dawkins et al 2001] and SPTLC2 (HSAN1C) [Rotthier et al 2010]. The SPT enzymes, encoded by these genes catalyze the de novo synthesis of sphingolipids. Sensory loss in these conditions usually starts in the adult. In rare cases early onset of symptoms is also reported. Dysesthesia with characteristic lancinating pain helps in clinical diagnosis but can be absent. Painless injuries and osteomyelitis requiring amputations are reported as well. The disease can be associated with sensorineural deafness. Motor involvement is mild to severe (including wheelchair requirement). Visceral autonomic features appear to be absent. * HSAN1B (OMIM 608088) with autosomal dominant inheritance is an adult-onset sensory neuropathy with cough and gastroesophageal reflux. This entity has been mapped to 3p24-p22 and was described in two independent families, but to date no causative pathogenic variant has been identified. * HSN1D (OMIM 613708). Pathogenic variants in ATL1, known to be associated with spastic paraplegia 3A (SPG3A), have also been identified in individuals with HSAN [Guelly et al 2011]. * HSN1E. Hereditary sensory neuropathy with dementia and hearing loss is an adult-onset autosomal dominant condition caused by pathogenic missense variants in DNMT1, encoding DNA methyltransferase 1 [Klein et al 2011]. Affected persons typically have early mortality and often require total care because of dementia, hearing loss, and loss of ambulation from predominant sensory ataxia. * HSN1F (OMIM 615632) is caused by pathogenic missense variants in ATL3 and is similar to HSN1D [Fischer et al 2014, Kornak et al 2014] Hereditary sensory and autonomic neuropathy type III (HSAN3, familial dysautonomia, or Riley-Day syndrome) is caused by pathogenic variants in ELP1 (IKBKAP) and is inherited in an autosomal recessive manner. Prevalence of HSAN3 is high in individuals of Ashkenazi Jewish descent as a result of two founder variants that account for more than 99% of mutated alleles. HSAN3 is a sensory neuropathy characterized by prominent autonomic manifestation. Absence of tears (alacrima) with emotional crying is one of the cardinal features. Lingual fungiform papillae are also absent. Hypotonia and feeding difficulties contribute to delay in acquisition of motor milestones. Affected individuals have gastrointestinal dysfunction, nausea and vomiting crises, recurrent pneumonia, and cardiovascular instability culminating in autonomic crisis. Sensitivity to pain and temperature perception is reduced but usually not as profoundly as with the other HSAN disorders. Hereditary sensory and autonomic neuropathy type IV (HSAN4, congenital insensitivity to pain with anhidrosis [CIPA]) results from the presence of two NTRK1 pathogenic variants. HSAN4 is characterized by profound sensory loss predominantly affecting perception of pain and temperature. As a consequence of the early onset of reduced pain perception, self-mutilating behavior (biting of tongue, lips, and fingertips) is common. Repeated fractures are secondary consequences. Anhidrosis caused by lack of sweat gland innervation results in poor thermoregulation and can cause recurrent febrile episodes which can be fatal. Intellectual disability is variable. Hereditary sensory and autonomic neuropathy type V (HSAN5) (OMIM 608654) shows marked clinical overlap to HSAN4 and has been reported to be caused by pathogenic variants in NGF [Einarsdottir et al 2004, Carvalho et al 2011]. However, some cases of clinically diagnosed HSAN5 appear to be caused by NTRK1 pathogenic variants as well. HSAN5 is inherited in an autosomal recessive manner. In HSAN5 anhidrosis is less prominent than in HSAN4. Selective loss of deep pain perception, painless fractures, and joint deformities have been described for this entity. Hereditary sensory and autonomic neuropathy type VI (HSAN6) (OMIM 614653) is characterized by dysautonomic symptoms, absent tearing, feeding difficulties, absent deep tendon reflexes, abnormal histamine test with no axon flare, distal contractures, motionless open-mouthed facies, severe psychomotor retardation, and early death [Edvardson et al 2012]. Only one affected family has been reported to date. Congenital insensitivity to pain (CIP) may be caused by pathogenic variants in either SCN9A or SCN11A: * Biallelic pathogenic loss-of-function variants in SCN9A [Cox et al 2006] cause the autosomal recessive channelopathy CIP. Individuals with CIP have painless injuries beginning in infancy but otherwise normal sensory responses. The complications of the disease follow the inability to feel pain, and most individuals have injuries to the lips or tongue caused by biting themselves in early childhood. Affected individuals usually have a history of unnoticed fractures. The insensitivity to pain appears to result from a defect in nociceptive transmission and not from axonal degeneration, as the nerves appear to be largely normal on examination. Individuals with SCN9A-related CIP have anosmia. See Congenital Insensitivity to Pain Overview. * Heterozygous de novo pathogenic gain-of-function variants in SCN11A, encoding the voltage-gated sodium channel NaV1.9 (OMIM 615548) [Leipold et al 2013, Woods et al 2015], can also lead to CIP. Hyperhidrosis, muscular weakness, severe gastrointestinal motility disturbances, and intolerance to moderate heat have also been described in affected individuals. ### Table 2. Comparison of HSAN/Sensory Neuropathy Subtypes View in own window SubtypeTypical Onset AgeMOIOMIMGenesClinical SignsSural Nerve Biopsy 1 HSAN1AdultAD162400 613640 613708 615632 614116SPTLC1 SPTLC2 ATL1 DNMT1 ATL3 * Loss of pain & temperature sensation * Osteomyelitis * Lancinating pain * Distal motor involvement (variable) * Facultative deafness * No visceral signs of autonomic involvement * Hearing loss, dementia, narcolepsy as distinguishing features in those w/DNMT1-related HSAN1 Distal loss of unmyelinated & myelinated fibers CMT2BAdultAD600882RAB7A * Acral ulcero-mutilating sensory neuropathy * Motor features are common Reduced density of myelinated fibers; larger ones more affected HSAN2ChildhoodAR201300 613115 614213WNK1 RETREG1 KIF1A SCN9A * Mutilations (hands, feet) * Acroosteolysis * Sensory loss * Absent or weak tendon reflexes * No myelinated fibers * Fewer unmyelinated fibers HSAN3CongenitalAR223900ELP1 (IKBKAP) * Prominent autonomic disturbances (vomiting/poor feeding, defective lacrimation, pyrexia, cardiovascular instability) * Hypotonia * Decreased or absent deep tendon reflexes * No fungiform papillae of the tongue * Hyperhidrosis, predominantly Ashkenazi Jews affected * Normal number of myelinated fibers * Severe decrease of unmyelinated fibers HSAN4CongenitalAR256800NTRK1 * No response to painful stimuli * Fever episodes * Sweat glands present but no sweating * ID in some cases * Corneal lesions * Joint deformities * Normal muscle strength/tendon reflexes * No unmyelinated axons * Fewer small myelinated neurons * Normal density of myelinated fibers HSAN5CongenitalAR608654NGF NTRK1 * No response to painful stimuli * No ID * Joint deformities * Fractures * Normal muscle strength/tendon reflexes Selective decrease of small myelinated & unmyelinated fibers HSAN6CongenitalAR614653DSTDysautonomic symptoms * Absent tearing * Contractures * Severe psychomotor retardation Not known MOI = mode of inheritance ID = intellectual disability 1\. According to Schenone [2005] ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with hereditary sensory and autonomic neuropathy type II (HSAN2) the following evaluations are recommended: * Neurologic examination to determine extent of sensory loss and involvement of autonomic and motor nervous system * Nerve conduction velocity (NCV) * Detailed family history * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Treatment is symptomatic and often involves a team including neurologists, orthopedic surgeons, and physiotherapists. Training in the care of the sensory-impaired limb is important and includes self-examination especially of the feet for any signs of trauma. A diabetic clinic is a good source of advice. Appropriate shoes and socks are recommended. It is best to prevent callous formation in neuropathic skin; once present, calluses should be treated with hydration and lipid-based unguents to prevent cracking and may require medical consultation. Cleaning and protection of wounds on neuropathic limbs in combination with antiseptic treatment to eradicate infections help prevent osteomyelitis and amputations. ### Surveillance The feet in particular should be inspected daily for injuries and sources of wear. Patients should be followed annually by centers with comprehensive care for diabetes and/or CMT. ### Agents/Circumstances to Avoid Avoid ill-fitting shoes or other sources of trauma to the feet or hands (e.g., use protective gloves when handling hot items when cooking). ### Evaluation of Relatives at Risk It is appropriate to evaluate at-risk sibs in early childhood in order to identify those who will develop sensory loss and would benefit from measures to prevent injury to limbs and/or self-mutilation. Molecular genetic testing can be used to clarify the genetic status of at-risk sibs if the pathogenic variants in the family are known. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu 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-hydroxybutyric 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	Hereditary Sensory and Autonomic Neuropathy Type II	c0270914	24,608	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK49247/	2021-01-18T21:20:35	{"mesh": ["D002607"], "synonyms": ["Hereditary Sensory and Autonomic Neuropathy Type 2", "HSANII", "HSAN2"]}
For a phenotypic description and a discussion of genetic heterogeneity of rippling muscle disease, see RMD2 (606072). Mapping In a 44-member pedigree segregating autosomal dominant RMD, Stephan et al. (1994) localized the responsible gene to the distal end of the long arm of chromosome 1 (maximum multipoint lod score of 3.56 at theta of 0.0) in a 12-cM region near D1S235. Stephan and Hoffman (1999) constructed a physical map of the region of 1q containing the RMD1 locus. They also narrowed the critical genetic interval containing the RMD1 locus in their family from 12 to 3 cM. A YAC/BAC contig spanning the nonrecombinant interval containing the RMD1 locus was assembled by STS content mapping and database searches. INHERITANCE \- Autosomal dominant MUSCLE, SOFT TISSUES \- Muscle cramps with exercise \- Muscle pain with exercise \- Muscle stiffness with exercise \- Muscle hyperirritability \- Muscle hypertrophy \- Muscle mounding \- Percussion-induced rapid rolling muscle contractions (PIRC) \- Muscle activity is electrically silent on EMG MISCELLANEOUS \- Genetic heterogeneity (see RMD, 606072 ) ▲ 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-hydroxybutyric 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	RIPPLING MUSCLE DISEASE 1	c1853698	24,609	omim	https://www.omim.org/entry/600332	2019-09-22T16:16:16	{"doid": ["0070308"], "mesh": ["C535686"], "omim": ["600332"], "orphanet": ["97238"]}
A number sign (#) is used with this entry because generalized epidermolysis bullosa simplex (EBS) can be caused by heterozygous mutation in either the keratin-5 gene (KRT5; 148040) on chromosome 12 or the keratin-14 gene (KRT14; 148066) on chromosome 17. Description Epidermolysis bullosa simplex (EBS) is a clinically and genetically heterogeneous skin disorder characterized by recurrent blistering of the skin following minor physical trauma as a result of cytolysis within basal epidermal cells. Most forms show autosomal dominant inheritance. The 3 main types include the generalized Koebner form, the more severe generalized Dowling-Meara form (131760), and the localized, mild Weber-Cockayne form (131800) (Fine et al., 2008). All 3 forms can be caused by mutation in the KRT5 or the KRT14 gene. See 601001 for a rare autosomal recessive form caused by mutation in the KRT14 gene. Davison (1965) referred to generalized distribution of bullous vesicles as epidermolysis simplex bullosa. The condition in which bullae were limited to the hands and feet was referred to as the Cockayne type of epidermolysis bullosa (131800). On the basis of an extensive study in Norway and review of the literature, Gedde-Dahl (1971) arrived at a classification of epidermolysis bullosa. EB simplex in this classification encompassed disorders characterized by bulla formation within the epidermis, basal cell vacuolization, and dissolution of tonofibrils on electron microscopy. The generalized Koebner form and the localized Weber-Cockayne type were believed to be allelic. Gedde-Dahl (1981) recognized at least 16 varieties of epidermolysis bullosa and suggested that dominant EB simplex can be clinically and genetically divided into at least 4 types: the generalized Koebner type, the localized Weber-Cockayne type, the mild Ogna type with fragile skin (131950), and a form with mottled pigmentation (131960). Fine et al. (1991) provided a revised classification of the subtypes of inherited epidermolysis bullosa based on clinical and laboratory criteria. Clinical Features Passarge (1965) observed 21 affected persons in 4 generations of a family with generalized epidermolysis bullosa simplex. The inheritance pattern was autosomal dominant. Hacham-Zadeh et al. (1988) described a large Arab family originating from Jerusalem in which 38 affected individuals spanning 4 generations had EBS. Onset occurred between birth and 2 weeks of age. The main clinical features were bullae, generalized, solitary, and in groups, with predilection to the skin of the palms and soles. Mild to moderate patchy hyperkeratosis of the palms and soles was found in 5 affected members of the family. Blisters in oral mucous membranes were noted and found in summer and in periods of fever. Hair, teeth, and nails were normal. Improvement was noted by progression of age from 5 to 23 years, and by some in summer and by others in winter. Ultrastructural studies from a fresh blister disclosed intraepidermal blister via cytolysis of basal cell cytoplasm. The pedigree indicated transmission of an autosomal dominant gene. However, in 1 instance, affected first cousins were married and all 6 of their offspring were affected. There was marked intrafamilial variability. Although the family was originally thought to have the Dowling-Meara form of EBS, Stephens et al. (1995) reclassified the phenotype as the Koebner type based on the lack of keratin filament clumping on electron microscopy. Mapping Epstein (1991) cited evidence that linkage to the keratin gene cluster on chromosome 12 had been demonstrated in at least 1 family with generalized epidermolysis bullosa simplex. In a large family with 14 affected members in 3 generations with generalized EBS, Ryynanen et al. (1991) found linkage to DNA marker D12S17, which is located on 12q (maximum lod score of 4.65 at theta = 0.0). In the full report (Ryynanen et al., 1991), the maximum lod score for linkage to D12S17 was given as 5.55 at theta = 0.0. Molecular Genetics In a family with the generalized form of epidermolysis bullosa simplex, Bonifas et al. (1991) found linkage to markers on chromosome 17 and identified a point mutation in the KRT14 gene (L384P; 148066.0001). In affected members of a large Irish family with generalized EBS, Humphries et al. (1993) identified a heterozygous mutation in the KRT14 gene (M272R; 148066.0007). In affected members of a large Finnish family with the generalized Koebner type of EBS in which Ryynanen et al. (1991) found linkage to 12q, Dong et al. (1993) identified a heterozygous mutation in the KRT5 gene (L463P; 148040.0002). In affected members of a family with autosomal dominant epidermolysis bullosa simplex, Stephens et al. (1995) identified a heterozygous mutation in the KRT5 gene (K173N; 148040.0006). One family member was homozygous for the K173N allele, having inherited it from each of her affected first-cousin parents. However, this patient showed no significant differences in either the clinical severity or the ultrastructural organization of the homozygous keratin intermediate filament cytoskeleton. These data demonstrated that the K173N mutation behaves as a fully dominant allele. Among 18 families with various forms of EBS, Pfendner et al. (2005) identified KRT5 mutations in 7 probands and KRT14 mutations in 11 probands, indicating that mutations in either gene can result in EBS at approximately equal frequencies. A large number (15 of 18) were de novo mutations. The clinical spectrum was highly variable. Genotype/Phenotype Correlations Livingston et al. (2001) reported a patient who presented at 3 to 4 days of age with widespread generalized blistering. Painful hyperkeratosis of the palms and soles developed in his teen years, whereas blistering improved somewhat with age. As an adult, he continued to get occasional blisters in the mouth and cutaneous blisters with increased heat and/or activity. His skin examination was striking for severe palmoplantar keratosis, underlying erythema in a 'glove and moccasin' distribution, and limited range of motion in the fingers. There was no scarring and no significant nail changes. Clinical, histologic, and ultrastructural features were consistent with a diagnosis of generalized EBS (Koebner subtype). Genetic analysis identified a heterozygous nonsense mutation in the KRT5 gene (K472X; 148040.0016), predicting the synthesis of a truncated keratin-5, missing the entire tail domain and a highly conserved motif in the central rod. Ultrastructural analysis of the patient's nonhyperkeratotic skin was remarkable for basal keratinocytes with dense and irregular keratin filaments proximal to the basement membrane. The occurrence of severe palmoplantar hyperkeratosis suggested that the keratin-5 tail domain may have important functions in palmoplantar tissues. History In skin fibroblast cultures of 3 patients from 3 kindreds with generalized EBS, Sanchez et al. (1983) found a 7-fold decrease in gelatin-specific neutral metalloprotease. Cultures from several other forms of epidermolysis bullosa showed no deficiency of this enzyme. Study of gelatinase activity from 13 cases of localized EBS found that 6 had low levels of the enzyme and 7 had normal levels. However, Winberg and Gedde-Dahl (1986) found that reduced production of gelatinase from dermal fibroblasts was not a uniform finding in the Koebner form of EBS. None of 6 patients tested showed this trait. Mulley et al. (1984) found that both the Koebner and the Weber-Cockayne types of EBS had suggestive linkage to Duffy blood group (Fy) on chromosome 1 (maximum lod score 1.5 at theta = 0.2). In 3 generations of an Irish kindred with the Koebner variety of epidermolysis bullosa, Humphries et al. (1990) and Ryynanen et al. (1991) found positive lod scores for 5 markers on 1q. In multilocus analysis, a lod score of 3 was obtained, with a maximum in the region of AT3 (107300) on 1q23. In 3 generations of a Finnish family with EBS, Ryynanen et al. (1991) found only low positive lod scores for 1q markers. EBS2 was the designation for the putative locus on chromosome 1 (Ryynanen et al., 1991). Hoyheim et al. (1991) excluded EBS from chromosome 1 by demonstration of negative scores in a region up to 0.10 on each side of F13B (134580), which is located at 1q31-q32.1. Humphries et al. (1990) excluded EBS from a region of more than 10 cM on each side of the nidogen gene (NID; 131390), located at 1q43. Epstein (1991) suggested that the linkage to chromosome 1 markers may have been in error. In reviewing the molecular genetics of epidermolysis bullosa, Epstein (1992) suggested that a defect in keratin intermediate filament proteins should have been suspected in EBS. Anton-Lamprecht and Schnyder (1982) described clumping of keratin intermediate filaments as the characteristic abnormality demonstrable by electron microscopy in the more severe Dowling-Meara subtype of EBS (131760). They also pointed to the family reported by Sutherland and Hinton (1981) in which a fragile site at 12q13 was associated with EBS. INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Oral blistering SKIN, NAILS, & HAIR Skin \- Blistering, generalized, recurrent (occurs after mild physical trauma) \- Hyperkeratosis of the palms and soles \- Milia (less common) \- Lack of scarring Electron Microscopy \- Cleavage within basal keratinocytes \- No clumping of keratin filaments in basal epidermal cells Nails \- Dystrophic nails (less common) MISCELLANEOUS \- Onset at birth or in early infancy \- Disease exacerbation during summer due to heat \- Improvement with age \- Blistering becomes confined to the palms and soles with age MOLECULAR BASIS \- Caused by mutation in the keratin 5 gene (KRT5, 148040.0002 ) \- Caused by mutation in the keratin 14 gene (KRT14, 148066.0001 ) ▲ 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-hydroxybutyric 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	EPIDERMOLYSIS BULLOSA SIMPLEX, GENERALIZED	c0079299	24,610	omim	https://www.omim.org/entry/131900	2019-09-22T16:41:33	{"doid": ["0080511"], "mesh": ["D016110"], "omim": ["131900"], "orphanet": ["79399"], "synonyms": ["Alternative titles", "EBS, GENERALIZED", "EPIDERMOLYSIS BULLOSA SIMPLEX, KOEBNER TYPE"], "genereviews": ["NBK1369"]}
EEC syndrome is a genetic developmental disorder characterized by ectrodactyly, ectodermal dysplasia, and orofacial clefts (cleft lip/palate). ## Epidemiology The exact prevalence is not known. More than 300 cases have been described in the literature. ## Clinical description The three cardinal signs of the syndrome are ectrodactyly and syndactyly of the hands and feet, cleft lip with or without cleft palate (that can result in speech defects), and abnormalities in several ectodermal structures including skin (i.e. hypopigmentated and dry skin, hyperkeratosis, skin atrophy), hair (i.e. fine and sparse hair and eyebrows), teeth (small, absent or dysplastic teeth), nails (nail dystrophy) and exocrine glands (reduction/absence of sweat, sebaceous and salivary glands). The syndrome presents a wide intra- and interfamilial clinical variability: the presence of the cardinal signs together is not mandatory and each one of them can be expressed in varying degrees of severity. Other associated clinical features include abnormalities of the genitourinary system (i.e. renal agenesis, urethral atresia, hydronephrosis), conductive or sensorineural hearing loss, choanal atresia, mammary gland/nipple hypoplasia, ophthalmological findings (i.e. lacrimal duct defects, photophobia, corneal ulcerations, keratitis, blepharitis, entropion), gland abnormalities (i.e. hypoplastic thymus, hypopituitarism, growth hormone deficiency), and on exceptional occasions, presence of a white sponge nevus, delayed developmental milestones, and malignant lymphoma. Patients do not have intellectual deficit. ## Etiology In more than 90% of cases, EEC is due to missense mutations in the sequence of the TP63 gene (3q27) encoding the TP63 transcription factor that is essential for ectoderm and limb development. These cases correspond to the classical EEC syndrome (EEC type 3) and seem to present some degree of genotype-phenotype correlation. The other cases correspond to EEC syndrome type 1, which shows associated clinical features such as malformedauricles and middle and inner ear malformations, and was mapped to 7q21. EEC type 2 does not exist anymore. EEC syndrome is an autosomal dominant disorder with incomplete penetrance (between 93 and 98%) and variable expression. ## Diagnostic methods The diagnosis is based on clinical examination, X-rays of the limbs and jaw, and, according to the associated features, kidney ultrasound, ophthalmologic examinations, and skin biopsy. Genetic testing may confirm the diagnosis. ## Antenatal diagnosis Antenatal diagnosis is based on ultrasonography during the second trimester of pregnancy which may reveal the structural abnormalities. Molecular analysis by chorionic villi sampling or by amniocentesis helps in confirming the diagnosis for families for which the disease-causing mutation was identified. ## Genetic counseling Genetic counseling should be offered to affected families informing them of the 50% risk an affected person has of transmitting the disease-causing mutation. Due to germline mosaicism, unaffected parents of a child with EEC syndrome have a 4% risk of having another affected child. ## Management and treatment Management is multidisciplinary and requires evaluation by orthopedic, plastic and dental surgeons, ophthalmologists, dermatologists, and speech therapists. Surgery allows correction of orofacial and dental abnormalities and improves the function and appearance of the limbs. Ophthalmologic care (e.g. artificial tears in case of dry eyes) is necessary to avoid complications such as cataract and corneal scarring. Hot temperatures, heavy clothing, and exercise must be avoided in case of hypohidrosis. ## Prognosis Prognosis is good with a near to normal life expectancy. Hypohidrosis (reduction/absence of sweat glands) presents the most life-threatening complications, as it can cause seizures, coma and eventually death when not managed correctly. [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-hydroxybutyric 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	EEC syndrome	c0406704	24,611	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1896	2021-01-23T18:57:32	{"gard": ["2076"], "mesh": ["C536189"], "omim": ["129900", "604292"], "umls": ["C0406704", "C1851841"], "icd-10": ["Q82.4"], "synonyms": ["Ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome"]}
Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of an enzyme that helps the body process drugs called thiopurines. These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body's immune system. Thiopurine drugs are used to treat some autoimmune disorders, including Crohn disease and rheumatoid arthritis, which occur when the immune system malfunctions. These drugs are also used to treat several forms of cancer, particularly cancers of blood-forming tissue (leukemias) and cancers of immune system cells (lymphomas). Additionally, thiopurine drugs are used in organ transplant recipients to help prevent the immune system from attacking the transplanted organ. A potential complication of treatment with thiopurine drugs is damage to the bone marrow (hematopoietic toxicity). Although this complication can occur in anyone who takes these drugs, people with TPMT deficiency are at highest risk. Bone marrow normally makes several types of blood cells, including red blood cells, which carry oxygen; white blood cells, which help protect the body from infection; and platelets, which are involved in blood clotting. Damage to the bone marrow results in myelosuppression, a condition in which the bone marrow is unable to make enough of these cells. A shortage of red blood cells (anemia) can cause pale skin (pallor), weakness, shortness of breath, and extreme tiredness (fatigue). Low numbers of white blood cells (neutropenia) can lead to frequent and potentially life-threatening infections. A shortage of platelets (thrombocytopenia) can cause easy bruising and bleeding. Many healthcare providers recommend that patients' TPMT activity levels be tested before thiopurine drugs are prescribed. In people who are found to have reduced enzyme activity, the drugs may be given at a significantly lower dose or different medications can be used to reduce the risk of hematopoietic toxicity. TPMT deficiency does not appear to cause any health problems other than those associated with thiopurine drug treatment. ## Frequency Studies suggest that less than 1 percent of individuals in the general population have TPMT deficiency. Another 11 percent have moderately reduced levels of TPMT activity that increase their risk of hematopoietic toxicity with thiopurine drug treatment. ## Causes TPMT deficiency results from changes in the TPMT gene. This gene provides instructions for making the TPMT enzyme, which plays a critical role in breaking down (metabolizing) thiopurine drugs. Once inside the body, these drugs are converted to toxic compounds that kill immune system cells in the bone marrow. The TPMT enzyme "turns off" thiopurine drugs by breaking them down into inactive, nontoxic compounds. Changes in the TPMT gene reduce the stability and activity of the TPMT enzyme. Without enough of this enzyme, the drugs cannot be "turned off," so they stay in the body longer and continue to destroy cells unchecked. The resulting damage to the bone marrow leads to potentially life-threatening myelosuppression. ### Learn more about the gene associated with Thiopurine S-methyltransferase deficiency * TPMT ## Inheritance Pattern The activity of the TPMT enzyme is inherited in a pattern described as autosomal codominant. Codominance means that two different versions of the gene are active (expressed), and both versions influence the genetic trait. The TPMT gene can be classified as either low-activity or high-activity. When the gene is altered in a way that impairs the activity of the TPMT enzyme, it is described as low-activity. When the gene is unaltered and TPMT activity is normal, it is described as high-activity. Because two copies of the gene are present in each cell, each person can have two low-activity copies, one low-activity copy and one high-activity copy, or two high-activity copies. People with two low-activity copies of the TPMT gene in each cell have TPMT deficiency and are at the greatest risk of developing hematopoietic toxicity when treated with thiopurine drugs unless they are given much less than the usual dose. People with one high-activity copy and one low-activity copy have moderately reduced enzyme activity and are also at increased risk of this complication unless given a significantly lower dose of the drug. People with two high-activity copies have normal TPMT activity and do not have an increased risk of hematopoietic toxicity with thiopurine drug treatment. [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-hydroxybutyric 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	Thiopurine S-methyltransferase deficiency	c0342801	24,612	medlineplus	https://medlineplus.gov/genetics/condition/thiopurine-s-methyltransferase-deficiency/	2021-01-27T08:24:37	{"gard": ["5173"], "mesh": ["C536512"], "omim": ["610460"], "synonyms": []}
Haemolytic anaemia due to glutathione reductase (GSR) deficiency is characterised by nearly complete absence of GSR activity in erythrocytes. ## Epidemiology It has been described in three children (one male and two females) born to consanguineous parents. ## Clinical description Both parents had intermediate levels of GSR activity. One child presented with favism and two with cataracts. ## Differential diagnosis This disease should be distinguished from glutathione reductase deficiency secondary to dietary riboflavin deficiency and from the acute pharmacologic phenocopy induced by carmustine (BCNU). ## Genetic counseling Transmission is autosomal recessive. ## Management and treatment GSR activity is not restored by riboflavin in vivo or by FAD in vitro. [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-hydroxybutyric 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	Hemolytic anemia due to glutathione reductase deficiency	None	24,613	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90030	2021-01-23T18:14:29	{"omim": ["618660", "618667"], "icd-10": ["D55.1"]}
Polyglucosan body myopathy type 1 is a rare, genetic, glycogen storage disorder characterized by polyglucosan accumulation in various tissues, manifesting with progressive proximal muscle weakness in the lower limbs and rapidly progressive, usually dilated, cardiomyopathy. Hepatic involvement and growth retardation may be associated. Early-onset immunodeficiency and autoinflammation, presenting with recurrent bacterial infections, have also 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-hydroxybutyric 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	Polyglucosan body myopathy type 1	c4014605	24,614	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=397937	2021-01-23T17:11:34	{"omim": ["615895"], "icd-10": ["E74.0"], "synonyms": ["PGBM1"]}
Bonnemann-Meinecke-Reich syndrome is a syndrome of multiple congenital anomalies characterized by an encephalopathy which predominantly occurs in the first year of life and presenting as psychomotor delay. Additional features of the disease include moderate dysmorphia, craniosynostosis, dwarfism (due to growth hormone deficiency), intellectual disability, spasticity, ataxia, retinal degeneration, and adrenal and uterine hypoplasia. The disease has been described in only two families, with each family having two affected siblings. An autosomal recessive inheritance has been suggested. There have been no further descriptions in the literature since 1991. [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-hydroxybutyric 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	Bonnemann-Meinecke-Reich syndrome	c1856973	24,615	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1261	2021-01-23T18:50:55	{"gard": ["2113"], "mesh": ["C565594"], "omim": ["225755"], "umls": ["C1856973"], "icd-10": ["Q04.8"], "synonyms": ["Encephalopathy-intracerebral calcification-retinal degeneration syndrome"]}
A disorder that is characterized by the presence of cerebrospinal fluid-filled nerve root cysts most commonly found at the sacral level of the spine, although they can be found in any section of the spine, which can cause progressively painful radiculopathy. ## Epidemiology The annual incidence of perineural cysts is estimated at approximately 5%, although large cysts that cause symptoms are relatively rare with annual incidence estimated at less than 1/2,000. Women are affected more frequently than men. ## Clinical description Patients with perineural cysts present with pain in the area of the nerves affected by the cyst, muscle weakness, difficulty sitting for prolonged periods, loss of sensation, loss of reflexes, pain when sneezing or coughing, swelling over the sacral area, parasthesias, headaches, sciatica, and bowel, bladder and sexual dysfunction. The cysts typically occur along the posterior nerve roots and can be valved or nonvalved. The main feature that distinguishes perineural cysts from other spinal lesions is the presence of spinal nerve root fibres within the cyst wall or in the cyst cavity. ## Etiology There are a number of conditions that can cause the cysts to become symptomatic, including traumatic injury, heavy lifting, childbirth, epidurals, and trauma to the spinal cord. It has also been observed that the herpes simplex virus can cause the body chemistry to change and that perineural cyst symptoms worsen during herpes virus outbreaks. ## Diagnostic methods Diagnosis is based on magnetic resonance imaging (MRI), computed topography (CT) or myelogram of patients experiencing lower back pain or sciatica. ## Differential diagnosis The main differential diagnoses are meningeal diverticula and long arachnoid prolongations, which can be distinguished by rapid filling on myelography compared to the delayed filling of perineural cysts. Differential diagnoses also include herniated lumbar discs, arachnoiditis and, in females, gynecological conditions. ## Genetic counseling The majority of perineural cysts are sporadic. However, in some cases cysts have been observed among relatives, suggesting the possibility of a familiar trait with autosomal transmission. ## Management and treatment Treatment involves lumbar drainage of the cerebrospinal fluid, CT scanning-guided cyst aspiration, decompressive laminectomy, cyst and/or nerve root excision and microsurgical cyst fenestration and imbrications. However, surgical treatment for perineural cysts is complicated by postoperative pseudomeningocele and intracranial hypotension, and recurrence of the cyst. Pain therapy may offer a nonsurgical alternative for the treatment of symptomatic perineural cysts. ## Prognosis Those who have progressive and prolonged symptoms may experience neurological damage if the cysts continue to compress nerve structures. [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-hydroxybutyric 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	Perineural cyst	c0520720	24,616	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=65250	2021-01-23T17:54:38	{"gard": ["9258"], "mesh": ["D052958"], "umls": ["C0520720"], "icd-10": ["G54.8"], "synonyms": ["Tarlov cyst"]}
A feeding disorder, in infancy or early childhood, is a child's refusal to eat certain food groups, textures, solids or liquids for a period of at least one month, which causes the child to not gain enough weight, grow naturally or cause any developmental delays.[1] Feeding disorders resemble failure to thrive, except that at times in feeding disorder there is no medical or physiological condition that can explain the very small amount of food the children consume or their lack of growth. Some of the times, a previous medical condition that has been resolved is causing the issue.[1] ## Contents * 1 Types * 2 Symptoms and signs * 2.1 Associated problems * 3 Diagnosis * 4 Treatments * 5 Epidemiology * 6 See also * 7 References ## Types[edit] Feeding disorder has been divided into six further sub-types:[2] 1. Feeding disorder of state regulation 2. Feeding disorder of reciprocity (neglect) 3. Infantile anorexia 4. Sensory food aversion 5. Feeding disorder associated with concurrent medical condition 6. Post-traumatic feeding disorder ## Symptoms and signs[edit] Children attempting to swallow different food textures often vomit, gag, or choke while eating. At feeding times they may react negatively to attempts to feed them, and refuse to eat.[3] Other symptoms include head turns, crying, difficulty in chewing or vomiting and spitting whilst eating. Many children may have feeding difficulties and may be picky eaters, but most of them still have a fairly healthy diet. Children with a feeding disorder however, will completely abandon some of the food groups, textures, or liquids that are necessary for human growth and development [4] Children with this disorder can develop much more slowly because of their lack of nutritional intake. In severe cases the child seems to feel socially isolated because of the lack of social activities involving foods.[3] ### Associated problems[edit] A few of the medical and psychological conditions that have been known to be associated with this disorder include:[5] * Gastrointestinal motility disorders * Oral-motor dysfunction * Failure to thrive * Prematurity * Food allergies * Sensory problems * Reflux * Feeding tube placement A child that is suffering from malnutrition can have permanently stunted mental and physical development. Getting treatment early is essential and can prevent many of the complications.[6] They can also develop further eating disorders later in life such as anorexia nervosa, or they could become a limited eater—though they could still be a healthy child they may become a picky eater. ## Diagnosis[edit] A barium swallow test is often performed, where the child is given a liquid or food with barium in it. This allows the consulting medical practitioners to trace the swallow-function on an X-ray or other investigative system such as a CAT scan. An endoscopic assignment test can also be performed, where an endoscope is used to view the oesophagus and throat on a screen. It can also allow viewing of how the patient will react during feeding.[7] ## Treatments[edit] There is no quick cure, and treatment will be based on what problems may be causing the feeding disorder. Depending on the condition, the following steps can be taken: increasing the number of foods that are accepted, increasing the amount of calories and the amount of fluids; checks for vitamin or mineral deficiencies; finding out what the illnesses or psychosocial problems are. To accomplish these goals patients may have to be hospitalized for extensive periods of time. Treatment involves professionals from multiple fields of study including, but not limited to; behavior analysts (Behavioral interventions),[8] occupational and speech therapist who specialize in feeding disorders, dietitians, psychologists and physicians. To obtain the best results, treatment should include a behavior modification plan under the guidance of multiple professionals.[9] If the child has oral motor difficulties related to the feeding disorder a pediatric occupational or speech therapist who is trained in feeding disorders and oral motor function should help develop a plan.[10] ## Epidemiology[edit] Some 25% to 40% of young children are reported to have feeding problems—mainly colic, vomiting, slow feeding, and refusal to eat.[11] It has been reported that up to 80% of infants with developmental handicaps also demonstrate feeding problems while 1 to 2% of infants aged less than one year show severe food refusal and poor growth.[12] Among infants born prematurely, 40% to 70% experience some form of feeding problem.[1] ## See also[edit] * Avoidant/restrictive food intake disorder ## References[edit] 1. ^ a b c "Feeding disorder of infancy or early childhood". Encyclopedia of Mental Disorders. Advameg, Inc. Retrieved 26 February 2011. 2. ^ Sexson, Sandra B. (2005). Child and adolescent psychiatry. Wiley-Blackwell. pp. 399. ISBN 1-4051-1768-0. 3. ^ a b "Feeding Disorders". Kennedy Krieger Institute. Archived from the original on 26 July 2011. Retrieved 8 July 2011. 4. ^ "Feeding Disorders". Feeding Clinic of Santa Monica. Archived from the original on 19 September 2018. Retrieved 8 July 2013. 5. ^ "Feeding Disorders". Kennedy Krieger Institute. 2012. Retrieved 16 December 2013. 6. ^ "Feeding Disorders". Archived from the original on 27 May 2010. Retrieved 18 July 2011. 7. ^ "Feeding Disorders and swallowing disorders". Retrieved 18 July 2011. 8. ^ Patel, M. R.; Piazza, C. C.; Martinez, C. J.; Volkert, V. M.; Christine, M. S. (2002). "An evaluation of two differential reinforcement procedures with escape extinction to treat food refusal". Journal of Applied Behavior Analysis. 35 (4): 363–374. doi:10.1901/jaba.2002.35-363. PMC 1284399. PMID 12555908. 9. ^ "5 Things to Know About Feeding Therapy". Harrison Speech Pathology. 2019-07-04. Retrieved 2019-08-14. 10. ^ Andrea Barkoukis, M.A., Natalie Staats Reiss, Ph.D., and Mark Dombeck, Ph.D. "Feeding Disorder of Early Childhood". Retrieved 26 June 2011.CS1 maint: uses authors parameter (link) 11. ^ Bernard-Bonnin, AC (2006). "Feeding problems of infants and toddlers". Canadian Family Physician. 52 (10). 12. ^ Kay, Jerald (2006). Essentials of Psychiatry. West Sussex: John Wiley & Sons Ltd. p. 1078. ISBN 0470018542. [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-hydroxybutyric 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	Feeding disorder	c0854145	24,617	wikipedia	https://en.wikipedia.org/wiki/Feeding_disorder	2021-01-18T18:28:57	{"mesh": ["D001068"], "wikidata": ["Q5441238"]}
In 2 brothers and a sister, aged 7 to 13 years, Sanchez-Corona et al. (1985) observed a seemingly 'new' autosomal recessive hereditary ataxia syndrome. Features included unusual facies (gross, rough and abundant hair, mild palpebral ptosis, thick lips, and down-curved corners of the mouth), dysarthria, delayed psychomotor development, scoliosis, foot deformities, and ataxia. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Coarse facies \- Wide forehead Eyes \- Mild palpebral ptosis Nose \- Small nose \- Anteverted nares Mouth \- Thick lips \- Downturned corners of mouth SKELETAL Spine \- Scoliosis Feet \- Foot deformities SKIN, NAILS, & HAIR Hair \- Abundant hair \- Rough hair NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Ataxia \- Dysarthria \- Hyporeflexia \- Hypotonia \- Extensor plantar response \- Cerebellar atrophy ▲ 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-hydroxybutyric 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	SPINOCEREBELLAR ATAXIA WITH DYSMORPHISM	c1849088	24,618	omim	https://www.omim.org/entry/271270	2019-09-22T16:22:09	{"mesh": ["C564802"], "omim": ["271270"], "orphanet": ["1185"]}
A number sign (#) is used with this entry because of evidence that Galloway-Mowat syndrome-8 (GAMOS8) is caused by homozygous mutation in the NUP133 gene (607613) on chromosome 1q42. One such family has been reported. Biallelic mutation in the NUP133 gene can also cause nephrotic syndrome type 18 (NPHS18; 618177). Description Galloway-Mowat syndrome-8 is an autosomal recessive disorder characterized by impaired psychomotor development, poor overall growth with microcephaly, and early-onset progressive nephrotic syndrome associated with focal segmental glomerulosclerosis on renal biopsy. Some patients may have seizures, and some may die in childhood (summary by Fujita et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300). Clinical Features Nakazato et al. (2002) reported a consanguineous Japanese family in which 4 sibs had delayed psychomotor development apparent in infancy and subsequently developed progressive and severe renal disease in the first years of life. Fujita et al. (2018) provided follow-up of this family. The patients had strabismus, hypotonia, profoundly impaired intellectual development, and overall growth deficiency with relative microcephaly (about -2.6 SD). One patient was noted to have dysmorphic features, including narrow forehead, enamel hypoplasia, and deviation of the thumbs. Three patients developed seizures, including one patient with severe refractory epilepsy. Brain imaging of one child showed mild cortical atrophy, although imaging in another child was normal. Two patients had hearing impairment. The patients developed nephrotic syndrome with proteinuria and microscopic hematuria in the first years of life. Renal biopsies, when performed, showed focal segmental glomerulosclerosis, interstitial fibrosis, tubular atrophy, cystic dilatation, and focal foot process fusion or effacement. The renal disease was progressive, and the patients developed edema, uremia, and hypertension. Two patients died at ages 2 and 4 years, and the other 2 underwent successful renal transplantation. Neuropathologic examination in 1 patient, who later died at age 19 years, showed focal cortical dysplasia, abnormal tangential cortical lamination, dysmorphic neurons, loss of pyramidal cells in the hippocampus, abnormal dendritic arborization, and abnormalities in the cerebellum. Inheritance The transmission pattern of GAMOS8 in the family reported by Nakazato et al. (2002) and Fujita et al. (2018) was consistent with autosomal recessive inheritance. Molecular Genetics In 3 affected members of a consanguineous Japanese family with GAMOS8, originally reported by Nakazato et al. (2002), Fujita et al. (2018) identified a homozygous splice site mutation in the NUP133 gene (607613.0004). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Analysis of patient cells showed that the mutation resulted in aberrant splicing and a significant reduction in NUP133 protein levels compared to controls. In vitro functional expression studies in HeLa cells showed that the mutant protein had impaired binding to NUP107 (607617), consistent with a loss of function. Expression of the mutation was unable to rescue the brain and renal tissue abnormalities observed in zebrafish embryos with morpholino knockdown of the nup133 gene. Animal Model Fujita et al. (2018) found ubiquitous expression of nup133 in various zebrafish embryos and adult tissue, with higher expression in the brain, testes, ovaries, skin, and kidney. Morpholino knockdown of the nup133 gene in zebrafish embryos resulted in small head and curved trunks, with later onset of edema and early death. The brain and renal tissue showed disorganization and underdeveloped glomeruli and abnormal podocytes. INHERITANCE \- Autosomal recessive GROWTH Other \- Poor overall growth HEAD & NECK Head \- Microcephaly Face \- Dysmorphic facial features (in some patients) \- Narrow forehead Eyes \- Strabismus Teeth \- Enamel hypoplasia CARDIOVASCULAR Vascular \- Hypertension secondary to renal disease GENITOURINARY Kidneys \- Nephrotic syndrome \- Focal segmental glomerulosclerosis \- Interstitial fibrosis \- Tubular atrophy \- Cystic dilatation \- Focal foot process fusion or effacement MUSCLE, SOFT TISSUES \- Hypotonia \- Edema secondary to renal dysfunction NEUROLOGIC Central Nervous System \- Global developmental delay \- Impaired intellectual development \- Seizures \- Cortical atrophy on brain imaging (patient A) \- Focal cortical dysplasia (patient A) \- Loss of pyramidal cells in the hippocampus (patient A) \- Cerebellar abnormalities (patient A) \- Abnormal tangential cortical lamination (patient A) \- Dysmorphic neurons (patient A) \- Abnormal dendritic arborization (patient A) LABORATORY ABNORMALITIES \- Proteinuria \- Hematuria \- Hypoalbuminemia \- Uremia MISCELLANEOUS \- Onset in infancy or early childhood \- Death in childhood may occur without renal transplantation \- One consanguineous Japanese family has been reported (last curated March 2019) MOLECULAR BASIS \- Caused by mutation in the nucleoporin, 133-kD gene (NUP133, 607613.0004 ) ▲ 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-hydroxybutyric 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	GALLOWAY-MOWAT SYNDROME 8	c0795949	24,619	omim	https://www.omim.org/entry/618349	2019-09-22T15:42:24	{"mesh": ["C537548"], "omim": ["618349"], "orphanet": ["2065"]}
Macular corneal dystrophy (MCD) is a rare, severe form of stromal corneal dystrophy (see this term) characterized by bilateral ill-defined cloudy regions within a hazy stroma, and eventually severe visual impairment. ## Epidemiology Prevalence of this form of corneal dystrophy is not known. Cases of MCD have been identified worldwide. The condition is most prevalent in India, Saudi Arabia, Iceland and parts of the USA. ## Clinical description Whitish opacities in the cornea usually appear during adolescence but may develop in early infancy, or as late as the 6th decade of life. The non-transparent areas progressively merge as the entire corneal stroma becomes cloudy, causing severe visual impairment usually before the 5th decade. The bilateral corneal opacities progressively extend through the entire thickness of the central and peripheral corneal stroma. The corneal stroma is thinner than normal. ## Etiology Most cases of MCD are caused by mutations in the CHST6 gene (16q22) encoding a protein involved in the production of keratan sulfate, which plays a role in the maintenance of corneal transparency. More than 125 mutations in this gene have been identified to date. ## Diagnostic methods MCD is characterized histopathologically by intracytoplasmic accumulations of non-sulfated keratan sulfate within the keratocytes and corneal endothelium, sparing the corneal epithelium. MCD is classified as a corneal stromal dystrophy but also involves the Descemet membrane and the corneal endothelium. ## Differential diagnosis The clinical features of MCD are similar to the corneal involvement found in the systemic mucopolysaccharidoses, such as mucopolysaccharidosis type IH and IS and the mucolipidoses (see these terms). ## Genetic counseling An autosomal recessive mode of inheritance has been shown in most cases, but some cases are of unknown etiology. ## Management and treatment Since the condition affects the entire corneal stroma, Descemet membrane and corneal endothelium, lamellar keratoplasty does not excise all damaged tissue. Corneal transplantation may therefore be needed. Vision can be restored by corneal grafting but opacities may recur in the graft after many years. [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-hydroxybutyric 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	Macular corneal dystrophy	c0024439	24,620	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98969	2021-01-23T18:32:27	{"gard": ["6953"], "mesh": ["D003317"], "omim": ["217800"], "umls": ["C0024439", "C1636149"], "icd-10": ["H18.5"], "synonyms": ["Corneal dystrophy Groenouw type II", "Fehr corneal dystrophy", "MCD"]}
Pseudohypoparathyroidism is a genetic disorder in which the body is unable to respond to parathyroid hormone. Parathyroid hormone helps control calcium, phosphorous, and vitamin D levels in the bones and blood. Hypoparathyroidism is a similar condition in which the body does not make enough parathyroid hormone instead of not being able to respond to it (as in pseudohypoparathyroidism). The symptoms of these two conditions are similar and are caused by low calcium levels and high phosphate levels in the blood. This may cause cataracts (clouding of the lens of the eye), dental problems, numbness, seizures, or tetany (muscle twitches and hand and foot spasms). These symptoms are usually first seen in childhood. There are two different types of pseudohypoparathyroidism, both of which are caused by spelling mistakes (mutations) in certain genes. Type 1 can be further divided into three sub-types. Click on the links below for more information on the various types of pseudohypoparathyroidism. Pseudohypoparathyroidism type 1A Pseudohypoparathyroidism type 1B Pseudohypoparathyroidism type 1C Pseudohypoparathyroidism type 2 [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-hydroxybutyric 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	Pseudohypoparathyroidism	c0033806	24,621	gard	https://rarediseases.info.nih.gov/diseases/10758/pseudohypoparathyroidism	2021-01-18T17:58:05	{"mesh": ["D011547"], "synonyms": []}
## Summary ### Clinical characteristics. Bohring-Opitz syndrome (BOS) is characterized by distinctive facial features and posture, growth failure, variable but usually severe intellectual disability, and variable anomalies. The facial features may include microcephaly or trigonocephaly / prominent (but not fused) metopic ridge, hypotonic facies with full cheeks, synophrys, glabellar and eyelid nevus flammeus (simplex), prominent globes, widely set eyes, palate anomalies, and micrognathia. The BOS posture, which is most striking in early childhood and often becomes less apparent with age, is characterized by flexion at the elbows with ulnar deviation and flexion of the wrists and metacarpophalangeal joints. Feeding difficulties in early childhood, including cyclic vomiting, have a significant impact on overall health; feeding tends to improve with age. Seizures are common and typically responsive to standard epileptic medications. Minor cardiac anomalies and transient bradycardia and apnea may be present. Affected individuals may experience recurrent infections, which also tend to improve with age. Isolated case reports suggest that individuals with BOS are at greater risk for Wilms tumor than the general population, but large-scale epidemiologic studies have not been conducted. ### Diagnosis/testing. The diagnosis of Bohring-Opitz syndrome (BOS) is established in a proband with suggestive clinical features and/or the identification of a constitutional heterozygous pathogenic variant in ASXL1 by molecular genetic testing. ### Management. Treatment of manifestations. Cyclic vomiting may be managed by identification and avoidance of triggers, daily maintenance medication, and early abortive treatment; G-tubes or GJ-tubes may decrease aspiration and improve nutrition. Due to the prevalence of obstructive sleep apnea, polysomnography should be considered. Referral to a craniofacial team should be considered for those with palatal abnormalities, micrognathia, or obstructive sleep apnea. Tracheostomy may be considered for those with recurrent aspiration who develop secondary lung disease, or in those with severe sleep apnea that is not adequately treated with noninvasive pressure support (e.g., CPAP, BiPAP) or surgical intervention (e.g., mandibular distraction). Standard management is indicated for seizures, congenital heart defects, intellectual disability, myopia, urinary tract infections, urinary retention, and renal stones. Prevention of primary manifestations. Adequate treatment of severe emesis can decrease hospitalizations, infectious exposures, and ascending aspiration. Surveillance: Renal ultrasound every three months from birth to age eight to screen for the development of Wilms tumor; frequent monitoring of growth and development; close monitoring of feeding intolerance with a gastroenterology specialist; regular follow up for vision optimization. Agents/circumstances to avoid. Triggers for vomiting should be avoided and managed with prophylactic antiemetics prior to the exposure. ### Genetic counseling. Bohring-Opitz syndrome (BOS) is typically the result of a de novo pathogenic variant in ASXL1. When BOS results from a de novo variant, the risk to the sibs of a proband is small. No individuals with BOS have been reported to reproduce. Although the vast majority of BOS occurs as the result of a de novo variant in ASXL1, molecular genetic testing can be used to evaluate a pregnancy at theoretically increased risk as a result of constitutional and/or germline mosaicism for an ASXL1 pathogenic variant in a clinically unaffected parent. ## Diagnosis Prior to the identification of the molecular cause of Bohring-Opitz syndrome (BOS), Hastings et al [2011] had proposed clinical diagnostic criteria for the condition. Ultimately, only five individuals used to develop these clinical diagnostic criteria were molecularly confirmed to have BOS. Therefore, the specificity of these diagnostic criteria is unclear. ### Suggestive Findings Bohring-Opitz syndrome should be suspected in individuals with the following clinical features [Bohring et al 1999, Bohring et al 2006, Hastings et al 2011, Magini et al 2012, Russell et al 2015]. Craniofacial appearance (Figure 1) #### Figure 1. Facial features of individuals with BOS at varying ages A-B. 2 years * Microcephaly or trigonocephaly / prominent (but not necessarily fused) metopic ridge * Glabellar and eyelid nevus flammeus (simplex) that fades with age * Prominent globes * Cleft lip * Palatal anomalies: cleft palate, high arched palate, or prominent palatine ridges * Micrognathia and/or retrognathia Growth and feeding * Intrauterine growth restriction * Severe feeding difficulties with chronic emesis that typically improves with age * Poor postnatal weight gain and linear growth, often exacerbated by severe feeding intolerance Neurologic * Developmental delay or intellectual disability in the severe-to-profound range with minimal or complete lack of expressive language * Seizures Respiratory. Recurrent infections (commonly respiratory) in early childhood that improve with age Sleep * Sleep disturbance * Obstructive sleep apnea Ophthalmologic * High myopia presenting in infancy that may worsen over the first years of life * Variable optic nerve and retinal anomalies BOS posture (Figure 2) #### Figure 2. Typical BOS posture with flexion at the elbows, ulnar deviation, flexion of the wrists and metacarpophalangeal joints, and hypertonic extremities with central hypotonia From Hastings et al [2011]. Republished with permission. * Flexion at the elbows with ulnar deviation and flexion of the wrists and metacarpophalangeal joints; most noticeable in early childhood and usually less obvious with age * Truncal hypotonia with hypertonia of the extremities ### Establishing the Diagnosis The diagnosis of Bohring-Opitz syndrome is established in a proband with suggestive clinical features (see Suggestive Findings) and/or by identification of a constitutional heterozygous pathogenic variant in ASXL1 on molecular genetic testing (see Table 1). Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, or more comprehensive genomic testing: * Single-gene testing. Sequence analysis of ASXL1 is performed first and followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found. * A multigene panel that includes ASXL1 and other genes of interest (see Differential Diagnosis) may also be considered. 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 if single-gene testing (and/or use of a multigene panel that includes ASXL1) fails to confirm a diagnosis in an individual with features of Bohring-Opitz syndrome. 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. ### Table 1. Molecular Genetic Testing Used in Bohring-Opitz Syndrome View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method ASXL1Sequence analysis 320/24 (83%) 4, 5 Gene-targeted deletion/duplication analysis 6None reported 7 Unknown 8NA 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. 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\. The denominator represents only those individuals in the literature who have undergone sequence analysis of ASXL1; some clinically diagnosed individuals whose information has been published have not undergone molecular genetic testing. 5\. Somatic mosaicism for ASXL1 variants, including BOS-associated variants, may be found in the elderly or in other non-BOS cohorts (i.e., cohorts of individuals with cancer); such variants may be reported in reference databases, leading to misclassification of potentially pathogenic variants [Carlston et al 2017]. See Molecular Genetics. 6\. 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. 7\. No data on detection rate of gene-targeted deletion/duplication analysis are available. 8\. In four individuals with features suggestive of BOS molecular genetic testing of ASXL1 failed to identify a pathogenic variant [Brunner et al 2000, Hastings et al 2010, Hastings et al 2011, Hoischen et al 2011]. It is unclear if these individuals have a different genetic syndrome with clinical features overlapping those of BOS. Greenhalgh et al [2003] reported two sibs with clinical features of BOS in whom a different diagnosis was subsequently confirmed [Bruel et al 2017]. ## Clinical Characteristics ### Clinical Description Bohring-Opitz syndrome (BOS) is a rare condition characterized by distinctive facial features and posture, variable but usually severe intellectual disability, growth failure, and variable anomalies. Feeding difficulties have a significant impact on overall health in early childhood; feeding tends to improve with age. This section summarizes clinical data from numerous case reports and case series; see Russell et al [2015] and references therein, Dangiolo et al [2015], and Suggested Reading. Additional references are cited where appropriate. Craniofacial. Individuals with BOS have a characteristic facial appearance (see Suggestive Findings), although significant variability is observed. The most striking and consistent features are a prominent glabellar nevus flammeus (simplex) that fades with age, synophrys that becomes more prominent with age, hypotonic facies with full cheeks, and prominent or proptotic eyes. The majority of affected individuals also have hypertrichosis with rapidly growing hair and nails. Other features widely, but variably, reported include cleft lip with or without cleft palate, high arched palate, widely spaced eyes (hypertelorism), depressed and wide nasal bridge, anteverted nares, and low-set ears with increased posterior angulation. Growth. Mild intrauterine growth restriction has been noted, but many infants are products of healthy pregnancies with average or low-average birth weights. Poor growth is typically noted in the first year of life and is often clinically attributed to chronic emesis and feeding intolerance. Adequate nutrition does play a role in early growth, but even those without feeding intolerance typically display poor long-term growth. Feeding. Most children have had feeding issues beginning in infancy and generally improving or resolving in early childhood. Historically, feeding issues have been presumed to be secondary to severe gastroesophageal reflux, but initial case reports did not produce diagnostic evidence of gastroesophageal reflux or demonstrate improvement on traditional antireflux therapies. Recent publications have suggested a neurogenic etiology, including cyclic vomiting with possible poor gastric motility, as the underlying cause of the chronic emesis [Russell et al 2015]. Given the frequency of emesis, there is a high risk for aspiration and dehydration, typically resulting in multiple hospitalizations. Development and behavior. All affected individuals reported in the literature have severe-to-profound intellectual disability. Few are able to speak, but many have been able to express basic needs using augmentative and alternative communication (AAC) devices as well as gestures with associated basic vocalizations. Individuals with BOS often have a happy and pleasant demeanor [Russell et al 2015]. Typically, they are able to recognize caregivers and have a social, interactive nature. Most are unable to walk independently, but some have had success using walkers and braces in late childhood. Given the recent increase in rate of diagnosis due to genomic testing, it is expected that affected individuals with a milder phenotype may be reported in the future. Neurologic. Seizures are common in individuals with BOS and are typically responsive to standard antiepileptic medications. Affected individuals have also been described to have truncal hypotonia with hypertonia of the extremities. A wide range of primary brain anomalies have been reported. Corpus callosum defects are the most common and range from hypoplastic to absent. Dandy-Walker malformation, delayed myelination, and enlarged ventricles have also been described. Cardiovascular. Idiopathic and transient bradycardia as well as apnea were widely reported in the initial literature that predated the identification of the genetic cause of BOS. Cardiovascular deaths associated with bradycardia and apnea account for four (33%) of the 12 deaths published in the literature (although none of those individuals had a molecular confirmation of BOS). Other minor cardiac anomalies including septal defects and cardiac hypertrophy have also been described in a small number of affected individuals. Respiratory. In addition to apnea and bradycardia, respiratory infections are common in infancy and account for about 42% of deaths (5/12). When chronic emesis is treated or improves with age, the rate of respiratory infections decreases [Russell et al 2015]. Tracheostomies have been necessary for some (see Management). Sleep. Obstructive sleep apnea and sleep disturbances, including difficulty falling asleep and staying asleep, are frequently reported. Affected individuals with micrognathia may also exhibit tongue-based airway obstruction. Ophthalmologic. Myopia, often severe, is common in individuals with BOS. Most affected individuals require corrective lenses in infancy. Retinal and optic nerve abnormalities including colobomas, retinal and optic nerve atrophy, and abnormal coloration of the retinas are also frequently reported. Immunologic. Recurrent infections may be frequent in early life, although immunodeficiency has not been reported in the literature. The frequency of infections typically declines with age. Urologic. Urinary retention and recurrent urinary tract infections have been reported in individuals with BOS [Russell et al 2015]. There also appears to be an increased risk for renal stones [Author, personal observation]. Skeletal. The typical BOS posture (see Suggestive Findings) is most notable in early childhood and usually becomes less obvious with age. Congenital contractures, dislocations, and pectus excavatum have also been reported. Malignancy. Isolated case reports suggest that children with BOS are at greater risk for Wilms tumor than the general population; large-scale epidemiologic studies have not been conducted due to the limited number of individuals diagnosed with BOS. Of three individuals with a clinical diagnosis of BOS and renal neoplasia, two had documented pathogenic variants in ASXL1 and bilateral Wilms tumor; Wilms tumor was diagnosed in one at age two years and in the other at age six years [Russell et al 2015]. Another individual with BOS had nephroblastomatosis on autopsy at age five months. This infant later underwent molecular genetic testing of ASXL1; no pathogenic variant was identified [Brunner et al 2000, Hoischen et al 2011]. Overall, Wilms tumor appears to affect about 7% of individuals with BOS. This risk estimate is based on a very small number of reported cases and thus is likely to change over time as larger cohorts of children and adults with BOS are investigated. The only other neoplastic process reported was medulloblastoma in a child age five years with clinical features of BOS in whom a pathogenic ASXL1 variant was not identified [Hastings et al 2010, Hoischen et al 2011]. Other * Annular pancreas has been described in some affected individuals. * Gallstones have been reported in several affected individuals [Author, personal observation]. * Historically, this condition had been associated with high infant mortality (27% based on data published before 2015), but the current survival rate is likely to be much better due to advances in pediatric care and more aggressive interventions [Russell et al 2015]. ### Genotype-Phenotype Correlations No genotype-phenotype correlations have been reported to date, but the total number of individuals in whom ASXL1 pathogenic variants have been identified is limited. ### Nomenclature BOS is occasionally known as Oberklaid-Danks syndrome after F Oberklaid and DM Danks, who described one of the early cases of BOS [Oberklaid & Danks 1975]. BOS is the more commonly used term. ### Prevalence The prevalence of BOS is unknown; out of 46 clinically diagnosed individuals reported in the literature, 20 had the diagnosis molecularly confirmed. Note: Not all clinically diagnosed individuals reported in the literature have undergone molecular genetic testing of ASXL1. ## Differential Diagnosis ### Table 2. Disorders to Consider in the Differential Diagnosis of Bohring-Opitz Syndrome (BOS) View in own window DisorderGene(s)MOIClinical Features of the Differential Diagnosis Disorder Overlapping w/BOSDistinguishing from BOS C syndrome (Opitz trigonocephaly syndrome) 1 (OMIM 211750)CD96AD * Severe DD/ID * Microcephaly * Trigonocephaly * Upslanting palpebral fissures * Retrognathia * Low-set ears Common in BOS, not in C syndrome: * Nevus flammeus (simplex) over glabella * BOS posture * Poor linear growth * Feeding difficulties * High myopia Shashi-Pena syndrome (ASXL2 syndrome) 2 (OMIM 617190)ASXL2AD * DD * Hypotonia * Feeding difficulties in infancy * Nevus flammeus (simplex) over the glabella * Facial characteristics (particularly widely spaced eyes, prominent globes, & low-set or posteriorly rotated ears) * Hypertrichosis (2 of 6 reported cases) Common in BOS: * Severe to profound ID * Microcephaly * BOS posture Common in Shashi-Pena syndrome: * Variable ID (borderline to severe) * Macrocephaly * Lesser feeding difficulties & normal weight gain * Episodic hypoglycemia of unknown etiology Bainbridge-Ropers syndrome (ASXL3-related disorder) 3ASXL3AD * Severe DD/ID w/minimal speech * Hypotonia * Feeding difficulties * Poor linear growth & weight gain * Microcephaly Common in BOS; not typical in Bainbridge-Ropers syndrome: * IUGR * Nevus flammeus (simplex) over the glabella * Prominent globes * Typical BOS posture Cornelia de Lange syndrome (CdLS)HDAC8 NIPBL RAD21 SMC1A SMC3AD XL 4 * DD/ID * Prenatal and postnatal growth restriction * Microcephaly * Hypertrichosis * Small feet * In HDAC8-related CdLS, nevus flammeus (simplex) over the glabella & widely spaced eyes 5 Common in BOS: * More severe feeding intolerance * High myopia * BOS posture * Prominent globes Common in CdLS: * Small hands & feet sometimes w/upper-limb reduction defects KLHL7-associated syndrome 6KLHL7AR * DD/ID * Feeding difficulties * IUGR * Seizures * Microcephaly * Hypoplastic corpus callosum * Facial characteristics: prominent eyes, anteverted nares * Facial nevus flammeus (simplex) * Hypertrichosis * Joint contractures * BOS posture In KLHL7-associated syndrome: * Absence of high myopia & retinal/optic nerve atrophy * Retinitis pigmentosa in childhood * Hyperthermia * Oropharyngeal muscle contraction AD = autosomal dominant; AR = autosomal recessive; DD/ID = developmental delay / intellectual disability; IUGR = intrauterine growth restriction; MOI = mode of inheritance; XL = X-linked 1\. The phenotypic spectrum of C syndrome is not well defined, apart from the reportedly more common features. The mode of inheritance is also unclear since the molecular etiology remains elusive. A Japanese individual with a clinical diagnosis of C syndrome had a chromosomal translocation that disrupted CD96 (also known as TACTILE), and another Japanese individual with a clinical diagnosis of C syndrome had a heterozygous missense variant in CD96 [Kaname et al 2007]. However, these findings have not been replicated since 2007, so it remains unclear whether pathogenic variants in CD96 could result in C syndrome. More recently, compound heterozygous pathogenic variants in IFT140 were found in an individual with a clinical diagnosis of C syndrome – along with clinical features suggestive of a ciliopathy, which had not been previously reported in C syndrome [Peña-Padilla et al 2017]. Thus, it is unclear whether this is distinct from "classic" C syndrome. 2\. Shashi et al [2016] 3\. Balasubramanian et al [2017], Kuechler et al [2017] 4\. NIPBL-, RAD21-, and SMC3-related CdLS are inherited in an autosomal dominant manner; HDAC8\- and SMC1A-related CdLS are inherited in an X-linked manner. 5\. Pathogenic variants in HDAC8 result in an X-linked subtype of CdLS that is more severe in males and bears facial resemblance to BOS, with features not typically seen in "classic" CdLS: nevus flammeus (simplex) over the glabella and widely spaced eyes [Kaiser et al 2014, Parenti et al 2016]. 6\. Angius et al [2016], Bruel et al [2017] ## Management ### Evaluations Following Initial Diagnosis To establish the spectrum of manifestations and medical needs in an individual diagnosed with Bohring-Opitz syndrome (BOS), the following evaluations are recommended if they have not already been completed. ### Table 3. Recommended Evaluations Following Initial Diagnosis of Bohring-Opitz Syndrome View in own window System/ConcernEvaluationComment GrowthWeight, length/height, & head circumference measurements plotted on standard growth chart * Goal: normal weight-for-length or body mass index * Expected final adult height: <2nd centile ENT/MouthCraniofacial evaluation if cleft lip/palate, micrognathia, or obstructive sleep apnea is presentIf mainly due to tongue-based airway obstruction, severe obstructive sleep apnea may be treatable by adenoidectomy or mandibular distraction. Gastrointestinal * Feeding evaluation (w/consideration of swallowing study) to assess for chronic emesis & aspiration risk * Consideration of gastric emptying time to assess for poor gastric motility NeurologicAssessment for signs/symptoms of seizuresIf present, consider neurology evaluation & head MRI. Evaluation by developmental specialists incl speech, occupational, & physical therapists CardiovascularEchocardiogram for cardiac anatomy RespiratoryAssessment for apnea/bradycardia (more common in younger individuals)Consider sleep study if sleep apnea is a concern. EyesOphthalmology evaluationFor high myopia & retinal/optic nerve defects GenitourinaryBaseline renal ultrasoundTo assess renal structure & screen for Wilms tumor MusculoskeletalOrthopedic evaluation if bony anomalies noted Miscellaneous/ OtherConsultation w/clinical geneticist &/or genetic counselor ### Treatment of Manifestations ### Table 4. Treatment of Manifestations in Individuals with BOS View in own window Manifestation/ConcernTreatmentConsiderations/Other Poor growth & feeding due to chronic severe emesis 1 * For cyclic vomiting: identification & avoidance of triggers, 2 daily maintenance medication, 3 & early abortive treatment at episode onset 4 * G-tubes or GJ-tubes often decrease aspiration & improve nutrition; 5 consider thickened feeds. Fundoplication & traditional antireflux management w/acid blockers are typically not beneficial if gastroesophageal reflux is not the underlying etiology. Cleft lip &/or palate * Primary closure of cleft lip along standard timeline * Consider leaving cleft palates unrepaired when speech is lacking. * Palate repair in a child at risk for obstructive apnea may ↑ risk. * Assess language & mobility to determine plan for palate closure & alveolar bone grafting. * Palate repair may be warranted in individuals w/language skills. Frequent infections &/or aspiration pneumonia 4Aggressive management of chronic emesis Fever or increase in emesis * Urinalysis & urine culture for possible urinary tract infection * Evaluation for other possible sources of infection, pain, or exposure SeizuresStandard antiepileptic medicationsMost individuals respond to monotherapy. Congenital heart defectsStandard management Respiratory symptomsTracheostomy may be effective in: * Creating a safe airway * Treating aspiration → lung disease * Treating severe obstructive sleep apnea not controlled by noninvasive pressure support (e.g., CPAP, BiPAP) or surgical management (e.g., adenoidectomy, mandibular distraction) Aspiration may also be amenable to treatment w/postpyloric feedings (e.g., by gastrojejunostomy). * Inhaled albuterol & inhaled steroids have improved respiratory status in some, although typical findings for reactive airway disease were lacking [Russell et al 2015]. * Descending aspiration of saliva can often be managed w/glycopyrrolate or salivary Botox injections. Sleep disturbancesMelatonin, treatment of anemia MyopiaCorrective lenses, often first prescribed in infancy Urinary retention, urinary tract infections, renal stonesStandard treatmentsAppropriate management of these conditions can improve emesis & hospitalization rate. 1\. If vomiting is well controlled, growth typically improves, hospitalizations for dehydration and aspiration decrease, and overall health and well-being improve, although the rate of linear growth and weight gain remains poor. Lifelong feeding interventions may not be required, so periodic reexamination is appropriate. 2\. Triggers such as vaccines, infections, and anesthesia have been reported, although this is not a reason to avoid vaccination and anesthesia: all children with BOS should receive the full course of standard vaccinations as recommended by the local authorities. 3\. Cyproheptadine has been used for daily maintenance therapy. 4\. Prophylactic treatment prior to a trigger exposure with antiemetics has been beneficial. Abortive treatment includes lorazepam, ondansetron, and acetaminophen or some combination of an antiemetic, pain reliever, and sedative. 5\. Most affected individuals with feeding difficulties require a permanent feeding tube (G-tube or GJ-tube). Thickened feeds can help with emesis, and while G-tubes often do not stop emesis completely, they can limit the amount of nutrition lost through vomiting. #### Developmental Delay / Intellectual Disability Management Issues The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country. Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the US, early intervention is a federally funded program available in all states. Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed. Ages 5-21 years. In the US, an IEP based on the individual's level of function should be developed by the local public school district. Affected children are permitted to remain in the public school district until age 21. All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life. Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. In the US: * Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. * Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. #### Motor Dysfunction Gross motor dysfunction * Physical therapy is recommended to maximize mobility. * Consider use of durable medical equipment as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers). Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing. Oral motor dysfunction. Assuming that the individual is safe to eat by mouth, feeding therapy – typically from an occupational or speech therapist – is recommended for affected individuals who have difficulty feeding due to poor oral motor control. Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC] for individuals who have expressive language difficulties. ### Prevention of Primary Manifestations Adequate treatment of severe emesis can decrease hospitalizations, infectious exposures, and aspiration. ### Surveillance The following are appropriate: * Renal ultrasound every three months from birth to age eight years to screen for the development of Wilms tumor [Russell et al 2015] * Frequent monitoring of growth and development with interventions as needed (see Treatment of Manifestations) * Close management of feeding intolerance with a gastroenterology specialist * Regular follow up with an ophthalmologist for vision optimization ### Agents/Circumstances to Avoid Triggers for vomiting should be avoided and managed with prophylactic antiemetics prior to the exposure (see Treatment of Manifestations). ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation 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-hydroxybutyric 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	Bohring-Opitz Syndrome	c0796232	24,622	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK481833/	2021-01-18T21:39:06	{"mesh": ["C537419"], "synonyms": ["Oberklaid-Danks Syndrome"]}
A number sign (#) is used with this entry because of evidence that hereditary hemorrhagic telangiectasia type 5 (HHT5) is caused by heterozygous mutation in the GDF2 gene (605120) on chromosome 10q11. Description Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant syndrome characterized by telangiectases and arteriovenous malformations (AVMs). Hallmark features are recurrent epistaxis due to telangiectases of the nasal mucosa; telangiectases on the lips, hands, and oral mucosa; solid-organ AVMs, particularly of the lungs, liver, and brain; and a family history of the same. Presentation with 3 of these criteria is considered diagnostic for HHT (summary by Wooderchak-Donahue et al., 2013). Clinical Features Wooderchak-Donahue et al. (2013) studied 3 individuals with features of hereditary hemorrhagic telangiectasia. The first patient was a 33-year-old woman who had onset of epistaxis in early childhood, with approximately 3 episodes a week in adulthood. She had several cutaneous telangiectases on her chest and face. Her father had died suddenly at 45 years of age and was suspected to have had HHT on the basis of autopsy findings, and a sib had recurrent spontaneous nosebleeds and stroke of unknown etiology at 43 years of age. Family members were unavailable for study. The second patient was a 37-year-old woman with onset of epistaxis at 30 years of age, with episodes varying from daily to once every 1 to 2 weeks. She had 15 to 20 dermal vascular malformations on her face, mouth, upper chest, upper mid-back area, and hands. She reported that the larger malformation had faded from a darker to a lighter pink over time. MRI of the brain did not show arteriovenous malformations (AVMs). However, hepatic MRI in this patient, who had abnormal liver enzymes and portal hypertension and had also been diagnosed with hepatopulmonary syndrome, showed vascular findings similar to those seen in HHT, with a slightly heterogeneous arterial phase and prominent, slightly corkscrew smaller branches of the hepatic artery as well as a suggestion of small focal nodular hyperplasia. Her father and sister had infrequent but recurring nosebleeds, but were not available for examination. The third patient was a 14-year-old boy who had onset of epistaxis at 3 years of age, with frequency ranging from once per week to several times per day. He had 80 to 100 telangiectases on his left arm, 2 on the palm of his right hand, and 1 possible lesion on his lower lip; biopsy report confirmed the lesions to be telangiectases. His father reportedly had frequent nosebleeds from childhood to early teens, but was unavailable for study. The first and third patients were not screened for solid organ involvement. Molecular Genetics Wooderchak-Donahue et al. (2013) performed exome sequencing in 38 unrelated patients who had been diagnosed with HHT, but in whom no mutations were found in the 3 known HHT-associated genes (ENG, 131195; ACVRL1, 601284; SMAD4, 600993), and identified heterozygosity for pathogenic missense variants in the GDF2 gene (605120.0001; 605120.0002) in 2 patients. Sanger sequencing of GDF2 in another 153 unrelated individuals with a suspected diagnosis of HHT revealed 1 more patient with a heterozygous missense mutation (605120.0003). All 3 mutation-positive individuals had epistaxis and dermal lesions described as telangiectases; however, Wooderchak-Donahue et al. (2013) noted that the skin lesions in these patients were less concentrated on the hands and mouth than in individuals with mutations in other HHT-associated genes, and some lesions were more similar in size and shape to the 'atypical capillary malformation' seen in CMAVM (608354), or had a distribution more typical of telangiectases seen in CMAVM. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Cutaneous telangiectases Nose \- Spontaneous, recurrent epistaxis Mouth \- Cutaneous telangiectases CARDIOVASCULAR Vascular \- Prominent, slightly corkscrew appearance of branches of hepatic artery on MRI (in one patient) CHEST External Features \- Cutaneous telangiectases ABDOMEN Liver \- Abnormal liver enzymes (in some patients) \- Portal hypertension (in some patients) \- Heterogeneous arterial phase on MRI (in one patient) \- Prominent, slightly corkscrew appearance of branches of hepatic artery on MRI (in one patient) SKIN, NAILS, & HAIR Skin \- Cutaneous telangiectases of face, upper chest, upper mid-back, upper extremities, and hands Skin Histology \- Telangiectases MISCELLANEOUS \- Incidence of 1 in 5,000-8,000 MOLECULAR BASIS \- Caused by mutation in the gene encoding growth/differentiation factor-2 (GDF2, 605120.0001 ) ▲ 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-hydroxybutyric 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	TELANGIECTASIA, HEREDITARY HEMORRHAGIC, TYPE 5	c0039445	24,623	omim	https://www.omim.org/entry/615506	2019-09-22T15:51:52	{"doid": ["1270"], "mesh": ["D013683"], "omim": ["615506"], "orphanet": ["774"], "genereviews": ["NBK1351"]}
Poland syndrome is characterized by an underdeveloped or absent chest muscle on one side of the body, absence of the breastbone portion (sternal) of the chest muscle, and webbing of the fingers of the hand on the same side. The cause of Poland syndrome is not known. This syndrome is nearly always sporadic. It tends to occur on the right side and is more common in boys than girls. Treatment typically involves surgical correction of the chest wall deformities. [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-hydroxybutyric 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	Poland syndrome	c0032357	24,624	gard	https://rarediseases.info.nih.gov/diseases/7412/poland-syndrome	2021-01-18T17:58:16	{"mesh": ["D011045"], "omim": ["173800"], "umls": ["C0032357"], "orphanet": ["2911"], "synonyms": ["Poland anomaly", "Poland syndactyly", "Poland sequence", "Unilateral defect of pectoralis muscle and syndactyly of the hand", "Poland's syndrome"]}
A number sign (#) is used with this entry because of evidence that congenital nonprogressive cone-rod synaptic disorder (CRSD) is caused by mutation in the gene encoding calcium-binding protein-4 (CABP4; 608965) on chromosome 11q13. Description Congenital nonprogressive cone-rod synaptic disorder is characterized by stable low vision, nystagmus, photophobia, a normal or near-normal fundus appearance, and no night blindness. Electroretinography shows an electronegative waveform response to scotopic bright flash, near-normal to subnormal rod function, and delayed and/or decreased to nonrecordable cone responses (Traboulsi, 2013; Khan, 2014). Clinical Features Zeitz et al. (2006) studied 3 patients from 2 unrelated families who exhibited electroretinographic (ERG) findings consistent with congenital stationary night blindness (CSNB; see 310500). The first family consisted of the index patient and his affected brother, 4 unaffected sibs, and their unaffected parents. The 2 patients presented with nystagmus and decreased visual acuity in early childhood. In both patients at age 15 years, best corrected visual acuity was 20/100 in both eyes. The disease course in the index patient was stationary for 30 years; however, he experienced a decrease in visual acuity near the time of the report. Neither patient complained about night blindness, and only the index patient developed moderate photophobia accompanied by a mild decrease in visual acuity. The 2 brothers were 39 and 45 years old at the time of the report. The index patient of the second family was the only affected member. He reported decreased visual acuity and night blindness at age 15 years. Visual acuity was reduced to 20/30 in both eyes. ERG showed a pattern typical for CSNB in general, with a well developed a-wave but a minimal b-wave. Littink et al. (2009) described a Dutch brother and sister who had decreased visual acuity and nystagmus since early childhood, associated with photophobia but not with night blindness. Examination at ages 12 and 10 years, respectively, showed visual acuities of 20/200 to 20/400, which had not changed over a 6-year period. Slit-lamp examination and funduscopy were unremarkable. Both sibs showed severely abnormal deutan color vision. Dark-adaptation curves were biphasic, with a slightly elevated final threshold. ERGs showed rod responses that were normal in the brother and low normal in the sister; both had absent cone a-waves and an electronegative configuration with absent b-waves. Cone responses were severely reduced, and 30-Hz photopic flicker responses showed the double-peak waveform characteristic of CSNB2. Rod responses showed an intact slow sensitive rod pathway, but an absent or severely abnormal fast insensitive rod pathway. Because the patients did not experience night blindness, Littink et al. (2009) designated the phenotype 'congenital cone-rod synaptic disorder.' Aldahmesh et al. (2010) reported 4 sibs, born of first-cousin Bedouin parents, who had very poor vision since infancy with nystagmus and lack of fixation or tracking. The proband was a 15-year-old girl who had a history of photophobia but not night blindness, with normal color vision. Examination revealed nystagmus and eccentric fixation, with a best-corrected visual acuity of 20/400 in both eyes; the visual acuity measurement was unchanged from early childhood, indicating the nonprogressive nature of the vision loss. Funduscopy was normal except for decreased foveal reflex, and ERG was extinguished under both photopic and scotopic conditions. The patient's 3 affected sibs exhibited a strikingly similar clinical profile; however, in 1 sister the ERG was not extinguished, but rather severely decreased under photopic conditions with normal implicit time on photopic flicker, and her scotopic ERG was borderline with a normal oscillatory potential. Two of the affected sibs had strabismus, which was surgically corrected. All 4 affected sibs had normal intellect and growth, and systemic evaluation was unremarkable. Aldahmesh et al. (2010) considered the phenotype to be 'LCA-like' (see 204000). Khan et al. (2013) studied 7 affected individuals from 3 consanguineous Saudi families with early-onset retinal dysfunction. Including the 4 previously reported Bedouin sibs by Aldahmesh et al. (2010), Khan et al. (2013) noted that all 11 patients had congenital nystagmus, low vision that was considered stable, and photophobia. All denied night blindness upon specific questioning, and all had a normal or near-normal fundus appearance. Affected individuals in the Saudi families had recordable ERGs similar to those of the 1 Bedouin sister, with an electronegative waveform to scotopic flash, near-normal or subnormal rod function, and decreased and delayed cone responses to photopic flash. Mapping In a Dutch brother and sister with congenital nonprogressive cone-rod synaptic disorder, Littink et al. (2009) performed genomewide homozygosity mapping and identified 2 homozygous regions, the largest of which was a 9-Mb region on 11q13.1-q13.5 that encompassed the CABP4 gene. In 4 Bedouin sibs with decreased visual acuity from infancy and extinguished or markedly reduced ERG responses, Aldahmesh et al. (2010) found only 1 shared block of homozygosity, with a minimal 3.29-Mb area of overlap on chromosome 11q13, encompassing 157 genes, including CABP4. Molecular Genetics In 2 Swiss brothers who had decreased visual acuity without night blindness and who exhibited ERG findings consistent with CSNB2 (300071) but were negative for mutation in the CACNA1F gene (300110), Zeitz et al. (2006) identified homozygosity for a 2-bp deletion in the CABP4 gene (800delAG; 608965.0001). In addition, a 15-year-old boy from an unrelated family of Swiss ancestry, who did experience night blindness and whose ERG showed a pattern typical for CSNB in general, was compound heterozygous for the 2-bp deletion and a missense mutation in CABP4 (R124C; 608965.0002). He was also hemizygous for an N735T missense mutation in the CACNA1F gene, as was his unaffected brother, and his mother was a heterozygous carrier of the variant. Zeitz et al. (2006) concluded that the CACNA1F variant was not itself disease-causing but might modify the phenotype. Zeitz et al. (2006) showed that these mutations reduced CABP4 transcript levels to 30 to 40% of those in controls. On the basis of haplotype reconstruction and the Swiss ancestry of both families, a common origin of the 2-bp deletion in all 3 apparently unrelated individuals was considered possible. In a Dutch brother and sister with congenital nonprogressive cone-rod synaptic disorder mapping to chromosome 11q13.1-q13.5, Littink et al. (2009) sequenced the CABP4 gene and identified homozygosity for a nonsense mutation (R216X; 608965.0003). Their unaffected parents were heterozygous for the mutation, which was not found in 300 ethnically matched alleles. Sequence analysis of all coding exons of CABP4 in 85 additional Dutch patients with cone or cone-rod dystrophy did not reveal any mutations, suggesting that CABP4 mutations are not a major cause for those progressive retinal dystrophies. In 4 Bedouin sibs with decreased visual acuity from infancy and extinguished or markedly reduced ERG responses mapping to chromosome 11q13, Aldahmesh et al. (2010) directly sequenced the CABP4 gene and identified homozygosity for a 1-bp insertion (608965.0004); their unaffected first-cousin parents and 1 unaffected brother were heterozygous carriers of the mutation. In 7 patients from 3 consanguineous Saudi families with early-onset retinal dysfunction, Khan et al. (2013) identified homozygosity for the same 1-bp insertion that had been identified in 4 Bedouin sibs by Aldahmesh et al. (2010). Haplotype analysis confirmed a shared haplotype surrounding the mutation for all 4 families. Khan et al. (2013) noted that all reported patients with homozygous mutations in the CABP4 gene had congenital nystagmus, low vision that was considered stable, photophobia, no night blindness, a normal or near-normal fundus, and a typically hyperopic refraction. The authors stated that the best designation for the CABP4 phenotype is 'congenital cone-rod synaptic disorder.' Among a cohort of 101 Dutch patients diagnosed with congenital stationary night blindness, Bijveld et al. (2013) analyzed 6 known CSNB-related genes and identified the R216X mutation in the CABP4 gene in 1 female patient. However, Bijveld et al. (2013) noted that this patient, as well as the previously reported Dutch sibs (Littink et al., 2009) who were also homozygous for R216X, exhibited a phenotype distinct from CSNB: their problems were almost exclusively cone-related, including relatively low visual acuity, hyperopia, severe nonspecific color vision defects, and photophobia, with a slightly elevated (1.0 log) dark adaptation threshold. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Decreased visual acuity from infancy or early childhood \- Nystagmus \- Photophobia \- Strabismus (in some patients) \- Night blindness (rare) \- Abnormal color vision (in some patients) \- Funduscopy unremarkable (in most patients) \- Decreased or absent foveal reflex (rare) \- Slightly elevated dark-adaptation threshold \- Rod responses normal or near-normal on electroretinography (ERG) \- Intact slow sensitive rod pathway \- Absent or severely abnormal fast insensitive rod pathway \- Severely reduced cone responses \- Nonrecordable ERG (in some patients) MISCELLANEOUS \- Congenital reduction in visual acuity is nonprogressive MOLECULAR BASIS \- Caused by mutation in the calcium-binding protein-4 gene (CABP4, 608965.0001 ) ▲ 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-hydroxybutyric 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	CONE-ROD SYNAPTIC DISORDER, CONGENITAL NONPROGRESSIVE	c0339535	24,625	omim	https://www.omim.org/entry/610427	2019-09-22T16:04:39	{"mesh": ["C536122"], "omim": ["610427"], "orphanet": ["215"], "synonyms": ["Alternative titles", "NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 2B, FORMERLY", "NIGHT BLINDNESS, CONGENITAL STATIONARY, INCOMPLETE, AUTOSOMAL RECESSIVE, FORMERLY"]}
## Cloning and Expression A number of pharmacologically well-characterized subtypes of adrenergic receptors are known, including alpha-1, alpha-2, beta-1, and beta-2. Of these, both B1AR and B2AR stimulate adenylate cyclase, although they subserve different physiologic functions. A variety of drugs, both agonists and antagonists, selective for either beta-1 or beta-2 receptors have important applications in clinical medicine. Frielle et al. (1987) reported the unexpected cloning of the human B1AR cDNA from a human placenta cDNA library screened with human genomic clone G-21. The G-21 clone, containing an intronless gene for an as yet unidentified putative receptor, was itself obtained by its cross-hybridization with the human gene encoding B2AR. The sequence of the cDNA encoding human B1AR was determined. The 2.4-kb cDNA for the human B1AR encodes a protein of 477 amino acid residues that is 69% homologous with the avian beta-adrenergic receptor but only 54% homologous with the human beta-2-adrenergic receptor. This suggested that the avian gene encoding BAR and the human gene encoding B1AR evolved from a common ancestral gene. Expression of the B1AR protein in Xenopus laevis oocytes conveyed adenylate cyclase responsiveness to catecholamines with a typical beta-1 specificity. This contrasts with the typical beta-2 subtype specificity observed when B2AR cDNAs expressed in the Xenopus laevis system. Thus, mammalian B1AR and B2AR are products of distinct genes, both of which are apparently related to the putative G-21 receptor. See review by Frielle et al. (1988). Ellis and Frielle (1999) cloned full-length ADRB2 cDNAs of about 2.75 and 3.0 kb from a placenta cDNA library. The cDNAs differ only in the utilization of alternative polyadenylation sites. Both 3-prime UTRs are AU rich, and each contains several potential binding sites for mRNA stability factors. Northern blot analysis detected the 3.0-kb transcript in placenta. RNase protection analysis detected both transcripts in all tissues examined, including placenta, heart, cerebral cortex, and lung, as well as in a neuroblastoma cell line. The 3.0-kb transcript was expressed at 5 to 6 times the level of the 2.75-kb transcript. Expression of both transcripts decreased in failing hearts compared with nonfailing control hearts. Gene Function Xu et al. (2003) presented evidence that ADRA2A (104210) and ADRB1 form heterodimers when coexpressed in cultured cells, and that ADRA2A expression affects the internalization and ligand-binding characteristics of ADRB1. Using nanoscale live-cell scanning ion conductance and fluorescence resonance energy transfer microscopy in cardiomyocytes from healthy adult rats and mice, Nikolaev et al. (2010) found that spatially confined beta-2 adrenergic receptor (ADRB2; 109690)-induced cAMP signals were localized exclusively to the deep transverse tubules, whereas functional beta-1 adrenergic receptors were distributed across the entire cell surface. In cardiomyocytes derived from a rat model of chronic heart failure, beta-2 adrenergic receptors were redistributed from the transverse tubules to the cell crest, which led to diffuse receptor-mediated cAMP signaling. Nikolaev et al. (2010) concluded that redistribution of beta-2 adrenergic receptors in heart failure changes compartmentation of cAMP and might contribute to the failing myocardial phenotype. Biochemical Features Magnusson et al. (1990) demonstrated autoantibodies against the beta-1-adrenergic receptor in some patients with idiopathic dilated cardiomyopathy (see 115200). ### Crystal Structure Warne et al. (2011) presented 4 crystal structures of the thermostabilized turkey beta-1-adrenergic receptor bound to the full agonists carmoterol and isoprenaline and the partial agonists salbutamol and dobutamine. In each case, agonist binding induced a 1-angstrom contraction of the catecholamine-binding pocket relative to the antagonist-bound receptor. Full agonists can form hydrogen bonds with 2 conserved serine residues in transmembrane helix 5 (ser5.42 and ser5.46), but partial agonists only interact with ser5.42. ### Mass Spectrometry Using mass spectrometry to identify endogenous lipids bound to 3 G protein-coupled receptors of class A, Yen et al. (2018) observed preferential binding of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) over related lipids and confirmed that the intracellular surface of the receptors contain hotspots for PtdIns(4,5)P2 binding. Endogenous lipids were also observed bound directly to the trimeric G-alpha(s)-beta-gamma protein complex (see 139320) of the adenosine A2A receptor (ADORA2A; 102776) in the gas phase. Using engineered G-alpha subunits (mini-G-alpha(s), 139320; mini-G-alpha(i), see 139310; and mini-G-alpha(12), 604394), Yen et al. (2018) demonstrated that the complex of mini-G-alpha(s) with the beta-1 adrenergic receptor (ADRB1) is stabilized by the binding of 2 PtdIns(4,5)P2 molecules. By contrast, PtdIns(4,5)P2 does not stabilize coupling between ADRB1 and other G-alpha subunits (mini-G-alpha(i) or mini-G-alpha(12)) or a high-affinity nanobody. Other endogenous lipids that bind to these receptors had no effect on coupling, highlighting the specificity of PtdIns(4,5)P2. Mapping By means of somatic cell hybrid analysis and in situ hybridization, Hoehe et al. (1989) localized the beta-1 adrenergic receptor gene to chromosome 10. Hoehe et al. (1989) concluded from linkage studies that the ADRB1R and ADRA2R loci are closely linked in the region 10q23-q25. Pulsed field gel electrophoresis showed that the 2 loci are in the same 250-kb segment. By in situ hybridization, Yang-Feng et al. (1990) regionalized the ADRA2R and ADRB1R genes to 10q24-q26. From studies by pulsed field gel electrophoresis, they concluded that the 2 genes are less than 225 kb apart. By linkage studies and interspecific backcrosses, Oakey et al. (1991) assigned the Adrb1r gene to the distal region of mouse chromosome 19. Molecular Genetics Mason et al. (1999) identified a nonsynonymous SNP (R389G; 109630.0001) in the ADRB1, which results in alterations of receptor-Gs interaction with functional consequences on signal transduction, consistent with its localization in a putative G-protein binding domain. Ranade et al. (2002) investigated the genetic determination of resting heart rate (607276) which had been found in several studies to show significant correlation with cardiovascular morbidity and mortality. Because signaling through the beta-1-adrenergic receptor is a key determinant of cardiac function, they tested whether polymorphisms in this receptor are associated with resting heart rate. They studied a cohort of more than 1,000 individuals of Chinese and Japanese descent, from nuclear families, and genotyped 2 polymorphisms: ser49 to gly (S49G; 109630.0002) and R389G in the ADRB1 gene. For comparison, polymorphisms in the beta-2- and beta-3-adrenergic receptors (109690; 109691) were also evaluated. The S49G polymorphism was significantly associated (P = 0.0004) with resting heart rate, independent of other variables, such as body-mass index, age, sex, ethnicity, exercise, smoking, alcohol intake, hypertension status, and treatment with beta blockers. The data supported a tentative model in which individuals heterozygous for the S49G polymorphism had mean heart rates intermediate to those of either type of homozygote, with Ser homozygotes having the highest mean heart rate and with Gly homozygotes having the lowest. Neither the R389G polymorphism in the ADRB1 gene nor polymorphisms in the ADRB2 and ADRB3 genes were associated with resting heart rate. The heritability of heart rate was 39.7% +/- 7.1%. Sustained cardiac adrenergic stimulation has been implicated in the development and progression of heart failure. Release of norepinephrine is controlled by negative feedback from presynaptic alpha-2-adrenergic receptors, and the targets of the released norepinephrine on myocytes are beta-1-adrenergic receptors. In transfected cells, the R389G variant of the beta-1-adrenergic receptor has increased function, and a polymorphic alpha-2C-adrenergic receptor, del322-325 (104250.0001), has decreased function. Small et al. (2002) hypothesized that this combination of receptor variants, which results in increased synaptic norepinephrine release and enhanced receptor function at the myocyte, would predispose persons to heart failure. Genotyping at these loci was performed in 159 patients with heart failure and 189 controls. Among black subjects, the adjusted odds ratio for heart failure among persons who were homozygous for del322-325 as compared with those with the other ADRA2C phenotypes was 5.65. There was no increase in risk for ADRB1 arg389 alone. However, there was a marked increase in the risk of heart failure among persons who were homozygous for both variants (adjusted odds ratio, 10.11). The patients with heart failure did not differ from the controls in the frequencies of 9 short tandem repeat alleles. Among white subjects, there were too few who were homozygous for both polymorphisms to allow an adequate assessment of risk. Small et al. (2002) suggested that genotyping at these 2 loci may be a useful approach for identifying persons at risk for heart failure or its progression who may be candidates for early preventive measures. Iwai et al. (2002) studied allele and genotype frequencies of the R389G polymorphism and clinical characteristics of 163 Japanese patients with dilated cardiomyopathy and 157 controls. They found that the gly389 allele was associated with a decreased risk of ventricular tachycardia (OR, 0.29 in patients carrying 1 or 2 copies of the gly389 allele; 95% CI, 0.13-0.64; p = 0.002). In a cohort of 931 Caucasian women, Dionne et al. (2002) found that the arg389 allele of ADRB1 was associated with greater body weight and BMI, with each arg389 allele being associated with a 2.91 kg greater body weight (p = 0.01) and a 0.86 kg greater BMI (p = 0.05). In a subset of 214 women who underwent fuller characterization, the authors found that each arg389 allele was associated with greater fat mass (3.71 kg; p = 0.008). In a study of 54 patients with congestive heart failure treated with the beta-blocker metoprolol, Lobmeyer et al. (2007) found that the ADRB1 R389G and the del322-325 ADRA2C polymorphisms synergistically influenced the ejection fraction response to beta-blocker therapy. Evolution Cagliani et al. (2009) analyzed the recent evolutionary history of the ADRB genes in humans, with particular concern to selective patterns. Their data suggested neutral selection for the ADRB1 gene, but deviations from neutrality for the ADRB2 and ADRB3 genes. Animal Model Rohrer et al. (1999) found that mice lacking both Adrb1 and Adrb2 had normal basal heart rate, blood pressure, and metabolic rate. However, stimulation with beta-receptor agonists or exercise revealed significant impairment in chronotropic range, vascular reactivity, and metabolic rate; maximal exercise capacity was not affected. Beta-receptor stimulation of cardiac inotropy and chronotropy was mediated almost exclusively by Adrb1, whereas vascular relaxation and metabolic rate were controlled by all 3 beta receptors. Compensatory alterations in cardiac muscarinic receptor density and vascular Adrb3 responsiveness were also observed in Adrb1/Adrb2 double-knockout mice. To determine whether the sympathetic nervous system is the efferent arm of diet-induced thermogenesis, Bachman et al. (2002) created mice that lacked the beta-adrenergic receptors ADRB1, ADRB2, and ADRB3. Beta-less mice on a chow diet had a reduced metabolic rate and were slightly obese. On a high-fat diet, beta-less mice, in contrast to wildtype mice, developed massive obesity that was due entirely to a failure of diet-induced thermogenesis. Bachman et al. (2002) concluded that the beta-adrenergic receptors are necessary for diet-induced thermogenesis and that this efferent pathway plays a critical role in the body's defense against diet-induced obesity. Mialet Perez et al. (2003) reported the targeted transgenic overexpression of beta-1 adrenergic receptor carrying the arg389 or the gly389 variant (109630.0001) in mouse ventricles, revealing an allele-specific cardiac phenotype that was recapitulated in human heart failure. Hearts from young arg389 mice had enhanced receptor function and contractility compared with gly389 hearts. Older arg389 mice displayed a phenotypic switch, with decreased beta-agonist signaling to adenylyl cyclase and decreased cardiac contractility compared with gly389 hearts. Arg389 hearts had abnormal expression of fetal and hypertrophy genes and calcium-cycling proteins, decreased adenylyl cyclase and G-alpha-s expression, and fibrosis with heart failure. This phenotype was recapitulated in homozygous, end-stage, failing human hearts. In addition, hemodynamic responses to beta-receptor blockade were greater in arg389 mice, and homozygosity for arg389 was associated with improvement in ventricular function during carvedilol treatment in heart failure patients. Mialet Perez et al. (2003) concluded that the human arg389 variant predisposes to heart failure by instigating hyperactive signaling programs leading to depressed receptor coupling and ventricular dysfunction, and influences the therapeutic response to beta-receptor blockade. Jahns et al. (2004) gave monthly immunizations against the second extracellular beta-1-receptor loop to inbred rats, all of which developed receptor-stimulating anti-beta-1-receptor-loop antibodies and, after 9 months, progressive severe left ventricular dilatation and dysfunction. The authors transferred sera from antibody-positive and antibody-negative rats every month to healthy rats of the same strain. All rats that received the anti-beta-1-receptor-loop antibody also developed a similar cardiomyopathic phenotype within a similar time frame. Jahns et al. (2004) concluded that an autoimmune attack directed against the cardiac beta-1-adrenergic receptor may play a causal role in idiopathic dilated cardiomyopathy. [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-hydroxybutyric 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	BETA-1-ADRENERGIC RECEPTOR	c2676080	24,626	omim	https://www.omim.org/entry/109630	2019-09-22T16:44:28	{"omim": ["109630"], "synonyms": ["Alternative titles", "ADRB1R", "B1AR"]}
Naevus flammeus nuchae Other namesStork bite or Nevus simplex SpecialtyDermatology Naevus flammeus nuchae, or colloquially stork bite, is a congenital capillary malformation present in newborns. It is a common type of birthmark in a newborn.[1] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 Outlook * 5 See also * 6 References * 7 External links ## Signs and symptoms[edit] Stork bites occur in a significant number of newborns, with estimates ranging from 22–40 percent[2] to 40–70 percent;[3] they are reported more frequently for white babies than for infants of other races.[2] They result from a dilation of capillaries in the skin,[3] and may become darker when the child cries or strains.[4] The birthmarks, which are pinkish and irregularly shaped, occur most frequently on the nape of the neck; however, they are also common on the forehead, eyelids and upper lip.[2] A baby may be born with a stork bite, or the birthmark may appear in the first months of life. They may also be found occasionally on other parts of the body. The skin is not thickened and feels no different from anywhere else on the body; the only difference is in appearance.[citation needed] ## Diagnosis[edit] A doctor can diagnose a stork bite with a simple visual inspection. No tests are needed.[citation needed] ## Treatment[edit] No treatment is needed. If a stork bite lasts longer than 3 years, it may be removed using laser surgery.[citation needed] ## Outlook[edit] Most stork bites on the face go away completely in about 18 months. Stork bites on the back of the neck usually do not go away.[5] ## See also[edit] * Midline naevus flammeus, also known as an angel's kiss or a salmon patch. * Mongolian spot * Naevus flammeus, better known as a port-wine stain. * Skin lesion ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. Page 169. ISBN 0-7216-2921-0. 2. ^ a b c Fletcher, Mary Ann (1998). Physical Diagnosis in Neonatals. Philadelphia, PA, US: Lippincott-Raven. p. 151. ISBN 978-0-397-51386-4. 3. ^ a b Habif, Thomas P. (2016). Clinical Dermatology. Amsterdam, Netherlands: Elsevier. p. 913. ISBN 978-0-323-26183-8. 4. ^ Zitelli, Basil John; McIntire, Sara C.; Nowalk, Andrew J. (2012). Zitelli and Davis' Atlas of Pediatric Physical Diagnosis (6 ed.). Philadelphia, PA, US: Elsevier Saunders. p. 351. ISBN 978-0-323-07932-7. 5. ^ MedlinePlus Encyclopedia: Stork bite ## External links[edit] Classification D * OMIM: 163100 * v * t * e Congenital malformations and deformations of integument / skin disease Genodermatosis Congenital ichthyosis/ erythrokeratodermia AD * Ichthyosis vulgaris AR * Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis * Lamellar ichthyosis * Harlequin-type ichthyosis * Netherton syndrome * Zunich–Kaye syndrome * Sjögren–Larsson syndrome XR * X-linked ichthyosis Ungrouped * Ichthyosis bullosa of Siemens * Ichthyosis follicularis * Ichthyosis prematurity syndrome * Ichthyosis–sclerosing cholangitis syndrome * Nonbullous congenital ichthyosiform erythroderma * Ichthyosis linearis circumflexa * Ichthyosis hystrix EB and related * EBS * EBS-K * EBS-WC * EBS-DM * EBS-OG * EBS-MD * EBS-MP * JEB * JEB-H * Mitis * Generalized atrophic * JEB-PA * DEB * DDEB * RDEB * related: Costello syndrome * Kindler syndrome * Laryngoonychocutaneous syndrome * Skin fragility syndrome Ectodermal dysplasia * Naegeli syndrome/Dermatopathia pigmentosa reticularis * Hay–Wells syndrome * Hypohidrotic ectodermal dysplasia * Focal dermal hypoplasia * Ellis–van Creveld syndrome * Rapp–Hodgkin syndrome/Hay–Wells syndrome Elastic/Connective * Ehlers–Danlos syndromes * Cutis laxa (Gerodermia osteodysplastica) * Popliteal pterygium syndrome * Pseudoxanthoma elasticum * Van der Woude syndrome Hyperkeratosis/ keratinopathy PPK * diffuse: Diffuse epidermolytic palmoplantar keratoderma * Diffuse nonepidermolytic palmoplantar keratoderma * Palmoplantar keratoderma of Sybert * Meleda disease * syndromic * connexin * Bart–Pumphrey syndrome * Clouston's hidrotic ectodermal dysplasia * Vohwinkel syndrome * Corneodermatoosseous syndrome * plakoglobin * Naxos syndrome * Scleroatrophic syndrome of Huriez * Olmsted syndrome * Cathepsin C * Papillon–Lefèvre syndrome * Haim–Munk syndrome * Camisa disease * focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis * Focal palmoplantar and gingival keratosis * Howel–Evans syndrome * Pachyonychia congenita * Pachyonychia congenita type I * Pachyonychia congenita type II * Striate palmoplantar keratoderma * Tyrosinemia type II * punctate: Acrokeratoelastoidosis of Costa * Focal acral hyperkeratosis * Keratosis punctata palmaris et plantaris * Keratosis punctata of the palmar creases * Schöpf–Schulz–Passarge syndrome * Porokeratosis plantaris discreta * Spiny keratoderma * ungrouped: Palmoplantar keratoderma and spastic paraplegia * desmoplakin * Carvajal syndrome * connexin * Erythrokeratodermia variabilis * HID/KID Other * Meleda disease * Keratosis pilaris * ATP2A2 * Darier's disease * Dyskeratosis congenita * Lelis syndrome * Dyskeratosis congenita * Keratolytic winter erythema * Keratosis follicularis spinulosa decalvans * Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome * Keratosis pilaris atrophicans faciei * Keratosis pilaris Other * cadherin * EEM syndrome * immune system * Hereditary lymphedema * Mastocytosis/Urticaria pigmentosa * Hailey–Hailey see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder Developmental anomalies Midline * Dermoid cyst * Encephalocele * Nasal glioma * PHACE association * Sinus pericranii Nevus * Capillary hemangioma * Port-wine stain * Nevus flammeus nuchae Other/ungrouped * Aplasia cutis congenita * Amniotic band syndrome * Branchial cyst * Cavernous venous malformation * Accessory nail of the fifth toe * Bronchogenic cyst * Congenital cartilaginous rest of the neck * Congenital hypertrophy of the lateral fold of the hallux * Congenital lip pit * Congenital malformations of the dermatoglyphs * Congenital preauricular fistula * Congenital smooth muscle hamartoma * Cystic lymphatic malformation * Median raphe cyst * Melanotic neuroectodermal tumor of infancy * Mongolian spot * Nasolacrimal duct cyst * Omphalomesenteric duct cyst * Poland anomaly * Rapidly involuting congenital hemangioma * Rosenthal–Kloepfer syndrome * Skin dimple * Superficial lymphatic malformation * Thyroglossal duct cyst * Verrucous vascular malformation * Birthmark [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-hydroxybutyric 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	Nevus flammeus nuchae	c4024829	24,627	wikipedia	https://en.wikipedia.org/wiki/Nevus_flammeus_nuchae	2021-01-18T18:50:26	{"wikidata": ["Q1419862"]}
A number sign (#) is used with this entry because of evidence that diaphanospondylodysostosis is caused by homozygous or compound heterozygous mutation in the BMPER gene (608699) on chromosome 7p14. Description Diaphanospondylodysostosis is a rare, recessively inherited, perinatal lethal skeletal disorder. The primary skeletal characteristics include small chest, abnormal vertebral segmentation, and posterior rib gaps containing incompletely differentiated mesenchymal tissue. Consistent craniofacial features include ocular hypertelorism, epicanthal folds, depressed nasal bridge with short nose, and low-set ears. The most commonly described extraskeletal finding is nephroblastomatosis with cystic kidneys, but other visceral findings have been described in some cases (summary by Funari et al., 2010). Clinical Features Prefumo et al. (2003) described 3 sibs, born to nonconsanguineous parents, with absent intrauterine ossification of the spinal column, rib abnormalities with unossified segments and posterior gaps, thoracic hypoplasia, and multiple intralobar nephrogenic rests in the kidneys. Whole body roentgenograms showed complete absence of ossification of the vertebral bodies throughout the spine and no ossification of the vertebral pedicles below the thoracic region. Autopsy revealed a normal spinal column in the lumbar and sacral regions that were cartilaginous and unossified. First trimester fetal nuchal translucency was measured in 2 of the pregnancies. Prefumo et al. (2003) proposed autosomal recessive inheritance since both sexes were affected. They also suggested that the dizygotic twins reported by Nisbet et al. (1999) may have had the same disorder. Gonzales et al. (2005) reported 4 patients from 3 families with similar radiologic findings comprising absent or severely delayed ossification of vertebral bodies. Other manifestations included a short neck, short and wide thorax, normally shaped limbs, hypoplastic nails, and nephroblastomatosis. The babies were stillborn or died soon after birth of respiratory insufficiency. One of the patients had previously been described by Maroteaux and Le Merrer (2002). Two patients were sibs born to consanguineous Malian parents. Gonzales et al. (2005) proposed to name this lethal autosomal recessive syndrome diaphanospondylodysostosis. Vatanavicharn et al. (2007) reported 6 additional patients from 4 families with diaphanospondylodysostosis. Typical facial features included hypertelorism, a short nose, depressed nasal bridge, low-set ears, and webbed neck. Other congenital anomalies in their patients were polymicrogyria, and trilobed liver. The majority of cases died in the neonatal period of respiratory insufficiency. One male patient was alive at 9 months of age with severe developmental delay and generalized hypotonia. Characteristic radiographic findings included unossified vertebral bodies below the T12 level to the sacrum, posterior rib gaps, missing ribs, and downward tilting pubic rami. The skull and long bones were normal. Histology of the rib gaps revealed cartilage interrupted by fasicles of skeletal muscle and dense fibrous tissue and patchy areas of skeletal ossification. Molecular analysis of PAX1 (167411) and MEOX1 (600147) exons and flanking intronic sequences excluded these 2 candidate genes. Mapping Funari et al. (2010) tested DNA samples from 4 unrelated cases of diaphanospondylodysostosis for autozygosity using whole-genome SNP data and identified 1 case in which there were 2 blocks of homozygosity larger than 5 Mbps that were not shared with an unaffected sib, on chromosomes 1 and 7, respectively. The 2 regions contained 35 Mb and comprised 166 known genes. Molecular Genetics Using a targeted capture-and-resequencing approach on DNA from a proband with diaphanospondylodysostosis, in whom 2 autozygous intervals had been found on chromosomes 1 and 7, Funari et al. (2010) identified homozygosity for a nonsense mutation in the BMPER gene (Q309X; 608699.0001) within the region of homozygosity on chromosome 7. Homozygosity was confirmed by Sanger sequencing in the proband, and both unaffected parents and an unaffected sib were heterozygous carriers of the mutation. Analysis of the BMPER gene in 3 additional unrelated probands with diaphanospondylodysostosis revealed compound heterozygosity for a deletion/insertion mutation and a splice site mutation in 1 proband (608699.0002 and 608699.0003, respectively) and for a missense (608699.0004) and a nonsense mutation (C546X; 608699.0005) in another proband. In the third proband, only a single nonsense mutation (Q172X) was found, suggesting that the other allele either resulted in a deletion or did not reside within the coding region. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation HEAD & NECK Head \- Large fontanelles Face \- Micrognathia Ears \- Low-set ears Eyes \- Hypertelorism \- Epicanthal folds Nose \- Flat nose \- Short nose \- Depressed nasal bridge Mouth \- Cleft palate Neck \- Short neck \- Webbed neck RESPIRATORY \- Respiratory distress/insufficiency Airways \- Tracheomalacia Lung \- Hypoplastic lungs CHEST External Features \- Bell-shaped thorax \- Short trunk \- Thoracic hypoplasia Ribs Sternum Clavicles & Scapulae \- Absent in utero rib ossification \- Posterior gaps in ribs \- Missing ribs \- Ribbon-like ribs ABDOMEN External Features \- Protuberant abdomen Liver \- Trilobed liver GENITOURINARY External Genitalia (Male) \- Inguinal hernia Kidneys \- Intralobular nephrogenic rests \- Cystic renal dysplasia \- Enlarged kidneys \- Nephroblastomatosis SKELETAL Spine \- Vertebral segmentation defects \- Zipper-like pedicles \- Delayed ossification of pedicles \- Unossified sacrum \- Unossified vertebral bodies (below level of T12) \- Absent in utero ossification of vertebral bodies \- Absent in utero ossification of pedicles Pelvis \- Downward tilt of pubic rami \- Narrow pelvis Hands \- Hypoplastic fingernails Feet \- Clubfeet \- Hammer toe SKIN, NAILS, & HAIR Nails \- Hypoplastic fingernails NEUROLOGIC Central Nervous System \- Polymicrogyria \- Hypotonia \- Developmental delay \- Lumbosacral meningocele PRENATAL MANIFESTATIONS \- Nuchal translucency Amniotic Fluid \- Oligohydramnios MISCELLANEOUS \- Majority of patients die in neonatal period secondary to respiratory insufficiency MOLECULAR BASIS \- Caused by mutation in the BMP binding endothelial regulator gene (BMPER, 608699.0001 ) ▲ 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-hydroxybutyric 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	DIAPHANOSPONDYLODYSOSTOSIS	c1842691	24,628	omim	https://www.omim.org/entry/608022	2019-09-22T16:08:28	{"mesh": ["C564305"], "omim": ["608022"], "orphanet": ["66637"], "synonyms": ["Alternative titles", "VERTEBRAL OSSIFICATION, DEFECT IN, WITH NEPHROGENIC RESTS"]}
A rare genetic disease characterized by sparse scalp hair, lateral thinning of eyebrows, mild facial dysmorphism (bulbous tip of the nose, long flat philtrum, thin upper lip vermilion, and protruding ears), and skeletal anomalies including cone-shaped phalangeal epiphyses, hip dysplasia, and short stature. Type 3 can be differentiated by the presence of severe brachydactyly due to short metacarpals. Cartilaginous exostoses are not present in both types. [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-hydroxybutyric 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	Trichorhinophalangeal syndrome type 1 and 3	c0432233	24,629	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=77258	2021-01-23T17:22:23	{"mesh": ["C536820"], "omim": ["190350", "190351"], "icd-10": ["Q87.1"]}
Pretibial epidermolysis bullosa is a rare form of epidermolysis bullosa, a condition characterized by fragile skin that blisters easily in response to minor injury or friction. In the pretibial form, specifically, the characteristic blisters and skin erosions develop predominantly on the front of the lower legs (known as the "pretibial region"). In some affected people, the feet, hands and/or nails may also be affected. Healing of the blisters is generally associated with hypertrophic scarring. Pretibial epidermolysis bullosa is caused by changes (mutations) in the COL7A1 gene and can be inherited in an autosomal dominant or autosomal recessive manner. Treatment is 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-hydroxybutyric 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	Pretibial epidermolysis bullosa	c0432321	24,630	gard	https://rarediseases.info.nih.gov/diseases/2155/pretibial-epidermolysis-bullosa	2021-01-18T17:58:12	{"mesh": ["C535494"], "omim": ["131850"], "umls": ["C0432321"], "orphanet": ["79410"], "synonyms": ["DEB-Pt", "Pretibial DEB", "Pretibial dystrophic epidermolysis bullosa"]}
Perception of sound within the human ear ("ringing of the ears") when no external sound is present For the Norwegian radio show, see Tinitus (radio show). Tinnitus Tinnitus often results in the perception of ringing Pronunciation * /ˈtɪnɪtəs/ or /tɪˈnaɪtəs/ SpecialtyOtorhinolaryngology, audiology SymptomsHearing sound when no external sound is present[1] ComplicationsPoor concentration, anxiety, depression[2] Usual onsetGradual[3] CausesNoise-induced hearing loss, ear infections, disease of the heart or blood vessels, Ménière's disease, brain tumors, inner ear tumors, emotional stress, traumatic brain injury, excessive earwax[2][4] Diagnostic methodBased on symptoms, audiogram, neurological exam[1][3] TreatmentCounseling, sound generators, hearing aids[2][5] Frequency~12.5%[5] Tinnitus is the perception of sound when no corresponding external sound is present.[1] While often described as a ringing, it may also sound like a clicking, buzzing, hiss, or roaring.[2] The sound may be soft or loud, low or high pitched, and often appears to be coming from one or both ears or from the head itself.[2] In some people, the sound may interfere with concentration and in some cases it is associated with anxiety and depression.[2] Tinnitus is usually associated with some degree of hearing loss and with decreased understanding in noise.[2] It is common, affecting about 10–15% of people.[5] Most, however, tolerate it well, and it is a significant problem in only 1–2% of people.[5] The word tinnitus comes from the Latin tinnire which means "to ring".[3] ## Contents * 1 Signs and symptoms * 1.1 Course * 1.2 Psychological effects * 2 Types * 2.1 Subjective tinnitus * 2.1.1 Hearing loss * 2.1.2 Associated factors * 2.2 Objective tinnitus * 2.3 Pulsatile tinnitus * 3 Pathophysiology * 4 Diagnosis * 4.1 Audiology * 4.2 Psychoacoustics * 4.3 Severity * 4.4 Pulsatile tinnitus * 4.5 Differential diagnosis * 5 Prevention * 6 Management * 6.1 Psychological * 6.2 Sound-based interventions * 6.3 Medications * 6.4 Bimodal neuromodulation * 6.5 Other * 6.6 Alternative medicine * 7 Prognosis * 8 Epidemiology * 8.1 Adults * 8.2 Children * 9 See also * 10 References * 11 External links Rather than a disease, tinnitus is a symptom that may result from various underlying causes and can may be generated at any level of the auditory system and structures beyond that system.[2] The most common causes are hearing damage, noise-induced hearing loss or age-related hearing loss, known as presbycusis.[2] Other causes include ear infections, disease of the heart or blood vessels, Ménière's disease, brain tumors, exposure to certain medications, a previous head injury, earwax, and sometimes, the tinnitus is suddenly perceived during a period of emotional stress.[2][4] It is more common in those with depression.[3] The diagnosis of tinnitus is usually based on the person's description.[3] It is commonly supported by an audiogram, an otolaryngological and a neurological examination.[1][3] The degree of interference with a person's life may be quantified with questionnaires.[3] If certain problems are found, medical imaging, such as magnetic resonance imaging (MRI), may be performed.[3] Other tests are suitable when tinnitus occurs with the same rhythm as the heartbeat.[3] Rarely, the sound may be heard by someone else using a stethoscope, in which case it is known as objective tinnitus.[3] Occasionally, spontaneous otoacoustic emissions, sounds produced normally by the inner ear, may result in tinnitus.[6] Prevention involves avoiding exposure to loud noise for longer periods or chronically.[2] If there is an underlying cause, treating it may lead to improvements.[3] Otherwise, typically, management involves psychoeducation or counseling as talk therapy.[5] Sound generators or hearing aids may help some.[2] However, there is no medication existing which can target the tinnitus directly. ## Signs and symptoms Tinnitus may be perceived in various locations, more commonly in one or both ears [7] or more central in the head. The noise can be described in many different ways but is reported as a noise inside a person's head or ear(s) in the absence of auditory stimulation. It often is described as a ringing noise, but in some people, it takes the form of a high-pitched whining, electric buzzing, hissing, humming, tinging, whistling, ticking, clicking, roaring, beeping, sizzling, a pure steady tone such as that heard during a hearing test, or sounds that slightly resemble human voices, tunes, songs, or animal sounds such as "crickets", "tree frogs", or "locusts (cicadas)".[4] Tinnitus may be intermittent or continuous: in the latter case, it may be the cause of great distress. In some individuals, the intensity may be changed by shoulder, neck, head, tongue, jaw, or eye movements,[8] also tinnitus loudness can vary between patients. The sound perceived may range from a quiet background noise to one that even is heard over loud external sounds. The specific type of tinnitus called objective tinnitus is characterized by hearing the sounds of one's own muscle contractions or pulse, which is typically a result of sounds that have been created by the movement of muscles near to one's ear, or sounds related to blood flow in the neck or face.[9] ### Course Due to variations in study designs, data on the course of tinnitus showed few consistent results. Generally, the prevalence increased with age in adults, whereas the ratings of annoyance decreased with duration.[10][11][12] ### Psychological effects Besides being an annoying condition to which most people adapt, persistent tinnitus may cause anxiety and depression in some people.[13][14] Tinnitus annoyance is more strongly associated with the psychological condition of the person than the loudness or frequency range.[15][16] Psychological problems such as depression, anxiety, sleep disturbances, and concentration difficulties are common in those with strongly annoying tinnitus.[17][18] 45% of people with tinnitus have an anxiety disorder at some time in their life.[19] Psychological research has focussed on the tinnitus distress reaction (TDR) to account for differences in tinnitus severity.[17][20][21][22] These findings suggest that among those people, conditioning at the initial perception of tinnitus, linked tinnitus with negative emotions, such as fear and anxiety from unpleasant stimuli at the time. This enhances activity in the limbic system and autonomic nervous system, thus increasing tinnitus awareness and annoyance.[23] ## Types A common tinnitus classification is into "subjective and objective tinnitus".[3] Tinnitus is usually subjective, meaning that the sounds the person hears are not detectable by means currently available to physicians and hearing technicians.[3] Subjective tinnitus has also been called "tinnitus aurium", "non-auditory" or "non-vibratory" tinnitus. In rare cases, tinnitus can be heard by someone else using a stethoscope. Even more rarely, in some cases it can be measured as a spontaneous otoacoustic emission (SOAE) in the ear canal. This is classified as objective tinnitus,[3] also called "pseudo-tinnitus" or "vibratory" tinnitus. ### Subjective tinnitus Subjective tinnitus is the most frequent type of tinnitus. It may have many possible causes, but most commonly it results from hearing loss. When the tinnitus is caused by disorders of the inner ear or auditory nerve it can be called otic (from the Greek word for ear).[24] These otological or neurological conditions include those triggered by infections, drugs, or trauma.[25] A frequent cause is traumatic noise exposure that damages hair cells in the inner ear.[citation needed] When there does not seem to be a connection with a disorder of the inner ear or auditory nerve, the tinnitus can be called non-otic. (i.e. not otic). In some 30% of tinnitus cases, the tinnitus is influenced by the somatosensory system, for instance, people can increase or decrease their tinnitus by moving their face, head, or neck.[26] This type is called somatic or craniocervical tinnitus, since it is only head or neck movements that have an effect.[24] There is a growing body of evidence suggesting that some tinnitus is a consequence of neuroplastic alterations in the central auditory pathway. These alterations are assumed to result from a disturbed sensory input, caused by hearing loss.[27] Hearing loss could indeed cause a homeostatic response of neurons in the central auditory system, and therefore cause tinnitus.[28] #### Hearing loss The most common cause of tinnitus is hearing loss. Hearing loss may have many different causes, but among those with tinnitus, the major cause is cochlear injury.[27] Ototoxic drugs also may cause subjective tinnitus, as they may cause hearing loss, or increase the damage done by exposure to loud noise. Those damages may occur even at doses that are not considered ototoxic.[29] More than 260 medications have been reported to cause tinnitus as a side effect.[30] In many cases, however, no underlying cause could be identified.[2] Tinnitus can also occur due to the discontinuation of therapeutic doses of benzodiazepines. It can sometimes be a protracted symptom of benzodiazepine withdrawal and may persist for many months.[31][32] Medications such as bupropion may also result in tinnitus.[33] In many cases, however, no underlying cause can be identified.[34] #### Associated factors Factors associated with tinnitus include:[35] * ear problems and hearing loss: * conductive hearing loss * acoustic shock * loud noise or music[36] * middle ear effusion * otitis * otosclerosis * Eustachian tube dysfunction * sensorineural hearing loss * excessive or loud noise; e.g. acoustic trauma * presbycusis (age-associated hearing loss) * Ménière's disease * endolymphatic hydrops * superior canal dehiscence * acoustic neuroma * mercury or lead poisoning * ototoxic medications * neurologic disorders: * Arnold–Chiari malformation * multiple sclerosis * head injury * giant cell arteritis * temporomandibular joint dysfunction * metabolic disorders: * vitamin B12 deficiency[37] * iron deficiency anemia * psychiatric disorders * depression * anxiety disorders * other factors: * vasculitis * Some psychedelic drugs can produce temporary tinnitus-like symptoms as a side effect * 5-MeO-DET[38] * diisopropyltryptamine (DiPT)[39] * benzodiazepine withdrawal[31][32] * intracranial hyper or hypotension caused by, for example, encephalitis or a cerebrospinal fluid leak ### Objective tinnitus Objective tinnitus can be detected by other people and is sometimes caused by an involuntary twitching of a muscle or a group of muscles (myoclonus) or by a vascular condition. In some cases, tinnitus is generated by muscle spasms around the middle ear.[9] Spontaneous otoacoustic emissions (SOAEs), which are faint high-frequency tones that are produced in the inner ear and can be measured in the ear canal with a sensitive microphone, may also cause tinnitus.[6] About 8% of those with SOAEs and tinnitus have SOAE-linked tinnitus,[need quotation to verify] while the percentage of all cases of tinnitus caused by SOAEs is estimated at about 4%.[6] ### Pulsatile tinnitus Some people experience a sound that beats in time with their pulse, known as pulsatile tinnitus or vascular tinnitus.[40] Pulsatile tinnitus is usually objective in nature, resulting from altered blood flow, increased blood turbulence near the ear, such as from atherosclerosis or venous hum,[41] but it can also arise as a subjective phenomenon from an increased awareness of blood flow in the ear.[40] Rarely, pulsatile tinnitus may be a symptom of potentially life-threatening conditions such as carotid artery aneurysm[42] or carotid artery dissection.[43] Pulsatile tinnitus may also indicate vasculitis, or more specifically, giant cell arteritis. Pulsatile tinnitus may also be an indication of idiopathic intracranial hypertension.[44] Pulsatile tinnitus can be a symptom of intracranial vascular abnormalities and should be evaluated for irregular noises of blood flow (bruits).[45] ## Pathophysiology It may be caused by increased neural activity in the auditory brainstem, where the brain processes sounds, causing some auditory nerve cells to become over-excited. The basis of this theory is that many with tinnitus also have hearing loss.[46] Three reviews of 2016 emphasized the large range and possible combinations of pathologies involved in tinnitus, which in turn result in a great variety of symptoms demanding specifically adapted therapies.[47][48][49][50] ## Diagnosis The diagnostic approach is based on a history of the condition and an examination of the head, neck, and neurological system.[34] Typically an audiogram is done, and occasionally medical imaging or electronystagmography.[34] Treatable conditions may include middle ear infection, acoustic neuroma, concussion, and otosclerosis.[51] Evaluation of tinnitus can include a hearing test (audiogram), measurement of acoustic parameters of the tinnitus like pitch and loudness, and psychological assessment of comorbid conditions like depression, anxiety, and stress that are associated with severity of the tinnitus.[citation needed] One definition of tinnitus, as compared to normal ear noise experience, is lasting five minutes at least twice a week.[52] However, people with tinnitus often experience the noise more frequently than this. Tinnitus can be present constantly or intermittently. Some people with constant tinnitus might not be aware of it all the time, but only for example during the night when there is less environmental noise to mask it. Chronic tinnitus can be defined as tinnitus with duration of six months or more.[53] ### Audiology Since most persons with tinnitus also have hearing loss, a pure tone hearing test resulting in an audiogram may help diagnose a cause, though some persons with tinnitus do not have hearing loss. An audiogram may also facilitate fitting of a hearing aid in those cases where hearing loss is significant. The pitch of tinnitus is often in the range of the hearing loss. ### Psychoacoustics Acoustic qualification of tinnitus will include measurement of several acoustic parameters like frequency in cases of monotone tinnitus or frequency range and bandwidth in cases of narrow band noise tinnitus, loudness in dB above hearing threshold at the indicated frequency, mixing-point, and minimum masking level.[54] In most cases, tinnitus pitch or frequency range is between 5 kHz and 10 kHz,[55] and loudness between 5 and 15 dB above the hearing threshold.[56] Another relevant parameter of tinnitus is residual inhibition, the temporary suppression or disappearance of tinnitus following a period of masking. The degree of residual inhibition may indicate how effective tinnitus maskers would be as a treatment modality.[57][58] An assessment of hyperacusis, a frequent accompaniment of tinnitus,[59] may also be made.[60] Hyperacusis is related to negative reactions to sound and can take many forms. One associated parameter that can be measured is Loudness Discomfort Level (LDL) in dB, the subjective level of acute discomfort at specified frequencies over the frequency range of hearing. This defines a dynamic range between the hearing threshold at that frequency and the loudness discomfort level. A compressed dynamic range over a particular frequency range can be associated with hyperacusis. Normal hearing threshold is generally defined as 0–20 decibels (dB). Normal loudness discomfort levels are 85–90+ dB, with some authorities citing 100 dB. A dynamic range of 55 dB or less is indicative of hyperacusis.[61][62] ### Severity The condition is often rated on a scale from "slight" to "severe" according to the effects it has, such as interference with sleep, quiet activities and normal daily activities.[63] Assessment of psychological processes related to tinnitus involves measurement of tinnitus severity and distress (i.e., nature and extent of tinnitus-related problems), measured subjectively by validated self-report tinnitus questionnaires.[17] These questionnaires measure the degree of psychological distress and handicap associated with tinnitus, including effects on hearing, lifestyle, health and emotional functioning.[64][65][66] A broader assessment of general functioning, such as levels of anxiety, depression, stress, life stressors and sleep difficulties, is also important in the assessment of tinnitus due to higher risk of negative well-being across these areas, which may be affected by or exacerbate the tinnitus symptoms for the individual.[67] Overall, current assessment measures are aimed to identify individual levels of distress and interference, coping responses and perceptions of tinnitus in order to inform treatment and monitor progress. However, wide variability, inconsistencies and lack of consensus regarding assessment methodology are evidenced in the literature, limiting comparison of treatment effectiveness.[68] Developed to guide diagnosis or classify severity, most tinnitus questionnaires have been shown to be treatment-sensitive outcome measures.[69] ### Pulsatile tinnitus If the examination reveals a bruit (sound due to turbulent blood flow), imaging studies such as transcranial doppler (TCD) or magnetic resonance angiography (MRA) should be performed.[70][71][72] ### Differential diagnosis Other potential sources of the sounds normally associated with tinnitus should be ruled out. For instance, two recognized sources of high-pitched sounds might be electromagnetic fields common in modern wiring and various sound signal transmissions. A common and often misdiagnosed condition that mimics tinnitus is radio frequency (RF) hearing, in which subjects have been tested and found to hear high-pitched transmission frequencies that sound similar to tinnitus.[73][74] ## Prevention Safety sign from the UK Government Regulations requiring ear protection Prolonged exposure to loud sound or noise levels can lead to tinnitus.[75] Custom made ear plugs or other measures can help with prevention. Employers may use hearing loss prevention programs to help educate and prevent dangerous levels of exposure to noise. Government organizations set regulations to ensure employees, if following the protocol, should have minimal risk to permanent damage to their hearing.[76] Several medicines have ototoxic effects, and can have a cumulative effect that can increase the damage done by noise. If ototoxic medications must be administered, close attention by the physician to prescription details, such as dose and dosage interval, can reduce the damage done.[77][78][79] ## Management If a specific underlying cause is determined, treating it may lead to improvements.[3] Otherwise, the primary treatment for tinnitus is talk therapy,[5] sound therapy, or hearing aids. There are no effective medications or supplements that treat tinnitus.[3][80][81][82] ### Psychological The best supported treatment for tinnitus is a type of counseling called cognitive behavioral therapy (CBT) which can be delivered via the internet or in person.[5][69][83] It decreases the amount of stress those with tinnitus feel.[84] These benefits appear to be independent of any effect on depression or anxiety in an individual.[83] Acceptance and commitment therapy (ACT) also shows promise in the treatment of tinnitus.[85] Relaxation techniques may also be useful.[3] A clinical protocol called Progressive Tinnitus Management for treatment of tinnitus has been developed by the United States Department of Veterans Affairs.[86] There is some tentative evidence supporting tinnitus retraining therapy, which is aimed at reducing tinnitus-related neuronal activity.[citation needed] ### Sound-based interventions The use of sound therapy by either hearing aids or tinnitus maskers may help the brain ignore the specific tinnitus frequency, but these methods are poorly supported by evidence, there are no negative effects.[3][87][88] There are several approaches for tinnitus sound therapy. The first is sound modification to compensate for the individual's hearing loss. The second is a signal spectrum notching to eliminate energy close to the tinnitus frequency.[89][90] There is some tentative evidence supporting tinnitus retraining therapy, which is aimed at reducing tinnitus-related neuronal activity.[3][91][90] There are preliminary data on an alternative tinnitus treatment using mobile applications, including various methods: masking, sound therapy, relaxing exercises and other.[92][93] These applications can work as a separate device or as a hearing aid control system.[94] ### Medications As of 2018[update] there were no medications effective for idiopathic tinnitus.[3][75][95] There is not enough evidence to determine if antidepressants[96] or acamprosate are useful.[97] There is no high-quality evidence to support the use of benzodiazepines for tinnitus.[3][95][98] Usefulness of melatonin, as of 2015, is unclear.[99] It is unclear if anticonvulsants are useful for treating tinnitus.[3][100] Steroid injections into the middle ear also do not seem to be effective.[101][102] There is no evidence to suggest that the use of betahistine to treat tinnitus is effective.[103] Botulinum toxin injection has been tried with some success in some of the rare cases of objective tinnitus from a palatal tremor.[104] Caroverine is used in a few countries to treat tinnitus.[105] The evidence for its usefulness is very weak.[106] ### Bimodal neuromodulation In 2020, information about recent clinical trials has indicated that bimodal neuromodulation may be a promising treatment for reducing the symptoms of tinnitus. It is a noninvasive technique that involves the paring of an electrical stimulus to the tongue that is associated with sounds.[107] Equipment associated with the treatments is available through physicians. Studies with it and similar devices continue in several research centers.[citation needed] ### Other There is some evidence supporting neuromodulation techniques such as transcranial magnetic stimulation;[3][108] transcranial direct current stimulation and neurofeedback. However, the effects in terms of tinnitus relief are still under debate. ### Alternative medicine Ginkgo biloba does not appear to be effective.[95][109] The American Academy of Otolaryngology recommends against taking melatonin or zinc supplements to relieve symptoms of tinnitus, and reported that evidence for efficacy of many dietary supplements—lipoflavonoids, garlic, homeopathy, traditional Chinese/Korean herbal medicine, honeybee larvae, other various vitamins and minerals—did not exist.[75] A 2016 Cochrane Review also concluded that evidence was not sufficient to support taking zinc supplements to reduce symptoms associated with tinnitus.[110] ## Prognosis While there is no cure, most people with tinnitus get used to it over time; for a minority, it remains a significant problem.[5] ## Epidemiology ### Adults Tinnitus affects 10–15% of people.[5] About a third of North Americans over 55 experience tinnitus.[111] Tinnitus affects one third of adults at some time in their lives, whereas ten to fifteen percent are disturbed enough to seek medical evaluation.[112] ### Children Tinnitus is commonly thought of as a symptom of adulthood, and is often overlooked in children. Children with hearing loss have a high incidence of tinnitus, even though they do not express the condition or its effect on their lives.[113][114] Children do not generally report tinnitus spontaneously and their complaints may not be taken seriously.[115] Among those children who do complain of tinnitus, there is an increased likelihood of associated otological or neurological pathology such as migraine, juvenile Meniere's disease or chronic suppurative otitis media.[116] Its reported prevalence varies from 12% to 36% in children with normal hearing thresholds and up to 66% in children with a hearing loss and approximately 3–10% of children have been reported to be troubled by tinnitus.[117] ## See also * Medicine portal * Auditory hallucination * Health effects from noise * List of people with tinnitus * List of unexplained sounds * Phantom vibration syndrome * Zwicker tone ## References 1. ^ a b c d Levine, RA; Oron, Y (2015). "Tinnitus". The Human Auditory System – Fundamental Organization and Clinical Disorders. Handbook of Clinical Neurology. 129. pp. 409–31. doi:10.1016/B978-0-444-62630-1.00023-8. ISBN 9780444626301. PMID 25726282. 2. ^ a b c d e f g h i j k l m "Tinnitus". NIH – National Institute on Deafness and Other Communication Disorders (NIDCD). 6 March 2017. Archived from the original on 3 April 2019. Retrieved 20 September 2019. 3. ^ a b c d e f g h i j k l m n o p q r s t u v w Baguley, D; McFerran, D; Hall, D (Nov 9, 2013). "Tinnitus" (PDF). The Lancet. 382 (9904): 1600–07. doi:10.1016/S0140-6736(13)60142-7. PMID 23827090. Archived (PDF) from the original on 2018-04-11. 4. ^ a b c Han BI, Lee HW, Kim TY, Lim JS, Shin KS (March 2009). "Tinnitus: characteristics, causes, mechanisms, and treatments". Journal of Clinical Neurology. 5 (1): 11–19. doi:10.3988/jcn.2009.5.1.11. PMC 2686891. PMID 19513328. 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Archived (PDF) from the original on 2017-09-29. ## External links Wikimedia Commons has media related to Tinnitus. * Tinnitus at Curlie * Baguley, David; Andersson, Gerhard; McFerran, Don; McKenna, Laurence (2013) [2004]. Tinnitus: A Multidisciplinary Approach (2nd ed.). Indianapolis, IN: Wiley-Blackwell. ISBN 978-1405199896. LCCN 2012032714. OCLC 712915603. * Langguth, B; Hajak, G; Kleinjung, T; Cacace, A; Møller, AR, eds. (2007). Tinnitus: pathophysiology and treatment. Progress in brain research no. 166 (1st ed.). Amsterdam; Boston: Elsevier. ISBN 978-0444531674. LCCN 2012471552. OCLC 648331153. Archived from the original on 2007. Retrieved 5 November 2012. * Møller, Aage R; Langguth, Berthold; Ridder, Dirk; et al., eds. (2011). Textbook of Tinnitus. New York: Springer. doi:10.1007/978-1-60761-145-5. ISBN 978-1607611448. LCCN 2010934377. OCLC 695388693, 771366370, 724696022. (subscription required) Classification D * ICD-10: H93.1 * ICD-9-CM: 388.3 * MeSH: D014012 * DiseasesDB: 27662 External resources * MedlinePlus: 003043 * eMedicine: ent/235 * Patient UK: Tinnitus * v * t * e Diseases of the outer and middle ear Outer ear * Otitis externa * Otomycosis Middle ear and mastoid * Otitis media * Mastoiditis * Bezold's abscess * Gradenigo's syndrome * Tympanosclerosis * Cholesteatoma * Perforated eardrum Symptoms * Ear pain * Hearing loss Tests * Otoscope * pneumatic * tympanometry * v * t * e Occupational safety and health Occupational diseases and injuries * Acrodynia * Asbestosis * Asthma * Barotrauma * Berylliosis * Brucellosis * Byssinosis ("brown lung") * Chalicosis * Chimney sweeps' carcinoma * Chronic solvent-induced encephalopathy * Coalworker's pneumoconiosis ("black lung") * Concussions in sport * Decompression sickness * De Quervain syndrome * Erethism * Exposure to human nail dust * Farmer's lung * Fiddler's neck * Flock worker's lung * Glassblower's cataract * Golfer's elbow * Hearing loss * Hospital-acquired infection * Indium lung * Laboratory animal allergy * Lead poisoning * Mesothelioma * Metal fume fever * Mule spinners' cancer * Noise-induced hearing loss * Phossy jaw * Pneumoconiosis * Radium jaw * Repetitive strain injury * Silicosis * Silo-filler's disease * Sports injury * Surfer's ear * Tennis elbow * Tinnitus * Writer's cramp Occupational hygiene * Occupational hazard * Biological hazard * Chemical hazard * Physical hazard * Psychosocial hazard * Hierarchy of hazard controls * Prevention through design * Exposure assessment * Occupational exposure limit * Occupational epidemiology * Workplace health surveillance Professions * Environmental health * Industrial engineering * Occupational health nursing * Occupational health psychology * Occupational medicine * Occupational therapist * Safety engineering Agencies and organizations * Canadian Centre for Occupational Health and Safety * European Agency for 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also * Environment, health and safety * Environmental toxicology * Ergonomics * Health physics * Indoor air quality * International Chemical Safety Card * National Day of Mourning (Canadian observance) * Process safety management * Public health * Risk management * Safety data sheet * Toxic tort * Workers' compensation * Category * Occupational diseases * Journals * Organizations * Commons * Glossary Authority control * BNF: cb12046073x (data) * GND: 4121423-7 * LCCN: sh85135532 * NDL: 00574754 [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-hydroxybutyric 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	Tinnitus	c0040264	24,631	wikipedia	https://en.wikipedia.org/wiki/Tinnitus	2021-01-18T18:55:48	{"mesh": ["D014012"], "umls": ["C0040264"], "icd-9": ["388.3"], "icd-10": ["H93.1"], "wikidata": ["Q192309"]}
A rare neurologic disease characterized by spastic paraparesis presenting in late childhood and hearing loss. Additional features may include retinal anomalies, lenticular opacities, short stature, hypogonadism, sensory deficits, tremor, dysdiochokinesia, elevated cerebrospinal fluid protein, and absent or prolonged somatosensory evoked potentials. Plasma and fibroblast levels of saturated very long-chain fatty acids are normal. There have been no further descriptions in the literature since 1986. [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-hydroxybutyric 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	Spastic paraparesis-deafness syndrome	c2931291	24,632	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2815	2021-01-23T17:02:54	{"gard": ["5555"], "mesh": ["C536692"], "omim": ["312910"], "umls": ["C2931291"], "icd-10": ["G11.4"], "synonyms": ["Spastic paraparesis-hearing loss syndrome", "Wells-Jankovic syndrome"]}
A number sign (#) is used with this entry because neurohypophyseal diabetes insipidus is caused by heterozygous mutation in the arginine vasopressin gene (AVP; 192340) on chromosome 20p13. An X-linked form of neurohypophyseal diabetes insipidus (304900) has been suggested, but the evidence is weak. Description Neurohypophyseal diabetes insipidus is an autosomal dominant disorder of free water conservation characterized by childhood onset of polyuria and polydipsia. Affected individuals are apparently normal at birth, but characteristically develop symptoms of vasopressin deficiency during childhood (summary by Wahlstrom et al., 2004). Clinical Features Normally the posterior pituitary hormones, antidiuretic hormone and oxytocin, are synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and transported within axons, possibly in a biologically inactive, bound form, to the posterior lobe of the pituitary where they are stored. One of the most dramatic examples of familial diabetes insipidus is that reported by Adolph Weil (1884) of Heidelberg and his son Alfred Weil (1908). Seven generations were affected. Dolle (1950-52) reported a follow-up on this family, which contained numerous instances of male-to-male transmission. Braverman et al. (1965) reported the postmortem findings in a case of pitressin-responsive diabetes insipidus. As in 5 previously reported cases, a striking decrease in the nerve cells of the supraoptic and paraventricular nuclei of the hypothalamus with associated mild gliosis was found. In this family the father and paternal grandmother were thought to have had diabetes insipidus. In the sibship of the male proband, 2 sisters had definite diabetes insipidus and a brother may have been affected. One child of each of 3 of the sibs was also thought to have the disorder. Dominant pedigrees of pitressin-responsive diabetes insipidus had been reported also by Pender and Fraser (1953), Moehlig and Schultz (1955) and Martin (1959). One would scarcely expect a defect in synthesis of antidiuretic hormone to behave as a dominant. Isolated deficiencies of other pituitary hormones (e.g., 'sexual ateliosis,' or isolated growth hormone deficiency; see 262400) usually behave as recessives. From studies of 5 affected members of a family with a 'dominant' form of central diabetes insipidus, Blackett et al. (1983) concluded that the disorder is predominantly a deficiency of arginine vasopressin (AVP; 192340) and its carrier protein, nicotine-stimulated neurophysin (NSN) but that significant partial deficiency of oxytocin (OT; 167050) and its carrier protein, estrogen-stimulated neurophysin (ESN), exists. Toth et al. (1984) reported an extensively affected Canadian kindred. Of 121 persons in 7 generations, 34 were affected. The disorder showed variability in age of onset and in severity and apparently spontaneous abatement in old age. Plasma ADH levels were very low in spite of adequate osmotic stimulation, e.g., with infusion of hypertonic saline. The level rose when furosemide was given, suggesting an osmoreceptor defect and a normal ADH response to volume change. The osmoreceptors are in the hypothalamus; volume receptors are mainly in the atria, aortic arch, and carotid arteries. Pedersen et al. (1985) studied 5 families. In 4, autosomal dominant inheritance was unquestionable. In the fifth (family C), the pattern was consistent with X-linked dominance. No linkage was found in 1 extensively affected kindred. Because of availability of a radioimmunoassay for plasma arginine vasopressin, it was possible to corroborate the diagnosis by such assays before and after water deprivation. An arginine vasopressin level lower than 2 pg/ml strongly suggested the diagnosis of what they termed cranial diabetes insipidus if at the same time serum osmolality was higher than 295 mosmol/kg. Laing et al. (1991) described a family with affected individuals in 4 generations. Autosomal dominant cranial diabetes insipidus was associated with a characteristic facial appearance, namely hypertelorism, broad and short nose, and long philtrum. Pivonello et al. (1998) evaluated biochemical parameters of bone metabolism and the bone mineral density (BMD) in patients with central diabetes insipidus, either treated or not treated with endonasal desmopressin. The patients were divided into 2 groups: patients who did not receive treatment with desmopressin for at least 1 year (group 1), and patients chronically treated with desmopressin since the diagnosis of diabetes insipidus (group 2). Serum osteocalcin concentrations were significantly lower in patients of both groups compared with healthy subjects. BMD was significantly decreased in patients of groups 1 and 2 compared with controls, both at lumbar spine and femoral neck. A significant inverse correlation was found between disease duration and BMD values. The authors concluded that patients with central diabetes insipidus had a significant bone impairment compared with healthy subjects, and that replacement with endonasal desmopressin at standard doses did not prevent or reverse the bone impairment. These findings suggested that in patients with central diabetes insipidus, bone status analysis is mandatory, and a bone-loss preventing treatment might be beneficial. Pivonello et al. (1999) presented evidence showing that a 6-month treatment with alendronate in patients with central diabetes insipidus was effective in significantly improving BMD at the lumbar spine, which was significantly worsened in untreated patients. They advocated alendronate treatment in patients with central diabetes insipidus with documented osteopenia or osteoporosis. Magnetic resonance imaging (MRI) had revealed isolated pituitary stalk (PS) thickening (PST) in certain cases of idiopathic or secondary central diabetes insipidus (CDI) due to infiltrative processes. Leger et al. (1999) studied 26 children with CDI and PST who underwent cerebral MRI at the age of 8 +/- 4 years and were followed (24 patients) by clinical and MRI evaluation, respectively, for 5.5 +/- 3.6 and 3.0 +/- 2 years in the absence of any treatment other than hormonal substitutive therapy. Complete anterior pituitary evaluation for 24 of the 26 patients revealed those suffering from associated growth hormone deficiency (see 262400) (14 patients: 1 with germinoma, 3 with histiocytosis, and 10 with idiopathic) and from multiple hormone deficiencies (7 patients: 3 with germinoma, 1 with histiocytosis, and 3 with idiopathic). At the first MRI evaluation, PS enlargement varied from 2.2 to 9.0 mm at a proximal (10 patients), distal (2 patients), or middle (6 patients) PS level, or along the entire PS (8 patients). The intrasellar content, which usually reflects the anterior pituitary gland, was normal (12 patients), small (8 patients), or enlarged (6 patients). At the last evaluation, a change in MRI features was found in 16 patients; morphologic and/or signal changes in the PST (16 patients, of whom 6 showed an increase in PST) and changes in anterior pituitary gland size (8 patients: 3 with increased, and 5 with decreased) were noted. The authors concluded that the natural history of idiopathic isolated CDI with PST is unpredictable, and, although germinoma should always be considered during the first 3 years of follow-up in patients showing CDI with PST requiring repeated investigations every 3 to 6 months, it remains a less frequent etiology for 15% of the cases. In a large cohort of patients with apparently idiopathic CDI or CDI of known etiology, Pivonello et al. (2003) evaluated the occurrence of circulating autoantibodies to AVP (192340)-secreting cells and correlated it to clinical, immunologic, and radiologic features. AVP-secreting cells were measured by an indirect immunofluorescence method. AVP-secreting cells were found in 23.3% of CDI patients: 21 idiopathic (32.8%) and 14 nonidiopathic (16.3%; chi square = 13.1; P less than 0.001). AVP-secreting cells were independently associated with age less than 30 years at disease onset (P = 0.001) in patients with idiopathic CDI and with history of autoimmune diseases (P = 0.006 and P = 0.02, respectively) and radiologic evidence of pituitary stalk thickening (P = 0.02 and P = 0.003, respectively) in both idiopathic and nonidiopathic CDI. The likelihood of autoimmunity in one patient with apparently idiopathic CDI with age of onset less than 30 years was 53%; it increased to 91% when history of autoimmune diseases was associated and to 99% when pituitary stalk thickening was further associated. The authors concluded that autoimmunity is associated with 1/3 of patients with apparently idiopathic CDI. Also, autoimmune CDI is highly likely in young patients with a clinical history of autoimmune diseases and radiologic evidence of pituitary stalk thickening. Conversely, autoimmunity probably represents an epiphenomenon in patients with nonidiopathic CDI. Wahlstrom et al. (2004) reported an American kindred with autosomal dominant neurohypophyseal diabetes insipidus. The index patient was a 78-year-old man noted to have hypotonic polyuria after a surgical procedure. He had experienced polyuria and polydipsia since childhood but had avoided medical attention by assiduously maintaining access to water at all times. His family had recognized that some members required large volumes of water, and to accommodate these individuals (known in the family as 'water dogs'), a number of extra wells had been dug on the family farm. Neuro 2A cells stably transfected with the mutant AVP-NP construct showed increased rates of apoptosis as assessed by flow cytometric methods. These observations supported the concept that cellular toxicity of abnormal AVP-NP gene products underlies the development of neurohypophyseal diabetes insipidus. Affected family members were found to have a mutation in the AVP gene (192340.0020), demonstrating that mutations affecting the AVP moiety can result in initiation of these pathologic processes. Mapping Phillips et al. (1986) and Repaske et al. (1990) used RFLPs of the contiguous vasopressin-neurophysin II gene (192340) and oxytocin-neurophysin I gene (OT; 167050) on chromosome 20 for linkage studies in 3 families with autosomal dominant neurohypophyseal diabetes insipidus. Cosegregation of the disease phenotype and RFLP haplotypes were informative with 12 members of 2 families yielding a maximum lod score of 2.71 at theta = 0.0. There was no failure of cosegregation, which, if found, would exclude this region as the site of the mutation. No large deletions, insertions, or rearrangements in the vasopressin gene were found. The work of Repaske et al. (1990) appeared to make it quite certain that the mutation in this disorder resides in the AVP gene. That mutation in other genes can lead to the same phenotype is, of course, possible. Molecular Genetics In a consanguineous Palestinian family with neurohypophyseal diabetes insipidus, Willcutts et al. (1999) identified a 301C-T mutation in exon 1 of the AVP gene (192340.0016), replacing proline-7 of mature AVP with leucine (Leu-AVP). All 3 affected children were homozygous for the mutation, and the parents were heterozygous, suggesting autosomal recessive inheritance. Serum Leu-AVP levels were elevated in all 3 children and further increased during water deprivation to as high as 30 times normal, as measured by radioimmunoassay. The youngest child (2 years old) was only mildly affected, but had Leu-AVP levels similar to her severely affected 8-year-old brother, suggesting to the authors that unknown mechanisms may partially compensate for a deficiency of active AVP in very young children. Christensen et al. (2004) screened for mutations in the AVP gene in 15 unrelated kindreds in which diabetes insipidus appeared to be segregating. In each of 6 kindreds, they identified a unique novel mutation, and in the other 9 kindreds, 7 different previously described mutations. All of the mutations occurred in heterozygous state. In an Asian American family, Christensen et al. (2004) identified a 1797T-C transition predicting a val67-to-ala substitution (V67A; 192340.0019). The authors noted that this mutation affects a region of the molecule unaffected by other identified mutations and produces only a minor change. The inheritance pattern in this family was atypical and suggested incomplete penetrance. The proband apparently inherited the disease through his affected mother, although allegedly neither of his maternal grandparents had a history of polyuria, but a brother of the maternal grandmother was affected. Animal Model An apparent defect in synthesis of vasopressin in the rat results in diabetes insipidus only in the homozygote, although the heterozygote shows reduced vasopressin. Oxytocin synthesis is not impaired (Valtin et al., 1965). Morphologic features suggest excessive activity of the hypothalamoneurohypophyseal system which controls secretion of vasopressin (Sokol and Valtin, 1965). Autosomal dominant diabetes insipidus is associated with oligosyndactyly in the mouse (Falconer et al., 1964). Majzoub et al. (1984), who referred to diabetes insipidus in the Brattleboro rat as semirecessive, demonstrated that the vasopressin gene is expressed but at a reduced level. They found that the hypothalamus of these rats contains detectable, although markedly reduced, levels of an mRNA indistinguishable in size from and similar in sequence to authentic vasopressin mRNA. Levels of oxytocin mRNA were the same in Brattleboro and normal rat hypothalami. Schmale et al. (1984) compared the vasopressin gene from normal and diabetes insipidus (Brattleboro) rats. Except for a single deletion of a G residue in the second exon (the region coding for the neurophysin carrier protein), the genes were identical. Blot analysis of hypothalamic RNA as well as transfection and microinjection experiments indicated that the mutant gene is correctly transcribed and spliced, but the resulting mRNA is not efficiently translated. Jirikowski et al. (1992) found that injection into the hypothalamus of purified mRNA from normal rat hypothalami or of synthetic copies of the vasopressin mRNA led to selective uptake, retrograde transport, and expression of vasopressin exclusively in the magnocellular neurons which are known to secrete oxytocin and vasopressin. Reversal of the diabetes insipidus for up to 5 days was observed within hours of the injection. Russell et al. (2003) established murine knockin models of 2 different naturally occurring human mutations that cause autosomal dominant neurohypophyseal diabetes insipidus. A mutation in the signal sequence of the AVP gene, ala-1 to thr (A-1T; 192340.0003), is associated with a relatively mild phenotype or delayed presentation in humans. This mutation caused no apparent phenotype in mice. In contrast, heterozygous mice expressing a mutation that truncates the AVP precursor, cys67 to ter (C67X; 192340.0005), exhibited polyuria and polydipsia by 2 months of age; these features of diabetes insipidus progressively worsened with age. Studies of the paraventricular and supraoptic nuclei revealed induction of the chaperone protein BiP (138120) and progressive loss of AVP-producing neurons relative to oxytocin-producing neurons. In addition, Avp gene products were not detected in the neuronal projections, suggesting retention of wildtype and mutant AVP precursors within the cell bodies. This murine model recapitulated many features of the human disorder and demonstrated that expression of the mutant AVP precursor leads to progressive neuronal cell loss, presumably through a dominant-negative effect. Phillips (2003) tabulated 21 disorders caused by mutations in 18 genes which demonstrated the dominant-negative phenomenon and were instances of hormone deficiency. History The cosegregation of diabetes insipidus of the autosomal dominant neurohypophyseal type with Huntington disease (Frontali et al., 1986) is compatible with linkage of the 2 loci. Pedersen et al. (1985) found a lod score of 1.172 for linkage of this form of diabetes insipidus and MN blood group (111300). Endocrine \- Neurohypophyseal diabetes insipidus Radiology \- Decreased bone mineral density (BMD) Facies \- Hypertelorism \- Broad and short nose \- Long philtrum Lab \- Arginine vasopressin deficiency \- Partial deficiency of oxytocin (OT) and its carrier protein, estrogen-stimulated neurophysin (ESN) \- Decreased nerve cells of the supraoptic and paraventricular nuclei of the hypothalamus with associated mild gliosis \- Low serum osteocalcin 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-hydroxybutyric 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	DIABETES INSIPIDUS, NEUROHYPOPHYSEAL	c0687720	24,633	omim	https://www.omim.org/entry/125700	2019-09-22T16:42:20	{"doid": ["12388"], "mesh": ["D020790"], "omim": ["125700"], "orphanet": ["178029", "30925"], "synonyms": ["Alternative titles", "DIABETES INSIPIDUS, PRIMARY CENTRAL", "DIABETES INSIPIDUS, CRANIAL TYPE"]}
Camelpox virus Virus classification (unranked): Virus Realm: Varidnaviria Kingdom: Bamfordvirae Phylum: Nucleocytoviricota Class: Pokkesviricetes Order: Chitovirales Family: Poxviridae Genus: Orthopoxvirus Species: Camelpox virus Camelpox is a disease of camels caused by the Camelpox virus of the family Poxviridae, subfamily Chordopoxvirinae, and the genus Orthopoxvirus. It causes skin lesions and a generalized infection. Approximately 25% of young camels that become infected will die from the disease, while infection in older camels is generally more mild.[1] Although rare, the infection may spread to the hands of those that work closely with camels.[2] Camelpox is endemic throughout the Middle East, Africa, and Asia. ## Contents * 1 Cause * 2 Transmission * 3 Replication * 4 Signs and symptoms * 5 Diagnosis and treatment * 6 Prevention * 7 Society and culture * 8 Notes and references ## Cause[edit] The Camelpox Virus (CMPV) that causes Camelpox is an Orthopoxvirus that is very closely related to the Variola virus that causes Smallpox. It is a large, brick-shaped, enveloped virus that ranges in size from 265-295 nm. The viral genetic material is contained in double stranded linear DNA consisting of 202,182 tightly packed base pairs.[3] The DNA is encased in the viral core. Two lateral bodies are found outside the viral core, and are believed to hold the enzymes required for viral reproduction.[4] The Camelpox virus most often affects members of family Camelidae. However, recent studies show that the disease can be transmitted to both humans and arthropods.[5] ## Transmission[edit] The Camelpox virus is spread in three ways: direct contact, indirect contact, and insect vectors. In direct contact infection, a camel becomes infected after direct contact with an infected camel. In indirect contact infection, a camel becomes infected after contact with an infected environment. The virus is spread through milk, saliva, ocular secretions, and nasal secretions, and has been shown to remain virulent outside of a host for 4 months.[6] The Camelpox virus has been isolated from camel ticks (Hyalomma dromedarii) removed from infected animals. It is believed that the ticks can transmit the disease from camel to camel. This theory is supported by increases in Camelpox infections immediately following heavy rains, during which the camel tick population increases greatly.[7] Transmission of Camelpox to humans was confirmed in 2009 when camel herders in India presented with infections of the hands and fingers. Although other cases of human infection have been reported, no other cases have been verified. Due to the close contact between camels and their human handlers in much of the world, it is believed that Camelpox is transmitted to humans via direct contact.[8] ## Replication[edit] The Orthopox virus that causes Camelpox behaves very similarly to the virus that causes Smallpox. After the virus attaches to a host cell, it injects its viral core (the shell containing its DNA) into the cell's cytoplasm. The virus carries DNA polymerase which is used to transcribe its genes. Eventually, the viral core dissolves, and the genetic material is bare within the cytoplasm. When all of the structural proteins have been produced, viral assembly takes place. The newly formed virus particles can be released during cell lysis, or they can derive a host cell produced membrane and be released via budding.[9] ## Signs and symptoms[edit] The incubation period of Camelpox is between 3 and 15 days. The resulting infection can be classified as acute or generalized. Generalized infections are usually found in camels over the age of three, and are characterized by swollen lymph nodes, fever, and the development of skin lesions. The lesions begin as papules, but develop into pustules. These external symptoms usually begin on the head and neck, but eventually spread throughout the body, being especially concentrated on the limbs and genitalia. Without treatment, the animal will generally recover from the infection in 4 to 6 weeks.[6] Acute infections are usually found in camels under the age of three, and result in mild to severe systemic infections. In addition to the symptoms that accompany a generalized infection, these animals experience internal lesions along the lining of the mouth, and respiratory and digestive tracts. They also experience loss of appetite and diarrhea. A large proportion of camels acutely infected with Camelpox die, although death is often attributed to a secondary infection.[10] Camelpox infections in humans result in mild skin lesions on the hands and fingers. Reports have been made that the lesions can be found on the mouth and lips if the patient drank milk from an infected camel, but these symptoms have not been confirmed.[8] ## Diagnosis and treatment[edit] Camelpox diagnosis can be based on symptoms. However, both Camel Contagious Ecthyma and Camel Papillomatosis cause indistinguishable symptoms under similar conditions.[11] Therefore, the best way to diagnose Camelpox is via Transmission Electron Microscopy evaluation of skin samples from infected animals. The Camelpox virus has a unique shape that is readily identifiable using this method. In cases where TEM technology is not available, serological tests are available to identify Camelpox as the causative agent for infection.[6] Additionally, researchers in India are working on a diagnostic polymerase chain reaction to quickly and effectively identify the Camelpox virus.[12] When the Camelpox virus is identified as the causative agent, the disease can be treated with anti-viral medications. The most common medication used to treat Camelpox is Cidofovir, a broad spectrum anti-viral that acts by inhibiting the viral DNA polymerase. Cidofovir has proven to be 100% effective at preventing death in infected camels.[13] ## Prevention[edit] Camelpox outbreaks have a negative effect on the local economies. Outbreaks often lead to the loss of young camels, and render older camels useless in terms of milk and meat production, and transportation. As such, attempts are often made to prevent transmission of the disease. An attenuated vaccine is currently available that provides long term protection against Camelpox if administered when the camel is at least 9 months old. An inactivated vaccine is also available, but must be administered yearly to maintain protection.[6] The Camelpox virus is sensitive to a number of common disinfectants. It can also be destroyed by autoclaving, short term exposure to UV light, and boiling for at least 10 minutes. These methods may be used by camel herders to minimize risk of environmental contamination.[6] ## Society and culture[edit] In 1995 Saddam Hussein admitted to having a number of top Iraqi scientists working to turn Camelpox into a biological weapon. Camelpox was chosen for two main reasons: the theory that the local population would be largely immune, and its relation to Smallpox. It is believed that the reported cases of Camelpox infection in humans is low due to an immunity gained from exposure to camels during early childhood. Therefore, a significant proportion of Iraq's population would be immune to Camelpox, while troops from non-Camel herding countries would be susceptible.[14] It is not believed that the research process was successful, or that the virus was ever produced in any great quantities.[15] ## Notes and references[edit] 1. ^ Fenner, Frank J.; Gibbs, E. Paul J.; Murphy, Frederick A.; Rott, Rudolph; Studdert, Michael J.; White, David O. (1993). Veterinary Virology (2nd ed.). Academic Press, Inc. ISBN 978-0-12-253056-2. 2. ^ Carter, G.R.; Wise, D.J. (2006). "Poxviridae". A Concise Review of Veterinary Virology. Retrieved 10 June 2006. 3. ^ Gubser, Caroline; Smith, Geoffrey (2001). "The sequence of Camelpox virus shows it is most closely related to Variola virus, the cause of smallpox". Journal of General Virology. 83 (4): 855–872. doi:10.1099/0022-1317-83-4-855. PMID 11907336. 4. ^ "Poxviruses". Retrieved 2 April 2012. 5. ^ Jezek, Z; Kriz, B (1983). "Camelpox and its risk to the human population". Journal of Hygiene, Epidemiology, Microbiology, and Immunology. 27 (1): 29–42. PMID 6304186. 6. ^ a b c d e "Camelpox" (PDF). Terrestrial Animal Health Code. World Organization for Animal Health. Archived from the original (PDF) on 17 June 2012. Retrieved 31 March 2012. 7. ^ Wernery, U; Kaaden (1997). "Orthopox virus infections in dromedary camels in the United Arab Emirates (UAE) during winter season". Journal of Camel Practice and Research. 4 (1): 51–55. 8. ^ a b Bera, BC (August 2011). "Zoonotic cases of camelpox infection in India". Journal of Veterinary Microbiology. 152 (1–2): 29–38. doi:10.1016/j.vetmic.2011.04.010. PMID 21571451. 9. ^ "Orthopoxvirus". Virus Zone. 10. ^ Pfeffer, M (January 1998). "Fatal Form of Camelpox Virus Infection". The Veterinary Journal. 155 (1): 107–109. doi:10.1016/s1090-0233(98)80045-2. PMID 9455166. 11. ^ Khalafalla, A (1998). "Epizootiology of Camel Pox, Camel Contagious Ecthyma and Camel Papillomatosis in the Sudan". Animal Production Under Arid Conditions. 2: 115–131. 12. ^ Balamurugan, Vinayagamurthy (March 2009). "A Polymerase Chain Reaction Strategy for the Diagnosis of Camelpox". Journal of Veterinary Diagnostic Investigation. 21 (2): 231–237. doi:10.1177/104063870902100209. PMID 19286503. 13. ^ Andrei, Graciela; Robert Snoeck (December 2010). "Cidofovir Activity against Poxvirus Infections". Viruses. 2 (12): 2803–2830. doi:10.3390/v2122803. PMC 3185586. PMID 21994641. 14. ^ Coghlan, Andy (17 April 2002). "Fear Over Camelpox as Bioweapon". NewScientist. Retrieved 4 April 2012. 15. ^ Pike, John. "Iraq Special Weapons". Federation of American Scientists. Retrieved 4 April 2012. Taxon identifiers * Wikidata: Q5025948 * Wikispecies: Camelpox virus * EoL: 540227 * IRMNG: 11459340 * NCBI: 28873 [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-hydroxybutyric 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	Camelpox	c0276185	24,634	wikipedia	https://en.wikipedia.org/wiki/Camelpox	2021-01-18T18:33:53	{"wikidata": ["Q21117332"]}
Autosomal dominant neuronal ceroid lipofuscinosis 4B is a form of adult neuronal ceroid lipofuscinosis, which is a rare condition that affects the nervous system. Signs and symptoms usually begin around age 30, but they can develop anytime between adolescence and late adulthood. Affected people generally experience behavioral abnormalities, dementia; difficulties with muscle coordination (ataxia); and involuntary movements such as tremors or tics. It can be caused by changes (mutations) in the DNAJC5 or CTSF gene and is inherited in an autosomal dominant 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-hydroxybutyric 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	Autosomal dominant neuronal ceroid lipofuscinosis 4B	c1834207	24,635	gard	https://rarediseases.info.nih.gov/diseases/1222/autosomal-dominant-neuronal-ceroid-lipofuscinosis-4b	2021-01-18T18:01:57	{"mesh": ["D009472"], "omim": ["162350"], "umls": ["C1834207"], "orphanet": ["228343"], "synonyms": ["CLN4B", "Kuf's disease, autosomal dominant", "Ceroid lipofuscinosis, neuronal, Parry type", "Ceroid lipofuscinosis, neuronal, 4B, autosomal dominant", "Neuronal ceroid lipofuscinosis 4B", "Adult neuronal ceroid lipofuscinosis 4B", "Kuf's disease type B", "CLN4B disease"]}
Not to be confused with Fibrocystic breast changes. Fibroadenoma Other namesBreast mice, breast mouse Histopathologic image of breast fibroadenoma. Core needle biopsy. H&E stain. SpecialtyGynecology Fibroadenomas are benign breast tumours characterized by an admixture of stromal and epithelial tissue. Breasts are made of lobules (milk producing glands) and ducts (tubes that carry the milk to the nipple). These are surrounded by glandular, fibrous and fatty tissues. Fibroadenomas develop from the lobules. The glandular tissue and ducts grow over the lobule to form a solid lump. Since both fibroadenomas, and breast lumps as a sign of breast cancer can appear similar, it is recommended to perform ultrasound analyses and possibly tissue sampling with subsequent histopathologic analysis in order to make a proper diagnosis. Unlike typical lumps from breast cancer, fibroadenomas are easy to move, with clearly defined edges.[1][2] Fibroadenomas are sometimes called breast mice or a breast mouse owing to their high mobility in the breast.[3] ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Pathology * 2.2 Cytology * 2.3 Macroscopic * 2.4 Microscopic * 3 Molecular pathology * 4 Diagnosis * 5 Treatment * 5.1 Non-invasive Surgical Interventions * 5.1.1 Cryoablation * 5.1.2 High Intensity Focused Ultrasound * 6 Epidemiology * 7 References * 8 External links ## Signs and symptoms[edit] Fibroadenomas are benign (not harmful in effect) tumours of the breast, most often present in women in their 20s and 30s.[4] Clinically, fibroadenomas are usually solid breast lumps that are: • Painless[4] • Firm or rubbery[4] • Mobile[4] • Solitary-round with distinct, smooth borders[4] People who have a simple fibroadenoma have a slightly increased risk of developing malignant (harmful) breast cancer.[4] Complex fibroadenomas may increase the risk of breast cancer.[4] In the male breast, fibroepithelial tumors are very rare, and are mostly phyllodes tumors. Exceptionally rare case reports exist of fibroadenomas in the male breast, however these cases may be associated with antiandrogen treatment.[5] ## Cause[edit] The cause of fibroadenoma is unknown (idiopathic).[6] A connection between fibroadenomas and reproductive hormones has been suggested which may explain why they present themselves during reproductive years, increase in size during pregnancy, and regress post-menopause.[6] Higher intake of fruits and vegetables, higher number of live births, lower use of oral contraceptives and moderate exercise are associated with lower frequency of fibroadenomas.[7] ### Pathology[edit] Macroscopic view of fibroadenoma of the breast Closeup of a fibroadenoma of the breast ### Cytology[edit] The diagnostic findings on needle biopsy consist of abundant stromal cells, which appear as bare bipolar nuclei, throughout the aspirate; sheets of fairly uniform-size epithelial cells that are typically arranged in either an antler-like pattern or a honeycomb pattern. These epithelial sheets tend to show typical metachromatic blue on Diff-Quik staining. Foam cells and apocrine cells may also be seen, although these are less diagnostic features.[8][9] The gallery images below demonstrate these features. Cellular fibroadenoma, also known as juvenile fibroadenoma, is a variant type of fibroadenoma with increased stromal cellularity.[10][11] ### Macroscopic[edit] Approximately 90% of fibroadenomas are less than 3 cm in diameter. However, these tumors have the potential to grow reaching a remarkable size, particularly in young individuals. The tumor is round or ovoid, elastic, and nodular, and has a smooth surface. The cut surface usually appears homogenous and firm, and is grey-white or tan in colour. The pericanalicular type (hard) has a whorly appearance with a complete capsule, while the intracanalicular type (soft) has an incomplete capsule.[9] ### Microscopic[edit] Fibroadenoma of the breast is a benign tumor composed of a biplastic proliferation of both stromal and epithelial components.[12][13] This biplasia can be arranged in two growth patterns: pericanalicular (stromal proliferation around epithelial structures) and intracanalicular (stromal proliferation compressing the epithelial structures into clefts). These tumors characteristically display hypovascular stroma compared to malignant neoplasms.[2][14][9] Furthermore, the epithelial proliferation appears in a single terminal ductal unit and describes duct-like spaces surrounded by a fibroblastic stroma. The basement membrane is intact.[15] ## Molecular pathology[edit] Up to 66% of fibroadenomas harbor mutations in the exon (exon 2) of the mediator complex subunit 12 (MED12) gene. In particular, these mutations are restricted to the stromal component.[16][17] ## Diagnosis[edit] A fibroadenoma is usually diagnosed through clinical examination, ultrasound or mammography, and often a biopsy sample of the lump.[8] Suspicious findings on imaging may result in a person needing a biopsy in order to gain a definitive diagnosis. There are three types of biopsies: Fine-needle aspiration, core-needle biopsy and surgical biopsy. The method of biopsy depends on the appearance, size and location of the breast mass.[18] * Fibroadenoma Histology (H&E). The image demonstrates intracanalicular morphology (top right) and pericanalicular morphology (bottom left) * Fibroadenoma, Fine Needle Aspiration Biopsy (Giemsa or DiffQuick stain). The image shows abundant bare bipolar stromal nuclei surrounding sheets of metachromatic epithelial cells. * Fibroadenoma, Fine Needle Aspiration Biopsy (Papanicolou stain). The image shows a sheet of epithelial cells in the typical antler pattern. * Histopathologic image of breast fibroadenoma. Core needle biopsy. Hematoxylin & eosin stain. * Histopathologic image of breast fibroadenoma showing proliferation of intralobular stroma compressing and distorting the epithelium. H&E stain. * Fibroadenoma in ultrasound * ## Treatment[edit] Fibroadenomas can be expected to shrink naturally and so, most are simply monitored.[19] Monitoring fibroadenomas involves regular check-ups to make sure that the breast mass is not growing and is not potentially cancerous.[19] Check-ups involve physical examinations performed every 3–6 months and optional diagnostic imaging performed every 6–12 months for 1–2 years.[19] Generally, surgery is only recommended if the fibroadenoma gets larger or causes increased symptoms.[20] They are removed with a small margin of normal breast tissue if the preoperative clinical investigations are suggestive of the necessity of this procedure. A small amount of normal tissue must be removed in case the lesion turns out to be a phyllodes tumour on microscopic examination.[9][21] Because needle biopsy is often a reliable diagnostic investigation, some doctors may decide not to operate to remove the lesion, and instead opt for clinical follow-up to observe the lesion over time using clinical examination and mammography to determine the rate of growth, if any, of the lesion. A growth rate of less than sixteen percent per month in women under fifty years of age, and a growth rate of less than thirteen percent per month in women over fifty years of age have been published as safe growth rates for continued non-operative treatment and clinical observation.[22] Some fibroadenomas respond to treatment with ormeloxifene.[23] Fibroadenomas have not been shown to recur following complete excision or transform into phyllodes tumours following partial or incomplete excision.[9] ### Non-invasive Surgical Interventions[edit] There are several non-invasive options for the treatment of fibroadenomas, including percutaneous radiofrequency ablation (RFA), cryoablation, and percutaneous microwave ablation.[24] With the use of advanced medical imaging, these procedures do not require invasive surgery and have the potential for enhanced cosmetic results compared with conventional surgery.[24] #### Cryoablation[edit] The FDA approved cryoablation of a fibroadenoma as a safe, effective, and minimally-invasive alternative to open surgical removal in 2001.[25] During cryoablation, ultrasound imaging is used to guide a probe into the mass of breast tissue. Extremely cold temperatures are then used to destroy the abnormal cells, and over time the cells are reabsorbed into the body.[26] The procedure can be performed as an outpatient surgery using local anesthesia, and leaves substantially less scarring than open surgical procedures and no breast tissue deformation.[citation needed] The American Society of Breast Surgeons recommends the following criteria to establish a patient as a candidate for cryoablation of a fibroadenoma:[25] 1. The lesion must be sonographically visible. 2. The diagnosis of a fibroadenoma must be confirmed histologically. 3. The lesion should be less than 4 cm in diameter. #### High Intensity Focused Ultrasound[edit] High Intensity Focused Ultrasound (HIFU) is a newer technique for the treatment of malignant and benign tumors of the breast and has shown promising results in the form of complete radiological removal of tumors.[27] An ultrasound beam is focused on a target in the breast and leads to tissue death and protein degradation by raising the temperature in that area.[27] Currently, the use of radiation is recommended in some cases, but HIFU in particular is not part of treatment guidelines.[28] Further research into the usefulness of HIFU, specifically in fibroadenoma, is required before more widespread use of the technique in fibroadenoma.[27] ## Epidemiology[edit] Of all breast tissue samples taken, fibroadenomas comprise about 50%, and this rate rises to 75% for tissue sample in women under the age of 20 years.[29] Fibroadenomas are more frequent among women in higher socioeconomic classes and darker-skinned people.[29] Body mass index and the number of full-term pregnancies were found to have a negative correlation with the risk of fibroadenomas.[29] There are no known genetic factors that influence the rate of fibroadenomas.[29] The rate of occurrence of fibroadenomas in women have been reported in literature to range from 7% to 13%.[29] ## References[edit] 1. ^ 22-251c.Fibroadenomas at Merck Manual of Diagnosis and Therapy Home Edition 2. ^ a b Tavassoli, F.A.; Devilee, P., eds. (2003). World Health Organization Classification of Tumours: Pathology & Genetics: Tumours of the breast and female genital organs. Lyon: IARC Press. ISBN 978-92-832-2412-9.[page needed] 3. ^ Dirbas, Fredrick M.; Scott-Conner, Carol E.H., eds. (2010). Breast surgery office management and surgical techniques. New York: Springer. p. 71. ISBN 978-1-4419-6075-7. 4. ^ a b c d e f g "Fibroadenomas of the Breast". cancer.org. Retrieved 13 November 2018. 5. ^ Shin SJ, Rosen PP (July 2007). "Bilateral presentation of fibroadenoma with digital fibroma-like inclusions in the male breast". Archives of Pathology & Laboratory Medicine. 131 (7): 1126–9. doi:10.1043/1543-2165(2007)131[1126:BPOFWD]2.0.CO;2 (inactive 22 December 2020). PMID 17617003.CS1 maint: DOI inactive as of December 2020 (link) 6. ^ a b Pruthi S, Jones KN (February 2013). "Nonsurgical management of fibroadenoma and virginal breast hypertrophy". Seminars in Plastic Surgery. 27 (1): 62–6. doi:10.1055/s-0033-1343997. PMC 3706058. PMID 24872742. 7. ^ Nelson ZC, Ray RM, Wu C, Stalsberg H, Porter P, Lampe JW, Shannon J, Horner N, Li W, Wang W, Hu Y, Gao D, Thomas DB (July 2010). "Fruit and vegetable intakes are associated with lower risk of breast fibroadenomas in Chinese women". The Journal of Nutrition. 140 (7): 1294–301. doi:10.3945/jn.109.119719. PMC 2884330. PMID 20484549. 8. ^ a b DeMay, M. (2007). Practical Principles of Cytopathology (Revised ed.). ASCP Press. p. 2007. ISBN 978-0-89189-549-7.[page needed] 9. ^ a b c d e Rosen, PP. (2009). Rosen's Breast Pathology (3rd ed.). ISBN 978-0-7817-7137-5.[page needed] 10. ^ Fekete P, Petrek J, Majmudar B, Someren A, Sandberg W (May 1987). "Fibroadenomas with stromal cellularity. A clinicopathologic study of 21 patients". Archives of Pathology & Laboratory Medicine. 111 (5): 427–32. PMID 3032124. 11. ^ Nassar, Hind. "Cellular fibroadenoma of breast". Retrieved 14 January 2013. 12. ^ Yang, Xiaofang; Kandil, Dina; Cosar, Ediz F.; Khan, Ashraf (2014). "Fibroepithelial Tumors of the Breast: Pathologic and Immunohistochemical Features and Molecular Mechanisms". Archives of Pathology & Laboratory Medicine. 138 (1): 25–36. doi:10.5858/arpa.2012-0443-RA. ISSN 0003-9985. PMID 24377809. 13. ^ "Fibroadenoma". Patholines.org. This page was last edited on 4 November 2019 14. ^ Pathology Outlines Website. [1] Accessed 12 February 2009. 15. ^ "Fibroadenoma of the breast". Retrieved 15 December 2007. 16. ^ Lim WK, Ong CK, Tan J, Thike AA, Ng CC, Rajasegaran V, Myint SS, Nagarajan S, Nasir ND, McPherson JR, Cutcutache I, Poore G, Tay ST, Ooi WS, Tan VK, Hartman M, Ong KW, Tan BK, Rozen SG, Tan PH, Tan P, Teh BT (August 2014). "Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma". Nature Genetics. 46 (8): 877–80. doi:10.1038/ng.3037. PMID 25038752. S2CID 7623650. 17. ^ Piscuoglio S, Murray M, Fusco N, Marchiò C, Loo FL, Martelotto LG, Schultheis AM, Akram M, Weigelt B, Brogi E, Reis-Filho JS (November 2015). "MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast". Histopathology. 67 (5): 719–29. doi:10.1111/his.12712. PMC 4996373. PMID 25855048. 18. ^ Tasoulis, MK. "Evaluation of breast mass". BMJ Best Practice. Retrieved 13 November 2018. 19. ^ a b c American College of Obstetricians Gynecologists' Committee on Practice Bulletins—Gynecology (June 2016). "Practice Bulletin No. 164: Diagnosis and Management of Benign Breast Disorders". Obstetrics and Gynecology. 127 (6): e141-56. doi:10.1097/aog.0000000000001482. PMID 27214189. S2CID 37836506. 20. ^ "Fibroadenoma – Diagnosis and treatment – Mayo Clinic". mayoclinic.org. Retrieved 13 November 2018. 21. ^ Rosai, J. (2004). Rosai and Ackerman's Surgical Pathology (9th ed.). ISBN 978-0-323-01342-0.[page needed] 22. ^ Gordon PB, Gagnon FA, Lanzkowsky L (October 2003). "Solid breast masses diagnosed as fibroadenoma at fine-needle aspiration biopsy: acceptable rates of growth at long-term follow-up". Radiology. 229 (1): 233–8. doi:10.1148/radiol.2291010282. PMID 14519878. 23. ^ Dhar A, Srivastava A (June 2007). "Role of centchroman in regression of mastalgia and fibroadenoma". World Journal of Surgery. 31 (6): 1178–84. doi:10.1007/s00268-007-9040-4. PMID 17431715. S2CID 22828570. 24. ^ a b Sag AA, Maybody M, Comstock C, Solomon SB (June 2014). "Percutaneous image-guided ablation of breast tumors: an overview". Seminars in Interventional Radiology. 31 (2): 193–202. doi:10.1055/s-0034-1376159. PMC 4078155. PMID 25049447. 25. ^ a b "Management of Fibroadenomas of the Breast : Official Statement" (PDF). American Society of Breast Surgeons. 29 April 2008. Retrieved 23 June 2020. 26. ^ WebMD – Cryotherapy Shrinks Benign Breast Lumps 27. ^ a b c Peek MC, Wu F (2018). "High-intensity focused ultrasound in the treatment of breast tumours". ecancermedicalscience. 12: 794. doi:10.3332/ecancer.2018.794. PMC 5804717. PMID 29434660. 28. ^ "BMJ Best Practice". bestpractice.bmj.com. Retrieved 13 November 2018. 29. ^ a b c d e Greenberg R, Skornick Y, Kaplan O (September 1998). "Management of breast fibroadenomas". Journal of General Internal Medicine. 13 (9): 640–5. doi:10.1046/j.1525-1497.1998.cr188.x. PMC 1497021. PMID 9754521. ## External links[edit] Classification D * ICD-10: D24 * ICD-9-CM: 217 * ICD-O: M9010/0-M9012, M9020, M9030 * MeSH: D018226 * DiseasesDB: 1595 External resources * MedlinePlus: 007216 * eMedicine: radio/109 * v * t * e Connective/soft tissue tumors and sarcomas Not otherwise specified * Soft-tissue sarcoma * Desmoplastic small-round-cell tumor Connective tissue neoplasm Fibromatous Fibroma/fibrosarcoma: * Dermatofibrosarcoma protuberans * Desmoplastic fibroma Fibroma/fibromatosis: * Aggressive infantile fibromatosis * Aponeurotic fibroma * Collagenous fibroma * Diffuse infantile fibromatosis * Familial myxovascular fibromas * Fibroma of tendon sheath * Fibromatosis colli * Infantile digital fibromatosis * Juvenile hyaline fibromatosis * Plantar fibromatosis * Pleomorphic fibroma * Oral submucous fibrosis Histiocytoma/histiocytic sarcoma: * Benign fibrous histiocytoma * Malignant fibrous histiocytoma * Atypical fibroxanthoma * Solitary fibrous tumor Myxomatous * Myxoma/myxosarcoma * Cutaneous myxoma * Superficial acral fibromyxoma * Angiomyxoma * Ossifying fibromyxoid tumour Fibroepithelial * Brenner tumour * Fibroadenoma * Phyllodes tumor Synovial-like * Synovial sarcoma * Clear-cell sarcoma Lipomatous * Lipoma/liposarcoma * Myelolipoma * Myxoid liposarcoma * PEComa * Angiomyolipoma * Chondroid lipoma * Intradermal spindle cell lipoma * Pleomorphic lipoma * Lipoblastomatosis * Spindle cell lipoma * Hibernoma Myomatous general: * Myoma/myosarcoma smooth muscle: * Leiomyoma/leiomyosarcoma skeletal muscle: * Rhabdomyoma/rhabdomyosarcoma: Embryonal rhabdomyosarcoma * Sarcoma botryoides * Alveolar rhabdomyosarcoma * Leiomyoma * Angioleiomyoma * Angiolipoleiomyoma * Genital leiomyoma * Leiomyosarcoma * Multiple cutaneous and uterine leiomyomatosis syndrome * Multiple cutaneous leiomyoma * Neural fibrolipoma * Solitary cutaneous leiomyoma * STUMP Complex mixed and stromal * Adenomyoma * Pleomorphic adenoma * Mixed Müllerian tumor * Mesoblastic nephroma * Wilms' tumor * Malignant rhabdoid tumour * Clear-cell sarcoma of the kidney * Hepatoblastoma * Pancreatoblastoma * Carcinosarcoma Mesothelial * Mesothelioma * Adenomatoid tumor [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-hydroxybutyric 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	Fibroadenoma	c0206650	24,636	wikipedia	https://en.wikipedia.org/wiki/Fibroadenoma	2021-01-18T18:29:34	{"mesh": ["D018226"], "umls": ["C1333137", "C0178421", "C0206650", "C0346158"], "icd-9": ["217"], "wikidata": ["Q1410808"]}
Pyruvate kinase deficiency Other namesErythrocyte pyruvate kinase deficiency[1] Phosphoenolpyruvate SpecialtyHematology SymptomsAnemia, tachycardia[2] CausesMutation in PKLR gene[3] Diagnostic methodPhysical exam, CBC[4] TreatmentBlood transfusion[4] Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells.[4][5] Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive. Pyruvate kinase deficiency is the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency.[6] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 Epidemiology * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] Gallstones Symptoms can be extremely varied among those suffering from pyruvate kinase deficiency. The majority of those suffering from the disease are detected at birth while some only present symptoms during times of great physiological stress such as pregnancy, or with acute illnesses (viral disorders).[7] Symptoms are limited to or most severe during childhood.[8] Among the symptoms of pyruvate kinase deficiency are:[2] * Mild to severe hemolytic Anemia * Cholecystolithiasis * Tachycardia * Hemochromatosis * Icteric sclera * Splenomegaly * Leg ulcers * Jaundice * Fatigue * Shortness of breath The level of 2,3-bisphosphoglycerate is elevated: 1,3-bisphosphoglycerate, a precursor of phosphoenolpyruvate which is the substrate for Pyruvate kinase, is increased and so the Luebering-Rapoport pathway is overactivated. This led to a rightward shift in the oxygen dissociation curve of hemoglobin (i.e. it decreases the hemoglobin affinity for oxygen): In consequence, patients may tolerate anemia surprisingly well.[9] ## Cause[edit] Pyruvate kinase deficiency is due to a mutation in the PKLR gene. There are four pyruvate kinase isoenzymes, two of which are encoded by the PKLR gene (isoenzymes L and R, which are used in the liver and erythrocytes, respectively). Mutations in the PKLR gene therefore cause a deficiency in the pyruvate kinase enzyme.[3][10] 180 different mutations have been found on the gene coding for the L and R isoenzymes, 124 of which are single-nucleotide missense mutations.[11] Pyruvate kinase deficiency is most commonly an autosomal recessive trait.[12] Although it is mostly homozygotes that demonstrate symptoms of the disorder,[2] compound heterozygotes can also show clinical signs.[11] ## Pathophysiology[edit] ATP-3D Pyruvate kinase is the last enzyme involved in the glycolytic process, transferring the phosphate group from phosphenol pyruvate to a waiting adenosine diphosphate (ADP) molecule, resulting in both adenosine triphosphate (ATP) and pyruvate. This is the second ATP producing step of the process and the third regulatory reaction.[7][13] Pyruvate kinase deficiency in the red blood cells results in an inadequate amount of or complete lack of the enzyme, blocking the completion of the glycolytic pathway. Therefore, all products past the block would be deficient in the red blood cell. These products include ATP and pyruvate.[2] Mature erythrocytes lack a nucleus and mitochondria. Without a nucleus, they lack the ability to synthesize new proteins so if anything happens to their pyruvate kinase, they are unable to generate replacement enzymes throughout the rest of their life cycle. Without mitochondria, erythrocytes are heavily dependent on the anaerobic generation of ATP during glycolysis for nearly all of their energy requirements.[14] With insufficient ATP in an erythrocyte, all active processes in the cell come to a halt. Sodium potassium ATPase pumps are the first to stop. Since the cell membrane is more permeable to potassium than sodium, potassium leaks out. Intracellular fluid becomes hypotonic, water moves down its concentration gradient out of the cell. The cell shrinks and cellular death occurs, this is called 'dehydration at cellular level'.[2][15][16] This is how a deficiency in pyruvate kinase results in hemolytic anaemia, the body is deficient in red blood cells as they are destroyed by lack of ATP at a larger rate than they are being created.[17] ## Diagnosis[edit] The diagnosis of pyruvate kinase deficiency can be done by full blood counts (differential blood counts) and reticulocyte counts.[18] Other methods include direct enzyme assays, which can determine pyruvate kinase levels in erythrocytes separated by density centrifugation, as well as direct DNA sequencing. For the most part when dealing with pyruvate kinase deficiency, these two diagnostic techniques are complementary to each other as they both contain their own flaws. Direct enzyme assays can diagnose the disorder and molecular testing confirms the diagnosis or vice versa.[6] Furthermore, tests to determine bile salts (bilirubin) can be used to see whether the gall bladder has been compromised.[18] ## Treatment[edit] Most affected individuals with pyruvate kinase deficiency do not require treatment. Those individuals who are more severely affected may die in utero of anemia or may require intensive treatment. With these severe cases of pyruvate kinase deficiency in red blood cells, treatment is the only option, there is no cure. However, treatment is usually effective in reducing the severity of the symptoms.[13][19] The most common treatment is blood transfusions, especially in infants and young children. This is done if the red blood cell count has fallen to a critical level.[12] The transplantation of bone marrow has also been conducted as a treatment option.[10] There is a natural way the body tries to treat this disease. It increases the erythrocyte production (reticulocytosis) because reticulocytes are immature red blood cells that still contain mitochondria and so can produce ATP via oxidative phosphorylation.[14] Therefore, a treatment option in extremely severe cases is to perform a splenectomy. This does not stop the destruction of erythrocytes but it does help increase the amount of reticulocytes in the body since most of the hemolysis occurs when the reticulocytes are trapped in the hypoxic environment of the spleen. This reduces severe anemia and the need for blood transfusions.[8] ## Epidemiology[edit] Pyruvate kinase deficiency happens worldwide, however northern Europe, and Japan have many cases. The prevalence of pyruvate kinase deficiency is around 51 cases per million in the population (via gene frequency).[13][20] ## See also[edit] * List of hematologic conditions ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): 266200 2. ^ a b c d e "Pyruvate Kinase Deficiency Clinical Presentation: History and Physical Examination". emedicine.medscape.com. Retrieved 2015-11-11. 3. ^ a b "Pyruvate kinase deficiency". Genetics Home Reference. 2015-11-09. Retrieved 2015-11-11. 4. ^ a b c "Pyruvate kinase deficiency: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-11-11. 5. ^ "Pyruvate kinase deficiency \| Disease \| Overview \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2015-11-11. 6. ^ a b Gallagher, Patrick G.; Glader, Bertil (2016-05-01). "Diagnosis of Pyruvate Kinase Deficiency". Pediatric Blood & Cancer. 63 (5): 771–772. doi:10.1002/pbc.25922. ISSN 1545-5017. PMID 26836632. 7. ^ a b Gordon-Smith, E.C. (1974). "Pyruvate kinase deficiency". Journal of Clinical Pathology. s3-8 (1): 128–133. doi:10.1136/jcp.27.suppl_8.128. PMC 1347209. PMID 4536359. 8. ^ a b "Pyruvate Kinase Deficiency: Practice Essentials, Background, Pathophysiology". 2016-08-23. Cite journal requires `\|journal=` (help) 9. ^ al.], [edited by] Ronald Hoffman ... [et (2013). Hematology basic principles and practice (6th ed.). Philadelphia, PA: Saunders/Elsevier. p. 703. ISBN 9781455740413.CS1 maint: extra text: authors list (link) 10. ^ a b Zanella, Alberto; Fermo, Elisa; Bianchi, Paola; Valentini, Giovanna (2005-07-01). "Red cell pyruvate kinase deficiency: molecular and clinical aspects". British Journal of Haematology. 130 (1): 11–25. doi:10.1111/j.1365-2141.2005.05527.x. ISSN 1365-2141. PMID 15982340. 11. ^ a b Christensen, Robert D.; Yaish, Hassan M.; Johnson, Charlotte B.; Bianchi, Paola; Zanella, Alberto (October 2011). "Six Children with Pyruvate Kinase Deficiency from One Small Town: Molecular Characterization of the PK-LR Gene". The Journal of Pediatrics. 159 (4): 695–697. doi:10.1016/j.jpeds.2011.05.043. PMID 21784452. 12. ^ a b Zanella, A.; Bianchi, P.; Fermo, E. (2007-06-01). "Pyruvate kinase deficiency". Haematologica. 92 (6): 721–723. doi:10.3324/haematol.11469. ISSN 0390-6078. PMID 17550841. 13. ^ a b c "Pyruvate Kinase Deficiency. Information about PKD \| Patient". Patient. Retrieved 2015-11-11. 14. ^ a b Wijk, Richard van; Solinge, Wouter W. van (2005-12-15). "The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis". Blood. 106 (13): 4034–4042. doi:10.1182/blood-2005-04-1622. ISSN 0006-4971. PMID 16051738. 15. ^ "Pyruvate Kinase Deficiency: Practice Essentials, Background, Pathophysiology". 2018-08-09. Cite journal requires `\|journal=` (help) 16. ^ Haematology Made Easy. AuthorHouse. 2013-02-06. p. 181. ISBN 9781477246511. 17. ^ Jacobasch, Gisela; Rapoport, Samuel M. (1996-04-01). "Chapter 3 Hemolytic anemias due to erythrocyte enzyme deficiencies". Molecular Aspects of Medicine. 17 (2): 143–170. doi:10.1016/0098-2997(96)88345-2. PMID 8813716. 18. ^ a b Disorders, National Organization for Rare (2003-01-01). NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. p. 496. ISBN 9780781730631. 19. ^ Davey, Patrick (2010-02-01). Medicine at a Glance. John Wiley & Sons. p. 341. ISBN 9781405186162. 20. ^ Beutler, Ernest; Gelbart, Terri (2000). "Estimating the prevalence of pyruvate kinase deficiency from the gene frequency in the general white population" (PDF). Blood. 95 (11): 3585–3588. doi:10.1182/blood.V95.11.3585. Archived from the original (PDF) on 2017-08-21. Retrieved 2016-11-25. ## Further reading[edit] * Hoffman, Ronald; Jr, Edward J. Benz; Silberstein, Leslie E.; Heslop, Helen; Weitz, Jeffrey; Anastasi, John (2013-02-12). Hematology: Diagnosis and Treatment. Elsevier Health Sciences. ISBN 978-1455776887. * Baroncian, Luciano (1994). "Prenatal Diagnosis of Pyruvate Kinase Deficiency" (PDF). Blood. 84 (7): 2354–2356. doi:10.1182/blood.V84.7.2354.2354. Archived from the original (PDF) on 3 January 2018. Retrieved 12 November 2015. ## External links[edit] Classification D * ICD-10: D55.2 * ICD-9-CM: 282.3 * OMIM: 266200 * MeSH: C564858 * DiseasesDB: 11090 External resources * MedlinePlus: 001197 * eMedicine: med/1980 * Patient UK: Pyruvate kinase deficiency Scholia has a topic profile for Pyruvate kinase deficiency. * v * t * e Diseases of red blood cells ↑ Polycythemia * Polycythemia vera ↓ Anemia Nutritional * Micro-: Iron-deficiency anemia * Plummer–Vinson syndrome * Macro-: Megaloblastic anemia * Pernicious anemia Hemolytic (mostly normo-) Hereditary * enzymopathy: Glucose-6-phosphate dehydrogenase deficiency * glycolysis * pyruvate kinase deficiency * triosephosphate isomerase deficiency * hexokinase deficiency * hemoglobinopathy: Thalassemia * alpha * beta * delta * Sickle cell disease/trait * Hereditary persistence of fetal hemoglobin * membrane: Hereditary spherocytosis * Minkowski–Chauffard syndrome * Hereditary elliptocytosis * Southeast Asian ovalocytosis * Hereditary stomatocytosis Acquired AIHA * Warm antibody autoimmune hemolytic anemia * Cold agglutinin disease * Donath–Landsteiner hemolytic anemia * Paroxysmal cold hemoglobinuria * Mixed autoimmune hemolytic anemia * membrane * paroxysmal nocturnal hemoglobinuria * Microangiopathic hemolytic anemia * Thrombotic microangiopathy * Hemolytic–uremic syndrome * Drug-induced autoimmune * Drug-induced nonautoimmune * Hemolytic disease of the newborn Aplastic (mostly normo-) * Hereditary: Fanconi anemia * Diamond–Blackfan anemia * Acquired: Pure red cell aplasia * Sideroblastic anemia * Myelophthisic Blood tests * Mean corpuscular volume * normocytic * microcytic * macrocytic * Mean corpuscular hemoglobin concentration * normochromic * hypochromic Other * Methemoglobinemia * Sulfhemoglobinemia * Reticulocytopenia * v * t * e Inborn error of carbohydrate metabolism: monosaccharide metabolism disorders Including glycogen storage diseases (GSD) Sucrose, transport (extracellular) Disaccharide catabolism * Congenital alactasia * Sucrose intolerance Monosaccharide transport * Glucose-galactose malabsorption * Inborn errors of renal tubular transport (Renal glycosuria) * Fructose malabsorption Hexose → glucose Monosaccharide catabolism Fructose: * Essential fructosuria * Fructose intolerance Galactose / galactosemia: * GALK deficiency * GALT deficiency/GALE deficiency Glucose ⇄ glycogen Glycogenesis * GSD type 0 (glycogen synthase deficiency) * GSD type IV (Andersen's disease, branching enzyme deficiency) * Adult polyglucosan body disease (APBD) Glycogenolysis Extralysosomal: * GSD type III (Cori's disease, debranching enzyme deficiency) * GSD type VI (Hers' disease, liver glycogen phosphorylase deficiency) * GSD type V (McArdle's disease, myophosphorylase deficiency) * GSD type IX (phosphorylase kinase deficiency) Lysosomal (LSD): * GSD type II (Pompe's disease, glucosidase deficiency) Glucose ⇄ CAC Glycolysis * MODY 2/HHF3 * GSD type VII (Tarui's disease, phosphofructokinase deficiency) * Triosephosphate isomerase deficiency * Pyruvate kinase deficiency Gluconeogenesis * PCD * Fructose bisphosphatase deficiency * GSD type I (von Gierke's disease, glucose 6-phosphatase deficiency) Pentose phosphate pathway * Glucose-6-phosphate dehydrogenase deficiency * Transaldolase deficiency * 6-phosphogluconate dehydrogenase deficiency Other * Hyperoxaluria * Primary hyperoxaluria * Pentosuria * Aldolase A 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-hydroxybutyric 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	Pyruvate kinase deficiency	c0340968	24,637	wikipedia	https://en.wikipedia.org/wiki/Pyruvate_kinase_deficiency	2021-01-18T18:48:42	{"gard": ["7514"], "mesh": ["C564858"], "umls": ["C0340968", "C1849472"], "icd-9": ["282.3"], "icd-10": ["D55.2"], "orphanet": ["766"], "wikidata": ["Q3043149"]}
Focal dystonia is a neurological condition, a type of dystonia, that affects a muscle or group of muscles in a specific part of the body, causing involuntary muscular contractions and abnormal postures. For example, in focal hand dystonia, the fingers either curl into the palm or extend outward without control. In musicians, the condition is called musician's focal dystonia, or simply, musician's dystonia. In sports, it may be involved in what is commonly referred to as the yips. ## Contents * 1 Causes * 2 Treatment * 3 Society * 4 References * 4.1 Sources ## Causes[edit] Current medical science does not precisely describe the causes of dystonia. Misfiring of neurons in the sensorimotor cortex, a thin layer of neural tissue that covers the brain, is thought to cause contractions. This misfiring may result from impaired inhibitory mechanisms during muscle contraction.[1] When the brain tells a given muscle to contract, it simultaneously silences muscles that would oppose the intended movement. It appears that dystonia interferes with the brain's ability to inhibit those surrounding muscles, leading to loss of selectivity.[1] The sensorimotor cortex is organized as discrete "maps" of the human body. Under normal conditions, each body part (such as individual fingers) occupies a distinct area on these cortical maps. In dystonia, these maps lose their distinct borders and overlap occurs.[2] Exploration of this initially involved over-training particular finger movements in non-human primates, which resulted in the development of focal hand dystonia. Examination of the primary somatosensory cortex in the trained animals showed grossly distorted representations of the maps pertaining to the fingers when compared to the untrained animals.[2] Additionally, these maps in the dystonic animals had lost the distinct borders that were noted in the untrained animals. Imaging studies in humans with focal dystonia have confirmed this finding.[3] Also, synchronous afferent stimulation of peripheral muscles induces organizational changes in motor representations, characterized both by an increase in map size of stimulated muscles and a reduction in map separation, as assessed using transcranial magnetic stimulation.[4] The cross-connectivity between areas that are normally segregated in the sensory cortex may prevent normal sensorimotor feedback and so contribute to the observed co-contraction of antagonist muscle groups, and inappropriately timed and sequenced movements that underlie the symptoms of focal dystonia. It is hypothesized that a deficit in inhibition caused by a genetically mediated loss of inhibitory interneurons may be the underlying cause of the deficits observed in dystonia.[1] While usually painless, in some instances the sustained contraction and abnormal posturing in dystonia cause pain. Focal dystonia most typically affects people who rely on fine motor skills—musicians, writers, surgeons, etc. It is thought that the excessive motor training those skills require may contribute to the development of dystonia as their cortical maps become enlarged and begin to overlap.[5] Focal dystonia is generally "task-specific", meaning that it is only problematic during certain activities. ## Treatment[edit] This condition is often treated with injections of botulinum neurotoxin A (BoNT/A). BoNT/A reduces the symptoms of the disorder but it is not a cure for dystonia. Since the root of the problem is neurological, doctors have explored sensorimotor retraining activities to enable the brain to "rewire" itself and eliminate dystonic movements. The work of several doctors such as Nancy Byl and Joaquin Farias has shown that sensorimotor retraining activities and proprioceptive stimulation can induce neuroplasticity, making it possible for patients to recover substantial function that was lost to focal dystonia.[6][7][8][9][10][11] Anticholinergics such as Artane can be prescribed for off-label use, as some sufferers have had success.[12] Bass guitarist and instructor Scott Devine said that he wears a glove while playing bass guitar because of the condition. He finds that the glove stops the involuntary finger movements. He says it works for him but does not suggest that it may work for everyone with the condition.[13] ## Society[edit] * Scott Adams, the writer of the Dilbert comics, has focal dystonia of the right hand, which impedes his artwork.[14] * Tom Adams, bluegrass banjo player, has focal dystonia in his right hand, and has switched to the guitar. * Badi Assad, Brazilian singer-guitarist, was diagnosed with focal dystonia in 1999; she eventually recovered and resumed her career.[15] * Andy Billups, bass guitarist with British rock group, The Hamsters, has made a partial recovery; he plays by using modified guitar plectrums. * Liona Boyd, Canadian classical guitarist, publicized as the "First Lady of the Guitar", retired from the concert stage for six years in 2003, due to focal dystonia that affected her right hand. She worked to retrain her right hand, and since 2009 has been performing again as a guitarist, singer, and songwriter.[16] * Berkley Breathed, American Pulitzer Prize winning comic strip artist and book writer/illustrator. Known for Bloom County, Opus, and others. His work was featured as that of the main character, as an adult, of the film Second Hand Lions. * Stuart Cassells, founder of the bagpipe rock group Red Hot Chilli Pipers, announced focal dystonia in September 2011; he has left the band. * Andrew Dawes, noted violinist and co-founder of the Orford String Quartet.[17] * Warren Deck, former tubist of the New York Philharmonic. * Keith Emerson, pianist and keyboard player * Leon Fleisher, an international concert pianist, dealt with this condition in his right hand beginning in the 1960s and switched to only left hand playing. In the 2000s, he regained use of his right hand and recommenced performing and recording with two hands. * Dominic Frasca, guitarist * Reinhard Goebel, Baroque violinist, switched to playing left-handed. * Gary Graffman, pianist, who changed to performing only with his left hand. * Jang Jae-in, Korean singer-songwriter and guitarist diagnosed with dystonia in her left hand in 2012. In 2015, on You Hee-yeol's Sketchbook, she announced that she quit playing guitar. * Alex Klein, principal oboist of the Chicago Symphony Orchestra[18] * David Leisner, classical guitarist, has recovered the full use of his hand after a decade of disability.[19] * Billy McLaughlin, guitarist, switched to playing left-handed when afflicted with dystonia. * Christian Münzner, ex-lead guitar of progressive extreme metal band Obscura * Apostolos Paraskevas, Greek-American classical guitarist-composer, was struck by focal dystonia to his right hand in 2009. He fully recovered in 2013 after 7,000 hours of personal work in re-constructing his technique. He was able to decode the condition as an unconscious behavioral habit and returned to performing professionally again. His rehabilitation was based on reducing tension in his hand and retraining his brain through proper, relaxed hand movements, practiced extensively. His article A Classical Guitarist's Story of Recovery from Focal Dystonia will be published in London on the Classical Guitar Magazine * Charlie Parr, American country blues musician from Minnesota[20] * Victor Wooten, bassist, suffers from it on both hands ## References[edit] 1. ^ a b c Hallet, Mark (2011). "Neurophysiology of dystonia: The role of inhibition". Neurobiology of Disease. 42 (2): 177–184. doi:10.1016/j.nbd.2010.08.025. PMC 3016461. PMID 20817092. 2. ^ a b Byl, NN; Merzenich, MM; Jenkins, WM. (1996). "A primate genesis model of focal dystonia and repetitive strain injury: I. Learning-induced dedifferentiation of the representation of the hand in the primary somatosensory cortex in adult monkeys". Neurology. 47 (2): 508–20. doi:10.1212/wnl.47.2.508. PMID 8757029. 3. ^ Bara-Jimenez, W; Catalan, MJ; Hallett, M; Gerloff, C (1998). "Abnormal somatosensory homunculus in dystonia of the hand". Annals of Neurology. 44 (5): 828–831. doi:10.1002/ana.410440520. PMID 9818942. 4. ^ Schabrun SM, Ridding MC (2007). "The influence of correlated afferent input on motor cortical representations in humans". Experimental Brain Research. 183 (1): 41–49. doi:10.1007/s00221-007-1019-8. PMID 17602215. 5. ^ Rosenkranz, Karin; Katherine Butler; Aaron Williamon; John C. Rothwell (November 18, 2009). "Regaining Motor Control in Musician's Dystonia by Restoring Sensorimotor Organization". The Journal of Neuroscience. 29 (46): 14627–14636. doi:10.1523/JNEUROSCI.2094-09.2009. PMC 2998172. PMID 19923295. 6. ^ TEDx Talk. Federico Bitti. Cervical Dystonia. Rewiring the brain through dance. https://www.youtube.com/watch?v=DwkHK3rfKO0 7. ^ TEDx Talk . Joaquin Farias. Dystonia. Your movement can heal your brain. https://www.youtube.com/watch?v=czW-xBvDtHY 8. ^ Glove and Mail. Choosing music over meds, one man's quest to retrain his brain to overcome dystonia. https://www.youtube.com/watch?v=IpcXkV_ex8Y 9. ^ Farias J, Yoshie M. Treatment efficacy in an ecologically valid neuropsycological treatment program of 120 professional musicians with focal dystonia, Galene Editions. Amsterdam 2012. ISBN 978-84-615-5124-8. 10. ^ Farias, J., Sarti-Martínez, MA. Title: "Elite musicians treated by specific fingers motion program to stimulate propiceptive sense", Congreso Nacional De La Sociedad Anatómica Española, Alicante (España), European Journal of Anatomy, p. 110 11. ^ Open Your Eyes. Freedom from Blepharospasm. Documentary. Out of the Box Productions. https://www.youtube.com/watch?v=BlWXcsjyswY 12. ^ Dystonia. The Canadian Movement Disorder group. http://cmdg.org/Dystonia/dystonia.htm 13. ^ Why I Wear "The Gloves" (starting at the 5:00 mark of the video) https://www.youtube.com/watch?v=wOVGrGBeqiI 14. ^ Sordyl, Samantha (2005-05-10). "Scott Adams, Drawing the Line". The Washington Post. Retrieved 2010-05-02. 15. ^ Badi Assad's web site 16. ^ "Biography". Liona Boyd - Classical Guitar. Retrieved 23 April 2018. 17. ^ http://www.wevancouver.com/news/202340481.html 18. ^ "Chicago Symphony Orchestra -". cso.org. Retrieved 23 April 2018. 19. ^ "2018 March Newsletter". Red Hot Chilli Pipers. Retrieved 23 April 2018. 20. ^ Rivera, Erica. "Man of constant sorrow: Charlie Parr's quiet battle to stay alive - City Pages". City Pages. Retrieved 23 April 2018. ### Sources[edit] * Tubiana, Raoul, Amadio, Peter C.; Medical Problems of the Instrumentalist Musician; UK; Martin Dunitz (2000); 295-397 * Rich, Robert F.; Mackin, Evelyn; Callahan, Anne; A. Lee Osterman; Terri M. Skirven; Schneider, Lawrence J. (2002). Hunter, Mackin & Callahan's Rehabilitation of the Hand and Upper Extremity (2 Volume Set). St. Louis: Mosby. pp. 2053–2075 ("Focal Hand Dystonia"). ISBN 978-0-323-01094-8. * Farias, Joaquin. "Limitless. How your movements can heal your brain. An essay on the neurodynamics of dystonia". Galene Editions 2016. * Farias, Joaquin. "Intertwined. How to induce neuroplasticity. A new approach to rehabilitating dystonias". Galene Editions 2012. * Farias, Joaquin. "Rebellion of the body. Understanding musician's Focal dystonia". Galene Editions 2004. * Leisner, David (2007). "Curing Focal Dystonia or How to Play the Guitar with Large Muscles". Guitar Review. 133: 10–15. * Pascual-Leone A (2001). "The brain that plays music and is changed by it". Ann. N. Y. Acad. Sci. 930 (1): 315–329. Bibcode:2001NYASA.930..315P. doi:10.1111/j.1749-6632.2001.tb05741.x. PMID 11458838.[permanent dead link] * Solomon, Jason W. (2007). "What Every Guitarist Should Know: A Guide to the Prevention and Rehabilitation of Focal Dystonia" (PDF). Guitar Review. 133: 2–9. Archived from the original (PDF) on 2007-10-20. * Farias, Joaquin \- Farias Technique * Gorrie, Jon. "Musician's Focal Dystonia" * v * t * e Music psychology Areas * Biomusicology * Cognitive musicology * Cognitive neuroscience of music * Culture in music cognition * Evolutionary musicology * Psychoacoustics Topics * Absolute pitch * Auditory illusion * Auditory imagery * Background music * Consonance and dissonance * Deutsch's scale illusion * Earworm * Embodied music cognition * Entrainment * Exercise and music * Eye movement in music reading * Franssen effect * Generative theory of tonal music * Glissando illusion * Hedonic music consumption model * Illusory continuity of tones * Levitin effect * Lipps–Meyer law * Melodic expectation * Melodic fission * Mozart effect * Music and emotion * Music and movement * Music in psychological operations * Music preference * Music-related memory * Musical gesture * Musical semantics * Musical syntax * Octave illusion * Relative pitch * Sharawadji effect * Shepard tone * Speech-to-song illusion * Temporal dynamics of music and language * Tonal memory * Tritone paradox Disorders * Amusia * Auditory arrhythmia * Beat deafness * Musical hallucinations * Musician's dystonia * Music-specific disorders * Tone deafness Related fields * Aesthetics of music * Bioacoustics * Ethnomusicology * Hearing * Melodic intonation therapy * Music education * Music therapy * Musical acoustics * Musicology * Neurologic music therapy * Neuronal encoding of sound * Performance science * Philosophy of music * Psychoanalysis and music * Sociomusicology * Systematic musicology * Zoomusicology Researchers * Jamshed Bharucha * Lola Cuddy * Robert Cutietta * Jane W. Davidson * Irène Deliège * Diana Deutsch * Tuomas Eerola * Henkjan Honing * David Huron * Nina Kraus * Carol L. Krumhansl * Fred Lerdahl * Daniel Levitin * Leonard B. Meyer * Max Friedrich Meyer * James Mursell * Richard Parncutt * Oliver Sacks * Carl Seashore * Max Schoen * Roger Shepard * John Sloboda * Carl Stumpf * William Forde Thompson * Sandra Trehub Books and journals * Music Perception * Musicae Scientiae (journal) * Musicophilia * Music, Thought, and Feeling * Psychology of Music (journal) * The World in Six Songs * This Is Your Brain on Music [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-hydroxybutyric 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	Focal dystonia	c0743332	24,638	wikipedia	https://en.wikipedia.org/wiki/Focal_dystonia	2021-01-18T19:02:51	{"gard": ["6458"], "mesh": ["D020821"], "wikidata": ["Q1428695"]}
Lafora disease Other namesLafora progressive myoclonic epilepsy or MELF[1] Gonzalo Rodríguez Lafora, discoverer of the disease SpecialtyNeurology Usual onsetlate childhood and adolescence, usually ages 8-19 years.[2] CausesMutation in either EMP2A or EMP2 genes.[3] Differential diagnosisOther progressive myoclonic epilepsies (sialidosis, myoclonic epilepsy with ragged red fibers, Unverricht-Lundborg disease), Juvenile Myoclonic Epilepsy, Subacute sclerosing panencephalitis, schizophrenia[2] PrognosisUniversally fatal; Most of the time, death occurs within 10 years after onset of initial symptoms. Lafora disease is a fatal autosomal recessive,[4] genetic disorder characterized by the presence of inclusion bodies, known as Lafora bodies, within the cytoplasm of the cells in the heart, liver, muscle, and skin.[5]:545 Lafora disease is also a neurodegenerative disease that causes impairment in the development of cerebral cortical neurons and is a glycogen metabolism disorder. Lafora disease, is a rare, adult-onset recessive neurodegenerative disease, which results in myoclonus epilepsy and usually results in death several years after the onset of symptoms. The disease is characterized by the accumulation of insoluble particles called Lafora bodies, which are derived from glycogen.[6] Lafora disease (LD) was described by the Spanish Neuropathologist Gonzalo Rodríguez Lafora (1886-1971) in 1911, while directing the Neuropathology Section at the Government Hospital for Mental Insane (current NIH, USA) Gonzalo Rodríguez Lafora was a disciple of Santiago Ramón y Cajal (Nobel laureate in Physiology or Medicine 1906) and one of the most brilliant exponents of the Cajal School or the Spanish Neurological School. Typically Lafora is very rare in children, adolescents and adults worldwide. However, Lafora disease has a higher incidence among children and adolescents with ancestry from regions where incestuous relationships are common, namely the Mediterranean (North Africa, Southern Europe), the Middle East, India, and Pakistan.[7] Dogs can also have the condition. In canines, Lafora disease can spontaneously occur in any breed, but the Miniature Wire Haired Dachshund, Bassett Hound, and the Beagle are predisposed to LD.[8] Most human patients with this disease do not live past the age of twenty-five, and death within ten years of symptoms is usually inevitable. Late on-set symptoms of this disease can begin at any age depending on the genes affected.[9] At present, there is no cure for this disease but there are ways to deal with symptoms through treatments and medications. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Lafora bodies * 4 Diagnosis * 5 Treatment * 6 Research * 7 References * 8 External links ## Signs and symptoms[edit] Symptoms of Lafora disease begin to develop during the early adolescent years, and symptoms progress as time passes. In the years before then, there is generally no indication of the presence of the disease, though in a few cases, the disease presents as a learning disorder around 5 years of age.[3] In extremely rare cases, symptoms may not show at all until as late as the 3rd decade of life, though these cases have slower progression than typical LD.[10] The most common feature of Lafora disease is seizures that have been reported mainly as occipital seizures and myoclonic seizures with some cases of generalized tonic-clonic seizures, atypical absence seizures, and atonic and complex partial seizures.[11][12] Other symptoms common with the seizures are drop attacks, ataxia, temporary blindness, visual hallucinations, and a quickly-developing and dramatic dementia.[4][11] Other common signs and symptoms associated with Lafora disease are behavioral changes due to the frequency of seizures.[13] Over time those affected with Lafora disease have brain changes that cause confusion, speech difficulties, depression, decline in intellectual function, impaired judgement and impaired memory.[13] If areas of the cerebellum are affected by seizures, it is common to see problems with speech, coordination, and balance in Lafora patients.[13] For dogs that are affected with Lafora disease, common symptoms are rapid shuddering, shaking, or jerking of the canine's head backwards, high pitched vocalizations that could indicate the dog is panicking, seizures, and as the disease progresses dementia, blindness, and loss of balance.[14] ## Genetics[edit] Lafora disease is an autosomal recessive disorder, caused by loss of function mutations in either laforin glycogen phosphatase gene (EPM2A) or malin E3 ubiquitin ligase gene (NHLRC1).[15][16] These mutations in either of these two genes lead to polyglucosan formation or lafora body formation in the cytoplasm of heart, liver, muscle, and skin.[15] EPM2A codes for the protein laforin, a dual-specificity phosphatase that acts on carbohydrates by taking phosphates off.[15] NHLRC1 encodes the protein malin, an E3 ubiquitin ligase, that regulates the amount of laforin.[15] Laforin is essential for making the normal structure of glycogen. When the mutation occurs on the EPM2A gene, laforin protein is downregulated and less amount of this protein is present or none is made at all. If there is also a mutation in the NHLRC1 gene that makes the protein malin, then laforin cannot be regulated and thus less of it is made. Less Laforin means more phosphorylation of glycogen, causing conformational changes, rendering it insoluble, leading to an accumulation of misformed glycogen, which has neurotoxic effects. Lafora disease has an autosomal recessive pattern of inheritance.[16] EPM2A gene found on chromosome 6q24 and NHLRC1 gene found on chromosome 6p22.3.[17] In a laforin mutation, glycogen would be hyperphosphorylated; this has been confirmed in laforin knock-out mice.[18] Research literature also suggests that over-activity of glycogen synthase, the key enzyme in synthesizing glycogen, can lead to the formation of polyglucosans and it can be inactivated by phosphorylation at various amino acid residues by many molecules, including GSK-3beta, Protein phosphatase 1, and malin.[19][20][21] As defective enzyme molecules participate in the production of these molecules (GSK-3beta, PP1, and malin), excessive glycogen synthase activity occurs in combination with mutations in laforin that phosphorylates the excess glycogen being made, rendering it insoluble. The key player missing is ubiquitin. It is not able to degrade the excess amount of the insoluble lafora bodies. Since mutations arise in malin, an e3 ubiquitin ligase, this directly interferes with the degradation of laforin, causing the laforin not to be degraded; it can then hyperphosphorylate.[22] ## Lafora bodies[edit] Lafora disease is distinguished by the presence of inclusions called "Lafora bodies" within the cytoplasm of cells. Lafora bodies are aggregates of polyglucosans or abnormally shaped glycogen molecules.[23] Glycogen in Lafora disease patients has abnormal chain lengths, which causes them to be insoluble, accumulate, and have a neurotoxic effect.[24] For glycogen to be soluble, there must be short chains and a high frequency of branching points, but this is not found in the glycogen in Lafora patients. LD patients have longer chains that have clustered arrangement of branch points that form crystalline areas of double helices making it harder for them to clear the blood-brain barrier.[24] The glycogen in LD patients also has higher phosphate levels and is present in greater quantities.[24] ## Diagnosis[edit] Lafora Disease is diagnosed by conducting a series of tests by a neurologist, epileptologist (person who specializes in epilepsy), or geneticist. To confirm the diagnosis, an EEG, MRI, and genetic testing are needed.[13] A biopsy may be necessary as well to detect and confirm the presence of Lafora bodies in the skin.[13] Typically, if a patient comes to a doctor and has been having seizures, as patients with LD characteristically have, these are the standard screening tests. ## Treatment[edit] Unfortunately there is no cure for Lafora Disease with treatment being limited to controlling seizures through anti-epileptic and anti-convulsant medications.[25] The treatment is usually based on the individual's specific symptoms and the severity of those symptoms. Some examples of medications include valproate, levetiracetam, topiramate, benzodiazepines, or perampanel.[26] Although the symptoms and seizures can be controlled for a long period by using anti-epileptic drugs, the symptoms will progress and patients lose their ability to perform daily activities leading to the survival rate of approximately 10 years after symptoms begin.[26] Quality of life worsens as the years go on, with some patients requiring a feeding tube so that they can get the nutrition and medication they need in order to keep functioning, but not necessarily living.[26] Recently Metformin is approved for the treatment. ## Research[edit] The disease is named after Gonzalo Rodríguez Lafora (1886–1971), a Spanish neuropathologist who first recognized small inclusion bodies in Lafora patients.[27] Since the discovery of Lafora Disease in early to mid 1900s there has not been too much research into it, until more recent years. Recent research is looking into how inhibition of glycogen synthesis, since increased glucose uptake causes increased glycogen, could potentially stop the formation of the Lafora Bodies in neurons in laforin-deficient mice models while also reducing the chances of seizures.[28] The adipocyte hormone Leptin is what this research targeted by blocking the leptin signaling to reduce glucose uptake and stop Lafora bodies from forming.[28] Other researchers are looking into the ways in which Lafora bodies are being regulated at the level of gene expression. There is specific research looking into how Laforin, a glycogen dephosphatase, gene expression is potentially being downregulated or mutations are arising in the DNA in LD allowing more phosphates to be present helping to render glycogen insoluble.[29] During the past two years (2015-2017), researchers in U.S., Canada, and Europe have formed the (LECI) Lafora Epilepsy Cure Initiative to try and find a cure for Lafora Disease with funding from the National Institutes of Health (NIH) led by Dr. Matthew Gentry at the University of Kentucky. Since researchers have found the two genes that cause LD, they are currently aiming to interrupt the process of how these mutations in those genes interfere with normal carbohydrate metabolism in mice models. They predict they will have one or more drugs ready for human clinical trials within the next few years.[30] ## References[edit] 1. ^ http://www.rightdiagnosis.com/medical/melf.htm 2. ^ a b "Progressive Myoclonus Epilepsy, Lafora Type". 3. ^ a b "Lafora Overview". 4. ^ a b Ianzano L, Zhang J, Chan EM, Zhao XC, Lohi H, Scherer SW, Minassian BA (2005). "Lafora progressive Myoclonus Epilepsy mutation database - EPM2A and NHLRC1 (EPM2B) genes". Hum. Mutat. 26 (4): 397. doi:10.1002/humu.9376. PMID 16134145. 5. ^ James, William D.; Berger, Timothy G. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 6. ^ Ortolano, S.; Vieitez, I.; Agis-Balboa, R. C.; Spuch, C. (2014). "Loss of GABAergic cortical neurons underlies the neuropathology of Lafora disease". Molecular Brain. 7: 7. doi:10.1186/1756-6606-7-7. PMC 3917365. PMID 24472629. 7. ^ Anna C Jansen, MD, PhD and Eva Andermann. "Progressive Myoclonus Epilepsy, Lafora Type".CS1 maint: multiple names: authors list (link) 8. ^ Kamm, Kurt. "Lafora disease research". www.canineepilepsy.co.uk. Retrieved 2017-11-07. 9. ^ Minassan (2000). "Lafora's Disease:Towards a Clinical, Pathologic, and Molecular Synthesis". Pediatr Neurol. 25 (1): 21–29. doi:10.1016/S0887-8994(00)00276-9. PMID 11483392. 10. ^ David S. Lynch, Nicholas W. Wood, and Henry Houlden (2016). "Late-onset Lafora disease with prominent parkinsonism due to a rare mutation in EPM2A". Neurology. Genetics. 2 (5): e101. doi:10.1212/NXG.0000000000000101. PMC 4988466. PMID 27574708.CS1 maint: multiple names: authors list (link) 11. ^ a b "Lafora disease \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-12-09. 12. ^ Jansen, Anna C.; Andermann, Eva (1993). "Progressive Myoclonus Epilepsy, Lafora Type". In Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E.; Bean, Lora J.H.; Mefford, Heather C.; Stephens, Karen; Amemiya, Anne; Ledbetter, Nikki (eds.). GeneReviews®. Seattle (WA): University of Washington, Seattle. PMID 20301563. 13. ^ a b c d e "Lafora Progressive Myoclonus Epilepsy". Epilepsy Foundation. Retrieved 2017-12-12. 14. ^ "Lafora Disease in Dogs - Symptoms, Causes, Diagnosis, Treatment, Recovery, Management, Cost". WagWalking. Retrieved 2017-12-12. 15. ^ a b c d Kecmanović, Miljana; Keckarević-Marković, Milica; Keckarević, Dušan; Stevanović, Galina; Jović, Nebojša; Romac, Stanka (2016-05-02). "Genetics of Lafora progressive myoclonic epilepsy: current perspectives". The Application of Clinical Genetics. 9: 49–53. doi:10.2147/TACG.S57890. ISSN 1178-704X. PMC 4859416. PMID 27194917. 16. ^ a b Reference, Genetics Home. "Lafora progressive myoclonus epilepsy". Genetics Home Reference. Retrieved 2017-12-12. 17. ^ Ianzano, Leonarda; Zhang, Junjun; Chan, Elayne M.; Zhao, Xiao-Chu; Lohi, Hannes; Scherer, Stephen W.; Minassian, Berge A. (October 2005). "Lafora progressive Myoclonus Epilepsy mutation database-EPM2A and NHLRC1 (EPM2B) genes". Human Mutation. 26 (4): 397. doi:10.1002/humu.9376. ISSN 1098-1004. PMID 16134145. 18. ^ Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando (26 August 2016). "Insights into Brain Glycogen Metabolism". Journal of Biological Chemistry. 291 (35): 18072–18083. doi:10.1074/jbc.M116.738898. PMC 5000057. PMID 27402852. 19. ^ Wang, Wei; Lohi, Hannes; Skurat, Alexander V.; DePaoli-Roach, Anna A.; Minassian, Berge A.; Roach, Peter J. (2007-01-15). "Glycogen metabolism in tissues from a mouse model of Lafora disease". Archives of Biochemistry and Biophysics. 457 (2): 264–269. doi:10.1016/j.abb.2006.10.017. ISSN 0003-9861. PMC 2577384. PMID 17118331. 20. ^ Sullivan, Mitchell A.; Nitschke, Silvia; Steup, Martin; Minassian, Berge A.; Nitschke, Felix (2017-08-11). "Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan". International Journal of Molecular Sciences. 18 (8): 1743. doi:10.3390/ijms18081743. ISSN 1422-0067. PMC 5578133. PMID 28800070. 21. ^ Ianzano, L; Zhao, XC; Minassian, BA; Scherer, SW (June 2003). "Identification of a novel protein interacting with laforin, the EPM2a progressive myoclonus epilepsy gene product". Genomics. 81 (6): 579–87. doi:10.1016/S0888-7543(03)00094-6. ISSN 0888-7543. PMID 12782127. 22. ^ Gentry, Matthew S.; Worby, Carolyn A.; Dixon, Jack E. (2005-06-14). "Insights into Lafora disease: Malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin". Proceedings of the National Academy of Sciences of the United States of America. 102 (24): 8501–8506. doi:10.1073/pnas.0503285102. ISSN 0027-8424. PMC 1150849. PMID 15930137. 23. ^ Turnbull, Julie; Girard, Jean-Marie; Lohi, Hannes; Chan, Elayne M.; Wang, Peixiang; Tiberia, Erica; Omer, Salah; Ahmed, Mushtaq; Bennett, Christopher (September 2012). "Early-onset Lafora body disease". Brain. 135 (9): 2684–2698. doi:10.1093/brain/aws205. ISSN 0006-8950. PMC 3437029. PMID 22961547. 24. ^ a b c Nitschke, Felix; Sullivan, Mitchell A; Wang, Peixiang; Zhao, Xiaochu; Chown, Erin E; Perri, Ami M; Israelian, Lori; Juana‐López, Lucia; Bovolenta, Paola (July 2017). "Abnormal glycogen chain length pattern, not hyperphosphorylation, is critical in Lafora disease". EMBO Molecular Medicine. 9 (7): 906–917. doi:10.15252/emmm.201707608. ISSN 1757-4676. PMC 5494504. PMID 28536304. 25. ^ Striano, Pasquale; Zara, Federico; Turnbull, Julie; Girard, Jean-Marie; Ackerley, Cameron A.; Cervasio, Mariarosaria; De Rosa, Gaetano; Del Basso-De Caro, Maria Laura; Striano, Salvatore (February 2008). "Typical progression of myoclonic epilepsy of the Lafora type: a case report". Nature Clinical Practice Neurology. 4 (2): 106–111. doi:10.1038/ncpneuro0706. ISSN 1745-8358. PMID 18256682. S2CID 19653919. 26. ^ a b c "Lafora Progressive Myoclonus Epilepsy". Epilepsy Foundation. Retrieved 2017-12-13. 27. ^ Lafora's disease at Who Named It? 28. ^ a b Rai, Anupama; Mishra, Rohit; Ganesh, Subramaniam (2017-12-15). "Suppression of leptin signaling reduces polyglucosan inclusions and seizure susceptibility in a mouse model for Lafora disease". Human Molecular Genetics. 26 (24): 4778–4785. doi:10.1093/hmg/ddx357. ISSN 0964-6906. PMID 28973665. 29. ^ Raththagala, Madushi; Brewer, M. Kathryn; Parker, Matthew W.; Sherwood, Amanda R.; Wong, Brian K.; Hsu, Simon; Bridges, Travis M.; Paasch, Bradley C.; Hellman, Lance M.; Husodo, Satrio; Meekins, David A.; Taylor, Adam O.; Turner, Benjamin D.; Auger, Kyle D.; Dukhande, Vikas V.; Chakravarthy, Srinivas; Sanz, Pascual; Woods, Virgil L.; Li, Sheng; Vander Kooi, Craig W.; Gentry, Matthew S. (January 22, 2015). "Structural Mechanism of Laforin Function in Glycogen Dephosphorylation and Lafora Disease" (PDF). Molecular Cell. 57 (2): 261–272. doi:10.1016/j.molcel.2014.11.020. PMC 4337892. PMID 25544560. 30. ^ "Researchers Coordinate Efforts to Find Cure for Lafora Disease". Epilepsy Foundation. Retrieved 2017-12-13. ## External links[edit] Classification D * ICD-10: G40.3 * ICD-9-CM: 333.2 * OMIM: 254780 * MeSH: D020192 * DiseasesDB: 30834 * Lafora disease - OxfordJournals.org * GeneReview/NCBI/NIH/UW entry on Progressive Myoclonus Epilepsy, Lafora Type * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis * v * t * e Seizures and epilepsy Basics * Seizure types * Aura (warning sign) * Postictal state * Epileptogenesis * Neonatal seizure * Epilepsy in children Management * Anticonvulsants * Investigations * Electroencephalography * Epileptologist Personal issues * Epilepsy and driving * Epilepsy and employment Seizure types Focal Seizures Simple partial Complex partial Gelastic seizure Epilepsy Temporal lobe epilepsy Frontal lobe epilepsy Rolandic epilepsy Nocturnal epilepsy Panayiotopoulos syndrome Vertiginous epilepsy Generalised * Tonic–clonic * Absence seizure * Atonic seizure * Automatism * Benign familial neonatal seizures * Lennox–Gastaut syndrome * Myoclonic astatic epilepsy * Epileptic spasms Status epilepticus * Epilepsia partialis continua * Complex partial status epilepticus Myoclonic epilepsy * Progressive myoclonus epilepsy * Dentatorubral–pallidoluysian atrophy * Unverricht–Lundborg disease * MERRF syndrome * Lafora disease * Juvenile myoclonic epilepsy Non-epileptic seizure * Febrile seizure * Psychogenic non-epileptic seizure Related disorders * Sudden unexpected death in epilepsy * Todd's paresis * Landau–Kleffner syndrome * Epilepsy in animals Organizations * Citizens United for Research in Epilepsy (US) * Epilepsy Action (UK) * Epilepsy Action Australia * Epilepsy Foundation (US) * Epilepsy Outlook (UK) * Epilepsy Research UK * Epilepsy Society (UK) [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-hydroxybutyric 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	Lafora disease	c1850764	24,639	wikipedia	https://en.wikipedia.org/wiki/Lafora_disease	2021-01-18T18:37:36	{"gard": ["8214"], "mesh": ["C564976", "D020192"], "umls": ["C1850764"], "icd-9": ["345.1"], "icd-10": ["G40.3"], "orphanet": ["501"], "wikidata": ["Q163905"]}
Pseudo-Hurler polydystrophy Other namesMucolipidosis III alpha/beta [1] Pseudo-Hurler polydystrophy is inherited in an autosomal recessive manner SpecialtyMedical genetics Pseudo-Hurler polydystrophy, also referred to as mucolipidosis III (ML III), is a lysosomal storage disease closely related to I-cell disease (ML II).[2] This disorder is called Pseudo-Hurler because it resembles a mild form of Hurler syndrome, one of the mucopolysaccharide (MPS) diseases. ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Signs and symptoms[edit] Symptoms of ML III are often not noticed until the child is 3–5 years of age. Patients with ML III are generally of normal intelligence (trait) or have only mild mental retardation. These patients usually have skeletal abnormalities, coarse facial features, short height, corneal clouding, carpal tunnel syndrome, aortic valve disease and mild enlargement of organs. Some children with severe forms of this disease do not live beyond childhood. However, there is a great variability among patients - there are diagnosed individuals with ML III living in their sixties.[citation needed] ## Pathophysiology[edit] As in Mucolipidosis II, Mucolipidosis III results from genetic defects in GlcNAc phosphotransferase (N-acetylglucosamine-1-phosphotransferase). However, ML III produces less severe symptoms and progresses more slowly, probably because the defect in GlcNAc phosphotranspherase lies in its protein recognition domain.[3] Therefore, the catalytic domain retains some of its activity, resulting in a smaller accumulation of carbohydrates, lipids, and proteins in the inclusion bodies.[citation needed] ## Diagnosis[edit] This section is empty. You can help by adding to it. (May 2017) ## Treatment[edit] There is no cure for Pseudo-Hurler Polydystrophy/Mucolipidosis IIIA. Treatment is limited to controlling or reducing symptoms associated with this disorder. Physio-therapy, particularly hydrotherapy has proven effective at relieving muscle stiffness and increasing mobility. The use of crutches, a wheelchair or scooters are treatment options as the metabolic bone disease progresses. The insertion of rods in the spine to stabilize the vulnerable areas can treat scoliosis. Heart valve replacement surgery may be necessary as this disorder progresses, Enzyme replacement therapy has been suggested as a potential treatment ## See also[edit] * Mucolipidosis * I-cell disease ## References[edit] 1. ^ "Mucolipidosis III alpha/beta \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 11 April 2019. 2. ^ Bargal R, Zeigler M, Abu-Libdeh B, et al. (August 2006). "When Mucolipidosis III meets Mucolipidosis II: GNPTA gene mutations in 24 patients". Mol. Genet. Metab. 88 (4): 359–63. doi:10.1016/j.ymgme.2006.03.003. PMID 16630736. 3. ^ Murray, R, Granner, D, and Rodwell, V. (2006). Harper's Illustrated Biochemistry. 27th ed. New York: Lange Medical Books/McGraw-Hill. ## External links[edit] Classification D * ICD-10: E77.0 * ICD-9-CM: 272.7 * OMIM: 252600 * MeSH: D009081 * DiseasesDB: 29378 * Mucolipidosis type 3 A at NIH's Office of Rare Diseases * mucolipidoses at NINDS \- original text of article derived from detail sheet available here * v * t * e Lysosomal storage diseases: Inborn errors of carbohydrate metabolism (Glycoproteinoses) Anabolism * Dolichol kinase deficiency * Congenital disorder of glycosylation Post-translational modification of lysosomal enzymes * Mucolipidosis: I-cell disease (ML II) * Pseudo-Hurler polydystrophy (ML III) Catabolism * Aspartylglucosaminuria * Fucosidosis * mannosidosis * Alpha-mannosidosis * Beta-mannosidosis * Sialidosis * Schindler disease Other * solute carrier family (Salla disease) * Galactosialidosis [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-hydroxybutyric 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	Pseudo-Hurler polydystrophy	c0033788	24,640	wikipedia	https://en.wikipedia.org/wiki/Pseudo-Hurler_polydystrophy	2021-01-18T18:43:34	{"gard": ["3806"], "mesh": ["D009081"], "umls": ["C0033788", "C2673375"], "icd-9": ["272.7"], "icd-10": ["E77.0"], "orphanet": ["577", "423461"], "wikidata": ["Q7254411"]}
Vulvar tumors are those neoplasms of the vulva. Vulvar and vaginal neoplasms make up a small percentage (3%) of female genital cancers.[1] They can be benign or malignant (vulvar cancer).[2][3][4][5] Vulvar neoplasms are divided into cystic or solid lesions and other mixed types.[6] Vulvar cancers are those malignant neoplasms that originate from vulvar epithelium, while vulvar sarcomas develop from non-epithelial cells such as bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.[7] Epithelial and mesenchymal tissue are the origin of vulvar tumors.[1] Malignant vulvar neoplasms makes up 6% of all reproductive organ cancer and 0.7% of the total cancers in women in the United States. One out of every 333 women will develop vulvar cancer. In the United States, vulvar cancer accounts for nearly 6% of cancers of the female reproductive organs and 0.7% of all cancers in women. In 2018, there will be 6,190 women diagnosed with cancer of the vulva with 1,200 women dying from it.[8] Malignant vulvar tumors can develop in the inner edges of the labia majora, labia minora, clitoris or in the Bartholin glands.[9] Research in preventing vulvar cancers includes investigations into the use of oncogenes, tumor suppressor genes, drug treatments, surgery, radiation therapy, chemotherapy, and lymph node mapping.[10] ## Contents * 1 Epithelial neoplasms * 1.1 Squamous tumors precursors * 1.2 Glandular Tumors * 1.3 Soft tissue Tumors * 1.4 Melanocytic Tumors * 1.5 Other * 1.6 Haematopoietic and lymphoid Tumors * 1.7 Secondary tumors[12] * 1.8 Benign cystic lesions * 1.8.1 Solid lesions * 1.8.2 Mesenchymal and other subcutaneious lesions * 2 See also * 3 References * 4 External links ## Epithelial neoplasms[edit] ### Squamous tumors precursors[edit] * Squamous cell carcinoma not otherwise specified * Basal cell carcinoma * Squamous intraepithelial neoplasia * Benign squamous lesions ### Glandular Tumors[edit] * Paget disease * Bartholin gland Tumors: carcinomas, adenoma and adenomyoma * Tumor arising from specialized ano-genital mammary-like glands * Adenocarcinoma of Shene gland origin * Adenocarcinoma of other types * Adenoma of minor vestibular glands * Mixed Tumors of the vulva * Tumors of skin appendage origin ### Soft tissue Tumors[edit] * Embryonal rhabdomyosarcoma (sarcoma botryoides) * Leiomyosarcoma * Fibrous histiocytoma * Proximal epithelioid sarcoma * Alveolar soft part sarcoma * Liposarcoma * Dermatofibrosarcoma protuberans * Deep angiomyxoma * Superficial angiomyxoma * Angiomyofibroblastoma * Cellular angiofibroma * Leiomyoma * Granular cell Tumor ### Melanocytic Tumors[edit] * Malignant melanoma * Congenital melanocytic naevus * Acquired melanocytic naevus * Blue naevus * Atypical melanocytic naevus of genital type * Dysplastic melanocytic naevus ### Other[edit] * Yolk sac Tumor * Merkel cell Tumor * Peripheral primitive neuroectodermal Tumor/Ewing sarcoma ### Haematopoietic and lymphoid Tumors[edit] * Malignant lymphoma * Leukemia[11] ### Secondary tumors[12][edit] ### Benign cystic lesions[edit] * Bartholin duct cysts and abscesses * Skene duct cyst * Mucinous cyst * Ciliated cyst * Gartner duct cyst * Cyst of the Canal of Nuck * Perineal hernia[13] #### Solid lesions[edit] * Epithelial lesions * Acrochordons, fibroepithelial polyps * Nevus * Seborrheic keratosis * Adenosis * Syringoma * Hidradenoma papilliferum * Anogential mammary-like glands[13] #### Mesenchymal and other subcutaneious lesions[edit] * Endometriosis * Hemangioma * Fibroma * Lipoma * Granular cell tumor * Leiomyoma * Angiomyofibroblastoma * Aggressive andiomyxoma * Teratoma * Osteochondroma * Neurofibroma * Schwannoma * Perineal nodular induration * Epidermal inclusion cyst[13] ## See also[edit] This article uses anatomical terminology. * Urethral caruncle * Vaginal cysts * Vaginal intraepithelial neoplasia ## References[edit] 1. ^ a b Vanni, Roberta; Porodo, Giuseppia (2007). "Vulva and Vagina tumors: an overview". atlasgeneticsoncology.org. Retrieved March 11, 2018. 2. ^ Birbrair A, Zhang T, Wang ZM, Messi ML, Olson JD, Mintz A, Delbono O (July 2014). "Type-2 pericytes participate in normal and tumoral angiogenesis". American Journal of Physiology. Cell Physiology. 307 (1): C25-38. doi:10.1152/ajpcell.00084.2014. PMC 4080181. PMID 24788248. 3. ^ Taylor, Elizabeth J. (2000). Dorland's Illustrated medical dictionary (29th ed.). Philadelphia: Saunders. p. 1184. ISBN 0721662544. 4. ^ Stedman's medical dictionary (28th ed.). Philadelphia: Lippincott Williams & Wilkins. 2006. p. Neoplasm. ISBN 0781733901. 5. ^ There are four main groups of vaginal neoplasms: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers.Tumor (American English) or tumour (British English), Latin for swelling, one of the cardinal signs of inflammation, originally meant any form of swelling, neoplastic or not. Current English, however, both medical and non-medical, uses tumor as a synonym for a neoplasm (a solid or fluid-filled cystic lesion that may or may not be formed by an abnormal growth of neoplastic cells) that appears enlarged in size.Some neoplasms do not form a tumor; these include leukemia and most forms of carcinoma in situ. Tumor is also not synonymous with cancer. While cancer is by definition malignant, a tumor can be benign, precancerous, or malignant. 6. ^ "Benign Neoplasms of the Vulva \| GLOWM". www.glowm.com. Retrieved 2018-03-10. 7. ^ "What Is Vulvar Cancer?". www.cancer.org. Retrieved 2018-03-10. 8. ^ "Key Statistics for Vulvar Cancer". www.cancer.org. Retrieved 2018-03-10. 9. ^ "NCI Dictionary of Cancer Terms". National Cancer Institute. Retrieved 2018-03-11. 10. ^ "What's New in Vulvar Cancer Research and Treatment?". www.cancer.org. Retrieved 2018-03-10. 11. ^ https://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb4/bb4-chap7.pdf 12. ^ Humphrey, Peter A.; Dehner, Louis P.; Pfeifer, John D. (10 March 2018). The Washington Manual of Surgical Pathology. Lippincott Williams & Wilkins. ISBN 9780781765275 – via Google Books. 13. ^ a b c HELLER, DEBRA S. (2015). "Benign Tumors and Tumor-like Lesions of the Vulva". Clinical Obstetrics and Gynecology. 58 (3): 526–535. doi:10.1097/grf.0000000000000133. PMID 26125957. S2CID 11112420. ## External links[edit] Classification D * ICD-10: C51, C79.8, D07.2, D28.0, D39.7 * MeSH: D014846 [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-hydroxybutyric 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	Vulvar tumors	c0042995	24,641	wikipedia	https://en.wikipedia.org/wiki/Vulvar_tumors	2021-01-18T19:10:03	{"mesh": ["D014846"], "umls": ["C0042995"], "wikidata": ["Q52601023"]}
Hydranencephaly is a rare condition in which the brain's cerebral hemispheres are absent and replaced by sacs filled with cerebrospinal fluid (CSF). Affected infants may appear and act normal at birth, but irritability and hypertonia often develop within a few weeks. Other signs and symptoms may include seizures, hydrocephalus, visual impairment, lack of growth, deafness, blindness, paralysis, and intellectual disabilities. Prognosis is typically poor with many affected children dying before one year of age. In rare cases, children may survive for several years or more. It has been suspected to be an inherited condition, although some researchers believe it may be caused by prenatal blockage of the carotid artery where it enters the cranium. Treatment is generally symptomatic and supportive; hydrocephalus may be treated with a shunt. [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-hydroxybutyric 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	Hydranencephaly	c0020225	24,642	gard	https://rarediseases.info.nih.gov/diseases/6681/hydranencephaly	2021-01-18T17:59:57	{"mesh": ["D006832"], "umls": ["C0020225"], "orphanet": ["2177"], "synonyms": ["Hydroanencephaly"]}
Softening or thinning of the skull in infants and children Craniotabes Cranial bones SpecialtyPediatrics Craniotabes is softening or thinning of the skull in infants and children, which may be normally present in newborns. It is seen mostly in the occipital and parietal bones. The bones are soft, and when pressure is applied they will collapse underneath it. When the pressure is relieved, the bones will usually snap back into place.[1][2] ## Contents * 1 Causes * 2 Diagnosis * 3 Management * 4 Etymology * 5 References * 6 External links ## Causes[edit] Any condition that affects bone growth, most notably rickets[3][4] (from vitamin D deficiency),[5] marasmus, syphilis, or thalassemia, can cause craniotabes if present during a time of rapid skull growth (most especially during gestation and infancy). It can be a "normal" feature in premature infants. It is the first sign in children and infants with rickets.[citation needed] ## Diagnosis[edit] Physical examination[citation needed] ## Management[edit] Management of craniotabes depends on the cause. The majority of craniotabes occurs in term infants and can be a normal finding. Commonly, craniotabes results from the position of the head inside the uterus weeks prior to delivery. Calcium and Vitamin D levels should be obtained to rule out rickets, and in mothers who have prenatal labs concerning for T. pallidum infection, neonates should be evaluated for congenital syphilis.[citation needed] ## Etymology[edit] The term (cranio- \+ tabes) is derived from the Latin words cranium for skull and tabes for wasting.[citation needed] ## References[edit] 1. ^ Harvey, Nicholas C.; Holroyd, Christopher; Ntani, Georgia; Javaid, Kassim; Cooper, Philip; Moon, Rebecca; Cole, Zoe; Tinati, Tannaze; Godfrey, Keith; Dennison, Elaine; Bishop, Nicholas J.; Baird, Janis; Cooper, Cyrus (2014). "Vitamin D supplementation in pregnancy: a systematic review". Health Technology Assessment (Winchester, England). 18 (45): 1–190. doi:10.3310/hta18450. ISSN 2046-4924. PMC 4124722. PMID 25025896. 2. ^ Prentice, Ann (July 2013). "Nutritional rickets around the world". The Journal of Steroid Biochemistry and Molecular Biology. 136: 201–206. doi:10.1016/j.jsbmb.2012.11.018. PMID 23220549. S2CID 19944113. 3. ^ Elidrissy, Abdelwahab T. H. (31 May 2016). "The Return of Congenital Rickets, Are We Missing Occult Cases?". Calcified Tissue International. 99 (3): 227–236. doi:10.1007/s00223-016-0146-2. PMID 27245342. S2CID 14727399. 4. ^ Paterson, Colin R.; Ayoub, David (October 2015). "Congenital rickets due to vitamin D deficiency in the mothers". Clinical Nutrition. 34 (5): 793–798. doi:10.1016/j.clnu.2014.12.006. PMID 25552383. 5. ^ Ercan, Makbule (2016). "Relationship between newborn craniotabes and vitamin D status". Northern Clinics of Istanbul. 3 (1): 15–21. doi:10.14744/nci.2016.48403. PMC 5175072. PMID 28058380. ## External links[edit] Classification D * SNOMED CT: 88034002 External resources * MedlinePlus: 001591 This article about a disease of musculoskeletal and connective tissue 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-hydroxybutyric 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	Craniotabes	c0392452	24,643	wikipedia	https://en.wikipedia.org/wiki/Craniotabes	2021-01-18T19:01:47	{"wikidata": ["Q5182155"]}
Distal trisomy 14q is a rare, partial duplication of the long arm of chromosome 14 characterized by variable clinical features, most commonly including growth retardation and low birth weight, hypotonia, developmental delay, intellectual disability, short stature, microcephaly, facial dysmorphism (frontal bossing, hypertelorism, bulbous nose, micrognathia, sparse hair and eyebrows), congenital heart defects, spasticity and hyperreflexia. [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-hydroxybutyric 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	Distal trisomy 14q	c2931702	24,644	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1705	2021-01-23T18:15:26	{"mesh": ["C538034"], "umls": ["C2931702"], "icd-10": ["Q92.3"], "synonyms": ["Distal duplication 14q", "Telomeric duplication 14q", "Trisomy 14qter"]}
Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a very rare inborn error of mitochondrial fatty acid oxidation characterized by variable manifestations ranging from asymptomatic individuals (in most cases) to those with failure to thrive, hypotonia, seizures, developmental delay and progressive myopathy. ## Epidemiology Approximately 50 patients have been identified worldwide to date. The Netherlands has an estimated birth prevalence of at least 1/50,000. ## Clinical description Most infants with SCAD deficiency identified through newborn screening programs have been well at the time of diagnosis and most have remained asymptomatic. In affected individuals manifestations include seizures, developmental delay (delayed sitting/walking and/or speech/social interaction), failure to grow with poor feeding, and usually muscle weakness and hypotonia. ## Etiology Symptomatic SCAD deficiency is due to mutations in the acyl-CoA dehydrogenase, C-2 to C-3 short chain ACADS gene (12q24.31) as well as additional as yet unidentified precipitating factors. ## Diagnostic methods SCAD deficiency has been defined as the presence of (1) increased butyrylcarnitine (C4) concentrations in plasma and/or increased ethylmalonic acid (EMA) concentrations in urine under non-stressed conditions (on at least two occasions) and (2) biallelic ACADS mutations or susceptibility variants 511C>T and 625G>A. Newborn screening programs in Austria, Hungary and Iceland now usually identify patients with SCAD deficiency at birth. Asymptomatic relatives may meet the diagnostic criteria for SCAD deficiency. ## Differential diagnosis Differential diagnoses include multiple acyl-CoA dehydrogenase deficiency (MADD), ethylmalonic encephalopathy and acute ackee fruit intoxication (see these terms). ## Antenatal diagnosis Antenatal diagnosis is not relevant as asymptomatic and symptomatic family members can have the same SCAD genotype. ## Genetic counseling SCAD deficiency is inherited in an autosomal recessive manner and genetic counseling is possible. ## Management and treatment Most patients are asymptomatic and no treatment is needed. Some symptomatic patients are given riboflavin and follow a low fat/high carbohydrate diet and avoid fasting. Acute metabolic acidosis can be treated by the administration of high levels of dextrose (with or without insulin) and IV fluids. Seizures can be treated with anticonvulsants but valproate should be avoided. Pregnancies should be monitored for complications such as acute fatty liver of pregnancy and preeclampsia (see these terms). Follow-up at a metabolic clinic should include the regular assessment of growth and development and nutritional status of patients. ## Prognosis The prognosis is good in asymptomatic patients but variable in those who display the disease 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-hydroxybutyric 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	Short chain acyl-CoA dehydrogenase deficiency	c0342783	24,645	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=26792	2021-01-23T18:56:00	{"gard": ["4822"], "mesh": ["C537596"], "omim": ["201470"], "icd-10": ["E71.3"], "synonyms": ["ACADS deficiency", "SCAD deficiency", "SCADD"]}
Genetic disorder Dubowitz syndrome This condition is inherited via autosomal recessive manner SpecialtyMedical genetics SymptomsIntrauterine growth retardation, short stature, microcephaly, mild mental retardation with behavior problems, eczema, and unusual and distinctive faci[1] Diagnostic method<rarediseases.org>The diagnosis is usually based upon clinical determination made by a geneticist (dysmorphologist) or physician. TreatmentDue to this rare syndrome and no known cures or treatments take into consideration that these people may develop slower than others and may need more specialized attention and personal care. One on one care may be appropriate in some cases to best fit their personal needs. Dubowitz syndrome is a rare genetic disorder characterized by microcephaly, stunted growth, and a receding chin. Symptoms vary among patients, but other characteristics include a soft, high-pitched voice, partial webbing of the fingers and toes, palate deformations, genital abnormalities, language difficulties, and an aversion to crowds.[2] The pathogenesis of the disease is yet to be identified, and no medical tests can definitively diagnose the disease.[3] The primary method of diagnosis is to identify facial phenotypes. Since it was first described in 1965 by English physician Victor Dubowitz, over 140 cases have been reported worldwide. Although the majority of cases have been reported from the United States, Germany, and Russia, the disorder appears to affect both genders and all ethnicities equally.[2] ## Contents * 1 Presentation * 2 Genetics * 2.1 Growth hormone * 2.2 Relationship to Smith–Lemli–Opitz syndrome * 3 Diagnosis * 4 Management * 5 Epidemiology * 6 History * 7 References * 8 External links ## Presentation[edit] Microcephaly is a characteristic in which the circumference of the head is smaller than normal due to improper development of the brain. It is caused by genetic disorders, infections, radiation, medications or alcohol abuse during pregnancy. Defects in the growth of the cerebral cortex lead to many of the features associated with microcephaly.[4] Microcephaly has a vast range of prognoses: some patients experience little to very mental retardation and can reach regular age-appropriate milestones. Others may experience severe mental retardation and neuromuscular side effects.[4] ## Genetics[edit] Dubowitz syndrome patient, frontal view Dubowitz syndrome patient, lateral view Although the pathology of Dubowitz syndrome is unknown, it is a heritable autosomal recessive disorder. Parents of people with Dubowitz syndrome are sometimes related, and there have been several cases of it occurring in monozygotic twins, siblings, and cousins.[5] There is great variability in symptoms between cases, especially in intelligence.[6] Although there is much evidence that Dubowitz syndrome is genetic, the symptoms are similar to fetal alcohol syndrome. Further studies are needed to determine whether alcohol influences whether Dubowitz syndrome manifests in people who are genetically vulnerable.[7] Breakdown of chromosomes is known to occur.[5] ### Growth hormone[edit] Dubowitz syndrome is accompanied by a deficiency in growth hormone.[8] People with Dubowitz syndrome have stunted growth, and growth hormones are secreted by the anterior pituitary of the brain. The main function of the anterior pituitary is to increase height during development. Other functions include regulating the immune system, increasing calcium retention, increasing muscle mass and stimulating gluconeogenesis. A deficiency in growth hormone may be caused by genetic mutations, malformations of the hypothalamus or pituitary gland during development, or damage to the pituitary.[9] In Dubowitz syndrome, the cause is likely the underlying mutations or disruption of brain structures during development. Growth hormone deficiency also correlates with low levels of IgG antibodies, a condition found in Dubowitz patients.[5] ### Relationship to Smith–Lemli–Opitz syndrome[edit] Researchers are investigating the genetic similarities between Dubowitz syndrome and Smith–Lemli–Opitz syndrome (SLOS). Patients with SLOS and Dubowitz syndromes have many of the same abnormalities, and the two disorders are hypothesized to be linked. Two characteristics of SLOS are a low cholesterol level and a high 7-Dehydrocholesterol level. Cholesterol is essential for several bodily functions, including maintaining cell membrane structure, embryogenesis, and synthesis of steroid and sex hormones. Impaired cholesterol synthesis or transport may account for most of the symptoms of both SLOS and Dubowitz syndrome. Although only a few patients with Dubowitz syndrome have been identified with altered cholesterol levels, researchers are exploring whether Dubowitz syndrome, like SLOS, is linked to a defect in the cholesterol biosynthetic pathway.[10] The pathology of Dubowitz syndrome is still unclear because of its rarity and the wide array of associated symptoms. Several studies have focused on different aspects of the disorder to try to find its exact cause and expression. One study examined the specific oral features in one patient.[11] Another found abnormalities in the brain, such as corpus callosum dysgenesis, an underdeveloped anterior pituitary and a brain stalk with an ectopic (misplaced) posterior pituitary.[12] ## Diagnosis[edit] There is no definitive test available for this condition. The diagnosis is based on the constellation of typical clinical features.[citation needed] ## Management[edit] There is currently no specific treatment for this condition. Management is supportive.[citation needed] In particular there is currently no known method of correcting microcephaly. However, there are a variety of symptomatic treatments that help to counter some of its adverse effects, such as speech and occupational therapies, as well as medication to control seizures and hyperactivity.[13] ## Epidemiology[edit] This condition is rare with ~200 cases reported between 1965 and 2018.[14] ## History[edit] This condition was first reported in 1965. ## References[edit] 1. ^ "Dubowitz syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-07-11. 2. ^ a b "Dubowitz syndrome". Encyclopedia of Genetic Disorders. Archived from the original on 2007-04-18. 3. ^ "Dubowitz Syndrome Support Network". 4. ^ a b Microcephaly Information Page at NINDS 5. ^ a b c Online Mendelian Inheritance in Man (OMIM): Rasmussen, Sonja A. Dubowitz Syndrome - 223370 6. ^ Ilyina HG, Lurie IW (1990). "Dubowitz syndrome: possible evidence for a clinical subtype". Am. J. Med. Genet. 35 (4): 561–5. doi:10.1002/ajmg.1320350423. PMID 2185633. 7. ^ Mathieu M, Berquin P, Epelbaum S, Lenaerts C, Piussan C (December 1991). "[Dubowitz syndrome. A diagnosis not to be missed]". Arch. Fr. Pediatr. (in French). 48 (10): 715–8. PMID 1793348. 8. ^ Hirano T, Izumi I, Tamura K (1996). "Growth hormone deficiency in Dubowitz syndrome". Acta Paediatr Jpn. 38 (3): 267–9. doi:10.1111/j.1442-200x.1996.tb03484.x. PMID 8741320. 9. ^ Rieser, Patricia (1979). "Growth Hormone Deficiency". Archived from the original on 2007-04-24. 10. ^ Ahmad A, Amalfitano A, Chen YT, Kishnani PS, Miller C, Kelley R (1999). "Dubowitz syndrome: a defect in the cholesterol biosynthetic pathway?". Am. J. Med. Genet. 86 (5): 503–4. doi:10.1002/(SICI)1096-8628(19991029)86:5<503::AID-AJMG21>3.0.CO;2-Y. PMID 10508998. 11. ^ Chan KM, King NM (2005). "Dubowitz syndrome: report of a case with emphasis on the oral features". J Dent Child (Chic). 72 (3): 100–3. PMID 16568913. 12. ^ Oguz KK, Ozgen B, Erdem Z (2003). "Cranial midline abnormalities in Dubowitz syndrome: MR imaging findings". Eur Radiol. 13 (5): 1056–7. doi:10.1007/s00330-002-1580-2. PMID 12695828. S2CID 1703841. 13. ^ "Microcephaly – Symptoms, Treatment and Prevention". The HealthCentralNetwork. Archived from the original on 2007-05-13. 14. ^ Innes AM, McInnes BL, Dyment DA (2018) Clinical and genetic heterogeneity in Dubowitz syndrome: Implications for diagnosis, management and further research. Am J Med Genet C Semin Med Genet ## External links[edit] Classification D * ICD-10: Q87.1 * OMIM: 223370 * MeSH: C535718 C535718, C535718 * DiseasesDB: 32652 External resources * Orphanet: 235 * v * t * e Congenital abnormality syndromes Craniofacial * Acrocephalosyndactylia * Apert syndrome * Carpenter syndrome * Pfeiffer syndrome * Saethre–Chotzen syndrome * Sakati–Nyhan–Tisdale syndrome * Bonnet–Dechaume–Blanc syndrome * Other * Baller–Gerold syndrome * Cyclopia * Goldenhar syndrome * Möbius syndrome Short stature * 1q21.1 deletion syndrome * Aarskog–Scott syndrome * Cockayne syndrome * Cornelia de Lange syndrome * Dubowitz syndrome * Noonan syndrome * Robinow syndrome * Silver–Russell syndrome * Seckel syndrome * Smith–Lemli–Opitz syndrome * Snyder–Robinson syndrome * Turner syndrome Limbs * Adducted thumb syndrome * Holt–Oram syndrome * Klippel–Trénaunay–Weber syndrome * Nail–patella syndrome * Rubinstein–Taybi syndrome * Gastrulation/mesoderm: * Caudal regression syndrome * Ectromelia * Sirenomelia * VACTERL association Overgrowth syndromes * Beckwith–Wiedemann syndrome * Proteus syndrome * Perlman syndrome * Sotos syndrome * Weaver syndrome * Klippel–Trénaunay–Weber syndrome * Benign symmetric lipomatosis * Bannayan–Riley–Ruvalcaba syndrome * Neurofibromatosis type I Laurence–Moon–Bardet–Biedl * Bardet–Biedl syndrome * Laurence–Moon syndrome Combined/other, known locus * 2 (Feingold syndrome) * 3 (Zimmermann–Laband syndrome) * 4/13 (Fraser syndrome) * 8 (Branchio-oto-renal syndrome, CHARGE syndrome) * 12 (Keutel syndrome, Timothy syndrome) * 15 (Marfan syndrome) * 19 (Donohue syndrome) * Multiple * Fryns 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-hydroxybutyric 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	Dubowitz syndrome	c0175691	24,646	wikipedia	https://en.wikipedia.org/wiki/Dubowitz_syndrome	2021-01-18T19:02:54	{"gard": ["6290"], "mesh": ["C535718"], "umls": ["C0175691"], "orphanet": ["235"], "wikidata": ["Q574741"]}
Myelodysplastic-myeloproliferative diseases SpecialtyHematology Myelodysplastic–myeloproliferative diseases are a category of hematological malignancies disorders which have characteristics of both myelodysplastic and myeloproliferative conditions.[1] When a hematological malignancy is characterised by normal differentiation of cells of myeloid cell line, it is referred to as myeloproliferative. On the other hand, when there is abnormal differentiation of cells of myeloid cell line, it is referred to as myelodysplastic.[citation needed] ## References[edit] 1. ^ "Myelodysplastic/myeloproliferative disease \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 11 July 2019. ## External links[edit] * http://www.cancer.gov/cancertopics/pdq/treatment/mds-mpd/Patient Classification D * MeSH: D054437 * v * t * e Myeloid-related hematological malignancy CFU-GM/ and other granulocytes CFU-GM Myelocyte AML: * Acute myeloblastic leukemia * M0 * M1 * M2 * APL/M3 MP * Chronic neutrophilic leukemia Monocyte AML * AMoL/M5 * Myeloid dendritic cell leukemia CML * Philadelphia chromosome * Accelerated phase chronic myelogenous leukemia Myelomonocyte AML * M4 MD-MP * Juvenile myelomonocytic leukemia * Chronic myelomonocytic leukemia Other * Histiocytosis CFU-Baso AML * Acute basophilic CFU-Eos AML * Acute eosinophilic MP * Chronic eosinophilic leukemia/Hypereosinophilic syndrome MEP CFU-Meg MP * Essential thrombocytosis * Acute megakaryoblastic leukemia CFU-E AML * Erythroleukemia/M6 MP * Polycythemia vera MD * Refractory anemia * Refractory anemia with excess of blasts * Chromosome 5q deletion syndrome * Sideroblastic anemia * Paroxysmal nocturnal hemoglobinuria * Refractory cytopenia with multilineage dysplasia CFU-Mast Mastocytoma * Mast cell leukemia * Mast cell sarcoma * Systemic mastocytosis Mastocytosis: * Diffuse cutaneous mastocytosis * Erythrodermic mastocytosis * Adult type of generalized eruption of cutaneous mastocytosis * Urticaria pigmentosa * Mast cell sarcoma * Solitary mastocytoma Systemic mastocytosis * Xanthelasmoidal mastocytosis Multiple/unknown AML * Acute panmyelosis with myelofibrosis * Myeloid sarcoma MP * Myelofibrosis * Acute biphenotypic leukaemia This oncology 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-hydroxybutyric 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	Myelodysplastic–myeloproliferative diseases	c1301355	24,647	wikipedia	https://en.wikipedia.org/wiki/Myelodysplastic%E2%80%93myeloproliferative_diseases	2021-01-18T18:41:37	{"gard": ["9351"], "mesh": ["D054437"], "orphanet": ["98275"], "wikidata": ["Q11668606"]}
It has been suggested that this article be split into a new article titled Vestibular neuritis. (Discuss) (June 2020) 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: "Labyrinthitis" – news · newspapers · books · scholar · JSTOR (May 2008) (Learn how and when to remove this template message) Labyrinthitis Other namesOtitis interna, vestibular neuronitis, vestibular neuritis Diagram of the inner ear SpecialtyOtorhinolaryngology Frequency35 million per year[1] Labyrinthitis, also known as vestibular neuritis,[2][3] is the inflammation of the inner ear.[4] Vestibular neuritis derives its name from the labyrinths that house the vestibular system, which senses changes in the head's position or the head's motion.[5] This results in a sensation of the world spinning and also possible hearing loss or ringing in the ears.[5] It can occur as a single attack, a series of attacks, or a persistent condition that diminishes over three to six weeks. It may be associated with nausea, vomiting, and eye nystagmus. The cause is often not clear. It may be due to a virus, but it can also arise from bacterial infection, head injury, extreme stress, an allergy, or as a reaction to medication. 30% of affected people had a common cold prior to developing the disease.[1] Either bacterial or viral labyrinthitis can cause a permanent hearing loss in rare cases.[6] This appears to result from an imbalance of neuronal input between the left and right inner ears.[7] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Mechanism * 4 Treatment * 4.1 Physical therapy * 4.2 Medication * 4.3 Other * 5 Prognosis * 6 Epidemiology * 7 References * 8 External links ## Signs and symptoms[edit] The main symptoms of labyrinthitis are severe vertigo and nystagmus. The most common symptom for vestibular neuritis is the onset of vertigo that has formed from an ongoing infection or trauma.[8] The dizziness sensation that is associated with vertigo is thought to be from the inner ear labyrinth.[9] Rapid and undesired eye motion (nystagmus) often results from the improper indication of rotational motion. Nausea, anxiety, and a general ill feeling are common due to the distorted balance signals that the brain receives from the inner ear system.[10] ## Causes[edit] Some people will report having an upper respiratory infection (common cold) or flu prior to the onset of the symptoms of vestibular neuritis; others will have no viral symptoms prior to the vertigo attack. Some cases of vestibular neuritis are thought to be caused by an infection of the vestibular ganglion by the herpes simplex type 1 virus.[7] However, the cause of this condition is not fully understood, and in fact, many different viruses may be capable of infecting the vestibular nerve. Acute localized ischemia of these structures also may be an important cause, especially in children, vestibular neuritis may be preceded by symptoms of a common cold. However, the causative mechanism remains uncertain.[11] This can also be brought on by pressure changes such as those experienced while flying or scuba diving.[12][13][14] ## Mechanism[edit] In the vestibular system, there are three canals that are semicircular in shape that input sensory clues.[15] These canals allow the brain to sense rotational motion and linear motion changes.[16] The brain then uses the sensory input clues and the visual input clues from the vestibular system to retain balance. The vestibulo–ocular reflex retains continuous visual focus during motion which is also the vestibular systems job during activity.[16] ## Treatment[edit] The treatment for vestibular neuritis depends on the cause. However, symptoms of vertigo can be treated in the same way as other vestibular dysfunctions with vestibular rehabilitation.[17] ### Physical therapy[edit] Typical treatments include combinations of head and eye movements, postural changes, and walking exercises. Specifically, exercises that may be prescribed include keeping eyes fixated on a specific target while moving the head, moving the head right to left at two targets at a significant distance apart, walking while keeping eyes fixated on a specific target, and walking while keeping eyes fixated on a specific target while also turning the head in different directions.[18] The main function behind repeating a combination of head and eye movements, postural changes and walking is that through this repetition, compensatory changes for the dysfunctions arising from peripheral vestibular structures may be promoted in the central vestibular system (brainstem and cerebellum).[18] Vestibular rehabilitation therapy is a highly effective way to substantially reduce or eliminate residual dizziness from labyrinthitis.[19] VRT works by causing the brain to use already existing neural mechanisms for adaptation, neuroplasticity, and compensation.[17] Vestibular neuritis rehabilitation is an effective and safe management to improve symptoms.[20] The vestibular neuritis rehabilitation can improve symptoms or resolve the symptoms which is dependent on each individual. [20] Rehabilitation strategies most commonly used are:[17] * Gaze stability exercises – moving the head from side to side while fixated on a stationary object (aimed at assisting the eye to fixate during head rotation without the input from the lost canal vestibulo–ocular reflex). An advanced progression of this exercise would be walking in a straight line while looking side to side by turning the head. * Habituation exercises – movements designed to provoke symptoms and subsequently reduce the negative vestibular response upon repetition. Examples of these include Brandt–Daroff exercises. * Functional retraining – including postural control, relaxation, and balance training. These exercises function by challenging the vestibular system. Progression occurs by increasing the amplitude of the head or focal point movements, increasing the speed of movement, and combining movements such as walking and head turning.[21] One study found that patients who believed their illness was out of their control showed the slowest progression to full recovery, long after the initial vestibular injury had healed.[22] The study revealed that the patient who compensated well was one who, at the psychological level, was not afraid of the symptoms and had some positive control over them. Notably, a reduction in negative beliefs over time was greater in those patients treated with rehabilitation than in those untreated. "Of utmost importance, baseline beliefs were the only significant predictor of change in a handicap at 6 months follow-up." ### Medication[edit] Vestibular neuritis is generally a self-limiting disease. Treatment with drugs is neither necessary nor possible. The effect of glucocorticoids has been studied, but they have not been found to significantly affect long-term outcome.[23] Symptomatic treatment with antihistaminics such as cinnarizine, however, can be used to suppress the symptoms of vestibular neuritis while it spontaneously regresses.[24] Prochlorperazine is another commonly prescribed medication to help alleviate the symptoms of vertigo and nausea. ### Other[edit] Because mood disorders can interfere with the vestibular compensation and adaptive plasticity, it suggested to address any co-occurring anxiety disorder and/or depression. Severe anxiety episodes are usually addressed by short-term benzodiazapine therapy. Long-term use of benzodiazapines such as diazepam, however, is not recommended due to the tolerance issues.[25] SSRIs and SSNRIs are among a number of first - line treatments for anxiety or depression. [26] ## Prognosis[edit] Recovery from acute labyrinthine inflammation generally takes from one to six weeks, but it is not uncommon for residual symptoms (dysequilibrium and/or dizziness) to last for a couple of months.[22] Recovery from a temporary damaged inner ear typically follows two phases: 1. An acute period, which may include severe vertigo and vomiting 2. approximately two weeks of sub-acute symptoms and rapid recovery ## Epidemiology[edit] Vestibular neuritis also known as labyrinthitis affects approximately 35 million people per year.[27] Vestibular neuritis typically occurs in those between 30 and 60 years of age.[27] There is no significant gender difference when determining who will get this disease.[27] In 95% of cases, vestibular neuritis is a one-time experience that results in most people fully recovering from it.[28] Vestibular rehabilitation showed a statistically significant increase in controlling symptoms over no intervention in people who have vestibular neuritis.[29] ## References[edit] 1. ^ a b Greco, A; Macri, GF; Gallo, A; Fusconi, M; De Virgilio, A; Pagliuca, G; Marinelli, C; de Vincentiis, M (2014). "Is vestibular neuritis an immune related vestibular neuropathy inducing vertigo?". Journal of Immunology Research. 2014: 459048. doi:10.1155/2014/459048. PMC 3987789. PMID 24741601. 2. ^ Ferri's Clinical Advisor 2016: 5 Books in 1. Elsevier Health Sciences. 2015. p. 735. ISBN 9780323378222. 3. ^ Hogue, JD (June 2015). "Office Evaluation of Dizziness". Primary Care. 42 (2): 249–258. doi:10.1016/j.pop.2015.01.004. PMID 25979586. 4. ^ "Labyrinthitis". National Library of Medicine. Retrieved 16 March 2018. 5. ^ a b "Clinical Methods: The History, Physical, and Laboratory Examinations". Annals of Internal Medicine. 113 (7): 563. 1990-10-01. doi:10.7326/0003-4819-113-7-563_2. ISSN 0003-4819. 6. ^ "NLM". 7. ^ a b Marill, Keith (2011-01-13). "Vestibular Neuronitis: Pathology". eMedicine, Medscape Reference. Retrieved 2011-08-07. 8. ^ Dewyer, Nicholas A.; Kiringoda, Ruwan; McKenna, Michael J. (2018), "Inner Ear Infections (Labyrinthitis)", Infections of the Ears, Nose, Throat, and Sinuses, Springer International Publishing, pp. 79–88, doi:10.1007/978-3-319-74835-1_7, ISBN 978-3-319-74834-4 9. ^ Murdin, Louisa; Hussain, Kiran; Schilder, Anne GM (2013-08-11), "Betahistine for symptoms of vertigo", in The Cochrane Collaboration (ed.), Cochrane Database of Systematic Reviews, John Wiley & Sons, Ltd, pp. CD010696, doi:10.1002/14651858.cd010696 10. ^ "Table 1: The Single Nucleotide Polymorphisms in cathepsin B protein mined from literature (PMID: 16492714)". doi:10.7717/peerj.7425/table-1. Cite journal requires `\|journal=` (help) 11. ^ Keith A Marill. "Vestibular Neuronitis". Retrieved 2008-06-28. 12. ^ Martin-Saint-Laurent A, Lavernhe J, Casano G, Simkoff A (March 1990). "Clinical aspects of inflight incapacitations in commercial aviation". Aviation, Space, and Environmental Medicine. 61 (3): 256–60. PMID 2317181. 13. ^ Farmer, Jr JC, ed. (1973). Labyrinthine Dysfunction During Diving. 1st Undersea and Hyperbaric Medical Society Workshop. UHMS Publication Number WS6-15-74. Undersea and Hyperbaric Medical Society. p. 11. Retrieved 2009-03-11. 14. ^ Kennedy RS (March 1974). "General history of vestibular disorders in diving". Undersea Biomedical Research. 1 (1): 73–81. PMID 4619861. Retrieved 2009-03-11. 15. ^ "Labyrinthitis". www.audiologicaldiagnostics.com. Retrieved 2019-12-02. 16. ^ a b "Germany". International Journal of Health Care Quality Assurance. 19 (4). 2017. doi:10.1108/ijhcqa.2006.06219dab.003. ISSN 0952-6862. 17. ^ a b c Burton M. J.; Monsell E. M.; Rosenfeld R. M. (2008). "Extracts from the cochrane library: Vestibular rehabilitation for unilateral peripheral vestibular dysfunction (review)". Otolaryngology–Head and Neck Surgery. 138 (4): 415–417. doi:10.1016/j.otohns.2008.02.004. PMID 18359346. S2CID 9907751. 18. ^ a b Walker, MF (January 2009). "Treatment of vestibular neuritis". Current Treatment Options in Neurology. 11 (1): 41–5. doi:10.1007/s11940-009-0006-8. PMID 19094835. S2CID 37693582. 19. ^ "Vestibular Rehabilitation Therapy (VRT)". Vestibular Disorders Association. 2011-12-27. Retrieved 2018-05-19. 20. ^ a b Fishman, Jonathan M; Burgess, Chris; Waddell, Angus (2010-07-07), "Corticosteroids for the treatment of idiopathic acute vestibular dysfunction (vestibular neuritis)", in The Cochrane Collaboration (ed.), Cochrane Database of Systematic Reviews, John Wiley & Sons, Ltd, pp. CD008607, doi:10.1002/14651858.cd008607 21. ^ "Physical Therapy Rehabilitation". Retrieved 2019-10-29. 22. ^ a b Bronstein, Adolfo (February 2002). "Visual and psychological aspects of vestibular disease". Current Opinion in Neurology. 15 (1): 1–3. doi:10.1097/00019052-200202000-00001. PMID 11796943. 23. ^ Fishman, JM; Burgess C; Waddell A (May 2011). "Corticosteroids for the treatment of idiopathic acute vestibular dysfunction (vestibular neuritis)". Cochrane Database Syst Rev (5): CD008607. doi:10.1002/14651858.CD008607.pub2. PMID 21563170. 24. ^ Scholtz, AW; Steindl R; Burchardi N; Bognar-Steinberg I; Baumann W (June 2012). "Comparison of the therapeutic efficacy of a fixed low-dose combination of cinnarizine and dimenhydrinate with betahistine in vestibular neuritis: a randomized, double-blind, non-inferiority study". Clin Drug Investig. 32 (6): 387–399. doi:10.2165/11632410-000000000-00000. PMID 22506537. S2CID 207301804. 25. ^ Solomon, D; Shepard, NT (July 2002). "Chronic Dizziness". Current Treatment Options in Neurology. 4 (4): 281–288. doi:10.1007/s11940-002-0028-y. PMID 12036501. S2CID 38952122. 26. ^ Vries, Ya (March 2016). "Influence of baseline severity on antidepressant efficacy for anxiety disorders: meta-analysis and meta-regression". British Journal of Psychiatry. 208 (6): 515–21. doi:10.1192/bjp.bp.115.173450. PMID 26989093. 27. ^ a b c Greco, A.; Macri, G. F.; Gallo, A.; Fusconi, M.; De Virgilio, A.; Pagliuca, G.; Marinelli, C.; de Vincentiis, M. (2014). "Is vestibular neuritis an immune related vestibular neuropathy inducing vertigo?". Journal of Immunology Research. 2014: 459048. doi:10.1155/2014/459048. ISSN 2314-7156. PMC 3987789. PMID 24741601. 28. ^ "Vestibular Neuritis". Cleveland Clinic. Retrieved 2019-11-15. 29. ^ McDonnell, Michelle N; Hillier, Susan L (2015-01-13). Cochrane ENT Group (ed.). "Vestibular rehabilitation for unilateral peripheral vestibular dysfunction". Cochrane Database of Systematic Reviews. 1: CD005397. doi:10.1002/14651858.CD005397.pub4. PMID 25581507. ## External links[edit] Classification D * ICD-10: H81.2, H83.0 * ICD-9-CM: 386.3,386.12 * MeSH: D007762 * DiseasesDB: 29290 * SNOMED CT: 23919004 External resources * MedlinePlus: 001054 * Patient UK: Labyrinthitis * Labyrinthitis at Curlie * v * t * e Disorders of hearing and balance Hearing Symptoms * Hearing loss * Excessive response * Tinnitus * Hyperacusis * Phonophobia Disease Loss * Conductive hearing loss * Otosclerosis * Superior canal dehiscence * Sensorineural hearing loss * Presbycusis * Cortical deafness * Nonsyndromic deafness Other * Deafblindness * Wolfram syndrome * Usher syndrome * Auditory processing disorder * Spatial hearing loss Tests * Hearing test * Rinne test * Tone decay test * Weber test * Audiometry * pure tone * visual reinforcement Balance Symptoms * Vertigo * nystagmus Disease * Balance disorder * Peripheral * Ménière's disease * Benign paroxysmal positional vertigo * Labyrinthitis * Labyrinthine fistula Tests * Dix–Hallpike test * Unterberger test * Romberg's test * Vestibulo–ocular reflex [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-hydroxybutyric 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	Labyrinthitis	c0022893	24,648	wikipedia	https://en.wikipedia.org/wiki/Labyrinthitis	2021-01-18T18:32:20	{"mesh": ["D007762"], "umls": ["C0022893"], "wikidata": ["Q2038371"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant otospondylomegaepiphyseal dysplasia (OSMEDA), also known as Weissenbacher-Zweymuller syndrome (WZS), is caused by heterozygous mutation in the COL11A2 gene (120290) on chromosome 6p21. Autosomal recessive otospondylomegaepiphyseal dysplasia (OSMEDB; 215150) is also caused by mutation in the COL11A2 gene. Description Otospondylomegaepiphyseal dysplasia (OSMED) is characterized by sensorineural deafness and relatively short extremities with abnormally large knees and elbows but normal total body length. The diagnostic radiologic findings are the enlarged epiphyses combined with a moderate platyspondyly, most marked in the lower thoracic region. There are no ocular abnormalities. Patients have typical facial features, including midface hypoplasia (summary by Giedion et al., 1982). Some patients have osteoarthritis (Brunner et al., 1994). Nomenclature Spranger (1998) reviewed the findings of disorders caused by mutation in the COL11A2 gene. He concluded that Weissenbacher-Zweymuller syndrome and nonocular Stickler syndrome are the same disorder and suggested the designation heterozygous OSMED. Pihlajamaa et al. (1998) likewise concluded that WZS and nonocular Stickler syndrome are identical and suggested that they be classified as the heterozygous type of OSMED. Clinical Features First described in 1964 as 'Pierre Robin syndrome with fetal chondrodysplasia,' the Weissenbacher-Zweymuller syndrome is characterized by neonatal micrognathia and rhizomelic chondrodysplasia with dumbbell-shaped femora and humeri, and regression of bone changes and normal growth in later years (Weissenbacher and Zweymuller, 1964; Haller et al., 1975). Catch-up growth after 2-3 years is one of the striking features. The patient reported by Weissenbacher and Zweymuller (1964) also had marked snub nose, cleft soft palate, glossoptosis, and hypognathia. Giedion et al. (1982) provided follow-up on this patient (case D), who was then 18 years of age. He had developed sensorineural deafness at age 5. He had no eye abnormalities. Enlarged epiphyses was a prominent radiologic feature. Giedion et al. (1982) reported 3 additional patients with a similar phenotype and proposed that the disorder be called otospondylomegaepiphyseal dysplasia (OSMED). He suggested autosomal recessive inheritance of the disorder because 2 of the patients were sibs. Brunner et al. (1994) reported a large Dutch kindred in which 16 members had characteristic facial features of Stickler syndrome (see 108300) in combination with hearing impairment. Cleft palate or mild arthropathy occurred in several patients, but ocular signs of Stickler syndrome (high myopia, vitreoretinal degeneration, and retinal detachment) were absent. Four of the affected individuals were born with the Pierre Robin sequence of micrognathia, glossoptosis, and cleft palate. More than half of affected family members reported painful joints, especially of the knees. Degenerative joint disease was documented radiographically in 3 individuals by x-ray of the spine and of the knees. Hearing loss was mostly high-tone perceptive and progressed slowly to involve all frequencies. Shortening of the fourth and fifth metatarsals was present in 2 affected members of the kindred. Both had been born with cleft palate and were considered severely affected. Shortening of the fifth metacarpals was also noted in 1 of them. All affected individuals were of normal stature, except 1 female who was just below the third percentile for height. A mild thorax deformity was noted in 4 cases (pectus excavatum in 2, and pectus carinatum in 2 others). Sirko-Osadsa et al. (1998) described a family with features of Stickler syndrome but without eye involvement. Affected members of the family had sensorineural hearing loss, cleft palate/uvula, micrognathia, malar flattening, joint pains, and multiple hereditary exostoses. Vuoristo et al. (2004) described a 3-generation family in which several members were diagnosed with nonocular Stickler syndrome. Sensorineural hearing loss was present in all 3 generations. The propositus was a 4-year-old boy who had Robin sequence at birth. Both the propositus and his father had a flat malar area and nasal bridge, and the nose was upturned. The father had symptoms and radiologic findings of osteoarthritis from the age of 29 years. At age 73 years, the affected grandmother showed extensive osteoarthritic changes in the spine. Her father had undergone hip replacement in mid-adulthood. Mapping Studying a large Dutch kindred segregating a nonocular Stickler syndrome phenotype unlinked to COL2A1 (120140), Brunner et al. (1994) found close linkage with polymorphic markers from the 6p22-p21.3 region. The highest lod score was 4.36 without recombination with D6S276. Since the gene encoding the alpha-2 chain of type XI collagen (COL11A2) maps to the same region, Brunner et al. (1994) suggested that mutation in this collagen gene may be the explanation for Stickler syndrome in this and some other families. Inheritance Pihlajamaa et al. (1998) proposed that OSMED occurs in both autosomal dominant and autosomal recessive (215150) forms due to heterozygous or homozygous mutations, respectively, in the COL11A2 gene. Molecular Genetics In affected members of the large Dutch kindred with a Stickler syndrome-like phenotype reported by Brunner et al. (1994), Vikkula et al. (1995) identified a heterozygous nonsense mutation in the COL11A2 gene (120290.0001). In affected members of a family with a diagnosis of nonocular Stickler syndrome, Sirko-Osadsa et al. (1998) identified a heterozygous 27-bp deletion within exon 39 of the COL11A2 gene (120290.0003). In affected members of a 3-generation family with a diagnosis of nonocular Stickler syndrome, Vuoristo et al. (2004) identified a heterozygous nonsense mutation in the COL11A2 gene (120290.0008). Pihlajamaa et al. (1998) analyzed DNA from the original patient reported by Weissenbacher and Zweymuller (1964) for mutations in 2 candidate genes expressed in cartilage, COL2A1 (120140) and COL11A2 (120290). No mutations were found in the COL2A1 gene but the COL11A2 gene contained a single-base mutation that converted a codon for an obligate glycine to a codon for glutamate at position 955 in the alpha-2 chain (G955E; 120290.0004). INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Midface hypoplasia Ears \- Sensorineural hearing loss Eyes \- No ocular symptoms Nose \- Anteverted nares Mouth \- Pierre-Robin sequence \- Cleft palate SKELETAL \- Epiphyseal dysplasia Spine \- Mild platyspondyly Limbs \- Joint pain \- Premature osteoarthritis \- Large epiphyses MISCELLANEOUS \- Allelic to OSMED ( 215150 ) and Weissenbacher-Zweymuller syndrome ( 277610 ) \- Also called 'heterozygous OSMED' and 'autosomal dominant OSMED' MOLECULAR BASIS \- Caused by mutation in the collagen XI, alpha-2 polypeptide gene (COL11A2, 120290.0001 ) ▲ 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-hydroxybutyric 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	OTOSPONDYLOMEGAEPIPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT	c1861481	24,649	omim	https://www.omim.org/entry/184840	2019-09-22T16:34:11	{"doid": ["0080046"], "mesh": ["C537494"], "omim": ["184840"], "orphanet": ["166100"], "synonyms": ["Alternative titles", "OSMED, HETEROZYGOUS", "WEISSENBACHER-ZWEYMULLER SYNDROME", "PIERRE ROBIN SYNDROME WITH FETAL CHONDRODYSPLASIA STICKLER SYNDROME, NONOCULAR TYPE, FORMERLY", "STICKLER SYNDROME, TYPE III, FORMERLY"], "genereviews": ["NBK1302"]}
Pontocerebellar hypoplasia type 5 (PCH5) is a very rare severe form of PCH (see this terme) with prenatal onset and characterized by fetal onset of clonus or seizures-like activity persisting in infancy and microencephaly leading to early postnatal death. There is significant overlap both in phenotype and in genotype between pontocerebellar hypoplasia types 4 and 5. ## Epidemiology PCH5 is reported in 3 siblings to date. ## Clinical description PCH5, clinically resembling PCH4 (see this term), is characterized by fetal onset of clonus or seizure-like episodes, microcephaly, cerebellar hypoplasia persisting in infancy and microencephaly leading to early postnatal death. ## Etiology PCH5 is caused by a compound heterozygosity for p.A307S plus splice site mutation in the gene. PCH5 transmission is autosomal recessive. ## Diagnostic methods Clinically similar to PCH4, PCH5 is demonstrated on autopsy. MRI demonstrates inferior olivary dysplasia, and pontocerebellar hypoplasia with the vermis much more degenerated than cerebellar hemispheres. Pathological findings show and increased degeneration with Purkinje and granule cells in the vermis. ## Antenatal diagnosis Antenatal diagnosis is possible by ultrasonic assessment of cerebellar width at 16-18 weeks gestation. [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-hydroxybutyric 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	Pontocerebellar hypoplasia type 5	c1857762	24,650	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166068	2021-01-23T18:26:18	{"gard": ["10709"], "mesh": ["C537745"], "omim": ["610204"], "umls": ["C1857762"], "icd-10": ["Q04.3"], "synonyms": ["Fetal-onset olivopontocerebellar hypoplasia", "PCH5"]}
Heart-hand syndrome type 3 is a very rare heart-hand syndrome (see this term), described in three members of a Spanish family to date, which is characterized by a cardiac conduction defect (sick sinus, bundle-branch block) and brachydactyly, resembling brachydactyly type C of the hands (see this term), affecting principally the middle phalanges in conjunction with an extra ossicle on the proximal phalanx of both index fingers. Feet abnormalities are more subtle. [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-hydroxybutyric 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	Heart-hand syndrome type 3	c1841657	24,651	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1342	2021-01-23T18:49:45	{"gard": ["2614"], "mesh": ["C535853"], "omim": ["140450"], "umls": ["C1841657"], "icd-10": ["Q87.2"], "synonyms": ["Atriodigital dysplasia type 3", "Cardiomelic syndrome type 3", "Heart-hand syndrome, Spanish type", "Heart-limb syndrome type 3"]}
Hyper IgD syndrome is the less severe form of a metabolic disorder known as mevalonate kinase deficiency. It is considered an auto-inflammatory disease, with recurrent episodic or chronic unexplained inflammation, characterized by periodic episodes of fever, and other symptoms such as joint pain, swollen lymph nodes, skin rash, headaches, and abdominal pain. Most episodes last several days and occur periodically throughout life. The frequency of episodes and their severity vary greatly from person to person. These attacks can occur spontaneously or be triggered by vaccinations, infections, and/or emotional or physical stress. Growth and development is usually not affected. Hyper IgD syndrome is caused by mutations in the MVK gene which provides instructions for making the mevalonate kinase enzyme. The mutations result in the partial deficiency of the enzyme. A more severe form of maevalonate kinase deficiency is known as mevalonic aciduria. It is inherited in an autosomal recessive manner. Treatment is with anakinra, and other medications, but not all patients show a complete response. In most cases, the frequency of the disease's episodes decreases over time. [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-hydroxybutyric 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	Hyper-IgD syndrome	c0398691	24,652	gard	https://rarediseases.info.nih.gov/diseases/2788/hyper-igd-syndrome	2021-01-18T17:59:56	{"mesh": ["D054078"], "omim": ["260920"], "umls": ["C0398691"], "orphanet": ["343"], "synonyms": ["Hyper IgD syndrome", "Hyperimmunoglobulinemia D and periodic fever syndrome", "Periodic fever Dutch type", "HIDS"]}
A rare, genetic, congenital limb malformation syndrome characterized by unilateral or bilateral fibular aplasia/hypoplasia, tibial campomelia, and lower limb oligosyndactyly involving the lateral rays. Upper limb oligosyndactyly and cleft lip/palate may also be associated. [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-hydroxybutyric 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	FATCO syndrome	c2931047	24,653	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2492	2021-01-23T18:36:11	{"gard": ["2622"], "mesh": ["C535856"], "umls": ["C2931047"], "icd-10": ["Q87.2"], "synonyms": ["Fibular aplasia-tibial campomelia-oligosyndactyly syndrome", "Hecht-Scott syndrome"]}
Autosomal recessive severe congenital neutropenia due to CSF3R deficiency is a rare, genetic, primary immunodeficiency disorder characterized by predisposition to recurrent, life-threatening bacterial infections associated with decreased peripheral neutrophil granulocytes (absolute neutrophil count less than 500 cells/microliter), resulting from recessively inherited loss-of-function mutations in the CSF3R gene. Full maturation of all three lineages in the bone marrow and refractoriness to in vivo rhG-CSF treatment are associated. [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-hydroxybutyric 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	Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	c4310764	24,654	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=420702	2021-01-23T16:58:47	{"omim": ["617014"], "icd-10": ["D70"]}
A number sign (#) is used with this entry because cerebral amyloid angiopathy (CAA) can be caused by mutation in the gene encoding the amyloid precursor protein (APP; 104760). Mutations in the APP gene can also cause autosomal dominant Alzheimer disease-1 (AD1; 104300), which shows overlapping clinical and neuropathologic features. Other forms of CAA include the Icelandic type (105150), caused by mutation in the CST3 gene (604312), and the so-called British (176500) and Danish (117300) types, both caused by mutation in the ITM2B gene (603904). Description Cerebral amyloid angiopathy, or cerebroarterial amyloidosis, refers to a pathologic process in which amyloid protein progressively deposits in cerebral blood vessel walls with subsequent degenerative vascular changes that usually result in spontaneous cerebral hemorrhage, ischemic lesions, and progressive dementia. APP-related CAA is the most common form of CAA (Revesz et al. (2003, 2009)). Clinical Features Wattendorff et al. (1982) reported a Dutch family in which 11 members had cerebral and cerebellar hemorrhage and infarction at ages ranging from 44 to 58 years. Affected family members comprised 5 sibships spanning 2 generations. The principal clinical characteristic was recurring cerebral hemorrhages, sometimes preceded by migrainous headaches or mental changes. Of the 11 who presented with acute stroke, all who survived eventually developed dementia. In addition, there were 5 family members who developed dementia, with or without accompanying stroke. Neuropathology showed hyaline thickening of the walls of cortical arterioles in 6 autopsied cases and 1 biopsy specimen. The arteries of the arachnoid showed marked tortuosity, concentric proliferation, and focal hyalinization. Amyloid was demonstrated in the hyalinized vessels but was not found outside the nervous system. The kindred of Wattendorff et al. (1982) was from Scheveningen, the patients were descendants of a couple who married in 1871. Luyendijk and Bots (1986) wrote: 'As the hereditary disease is well-known to the co-members of the respective families they usually inform the doctors on the probable diagnosis themselves, when such a patient is admitted into the hospital. Besides which they usually add all kinds of genealogical information.' The disorder was referred to as HCHWAD for 'hereditary cerebral hemorrhage with amyloidosis, Dutch type.' In studies of the Dutch form of hereditary cerebral hemorrhage with amyloidosis, van Duinen et al. (1987) demonstrated that the vascular amyloid deposits were related to the beta-protein associated with Alzheimer disease and Down syndrome (190685). The findings indicated that the 'Dutch type' is genetically distinct from the 'Icelandic type' of cerebroarterial amyloidosis (105150), which is due to a defect in cystatin C (CST3; 604312). Luyendijk et al. (1988) described 136 patients with hereditary cerebral hemorrhage, all belonging to families originally resident in Katwijk, Netherlands. No genealogic connection had been established between the Dutch and Icelandic pedigrees. Moreover, the findings in all of the Dutch cases were identical and differed from the findings in the Icelandic cases in age at onset and involvement of cystatin C. Among 78 males and 58 females with HCHWAD, Luyendijk et al. (1988) found that the sex ratio for the proven cases was nearly equal (29 males and 26 females). There were numerous examples of father-to-son transmission. Roosen et al. (1985) and Smith et al. (1985) provided case reports of patients with intracerebral hemorrhage or transient ischemic attacks, respectively, resulting from cerebral amyloid angiopathy. Cosgrove et al. (1985) reviewed 24 cases of autopsy-proven cerebral amyloid angiopathy; death was caused by intracranial hemorrhage in 16. None had systemic amyloidosis. Haan et al. (1990) found that all 16 patients they examined with the Dutch type of hereditary cerebral hemorrhage with amyloidosis had psychiatric abnormalities; dementia was present in 12. Three patients tested twice at an interval of some years exhibited progressive intellectual deterioration and memory disturbance; in 2 of them there was no evidence of intercurrent strokes. Fernandez-Madrid et al. (1991) reported a 63-year-old woman of Dutch extraction living in the United States with HCHWA confirmed by molecular analysis. The patient was normotensive and was well until age 47 years, when she began to have attacks approximately every 2 weeks. Iglesias et al. (2000) reported a patient of Spanish descent who presented at age 62 years with intracerebral hemorrhage in a background of progressive mental deterioration. Neuroimaging revealed fine tram-line bilateral occipital calcifications, extensive leukoencephalopathy, and bilateral external carotid artery dysplasia. Skin biopsy with ultrastructural study revealed novel changes in the basal lamina of capillaries, with multilayered appearance and round-shaped microcalcifications. Of 19 next of kin who survived beyond 60 years of age, 6 had brain disorders; 4 of the 6 presented at least 3 components of the syndrome. The proband's mother had died at age 83 with profound dementia; one sister, who was diagnosed with dementia with occipital calcifications and leukoencephalopathy at age 67, died 2 years later from intracranial hemorrhage; a brother had an occipital hemorrhage at age 58, at which time occipital calcifications and leukoencephalopathy were discovered; and another brother died after a minor stroke at age 70 with dementia, occipital calcifications, and external carotid artery dysplasia. Iglesias et al. (2000) suggested that this represented a novel familial cerebrovascular entity with widespread microvascular calcifications and presumably autosomal dominant inheritance. They suggested the acronym FOCHS-LADD, for 'familial occipital calcifications, hemorrhagic strokes, leukoencephalopathy, arterial dysplasia, and dementia.' Iglesias et al. (2000) emphasized that subjects had no seizures, facial angioma, or intracranial vascular malformation, and that arterial hypertension was neither constant nor severe. Grabowski et al. (2001) reported a 3-generation Iowa family with autosomal dominant dementia beginning in the sixth or seventh decade of life. The proband and an affected brother had progressive aphasic dementia, leukoencephalopathy, and occipital calcifications. Neither had intracerebral hemorrhage. Neuropathologic examination of the proband revealed severe cerebral amyloid angiopathy, widespread neurofibrillary tangles, and extensive distribution of beta-amyloid-40 in plaques. Using T2 gradient-echo MRI, van den Boom et al. (2005) identified microbleeds (less than 5 mm in diameter) in 18 (69%) of 27 patients with HCHWAD confirmed by genetic analysis. Three of the patients with microbleeds were asymptomatic. The microbleeds occurred at the gray-white matter junction in the cerebral hemispheres or in the cerebellum; none were found in the basal ganglia, thalamus, or brainstem. Mutation carriers with hypertension had more microbleeds in the cerebellum than those without hypertension, but there was no association between number of microbleeds and hypertension. Twenty-two (81%) mutation carriers had white matter hyperintensities, and 16 (62%) had intracranial hemorrhages. All hemorrhages were supratentorial and spared the thalamus and basal ganglia. The number of microbleeds correlated with increasing age, possibly reflecting disease progression. Obici et al. (2005) reported an Italian family with autosomal dominant cerebral amyloid angiopathy. Clinically, the patients had multiple intracerebral hemorrhages, but only 1 affected family member had cognitive impairment. Neuropathologic analysis of 2 patients showed severe selective cerebroarterial amyloidosis in leptomeningeal and cortical vessel walls with secondary microvascular degeneration and 'vessel-within-vessel' changes. There were no parenchymal amyloid plaques or neurofibrillary tangles. Bugiani et al. (2010) reported 4 unrelated Italian families with autosomal dominant hereditary cerebral hemorrhage with amyloidosis caused by a heterozygous mutation in the APP gene (E693K; 104760.0014). Affected individuals presented with recurrent headache and multiple hemorrhagic strokes between age 44 and 63, followed by epilepsy and cognitive decline in most of them. Several affected individuals became comatose or bedridden, and some died as a result of cerebral hemorrhage. Neuroimaging demonstrated small to large hematomas, subarachnoid bleeding, scars with hemosiderin deposits, multi-infarct encephalopathy, and leukoaraiosis. Multiple brain regions were involved, including both gray and white matter. Postmortem examination of 1 patient showed many small vessels with thickened and/or split walls due to a hyaline congophilic material that was immunoreactive for beta-amyloid-40. Most of the abnormal vessels were in the leptomeninges, in the cerebral and cerebellar cortex, and in the white matter close to the cortex. Beta-amyloid-40 was also detectable in cortical capillaries, and beta-amyloid-42 was found in neuropil of the gray structures. Neurofibrillary tangles and neuritic plaques were not present. The progression of the clinical phenotype correlated with that pathologic findings. Pathogenesis Torack (1975) reported the postmortem studies of 3 patients with congophilic angiopathy who had a surgical procedure and died from a subsequent massive hemorrhagic episode. Two of the patients had clinical evidence of a dementing syndrome. Ultrastructural studies confirmed the amyloid nature of the congophilic material in the 2 biopsied cases. The deposition of amyloid in these cases was believed to be a primary event and related to a generalized systemic disorder. Cerebral amyloid angiopathy is frequently found in demented and nondemented elderly persons. Natte et al. (2001) investigated the relationship between the amount of cerebral amyloid angiopathy and the presence of dementia in 19 patients with hereditary cerebral hemorrhage with amyloidosis of the Dutch type. They found that the amount of cerebral amyloid angiopathy, as quantified by computerized morphometry, was strongly associated with the presence of dementia independent of neurofibrillary pathology, plaque density, or age. A semiquantitative score, based on the number of amyloid beta-laden severely stenotic vessels, completely separated demented from nondemented patients. The results suggested that extensive (more than 15 amyloid beta-laden severely stenotic vessels in 5 frontal cortical sections) CAA alone is sufficient to cause dementia in hereditary cerebral hemorrhage with amyloidosis of the Dutch type. Revesz et al. (2003) reviewed the pathology and genetics of APP-related CAA and discussed the different neuropathologic consequences of different APP mutations. Those that result in increased beta-amyloid-40 tend to result in increased deposition of amyloid in the vessel walls, whereas those that result in increased beta-amyloid-42 tend to result in parenchymal deposition of amyloid and the formation of amyloid plaques. These latter changes are common in classic Alzheimer disease. Attems et al. (2004) presented evidence that deposition of beta-amyloid in cerebral capillary amyloidosis is distinct from the deposition of beta-amyloid in cerebral arterial amyloidosis. Neuropathologic examination of 100 postmortem brains from elderly patients showed AD pathology in 8 (22.2%) of 36 nondemented individuals and in 42 (65.6%) of 64 individuals with a clinical diagnosis of dementia. The results indicated that CAA is characterized by beta-amyloid-40 and -42 deposits in leptomeningeal and cortical arterial vessels, with heavier deposition of beta-amyloid-40. Involvement of the capillaries was rare. In contrast, capillary CAA was characterized by globular deposition of beta-amyloid-42 in the glial limitans of cortical capillaries and in pericapillary compartments, often in conjunction with parenchymal beta-amyloid-42 deposits. Attems et al. (2004) postulated that the deposition in capillaries was a result of drainage of beta-amyloid-42 from senile and neuritic plaques, i.e., from perivascular drainage along basement membranes in the central nervous system. In a study of 17 patients with cerebral amyloid angiopathy, 72 with AD, and 58 controls, Verbeek et al. (2009) found that patients with CAA had strongly decreased CSF levels of beta-amyloid-40 and beta-amyloid-42 compared to both AD patients and controls. CSF tau levels were significantly higher in the AD patients compared with the CAA group, although the concentrations among CAA patients were also higher than in controls. The combination of beta-amyloid-42 and total tau discriminated CAA from controls, with an area under the receiver operator curve (ROC) of 0.98. The data were consistent with CAA neuropathologic evidence indicating that beta-amyloid-40 and -42 are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that usually transport these amyloid proteins to the CSF. Mapping By linkage analysis, Van Broeckhoven et al. (1990) determined that the APP gene on chromosome 21 was a candidate gene for the Dutch form of cerebroarterial amyloidosis. Molecular Genetics In 2 patients from presumably unrelated Dutch families with hereditary cerebral hemorrhage with amyloidosis, Levy et al. (1990) identified a glu693-to-gln mutation in the APP gene (E693Q; 104760.0001). The authors noted that amyloid precursor proteins in the Dutch and Icelandic forms of cerebroarterial amyloidosis are both protease inhibitors and both have been found to have a substitution in their genes that give rise to a substitution of glutamine (see 604312.0001). Prelli et al. (1990) demonstrated that both the normal and the variant alleles were expressed in vascular amyloid in this disorder. Graffagnino et al. (1994) failed to find the amyloid mutation in any of 48 consecutive patients with sporadic intracerebral hemorrhage admitted to Duke University Hospital. No pathologic examinations were made to determine if any of these patients had amyloid deposition. In 4 affected members of an Italian family with cerebral amyloid angiopathy, Obici et al. (2005) identified a mutation in the APP gene (104760.0019). In 2 brothers from an extensive Iowa kindred with progressive dementia and cerebroarterial amyloidosis, Grabowski et al. (2001) identified a heterozygous mutation in the APP gene (N694D; 104760.0016). Greenberg et al. (2003) identified the N694D mutation in 2 affected members of the Spanish family reported by Iglesias et al. (2000). Rovelet-Lecrux et al. (2006) identified duplication of the APP gene (104760.0020) in affected members of a family with early-onset Alzheimer disease and prominent cerebral amyloid angiopathy. ### Modifier Genes The majority of beta-amyloid CAA is sporadic, affecting elderly individuals who may or may not have accompanying Alzheimer disease pathology. The incidence of both diseases steadily increases with age, with the incidence of CAA reaching 50% in those older than 70 years (Revesz et al., 2009). Greenberg et al. (1995) found that the presence of apolipoprotein E4 (107741) significantly increased the odds ratio for moderate or severe cerebral amyloid angiopathy, even after controlling for the presence of Alzheimer disease. Yamada et al. (1996) reported a lack of association between the E4 allele and cerebral amyloid angiopathy in elderly Japanese patients. Nicoll et al. (1996, 1997) did not find an association between the E4 allele and CAA-related hemorrhage. However, they did find a high frequency of the E2 allele in patients with CAA-related hemorrhage, regardless of the presence of AD. The authors suggested that patients with the E2 allele may be protected from parenchymal AD but may be susceptible to the rupture of amyloid-laden vessels. In a postmortem study, Greenberg et al. (1998) found an association between apolipoprotein E2 and vasculopathy in cerebral amyloid angiopathy. Of 75 brains with complete amyloid replacement of vessel walls, only 23 had accompanying signs of hemorrhage in cracks of the vessel wall. The frequency of apolipoprotein E2 was significantly higher in the group with vasculopathy. The authors suggested that apolipoprotein E2 and E4 might promote hemorrhage through separate mechanisms: E4 by enhancing amyloid deposition and E2 by promoting rupture. Hemorrhages related to amyloid angiopathy generally occur in the cortical and cortico-subcortical (lobar) brain regions where vascular amyloid deposits are most frequent, and occur less commonly in the cerebellum. Most patients recover from an initial lobar hemorrhage. Recurrent lobar hemorrhages are relatively common, however, and may cause greater morbidity and mortality than first hemorrhages. O'Donnell et al. (2000) identified a specific apolipoprotein E genotype as a risk factor for early recurrence: carriers of the E2 (107741.0001) or E4 (107741.0016) allele had an increased risk for early recurrence compared to individuals with the E3/E3 (107741.0015) genotype. Animal Model Herzig et al. (2004) found that transgenic mice expressing the human E693Q APP mutation developed extensive cerebral amyloid angiopathy in the leptomeningeal and cortical vessels, cerebral hemorrhages, and neuroinflammation with astrogliosis similar to that found in HCHWAD. Human APP mRNA was detected in neurons and neuronal processes, but not in vessel walls. There was smooth muscle degeneration and irregular thickening of the basement membrane in some vessels, whereas the endothelial cell layer appeared to be intact, and there was no parenchymal amyloid deposition. The ratio of amyloid-beta(40) to amyloid-beta(42) was approximately 4-fold higher than in wildtype mice or human Alzheimer disease. Herzig et al. (2006) extended their earlier studies by developing several murine models of APP-related CAA and APP-related parenchymal amyloid deposition. The findings indicated that APP-related CAA is sufficient to induce cerebral hemorrhage and neuroinflammation; the origin of vascular amyloid is mainly neuronal; APP-related CAA results largely from impaired clearance; a high ratio of beta-40 to beta-42 favors vascular over parenchymal amyloidosis; and genetic factors such as ApoE (107741) can modulate the occurrence of hemorrhages. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Vascular \- Cerebral amyloid angiopathy \- Cerebral artery amyloidosis (amyloid deposition in cerebral arteries) \- Cerebral ischemia \- Recurrent strokes \- Cerebral infarction \- Recurrent cerebral and cerebellar hemorrhage \- Microbleeds (less than 5 mm in diameter) occur at the gray-white matter junction in the cerebral hemispheres and cerebellum and do not occur in the thalamus, basal ganglia, or brainstem \- Hyaline thickening of cerebral arteries \- Tortuous cerebral arteries NEUROLOGIC Central Nervous System \- Dementia, progressive, with onset of disease MISCELLANEOUS \- Onset in middle age (44 to 60 years) \- Allelic to early-onset familial Alzheimer disease (AD1, 104300 ) MOLECULAR BASIS \- Caused by mutation in the amyloid precursor protein gene (APP, 104760.0001 ) ▲ 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-hydroxybutyric 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	CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED	c2931672	24,655	omim	https://www.omim.org/entry/605714	2019-09-22T16:11:06	{"doid": ["0070028"], "mesh": ["C537944"], "omim": ["605714"], "orphanet": ["324703", "324718", "324713", "324723", "324708", "100006", "85458"], "synonyms": ["Hereditary cerebral hemorrhage with amyloidosis, Iowa type", "ABeta amyloidosis, Piedmont type", "CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED, IOWA VARIANT", "Alternative titles", "CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED, ARCTIC VARIANT", "Hereditary cerebral hemorrhage with amyloidosis, Piedmont type", "HCHWA, Flemish type", "ABetaE22K amyloidosis", "Hereditary cerebral hemorrhage with amyloidosis, Italian type", "AMYLOIDOSIS, HEREDITARY, WITH CEREBRAL HEMORRHAGE, DUTCH VARIANT", "ABetaL34V-related amyloidosis", "ABetaA21G-related amyloidosis", "HCHWA, Italian type", "CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED, DUTCH VARIANT", "ABetaE22G amyloidosis", "Hereditary cerebral hemorrhage with amyloidosis, Flemish type", "CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED, ITALIAN VARIANT", "HCHWA, Piedmont type", "CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED, FLEMISH VARIANT", "AMYLOIDOSIS, CEREBROARTERIAL, APP-RELATED", "ABeta amyloidosis, Flemish type", "HCHWA, Arctic type", "ABetaD23N amyloidosis", "HCHWA, Iowa type", "Hereditary cerebral hemorrhage with amyloidosis, Arctic type"]}
Acute flaccid myelitis (AFM) is a condition that affects the spinal cord leading to muscle weakness and loss of reflexes. Most people who develop AFM have had a viral illness with flu-like symptoms one to four weeks before symptoms of AFM. Symptoms of AFM include sudden onset (acute) of weakness in the arm(s) or leg(s), loss of muscle tone, and decreased or absent reflexes. Other symptoms may include pain, facial weakness, and difficulty swallowing, speaking, or moving the eyes. It is not clear why some people develop AFM and others do not. Diagnosis is based on the symptoms, a clinical exam, an MRI of the spine, and other laboratory testing. Most people with AFM continue to have muscle weakness for months to years. Sometimes the muscles involved with breathing become weakened, and ventilator support is necessary to help with breathing. The long-term outcome for people with AFM is unknown. Treatment is focused on managing the symptoms and includes aggressive physical therapy. [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-hydroxybutyric 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	Acute flaccid myelitis	c4290000	24,656	gard	https://rarediseases.info.nih.gov/diseases/13142/acute-flaccid-myelitis	2021-01-18T18:02:18	{"synonyms": []}
Attenuated familial adenomatous polyposis (AFAP) is an inherited condition that increases the chance to develop cancer of the large intestine (colon) and rectum. It is a milder form of classic familial adenomatous polyposis (FAP) and is characterized by fewer colon polyps (an average of 30) and a delay in the development of colon cancer (average age 50 to 55 years). Other signs and symptoms may include benign or malignant tumors of the duodenum (a section of the small intestine) and, in rare cases, other symptoms of FAP. AFAP is caused by mutations in the APC gene and is inherited in an autosomal dominant manner. AFAP is generally managed with regular screening to detect if and when polyps develop. [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-hydroxybutyric 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	Attenuated familial adenomatous polyposis	c2674616	24,657	gard	https://rarediseases.info.nih.gov/diseases/8532/attenuated-familial-adenomatous-polyposis	2021-01-18T18:02:00	{"mesh": ["C538265"], "omim": ["175100"], "umls": ["C2674616"], "orphanet": ["220460"], "synonyms": ["Attenuated FAP", "AFAP", "Mild form of FAP", "Attenuated familial polyposis coli", "Attenuated adenomatous polyposis coli", "AAPC"]}
A number sign (#) is used with this entry because of evidence that short-rib thoracic dysplasia-17 with or without polydactyly (SRTD17) is caused by homozygous or compound heterozygous mutation in the TCTEX1D2 gene (617353) on chromosome 3q29. Description Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia with or without polydactyly, see SRTD1 (208500). Clinical Features Schmidts et al. (2015) studied 5 affected children from 3 unrelated families with a clinical diagnosis of Jeune asphyxiating thoracic dysplasia based on clinical and radiologic findings including short ribs with small or narrow thorax, small ilia with trident acetabulum and spurs, handlebar clavicles, and brachydactyly. Polydactyly was also present in 4 of the 5 patients. None exhibited renal, hepatic, or ocular features, although Schmidts et al. (2015) noted that such features might emerge with age. Molecular Genetics By whole-exome sequencing in 69 patients from 60 families clinically diagnosed with Jeune asphyxiating thoracic dysplasia, Schmidts et al. (2015) identified homozygosity for a splice site mutation in the TCTEX1D2 gene (617353.0001) in the proband from a consanguineous Turkish family (UCL82). Analysis of an additional 154 exomes from SRTD patients and Sanger sequencing of TCTEX1D2 in another 69 SRTD cases that previously had been excluded for mutations in known SRTD-associated genes revealed compound heterozygosity for a nonsense mutation (R88X; 617353.0002) and a deletion/insertion frameshift mutation (617353.0003) in the proband from a nonconsanguineous French family (INS). The mutations segregated with disease in each family and were not found in public variant databases. In a consanguineous Yemeni family (UCL4), exome copy number variant analysis revealed homozygosity for a more than 10-kb deletion removing the start codon and exons 1 and 2 of the TCTEX1D2 gene in an affected brother and sister, who were negative for mutation in known SRTD-associated or other ciliary-component genes. The deletion also removed exons 2 to 5 of a neighboring pancreatic development-associated gene, TM4SF19, which the authors stated was unlikely to be involved in SRTD. RT-PCR on RNA from patient blood lymphocytes detected no TCTEX1D2 transcript, indicating likely nonsense-mediated decay of the mutant transcript. In this family, the homozygous deletion was also found in an affected male sib who died at age 2 months of respiratory failure, as well as in an older brother and sister who exhibited only short stature, with mild brachydactyly and slight shortening of lower limb distal segments. The older sister was also reported to have had pectus carinatum in childhood. Noting that brachydactyly and short stature can occur in SRTD but are not specific for the condition, Schmidts et al. (2015) suggested that the SRTD phenotype was not fully penetrant in the Yemeni family. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature CHEST External Features \- Narrow thorax Ribs Sternum Clavicles & Scapulae \- Short horizontal ribs SKELETAL Pelvis \- Trident acetabulum with spurs Hands \- Brachydactyly \- Polydactyly (in some patients) Feet \- Polydactyly (in some patients) MISCELLANEOUS \- Evidence of reduced penetrance in 1 family MOLECULAR BASIS \- Caused by mutation in the TCTEX1 domain-containing protein 2 gene (TCTEX1D2, 617353.0001 ) ▲ 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-hydroxybutyric 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	SHORT-RIB THORACIC DYSPLASIA 17 WITH OR WITHOUT POLYDACTYLY	c0432195	24,658	omim	https://www.omim.org/entry/617405	2019-09-22T15:45:52	{"omim": ["617405"], "orphanet": ["93426"]}
A rare peroxisome biogenesis disorder (the most severe variant of Peroxisome biogenesis disorder spectrum) characterized by neuronal migration defects in the brain, dysmorphic craniofacial features, profound hypotonia, neonatal seizures, and liver dysfunction. ## Epidemiology The birth prevalence of Peroxisome biogenesis disorder (PBD) is estimated to be around 1/50,000 in North America, and around 1/500,000 in Japan. The highest incidence of Zellweger syndrome (ZS) was reported in the Saguenay-Lac St Jean region of Quebec (around 1/12,000). ## Clinical description Onset is in the neonatal period, reflecting both organ malformations that occurred in utero and progressive disease due to ongoing peroxisome dysfunction. Infants present with characteristic dysmorphic craniofacial features (flattened facies, large anterior fontanel, split sutures, prominent high forehead, flattened occiput, upslanting palpebral fissures, epicanthal folds, and broad nasal bridge), profound hypotonia and seizures. Macrocephaly or microcephaly, high arched palate, micrognathia and redundant neck skin folds may be present. Skeletal abnormalities (chondrodysplasia punctata, most often in the patella and hips) and subcortical renal cysts are frequent. There is often failure to thrive, hepatomegaly, jaundice, and coagulopathy. Eye findings include cataracts, glaucoma, pigmentary retinopathy, nystagmus, corneal clouding and optic nerve atrophy. Visual changes and loss are progressive. Sensorineural hearing loss may be present. Cryptorchidism and hypospadias (male) and clitoromegaly (female) may occur. CNS function is severely affected and infants have profound psychomotor delay. ## Etiology PBD is caused by mutations in one of 13 PEX genes encoding peroxins. Mutations in these genes lead to abnormal peroxisome biogenesis. ## Diagnostic methods ZS is often suspected on physical examination and confirmed with biochemical evaluation. Plasma very-long-chain fatty acid (VLCFA) levels indicate defects in peroxisomal fatty acid metabolism with elevated plasma concentrations of C26:0 and C26:1 and elevated ratios of C24/C22 and C26/C22. Erythrocyte membrane concentrations of plasmalogens C16 and C18 are reduced. Plasma pipecolic acid levels are increased. Sequence analysis of the 13 PEX genes can be performed. MRI can be used to identify perisylvian polymicrogyria, and other developmental brain malformations. ## Differential diagnosis The main differential diagnoses include Usher syndrome I and II, other PBD disorders (see these terms), single enzyme defects in peroxisome fatty acid beta-oxidation, and disorders that feature severe hypotonia, neonatal seizures, liver dysfunction or leukodystrophy. ## Antenatal diagnosis Prenatal screening for VLCFA levels and plasmalogen synthesis can be performed on cultured amniocytes and chorionic villus sampling in suspected or high-risk pregnancies. If disease causing alleles in the carrier parents have been identified, prenatal diagnosis by DNA testing can be performed as well as preimplantation genetic diagnosis. ## Genetic counseling ZS is inherited in an autosomal recessive manner, so genetic counseling is possible. ## Management and treatment There is no cure for ZS. Standard epileptic drugs are used for seizure control. Hepatic coagulopathy can be treated with vitamin K supplementation while cholestasis may require the provision of all fat soluble vitamins. A gastrostomy tube may be needed to allow for adequate calorie intake. Foods rich in phytanic acids (i.e. cow's milk) should be restricted. Supplementation of mature bile acids, cholic and chenodeoxycholic acid may help improve liver disease in infants with severe hepatopathy. As ZS patients cannot biosynthesize DHA, it can also be provided. ## Prognosis Regardless of interventions, prognosis is poor with most infants dying within the first year of life secondary to respiratory compromise related to infection or intractable epilepsy. [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-hydroxybutyric 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	Zellweger syndrome	c0043459	24,659	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=912	2021-01-23T18:17:16	{"gard": ["7917"], "mesh": ["D015211"], "omim": ["214100", "214110", "614859", "614862", "614866", "614870", "614872", "614876", "614882", "614883", "614886", "614887", "617370"], "umls": ["C0043459"], "icd-10": ["Q87.8"], "synonyms": ["Cerebrohepatorenal syndrome", "ZS"]}
For a phenotypic description and a discussion of genetic heterogeneity of otosclerosis, see OTSC1 (166800). Van Den Bogaert et al. (2001) performed linkage analysis in a Belgian family in which otosclerosis segregated as an autosomal dominant disorder. After excluding linkage to OTSC1 (166800) on chromosome 15, they found linkage on 7q, with a multipoint lod score of 3.54. Analysis of key recombinant individuals mapped this second otosclerosis locus, which they designated OTSC2, to a 16-cM interval on 7q34-q36 between markers D7S495 and D7S2426. [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-hydroxybutyric 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	OTOSCLEROSIS 2	c1854022	24,660	omim	https://www.omim.org/entry/605727	2019-09-22T16:11:05	{"mesh": ["C565302"], "omim": ["605727"]}
Ritchie et al. (1986) observed wide variability in the amounts of total phenolic metabolites of debrisoquine (124030) excreted among subjects. There was none detectable in some persons (of either extensive or poor metabolizer phenotypes; see 608902), whereas in others, 15 to 20% of dose was excreted in the phenolic form. Ritchie et al. (1986) described 2 sisters who developed hematotoxicity from carbimazole, an antithyroid drug, administered in usual dosage. Both sisters had very high levels of excreted phenolic derivatives of debrisoquine when tested for metabolism of that substance. It may be that this is a polymorphism of carbimazole (and debrisoquine) metabolism independent of the polymorphism of 4-hydroxylation of debrisoquine. The 2 sisters developed agranulocytosis after taking carbimazole for 17 and 24 days, respectively. The hematotoxicity is thought to be due to the thiourea moiety that it contains. Metabolic oxidation of the thiourea group can result in production of highly reactive and, hence, toxic metabolites that may bind to cellular macromolecules. The enhanced ability to form phenolic metabolites of debrisoquine may reflect an unusual oxidative pathway which also results in hematotoxic metabolites of carbimazole. Ritchie et al. (1986) also studied phenolic metabolites of debrisoquine in 43 control subjects and in 6 blood relatives of the sisters. The findings suggested the existence of 3 genotype groups with appreciable overlap. Prenatal exposure to methimazole, the active metabolite of carbimazole which is used in the treatment of maternal Graves disease (275000), has been associated with scalp defects and aplasia cutis congenita (107600) (Martin-Denavit et al., 2000). Greenberg (1987) and Wilson et al. (1998) described choanal atresia (608911) and hypoplastic nipples (see 113700) after prenatal exposure to methimazole. Barbero et al. (2004) described 3 patients with choanal atresia whose mothers received methimazole during pregnancy for the treatment of thyrotoxicosis (Graves disease; Hashimoto thyroiditis, 140300). Inheritance \- Autosomal recessive Heme \- Carbimazole toxicity \- Agranulocytosis ▲ 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-hydroxybutyric 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	CARBIMAZOLE SENSITIVITY	c1859352	24,661	omim	https://www.omim.org/entry/212060	2019-09-22T16:30:15	{"omim": ["212060"]}
Lethal arteriopathy syndrome due to fibulin-4 deficiency is a rare, genetic, vascular disorder characterized by severe aneurysmal dilatation, elongation, and tortuosity of the thoracic aorta, its branches and pulmonary arteries with stenosis at various typical locations, typically resulting in infantile demise. Variable associated features may include cutis laxa, long philtrum with thin vermillion border, hypertelorism, sagging cheeks, arachnodactyly, joint laxity and pectus deformities. [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-hydroxybutyric 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	Lethal arteriopathy syndrome due to fibulin-4 deficiency	c3280798	24,662	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314718	2021-01-23T18:03:01	{"omim": ["614437"]}
Northern epilepsy syndrome Other namesNeuronal ceroid lipofuscinosis, Northern epilepsy variant This condition is inherited in an autosomal recessive manner. Northern epilepsy syndrome (NE), or progressive epilepsy with mental retardation (EPMR), is a subtype of neuronal ceroid lipofuscinosis and a rare disease that is regarded as a Finnish heritage disease. Unlike most Finnish heritage diseases, this syndrome has been reported only in Finland.[1] The disease is characterized by seizures in early childhood that progressively get worse until after puberty. Once the onset of seizures occurs, mental degradation is seen. This continues into adulthood, even after seizure frequency has decreased. The cause of the disease is a missense mutation on chromosome 8. The creation of a new protein occurs, and the lipid content of the brain is altered because of it. The ratio of the mutation carriers is 1:135. There is nothing that has been found to stop the progression of the disease, but symptomatic approaches, such as the use of benzodiazepines, have helped control seizures.[2][3][4] ## Contents * 1 Characteristics * 1.1 Early childhood * 1.2 Adolescence * 1.3 Adulthood * 2 Genetic causes * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 Prognosis * 7 History * 8 See also * 9 References * 10 External links ## Characteristics[edit] ### Early childhood[edit] Northern epilepsy syndrome causes recurrent seizures between the ages of five to ten. These seizures, that may last up to 15 minutes, can be classified mostly as tonic-clonic, but partial seizures could also occur. The seizures commonly involve muscle rigidity, convulsions and loss of consciousness. Generally, the recurrence is one to two times per month. In the years following the onset of seizures, a noticeable decrease in intellectual capacity is observed.[3] ### Adolescence[edit] During puberty, seizure frequency increases to one to two times per week.[4] Mental function has a rapid decline, as observed by a lack of coordination, failure to complete education and fine motor activities.[3] In rare cases, some suffered from loss of vision.[2] ### Adulthood[edit] Seizure frequency is reduced to four to six seizures per year.[3] By this time, they are mentally and physically incapable to live without assistance due to the total mental degradation. Life expectancy is at least 50 years of age, which is shorter than the average worldwide age of 70.[4] ## Genetic causes[edit] Northern epilepsy syndrome is caused by an inherited autosomal recessive mutation in the telomeric region of the short arm of chromosome 8. There are at least ten mutations within the chromosome that cause the disease, and the most common missense mutation occurs at codon 24, where a glycine takes the place of an arginine. This primary mutation can also be paired with a missense at codon 237, where an arginine takes the place of a glycine. When the two mutations interact, a lengthened progression of the disease is observed.[5] The primary mutation (Arg24Gly) creates the protein CLN8. 1 in every 135 people of Finnish descent were reported to be a carrier of the mutation.[2] The difference between 1-CLN8 and 2-CLN8 is the amount of mutations and the mutation's location in the chromosome.[2] ## Pathophysiology[edit] An accumulation of transmembrane protein is seen in the brain tissue of Northern epilepsy patients. This protein is a 286 amino acid transmembrane protein that has not been identified before, meaning that it is unique to Northern epilepsy syndrome.[4] CLN8 has been linked to the accumulation of subunit c of mitochondrial ATP synthase and a small amount of sphingolipid activator proteins in the neurons. β-amyloid, a peptide involved in Alzheimer's disease, is also seen in this protein accumulation.[4] ## Diagnosis[edit] A patient’s DNA is sequenced from a blood sample with the use of the ABI Big Dye Terminator v.3.0 kit. Since this is a genetic disease, the basis of diagnosis lies in identifying genetic mutations or chromosomal abnormalities. The DNA sequence can be run with CLN8 Sanger sequencing or CLN8 Targeted Familial Mutations whether its single, double, or triple exon sequencing.[2] Also, preliminary evidence of the disease can be detected by means of MRI and EEG.[4] These tests identify lipid content of the brain, and any anomaly from the norm may be linked to Northern epilepsy.[citation needed] ## Treatment[edit] Current available treatment is limited to treating the symptoms, not the cause. Seizure frequency can be regulated by the use of drugs such as Clonazepam (or other benzodiazepines) and sodium valproate. Clonazepam functions by increasing GABA activity at the GABAA receptor. GABA is an inhibitory neurotransmitter, and therefore its increased activity hyperpolarizes cells. Clonazepam has been effective in minimising seizure activity, especially during puberty.[4] Sodium valproate prevents the depolarization of the cell by blocking sodium ion channels and inhibitory GABA enzymes. Both of these anticonvulsants lead to depression of the central nervous system.[citation needed] ## Prognosis[edit] Life expectancy is only moderately affected by NE because the rate of disease progression is slow. Patients usually survive past 40–50 years of age.[6] ## History[edit] Northern epilepsy originated in northern Finland, and it still appears to only affect individuals of Finnish ancestry. 1 in 10,000 individuals who live or are from the region of Kainuu in northern Finland have the condition.[citation needed] Northern epilepsy was not initially recognized as a Neuronal ceroid lipofuscinosis (NCL). In 1999, it was found to be the first disease identified caused by mutations in the CLN8 gene. The disease is now known as the mildest form of NCL.[7] There are two forms of this mutated gene: 1-CLN8 and 2-CLN8. 1-CLN8 is known as Northern epilepsy syndrome, while 2-CLN8 is primarily from Turkish descent.[2] ## See also[edit] * Epilepsy * Neuronal ceroid lipofuscinosis * CLN8 ## References[edit] 1. ^ Krystyna E. Wiśniewski; Nanbert Zhong; Jeffrey C. Hall (2001). Batten disease: diagnosis, treatment, and research. Academic Press. p. 243. ISBN 978-0-12-017645-8. page 125 2. ^ a b c d e f "NEURONAL CEROID LIPOFUSCINOSIS 8 VIA THE CLN8 GENE". Prevention Genetics. Retrieved 23 March 2014. 3. ^ a b c d "Northern epilepsy". U.S. National Library of Medicine. Retrieved 23 March 2014. 4. ^ a b c d e f g Ranta, S; Lehesjoki AE (2000). "Northern epilepsy, a new member of the NCL family". Neurological Sciences. 21 (1 Supplement): S43–S47. doi:10.1007/s100720070039. PMID 11073227. S2CID 11677694. 5. ^ Siintola, E; Lehesjoki AE; Mole SE (2006). "Molecular genetics of the NCLs -- status and perspectives". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1762 (10): 857–864. doi:10.1016/j.bbadis.2006.05.006. PMID 16828266. 6. ^ Herva, Riitta; Tyynelä, Jaana; Hirvasniemi, Aune; Syrjäkallio-Ylitalo, Marja; Haltia, Matti (2000-04-01). "Northern Epilepsy: A Novel Form of Neuronal Ceroid-Lipofuscinosis". Brain Pathology. 10 (2): 215–222. doi:10.1111/j.1750-3639.2000.tb00255.x. ISSN 1750-3639. PMID 10764041. S2CID 43726125. 7. ^ Warrier, V; Vieirab M; Mole SE (2013). "Genetic basis and phenotypic correlations of the neuronal ceroid lipofusinoses". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1832 (11): 1827–1830. doi:10.1016/j.bbadis.2013.03.017. PMID 23542453. ## External links[edit] Classification D * ICD-10: E75.4 * OMIM: 610003 * DiseasesDB: 33514 External resources * Orphanet: 1947 [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-hydroxybutyric 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	Northern epilepsy syndrome	c1864923	24,663	wikipedia	https://en.wikipedia.org/wiki/Northern_epilepsy_syndrome	2021-01-18T19:03:06	{"gard": ["2163", "4010"], "mesh": ["C537952"], "umls": ["C1864923"], "orphanet": ["1947"], "wikidata": ["Q7059204"]}
A rare cutaneous variant of lichen planus which affects hair follicles. It may occur on its own or in association with more common forms of lichen planus, usually classical type and/or oral lichen planus. ## Epidemiology The prevalence is unknown. LPP is more frequent in women than in men. ## Clinical description The disease manifests in adulthood (40-60 years of age), with some rare cases in childhood. Patients present with peri-follicular inflammation and hair loss. They may be asymptomatic or have itch or discomfort. The scalp is the commonest area affected but any hair bearing skin may be affected, like for example the axillae or the pubic area. Perifollicular erythema, scales, and/or keratotic plugs are seen at the edge of the affected area. Single or multiple lesions of scarring alopecia lacking follicular orifices are typical. Two other variants of LPP can be observed: frontal fibrosing alopecia (FFA), and Lassueur-Graham-Little syndrome (see these terms). In FFA, there is symmetrical, progressive anterior hairline loss of the scalp associated with eyebrow loss. The Lassueur-Graham-Little syndrome constitutes a combination of lichen planus follicularis of the scalp with follicular keratosis and noncicatricial alopecia of the axillae and pubes. ## Etiology Etiology is unknown but LPP is thought to be an autoimmune disorder in which T-lymphocytes attack and destroy keratinocytes expressing unknown target antigens. Triggering factors could be pharmacologic agents, contact sensitizers or infectious agents. ## Diagnostic methods Diagnosis is based on clinical and histopathological findings. Biopsy of an inflammatory lesion shows a band-like perifollicular lymphocytic infiltrate at the level of the isthmus and infundibulum. There may be vacuolar changes of the basal layer and follicular plugging. In more advanced lesions, perifollicular fibrosis and replacement of hair follicles by fibrosis are found. Diagnosis is difficult in the later stages when inflammation disappears. ## Differential diagnosis Differential diagnosis includes discoid lupus erythematosus (DLE), folliculitis decalvans, mucous membrane pemphigoid (see these terms), seborrheic dermatitis, alopecia areata, and central centrifugal cicatricial alopecia (CCCA). ## Management and treatment There is no long-term effective treatment for LPP. Current treatments aim at slowing down progression of hair loss and reduction of symptoms. Topical, intralesional and oral corticosteroids are the mainstay of treatment. Unfortunately, relapse is common. Other options for treatment include hydroxychloroquinine, ciclosporin and methotrexate. ## Prognosis LPP can progress slowly or rapidly. Some cases may spontaneously resolve but others are progressive. [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-hydroxybutyric 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	Lichen planopilaris	c0023645	24,664	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=525	2021-01-23T18:11:06	{"gard": ["3247"], "mesh": ["C535892"], "umls": ["C0023645"], "icd-10": ["L66.1"], "synonyms": ["Follicular lichen planus", "LPP", "Lichen follicularis", "Lichen planus follicularis"]}
Frank-Ter Haar syndrome is a rare inherited condition characterized by multiple skeletal abnormalities, developmental delay, and characteristic facial features (unusually large cornea, flattened back of the head, wide fontanels, prominent forehead, widely spaced eyes, prominent eyes, full cheeks, and small chin). Less than 30 cases have been reported worldwide. Protruding ears, prominent coccyx bone (or tail bone), and congenital heart defects are also frequently present. This condition is caused by mutations in the SH3PXD2B gene and is thought to be inherited in an autosomal recessive fashion. [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-hydroxybutyric 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	Frank Ter Haar syndrome	c1855305	24,665	gard	https://rarediseases.info.nih.gov/diseases/5138/frank-ter-haar-syndrome	2021-01-18T18:00:26	{"mesh": ["C537274"], "omim": ["249420"], "umls": ["C1855305"], "orphanet": ["137834"], "synonyms": ["Ter Haar syndrome", "Autosomal recessive Melnick-Needles syndrome (formerly)", "Megalocornea, multiple skeletal anomalies, and developmental delay"]}
A mitochondrial disorder of long chain fatty acid oxidation characterized in most patients by onset in infancy/ early childhood of hypoketotic hypoglycemia, metabolic acidosis, liver disease, hypotonia and, frequently, cardiac involvement with arrhythmias and/or cardiomyopathy. ## Epidemiology The worldwide birth prevalence is estimated at 1/250,000. However around the Baltic Sea the frequency is higher; birth prevalence is predicted to be 1/120,000 in Poland and 1/20,000 in the Pomeranian district. ## Clinical description Most patients display a severe phenotype that presents in infancy, usually from the neonatal period up until 12 months of age. The disease manifests as hypoketotic hypoglycemia, metabolic acidosis, hypotonia, liver involvement with hepatic encephalopathy, cardiomyopathy and arrhythmias. Clinical presentation is frequently preceded by fasting and/or intercurrent illness and often presents with hypoketotic hypoglycemia. Chronic peripheral neuropathy and pigmentary retinopathy develop over time in many surviving patients. Rarer presentations of LCHADD are sudden cardiac arrest or sudden infant death. HELLP syndrome (see this term) often occurs in pregnant women carrying a fetus affected with LCHADD. ## Etiology LCHADD is caused by the isolated deficiency of long chain 3-hydroxyacyl-CoA dehydrogenase, an enzyme of the mitochondrial trifunctional protein complex (TFP). TFP is a heterooctamer of 4 alpha and 4 beta subunits. LCHADD is due to mutations in the HADHA gene (2p23) which encodes for the alpha subunit of TFP. The majority of patients with LCHADD of European origin are homozygous for the common LCHADD alpha-subunit mutation 1528G>C, that is located at the catalytic site of the LCHAD domain. ## Diagnostic methods Urine organic acids show a C6-C14 (hydroxy) dicarboxylic aciduria. Blood acylcarnitine analysis shows increased long chain hydroxyacylcarnitine species (C14-OH, C16-OH, C18-OH, and C18:1-OH). Confirmation is by molecular analysis of the HADHA gene that frequently demonstrates homozygocity for the 1528G>C mutation. Enzyme analysis of cultured fibroblasts or lymphocytes shows isolated deficiency of long chain 3-hydroxyacyl-CoA dehydrogenase activity. Newborn screening for LCHADD is available in Austria, Czech Republic, Denmark, Germany, Hungary, Iceland, Netherlands and Portugal. ## Differential diagnosis Mitochondrial trifunctional protein deficiency (TFPD; see this term) is clinically indistinguishable from LCHADD. Some patients present as sudden infant death so this also needs to be excluded. ## Antenatal diagnosis Prenatal diagnosis is by molecular analysis for established mutation(s) within the family and/or by measuring enzyme activity in chorionic villi samples. ## Genetic counseling LCHADD is inherited autosomal recessively and genetic counseling is available. ## Management and treatment Treatment involves strict adherence to a low fat diet with restriction of long chain fatty acid intake and substitution with medium chain fatty acids and avoidance of fasting as well as limitation of exercise or exposure to environmental extremes. An emergency regimen should be available for all patients and medical attention should be sought at the first sign of any decompensation. Treatment is lifelong. ## Prognosis The prognosis for clinically detected LCHADD patients was generally poor but due to early detection and current treatments, it is improving, with a significant number of patients surviving into adulthood. [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-hydroxybutyric 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	Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency	c1969443	24,666	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=5	2021-01-23T18:15:02	{"gard": ["6867"], "mesh": ["C566945"], "omim": ["609016"], "umls": ["C0342786", "C1969443"], "icd-10": ["E71.3"], "synonyms": ["LCHAD deficiency", "LCHADD", "Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency"]}
A number sign (#) is used with this entry because X-linked lymphoproliferative syndrome-1 (XLP1) is caused by mutation in the SH2D1A gene (300490), encoding SLAM-associated protein (SAP), on chromosome Xq25. Description X-linked lymphoproliferative syndrome, or Duncan disease, is a primary immunodeficiency characterized by severe immune dysregulation often after viral infection, typically with Epstein-Barr virus (EBV). It is a complex phenotype manifest as severe or fatal mononucleosis, acquired hypogammaglobulinema, hemophagocytic lymphohistiocytosis (HLH), and/or malignant lymphoma. Other features may include aplastic anemia, red cell aplasia, and lymphomatoid granulomatosis (Purtilo et al., 1977; Purtilo, 1981; Purtilo and Grierson, 1991; Coffey et al., 1998; Booth et al., 2011). ### Genetic Heterogeneity of X-linked/Autosomal Lymphoproliferative Syndrome See XLP2 (300635), caused by mutation in the XIAP gene (300079), also on Xq25; LPFS1 (613011), caused by mutation in the ITK gene (186973) on chromosome 5q33; LPFS2 (615122), caused by mutation in the CD27 gene (186711) on chromosome 12p13; and LPFS3 (618261), caused by mutation in the CD70 gene (TNFSF7; 602840) on chromosome 19p13. Clinical Features Purtilo et al. (1974, 1975) reported a kindred by the name of Duncan in which 6 males died between the ages of 2 and 19 years from a lymphoproliferative disease. The subtle, progressive combined variable immunodeficiency disease was characterized by benign or malignant proliferation of lymphocytes and histiocytosis, as well as alterations in concentrations of serum immunoglobulins. In at least 3 of 6 boys, infectious mononucleosis occurred during or preceding the terminal events. Fever, pharyngitis, lymphadenopathy, hepatosplenomegaly, atypical lymphocytosis, and a spectrum ranging from agammaglobulinemia to polyclonal hypergammaglobulinemia occurred. At necropsy, the thymus glands and thymic-dependent areas in the lymph nodes and spleen were depleted of lymphocytes. Hematopoietic organs, viscera, and central nervous system were diffusely infiltrated by lymphocytes, plasma cells, and histiocytes, some containing erythrocytes. Two of the 6 males, half sibs, had lymphomas of the ileum and central nervous system. The authors raised the possibility that 'the Epstein-Barr virus or other viruses triggered the fatal proliferation of lymphocytes and that progressive attrition of T-cell function allowed uncontrolled lymphoproliferation.' In addition to the kindred described by Purtilo and his colleagues, the kindred in which 4 young male cousins died of infectious mononucleosis, as reported by Bar et al. (1974), and the kindred with agammaglobulinemia developing after infectious mononucleosis in 3 maternal male cousins, as reported by Provisor et al. (1975), may be examples of Duncan disease. Hamilton et al. (1980) abbreviated the designation of this disease to XLP (X-linked lymphoproliferative) syndrome. They reported studies of 59 affected males in 7 unrelated kindreds ascertained through an XLP registry. Thirty-four patients died of infectious mononucleosis, 8 had fatal infectious mononucleosis with immunoblastic sarcoma, 9 had depressed immunity following Epstein-Barr virus infection, and 8 developed lymphoma. Purtilo et al. (1982) reviewed 100 cases of XLP in 25 kindreds, and suggested 4 major interrelated phenotypes: infectious mononucleosis (IM), malignant B-cell lymphoma (ML), aplastic anemia (AA), and hypogammaglobulinemia (HGG). Eighty-one of the patients died; 2 were asymptomatic but showed immunodeficiency to EBV; 75 had IM and, concurrently, 17 of this group had AA; all with AA died within a week. On the other hand, AA did not accompany HGG or ML. In 9, IM appeared to evolve into ML; however, most patients with ML showed no obvious antecedent IM. In 1, IM occurred after recurrent ML. Twenty-six of 35 lymphomas were in the terminal ileum. Heterozygous women (mothers of boys with XLP) showed abnormally elevated titers of antibodies to EBV. Sullivan et al. (1980) found deficient activity of natural killer (NK) cells from patients with XLP. Sullivan et al. (1983) studied 2 males with XLP before and during acute fatal Epstein-Barr virus infection. Before EBV infection, both showed normal cellular and humoral immunity. Death in both cases was caused by liver failure: one developed extensive hepatic necrosis; the other developed massive infiltration of the liver with EBV-infected immunoblasts after aggressive immunosuppressive therapy. Sullivan et al. (1983) proposed that an aberrant immune response triggered by acute EBV infection results in unregulated anomalous killer and natural killer cell activity against EBV infected and uninfected cells. They further suggested that the global cellular immune defects in males with XLP who survive EBV infection represent an epiphenomenon. Purtilo and Grierson (1991) reported that during the previous decade 240 males with XLP within 59 unrelated kindreds had been identified worldwide. One-half of the patients had developed fatal infectious mononucleosis at an average age of about 2.5 years, and death occurred on average only 33 days following onset of illness. About one-third had acquired hypogammaglobulinemia and another one-fourth had developed malignant lymphoma, most of which were of the Burkitt type involving the ileocecal region. Although hypogammaglobulinemia and malignant lymphoma were associated with longer survivals, no patient had been documented as living into the fifth decade of life. Seemayer et al. (1995) reviewed XLP 25 years after Purtilo's first observations in 1969. Purtilo established a registry in 1980 to serve as a worldwide resource for the diagnosis, treatment, and research of this condition. After Purtilo's death in late 1992, the registry and research unit continued to function as a worldwide consultative service. By 1995, some 272 affected members of 80 kindreds had been identified. Approximately 10% of the boys who inherited the mutated XLP gene were immunologically abnormal, even before evidence of EBV exposure. Coffey et al. (1998) noted that the average age of disease onset in XLP is 2.5 years, with 100% mortality by the age of 40 years. Following infection with EBV, patients mount a vigorous, uncontrolled polyclonal expansion of T and B cells. The primary cause of death is hepatic necrosis and bone marrow failure. The extensive tissue destruction of the liver and bone marrow appears to stem from the uncontrolled cytotoxic T-cell response. Systemic vasculitis is an uncommon manifestation of XLP. Dutz et al. (2001) described a patient who died as a result of chronic systemic vasculitis and fulfilled clinical criteria for the diagnosis of XLP. Sequencing of the SH2D1A gene revealed a novel point mutation affecting the SH2 domain. The patient presented with virus-associated hemophagocytic syndrome, and later chorioretinitis, bronchiectasis, and hypogammaglobulinemia developed. He further developed mononeuritis and fatal respiratory failure. Evidence of widespread small and medium vessel vasculitis was noted at autopsy with involvement of retinal, cerebral, and coronary arteries as well as the segmental vessels of the kidneys, testes, and pancreas. Immunohistochemical analysis showed that the vessel wall infiltrates consisted primarily of CD8+ T cells, implying a cytotoxic T-lymphocyte response to antigen. Epstein-Barr virus DNA was detected by PCR in arterial wall tissue microdissected from infiltrated vessels, suggesting that the CD8+ T cells were targeting EBV antigens within the endothelium. Dutz et al. (2001) proposed that functional inactivation of the SH2D1A gene impairs the immunologic response to EBV, resulting in systemic vasculitis. Verhelst et al. (2007) reported a boy with SAP deficiency who developed limbic encephalitis. He was diagnosed and treated for cervical B-cell non-Hodgkin lymphoma at age 9 years. At age 15, during hospitalization for pneumonia, blood tests revealed hypogammaglobulinemia for the first time. At age 16, he presented with seizures, decreased alertness, short-term memory loss, and hemiparesis. MRI and cerebral biopsy showed vasculitis with infiltration of T lymphocytes and granulomas. Despite aggressive treatment, he showed further deterioration and died 10 months later. There was absence of SAP protein on immunostaining of the patient's lymphocytes, but no mutation was identified in the SH2D1A gene. There was no family history of a similar disorder. Booth et al. (2011) performed a retrospective analysis of 91 patients with genetically confirmed XLP1 ascertained worldwide, including 43 who had hematopoietic stem cell transplant (HSCT) and 48 without transplant. The most common presenting feature was hemophagocytic lymphohistiocytosis (HLH), which occurred in 39.6% of patients, and the most common overall feature was dysgammaglobulinemia, which occurred in 50% of patients at some point during the illness. Twenty-two patients had malignant lymphoproliferative disease, including 18 with B-cell non-Hodgkin lymphoma. Fifty-one (64.6%) of 79 patients tested were EBV-positive. There was no significant difference in mortality between those with and without documented EBV infection, but those with EBV infection had a higher frequency of HLH. The mortality for patients presenting with HLH was 65.6%, with a median age at presentation of 3 years, 2 months. Overall survival after transplant was 81.4%; however, survival fell to 50% in patients with HLH as a feature of disease. Untransplanted patients had an overall survival of 62.5% with the majority on immunoglobulin replacement therapy, but the outcome for those untransplanted after HLH was extremely poor, at only 18.8%. Overall, the study indicated that hematopoietic stem cell transplant should be undertaken in all XLP1 patients with HLH, because outcome without transplant is extremely poor, whereas the outcome of HSCT for other manifestations of XLP1 is very good. Diagnosis Purtilo and Grierson (1991) concluded that the diagnosis of XLP in affected males and female carriers was 99% accurate based on results of linkage to DXS42 RFLPs (lod = 19.4) and 95% accurate with RFLP probes to DXS37 (lod = 11.8). By linkage analysis, they detected males with the XLP gene before EBV infection occurred. Using RFLP analysis, Grierson et al. (1993) evaluated 10 families in which a single male had died of infectious mononucleosis. The authors suggested that, in such families, Epstein-Barr virus-seronegative males must be considered at risk for XLP and should be identified pre-EBV infection in order to maximize survival. One family in the study was determined to have XLP; 3 other families in the study had carriers of XLP, and 3 families were determined not to have XLP. ### Prenatal Diagnosis Skare et al. (1992) made the diagnosis of XLP prenatally by analyzing closely linked RFLP markers of cells obtained at amniocentesis at 15 weeks' gestation. By use of DNA markers applied to chorionic villus sampling (CVS) material, Mulley et al. (1992) identified with high reliability an unaffected male fetus, brother of an affected male. By HLA-DR typing of the CVS, they also showed that the fetus was DR-identical to the affected sib. Clinical Management Williams et al. (1993) reported successful bone marrow transplantation in an 11-year-old boy with Duncan syndrome, with restoration of an apparently normal host immune response to EBV. They presented this as evidence that the primary abnormality in this disorder resides in bone marrow-derived cells. Vowels et al. (1993) described a boy with this disorder in whom transplantation of cord-blood stem cells from an HLA-identical sib resulted in correction of the genetic defect and the hypogammaglobulinemia. Cord blood collected at birth contains 5 to 10 times more marrow progenitor cells than the peripheral blood of older infants or children, and the volume of blood and nucleated cells that can be collected is substantial. The authors noted that cord blood had successfully been transplanted into patients with aplastic anemia and leukemia, resulting in repopulation of the bone marrow and immune systems. Arkwright et al. (1998) reported a sibship of 4 males born to unrelated parents, 3 of whom had X-linked lymphoproliferative disease. The proband was born at 33 weeks' gestation and developed neonatal varicella zoster infection complicated by tibial osteomyelitis. At 18 months of age, he developed infectious mononucleosis complicated by hepatitis and aplastic anemia. The latter responded well to oral corticosteroids, broad-spectrum antibiotics, and acyclovir. He later developed hypoglobulinemia and required regular intravenous infusions of immunoglobulin. An older brother was healthy until the age of 7, when he developed a fulminant cytomegalovirus infection (hemophagocytic lymphohistiocytosis). This responded to etoposide-based chemotherapy and a successful allogenic bone marrow transplant from his normal sib. At 4 months of age, another brother was shown by RFLP and microsatellite markers flanking the XLP locus to have inherited the high-risk haplotype. Although healthy, he was receiving prophylactic intravenous immunoglobulin infusions. This sibship demonstrated the varied clinical manifestations of X-linked lymphoproliferative disease. Schuster and Kreth (1999) stated that the only means available to prevent EBV- and non-EBV-related complications in later life is early transplantation of allogeneic hematopoietic stem cells, i.e., cord blood or bone marrow (Vowels et al., 1993; Williams et al., 1993). The age of the patient at the time of transplantation appeared to be critical. Whereas 4 of 8 XLPD patients who underwent stem cell transplantation before the age of 15 years were alive and well for more than 2 years posttransplantation, all 4 boys older than 15 years of age at the time of transplantation died within 90 days of complications. Mapping Skare et al. (1987, 1987) demonstrated linkage of XLP with marker DXS42, which maps to Xq24-q27 (lod score of 5.26). Haplotype analysis refined the XLP locus distal to DXS42 and proximal to DXS99. Skare et al. (1989) extended the linkage information on the family they reported in 1987 and studied 6 additional families, all of which corroborated the close linkage to DXS42 (1% recombination; lod = 17.5) and DXS37 (maximum lod = 13.3 at theta = 0.0.) Hayoz et al. (1988) identified a large, extensively affected Swiss family with XLP, ascertained through a patient with acquired hypogammaglobulinemia associated with a mononucleosis syndrome at the age of 18 years; the patient died at 19. In this family, a new mutation in the F8 gene (300841) causing hemophilia A (306700) had occurred, resulting in a woman who was a carrier of both genes. She had a son with hemophilia, a daughter who was a carrier of both disorders, and a son who was free of both disorders. The doubly-heterozygous daughter had 1 son with XLPD and 1 son who was doubly affected. The observations suggested that the hemophilia A locus and the XLPD locus are far apart, a conclusion that was supported by other mapping data. Harris et al. (1988) excluded linkage of XLP to 28 X-linked probes. Harris and Docherty (1988) found no particular chromosomal abnormalities in this disorder. One of their patients was found to have the Klinefelter syndrome, having inherited 2 copies of his maternal XLPD-carrying X chromosome. Wyandt et al. (1989) found deletion of part of band Xq25 in a male with this disorder; others found the same deletion in the mother and a sister. Skare et al. (1989) reported family linkage studies of the XLP-causing gene with several Xq DNA markers. They also reported 1 male of 14 unrelated affected persons who had a deletion in Xq which was thought to involve about one-half of Xq25. This male retained sequences at all 5 loci that had been found to be closely linked to XLP, but lacked DXS6 which by somatic hybrid mapping had been assigned to Xq26-qter. In a large Swiss family with XLP, Sylla et al. (1989) demonstrated linkage of XLP to marker DXS37, which is located in Xq25-q26. Multipoint linkage analysis showed that the XLP locus is distal to DXS11 but proximal to HPRT (308000). Sanger et al. (1990) demonstrated an interstitial deletion involving a portion of Xq25 in an affected male as well as in 1 sister and their mother. Using blot hybridization, Skare et al. (1993) identified 3 XLP males with deletions of Xq25 encompassing marker DXS739. Molecular Genetics In 9 unrelated patients with X-linked lymphoproliferative syndrome, Coffey et al. (1998) identified mutations in the SH2D1A gene (300490.0001-300490.0009). In 2 brothers with early-onset non-Hodgkin lymphoma, but no clinical or laboratory evidence of EBV infection, Brandau et al. (1999) identified a deletion of exon 1 of the SH2D1A gene (300490.0010). Other SH2D1A mutations were identified in 2 additional unrelated patients without evidence of EBV infection; 1 had non-Hodgkin lymphoma and 1 had signs of dysgammaglobulinemia. Development of dysgammaglobulinemia and lymphoma without evidence of prior EBV infection in 4 patients suggested that EBV is unrelated to these particular phenotypes, in contrast to fulminant or fatal infectious mononucleosis. No SH2D1A mutations were found in 3 families in which clinical features were suggestive of XLP. Sumegi et al. (1999) reviewed the molecular basis of Duncan disease. They tabulated 15 mutations in the SH2D1A gene. Heterogeneity Rigaud et al. (2006) studied a cohort of 18 families with an inherited disease diagnosed as X-linked lymphoproliferative syndrome. Among them, 15 were found to harbor mutations in the SH2D1A gene. However, in affected individuals from 3 families, Rigaud et al. (2006) failed to detect mutations in the SH2D1A gene or any of its regulatory regions. Unlike SAP-deficient patients with XLP, these patients often had splenomegaly, noticed as their first clinical manifestation of this condition. Further investigations demonstrated that in these 3 families, XLP was caused by insufficiency of XIAP (300079). Pathogenesis Nichols et al. (2005) observed that Sh2d1a -/- mice lacked NKT cells in the thymus and peripheral organs. The defect in NKT cell ontogeny was hematopoietic cell-autonomous and could be rescued by reconstitution of Sh2d1a expression within Sh2d1a -/- bone marrow cells. Nichols et al. (2005) also studied 17 individuals with XLP and differing SH2D1A genotypes. All 17 lacked NKT cells, and a female XLP carrier showed completely skewed X chromosome inactivation within NKT cells, but not T or B cells. Nichols et al. (2005) concluded that SH2D1A is a crucial regulator of NKT cell ontogeny, and that the absence of NKT cells may contribute to the XLP phenotype, including abnormal antiviral and antitumor immunity and hypogammaglobulinemia. Ma et al. (2005) analyzed 14 XLP patients from 9 families and found normal B-cell development but a marked reduction in the number of memory B cells; the few detected were IgM+, revealing deficient isotype switching in vivo. However, XLP B cells underwent proliferation and differentiation in vitro as efficiently as control B cells, indicating that the block in differentiation in vivo is B-cell extrinsic. XLP CD4+ (186940) T cells did not efficiently differentiate into IL10+ (124092) effector cells or provide optimal B-cell help in vitro; provision of exogenous IL10 or ectopic expression of SH2D1A, which increased IL10 production by T cells, improved the B-cell help. Ma et al. (2005) suggested that insufficient IL10 production may contribute to hypogammaglobulinemia in XLP. Using immunohistochemistry and flow cytometric analysis, Ma et al. (2006) found that IgM-positive/CD27 (TNFRSF7; 186711)-positive B cells from XLP patients were morphologically and functionally similar to those from normal donors. The authors suggested that production of affinity-matured IgM by these cells may protect against pathogens to which a normal immune response is elicited in XLP patients. By studying T-cell receptor (TCR; see 186740) restimulation of preactivated T cells from EBV-naive XLP patients after prolonged exposure to IL2 (147680), Snow et al. (2009) found that activated T cells from these patients were specifically and substantially less sensitive to restimulation-induced cell death (RICD). Silencing SAP or NTBA (SLAMF6; 606446) expression recapitulated resistance to RICD in normal T cells, indicating that both molecules are necessary for optimal TCR-induced apoptosis. TCR restimulation triggered increased recruitment of SAP to NTBA, and these proteins functioned to augment TCR-induced signal strength and induction of downstream proapoptotic target genes, including FASL (TNFSF6; 134638) and BIM (BCL2L11; 603827). Snow et al. (2009) proposed that XLP patients are inherently susceptible to antigen-induced lymphoproliferative disease and fulminant infectious mononucleosis due to compromised RICD. History Schuster and Kreth (1999) attributed the first report of a family with XLP to Hambleton and Cottom (1969), who described a family in which 2 brothers suffered from hypogammaglobulinemia and malignant lymphoma following infectious mononucleosis. INHERITANCE \- X-linked recessive RESPIRATORY Nasopharynx \- Pharyngitis Lung \- Lymphoid granulomatosis ABDOMEN Liver \- Hepatomegaly \- Fulminant hepatitis \- Liver failure Spleen \- Splenomegaly NEUROLOGIC Central Nervous System \- Meningitis \- Encephalitis \- Hepatic encephalopathy HEMATOLOGY \- Anemia \- Thrombocytopenia \- Pancytopenia \- Atypical lymphocytosis IMMUNOLOGY \- Lymphadenopathy \- Combined variable immunodeficiency involving B and T cells \- Normal number of B cells \- Normal number of T cells \- Reduced CD4+/CD8+ ratio with CD8+ predominance \- Reduced natural killer cell activity \- Fulminant infectious mononucleosis \- Histology shows large regions of necrosis in lymph nodes, thymus, bone marrow, and spleen NEOPLASIA \- Hemophagocytic lymphohistiocytosis \- Lymphoma LABORATORY ABNORMALITIES \- Reduced IgG levels \- Increased IgM levels MISCELLANEOUS \- Reduced life expectancy, death by 10 years of age in 70% of patients MOLECULAR BASIS \- Caused by mutations in the SH2 domain protein 1A gene (SH2D1A, 300490.0001 ) ▲ 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-hydroxybutyric 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	LYMPHOPROLIFERATIVE SYNDROME, X-LINKED, 1	c0549463	24,667	omim	https://www.omim.org/entry/308240	2019-09-22T16:18:05	{"doid": ["0060705"], "mesh": ["D008232"], "omim": ["308240"], "icd-10": ["D82.3"], "orphanet": ["2442", "538931"], "synonyms": ["Alternative titles", "XLP", "LYMPHOPROLIFERATIVE DISEASE, X-LINKED", "LYP", "DUNCAN DISEASE", "EPSTEIN-BARR VIRUS INFECTION, FAMILIAL FATAL", "EBV INFECTION, SEVERE, SUSCEPTIBILITY TO", "INFECTIOUS MONONUCLEOSIS, SEVERE, SUSCEPTIBILITY TO", "IMMUNODEFICIENCY, X-LINKED PROGRESSIVE COMBINED VARIABLE", "IMMUNODEFICIENCY 5", "PURTILO SYNDROME"], "genereviews": ["NBK1406"]}
A number sign (#) is used with this entry because combined pituitary hormone deficiency-2 (CPHD2) is caused by homozygous or compound heterozygous mutation in the PROP1 gene (601538) on chromosome 5q35. For discussion of phenotypic and genetic heterogeneity of combined pituitary hormone deficiency, see CPHD1 (613038). Clinical Features Panhypopituitary dwarfism is not excessively rare, there probably being 7,000 to 10,000 cases in the United States. Many cases are due to craniopharyngioma and other nongenetic causes. The form inherited as an autosomal recessive is probably rare. (See also the rare X-linked form (312000).) Multiple cases in multiple sibships observed among the Hutterites, a religious isolate in the United States and Canada, indicate the recessive inheritance of panhypopituitarism (McKusick and Rimoin, 1967). McArthur et al. (1985) studied the natural history of the Hutterite panhypopituitarism. The patients showed sequential loss of anterior pituitary tropic hormones. Three untreated sibs developed deficiency of growth hormone (GH; 139250) and gonadotropin (see 118850) in the first decade of life, with subsequent loss of thyroid-stimulating hormone (TSH; see 188540) function, and finally development of ACTH deficiency (210400) in the third decade. In a second family, deficiency of GH, gonadotropins, and TSH were evident in the first decade. Southern blot analysis showed no abnormality of growth hormone genes; linkage studies excluded close linkage to HLA. Furthermore, the familial cases in the inbred population of certain areas of Switzerland and of the Island of Veglia (Krk) in the Adriatic, observed by Hanhart (1925, 1953), are probably examples. The nature of most panhypopituitarism as a congenital malformation with little indication of a mendelian basis is supported by the observation by Rosenfield et al. (1967) of 16-year-old identical twins, one normal and one with panhypopituitarism. Kirchhoff et al. (1954) described 3 dwarfed sibs who may have had panhypopituitarism, the oldest being almost 18 years old. Selye (1947) pictured 3 brothers, aged 25, 22, and 11 years, with panhypopituitarism. The cases described by Schmolck (1907) may have been of the panhypopituitary type. Bailey et al. (1967) reported 2 families with a total of 5 affected. In one, the parents were first cousins. Steiner and Boggs (1965) described brother and sister, offspring of first-cousin parents, with congenital absence of the pituitary, leading to hypothyroidism, hypoadrenalism, and hypogonadism. A third sib was probably also affected and died, presumably of hypoglycemia, in the newborn period. The sella turcica was normal in size. The disorder reported by Sadeghi-Nejad and Senior (1974) may be the same or an allelic disorder. A male newborn developed hypoglycemic convulsions. Diagnostic studies showed evidence of deficiency of thyrotropin, growth hormone, and prolactin (176760). The child thrived on replacement therapy. A female sib died in the first day of life with similar clinical findings and at autopsy showed absence of the anterior pituitary and atrophic adrenal glands. Pinto et al. (1997) noted that the finding of 'pituitary stalk interruption syndrome' (PSIS) by MRI is a clinical marker of permanent growth hormone deficiency. Some patients with PSIS have isolated GHD, whereas some have other pituitary hormone deficiencies. In a comparison of 16 patients with PSIS and isolated GHD with 35 patients with PSIS and other pituitary deficiencies, Pinto et al. (1997) concluded that most patients with GHD associated with multiple anterior pituitary abnormalities and PSIS had features suggestive of an antenatal origin. Fluck et al. (1998) followed 2 apparently unrelated consanguineous CPHD families (12 individuals total), with 5 affected individuals (3 males and 2 females), for more than 2 decades. The authors noted that there was variability in the phenotype, even among these patients who all carried the same mutation (R120C; 601538.0001). The age at diagnosis, ranging from 9 months to 8 years of age, was dependent on the severity of symptoms. Although in 1 patient TSH deficiency was the first symptom of the disorder, all patients exhibited severe growth retardation and failure to thrive, which was primarily (4 individuals) caused by GH deficiency. The secretion of the pituitary-derived hormones GH, PRL, TSH, LH, and FSH declined gradually with age, following a different pattern in each individual; therefore, the deficiencies developed over a variable period of time. All 5 patients entered puberty spontaneously, and the 2 females also experienced menarche before replacement therapy was necessary. Mendonca et al. (1999) studied 2 unrelated females with CPHD: patient 1 presented at 8.8 years with severe short stature, slightly enlarged sella turcica by x-ray, and a diffusely enlarged pituitary gland with hyperintense enhanced signal on T1 weighted image at coronal and sagittal views on magnetic resonance imaging (MRI). MRI repeated at age 15 years revealed a marked reduction of pituitary height. Patient 2 presented at 27 years with short stature, no pubertal development, normal sella turcica, and a pituitary gland of reduced size and normal intensity on MRI. Both patients had normal pituitary stalks and normally located neurohypophyses. Both had deficiencies of GH, TSH, PRL, LH, and FSH. Patient 1 had normal cortisol secretion at 8.8 years but by 16.6 years had developed partial cortisol deficiency, whereas patient 2 maintained normal cortisol secretion at 28.4 years. The authors concluded that a large sella turcica and an enlarged pituitary anterior lobe with hyperintense enhanced T1 signal on MRI suggests PROP1 deficiency; that pituitary morphology can change during follow-up of patients with PROP1 mutations; and that hormonal deficiencies associated with PROP1 mutations can include the adrenal axis. Rosenbloom et al. (1999) investigated a large Dominican kindred with PROP1 deficiency presenting as CPHD, the largest such family reported to that time. Eight patients, aged 17 to 40 years, in 2 sibships with possibly related mothers but no parental consanguinity, had marked short stature and were sexually immature. Affected individuals had similarities to and significant differences from patients with insulin-like growth factor (IGF1; 147440) deficiency due to GH receptor (GHR; 600946) deficiency (see Laron syndrome, 262500), who have normal thyroid function and sexual maturation. The differences from patients with GHR deficiency included normal hand and foot length in 7 of 8 patients, normal arm span with relatively long legs, and persistence of extremely low levels of IGF1 into adulthood; similarities included the degree of growth failure, frequent but not uniform increased body weight for height or body mass index, and the presence of limited elbow extensibility and blue sclerae in 6 of 8 patients. While 3 patients had markedly increased sella turcica area for height age and bone age, the degree of sellar enlargement was variable in these 2 sibships. Congenital hypoplasia of the anterior pituitary gland is the most common MRI finding in patients with PROP1 mutations. Riepe et al. (2001) studied 2 brothers with CPDH prospectively for almost 12 years with respect to variations in pituitary size. Both showed combined pituitary hormone deficiency of GH, TSH, PRL, and the gonadotropins FSH and LH, as is typical for PROP1 deficiency; retesting at ages 12 and 15 years, respectively, revealed developing insufficiency of ACTH and cortisol secretory capacity as well in both patients. Computerized tomography (CT) revealed an enlarged pituitary in the older brother at 3.5 years of age. Repeated MRI after 12 years showed a constant hypoplasia of the anterior pituitary lobe. Similarly, MRI of the younger brother showed a constant enlargement of the anterior pituitary gland until age 10 years. At the age of 11 years, the anterior pituitary was hypoplastic. The authors concluded that early pituitary enlargement may be the typical course in such patients in whom pituitary surgery is not indicated. Reynaud et al. (2004) reported the natural history of hypopituitarism in a large Tunisian kindred including 29 subjects from the same consanguineous family. The index case was a 9-year-old girl with severe growth retardation due to complete GH deficiency and partial corticotroph, lactotroph, and thyrotroph deficiencies. MRI showed a hyperplastic anterior pituitary. Thirteen of the 28 relatives examined had hypopituitarism. In the 14 patients, previously untreated, height was -5.7 +/- 1.7 SD score, and puberty was spontaneously initiated in only 2 females. Complete GH deficiency was found in all 12 patients investigated, of whom 11 had thyrotroph deficiency; 8 of 10 investigated had corticotroph deficiency. To analyze the prevalence of adrenal insufficiency in patients with PROP1 defects and to characterize the temporal pattern of anterior pituitary failure, Bottner et al. (2004) performed a retrospective longitudinal analysis of 9 patients with PROP1 mutations who were under medical supervision. All patients initially presented with growth failure at a mean age of 4.9 +/- 0.8 years. They were first diagnosed with GH and TSH deficiency, and replacement therapy was instituted at 6.1 +/- 1.1 and 6.8 +/- 1.2 years, respectively. All 7 patients who reached pubertal age required sex hormone substitution at 15.0 +/- 0.7 yr. Repeated functional testing of the anterior pituitary axes revealed a progressive decline with age in peak levels of GH, TSH, prolactin, and LH/FSH. All patients developed at least partial adrenal insufficiency with a gradual decline of the function of the pituitary adrenal axis and eventually required substitution with hydrocortisone at a mean age of 18.4 +/- 3.5 years. The authors concluded that anterior pituitary function in patients with PROP1 mutations deteriorates progressively and includes adrenal insufficiency as a feature of this condition, which has important clinical relevance in childhood and adolescence. Voutetakis et al. (2004) used long-term MRI findings to characterize the morphologic abnormalities of the pituitary gland in 15 patients with CPHD caused by PROP1 gene mutations. Small pituitary gland was detected in 7 patients (25.2 +/- 14.4 years of age), normal pituitary size in 3 patients (10.2 +/- 5.8 years of age), and pituitary enlargement in 5 patients (6.5 +/- 2.7 years of age). The pituitary enlargement consisted of a nonenhancing mass lesion interposed between the normally enhancing anterior lobe and the neurohypophysis. The pituitary stalk was displaced anteriorly, whereas the neurohypophysis was orthotopic, displaying a normal signal. Spontaneous regression of the mass lesion with normalization of the pituitary stalk position was observed in 3 patients. The authors concluded that while a small pituitary gland is usually observed in older subjects, a significant number of young patients with PROP1 gene mutations demonstrate pituitary enlargement with subsequent regression. Molecular Genetics In affected members of 4 CPHD families, who showed deficiency of growth hormone (GH; 139250), prolactin (PRL; 176760), thyrotropin (TSH; see 188540), luteinizing hormone (LH; see 152780), and follicle-stimulating hormone (FSH; see 136530), but normal levels of adrenocorticotrophic hormone (ACTH; see 176830), Wu et al. (1998) identified homozygosity or compound heterozygosity for inactivating mutations of the PROP1 gene (601538.0001-601538.0003, respectively). In contrast to individuals with CPHD1 (613038), who have mutations in the human homolog of the mouse Pit1 gene, POU1F1 (173110), those with PROP1 mutations cannot produce LH or FSH at a sufficient level and do not enter puberty spontaneously. These results identified a major cause of combined pituitary hormone deficiency in humans and suggested a direct or indirect role for PROP1 in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes, and caudomedial thyrotropes. In 5 affected individuals from 2 apparently unrelated consanguineous CPHD families, Fluck et al. (1998) identified homozygosity for the R120C mutation in the PROP1 gene (601538.0001). The authors noted that there was variability in age of onset and severity of symptoms, even among these patients with the same mutation. PROP1 deficiency should be considered as a potential cause of all familial cases of CPHD. In 10 independently ascertained CPHD kindreds, Cogan et al. (1998) found that 55% (11 of 20) of the PROP1 alleles were 301delAG (602538.0002). Fofanova et al. (1998) analyzed the POU1F1 (173110) and PROP1 genes in 14 Russian children with CPHD, 7 unrelated and 7 from 4 families, who had complete GH and complete or partial PRL and TSH deficiencies. A missense mutation in POU1F1 was identified in 1 patient, and 8 other patients were found to be homozygous or compound heterozygous for 2 different deletions in the PROP1 gene, 149delGA (601538.0004) and 296delGA (601538.0005), respectively. All parents were of normal stature and each was heterozygous for a wildtype allele and 1 of the deletions, respectively. In 2 unrelated females with CPHD involving GH, TSH, PRL, LH, and FSH, 1 of whom also had partial cortisol deficiency, Mendonca et al. (1999) identified homozygosity for a 2-bp deletion in the PROP1 gene (601538.0002). In 8 patients from a large Domenican COPD kindred, Rosenbloom et al. (1999) identified homozygosity for the 296delGA mutation in the PROP1 gene. In 10 CPHD patients from a large Brazilian kindred, 9 of whom were born of consanguineous marriages, Pernasetti et al. (2000) identified homozygosity for a 2-bp deletion in the PROP1 gene (301delAG; 601538.0002). All affected patients presented complete absence of puberty and low GH, PRL, TSH, LH, and FSH associated with severe hypoplasia of the pituitary gland, as seen by MRI. The authors observed ACTH/cortisol insufficiency in 5 of 6 of the older patients and in 1 11-year-old patient, and suggested that the phenotype of this mutation includes late-onset adrenal insufficiency. Agarwal et al. (2000) analyzed the PROP1 gene in a large consanguineous Indian pedigree with CPHD and identified homozygosity for a 13-bp deletion in affected individuals, predicted to generate a null allele (601538.0007). Severe cortisol deficiency was observed in 2 patients in this family, suggesting a role for PROP1 in the differentiation and/or maintenance of corticotroph cells in the mature anterior pituitary. Vallette-Kasic et al. (2001) screened the PROP1 gene in 23 CPHD patients and identified homozygosity or compound heterozygosity for 4 different mutations in 9 patients from 8 unrelated families. All mutations were located in exon 2 and affected only 2 different sites (see 601538.0005 and 601538.0009-601538.0011). All of the patients were born to unaffected parents, and consanguinity was documented in 2 patients. They had complete GH, LH-FSH, and TSH deficiencies, and normal basal levels of PRL with blunted PRL response to TRH; delayed ACTH deficiency was diagnosed in 4 patients. All had complete hypogonadotrophic hypogonadism and none entered puberty spontaneously. MRI showed a hypoplastic anterior pituitary 7 patients and in 2 patients, there was initial hyperplasia with subsequent hypoplasia on a later study; 2 patients also showed an enlarged sella turcica. Vallette-Kasic et al. (2001) stated that, in keeping with previous reports, they found no correlation between phenotype and genotype. In 2 brothers with CPHD who both had early hyperplasia and later hypoplasia of the anterior pituitary by MRI, Riepe et al. (2001) identified compound heterozygosity for inactivating mutations in the PROP1 gene, 301delAG and 150delA (601538.0008). The panhypopituitarism in the Hutterite cases reported by McKusick and Rimoin (1967) were shown to be due to the common 2-bp deletion (301-302delAG) in the PROP1 gene (601538.0002) (Mosely et al., 2002). Reynaud et al. (2004) studied 3 brothers with CPHD from a consanguineous family of Tunisian descent. The brothers had been referred for cryptorchidism and/or delayed puberty, and initial investigations revealed hypogonadotropic hypogonadism. One of the patients had psychomotor retardation, intracranial hypertension, and minor renal malformations. The brothers reached normal adult height and developed GH and TSH deficiencies after age 30. Reynaud et al. (2004) identified homozygosity for a nonsense mutation in the PROP1 gene (W194X; 601538.0010) in the affected brothers, and concluded that PROP1 mutations should be considered among the genetic causes of initially isolated hypogonadotropic hypogonadism. Pathogenesis Inactivating mutations in PROP1 perturb ontogenesis of pituitary gonadotropes, somatotropes, lactotropes, and thyrotropes. These developmental defects result in deficiencies of PRL, LH, FSH, GH, or TSH. Clinical Management Individuals with PROP1 mutations that cause GH and TSH deficiencies respond to GH and thyroid hormone replacement. Those with PROP1 mutations that cannot produce luteinizing or follicle-stimulating hormone at a sufficient level may not enter puberty spontaneously which may require gonadotropin replacement. Some older affected individuals have been reported to develop adrenal insufficiency in their third to fifth decades due to ACTH deficiency (202200) (Fluck et al., 1998). Lee et al. (2004) reported 3 adult sibs, aged 18 to 25 years, with short stature, hypothyroidism, and lack of pubertal maturation, who were homozygous for the 301delAG PROP1 deletion (601538.0002). They treated them in adulthood with GH for 4 to 5 years and thyroid replacement before sex steroid replacement therapy. Despite delay in treatment and fairly advanced bone age, all responded to these therapies with a dramatic increase in linear growth. The authors concluded the substantial linear growth in adult sibs with a PROP1 mutation illustrates that despite an advanced bone age, linear growth potential remains in adulthood in the setting of sex steroid deficiency. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature (if untreated) NEUROLOGIC Central Nervous System \- Hypoglycemic seizures METABOLIC FEATURES \- Neonatal hypoglycemia ENDOCRINE FEATURES \- Sequential loss of anterior pituitary tropic hormones \- Panhypopituitarism \- Hypothyroidism \- Hypoadrenalism \- Hypogonadism LABORATORY ABNORMALITIES \- Low or absent growth hormone (GH) \- Low or absent thyroid-stimulating hormone (TSH) \- Low or absent follicle-stimulating hormone (FSH) \- Low or absent luteinizing hormone (LH) \- Low or absent prolactin (PL) \- Low or absent adrenocorticotropic hormone (ACTH) MOLECULAR BASIS \- Caused by by mutations in the prophet of Pit1, paired-like homeodomain transcription factor gene (PROP1, 601538.0001 ) ▲ 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-hydroxybutyric 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	PITUITARY HORMONE DEFICIENCY, COMBINED, 2	c0242343	24,668	omim	https://www.omim.org/entry/262600	2019-09-22T16:23:20	{"doid": ["9406"], "mesh": ["C580003"], "omim": ["262600"], "orphanet": ["90695", "95494"], "synonyms": ["Alternative titles", "PANHYPOPITUITARISM", "ATELIOTIC DWARFISM WITH HYPOGONADISM", "PITUITARY DWARFISM III", "HANHART DWARFISM"], "genereviews": ["NBK1347"]}
Midline cervical cleft (MCC) is a rare congenital anomaly characterized by the presence at birth of a vertical, atrophic and usually erythematous skin defect, lacking adnexal elements in the midline of the neck that may be attached to a subcutaneous fibrous cord of variable length; a superior skin tag; and an inferior, short (usually about 1 cm in length) sinus (possibly with presence of discharge). If untreated (by surgical removal) complications include restriction of neck extension due to contracture and scarring. It is sometimes associated with other developmental defects such as bifid mandible, thyroglossal duct and branchial cysts, and microgenia. [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-hydroxybutyric 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	Midline cervical cleft	c1274890	24,669	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141288	2021-01-23T17:23:38	{"umls": ["C1274890"], "icd-10": ["Q18.8"]}
A number sign (#) is used with this entry because of evidence that myofibrillar myopathy-7 (MFM7) is caused by homozygous mutation in the KY gene (605739) on chromosome 3q22. Description Myofibrillar myopathy-7 is an autosomal recessive muscle disorder characterized by early childhood onset of slowly progressive muscle weakness primary affecting the lower limbs and associated with joint contractures (summary by Straussberg et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419). Clinical Features Straussberg et al. (2016) reported 2 adult brothers, born of consanguineous Israeli Arab parents, with onset of a slowly progressive myopathy from infancy. The lower limbs were primarily affected with weakness and muscle atrophy; upper limb involvement became apparent later, and both patients had atrophy of the lateral tongue margins. Other features included congenital bilateral equinovarus foot deformity, Achilles tendon contractures, elbow contractures, mild facial weakness, and kyphosis with rigid spine. The younger brother had intellectual disability and behavioral disorders, whereas the older brother had normal cognitive and speech development. Muscle biopsy showed myopathic changes with fiber-size variation, rounded, atrophied, and necrotic fibers, internalized nuclei, and occasional myophagocytosis. Electron microscopy showed unstructured core targetoid defects with streaming and thickening of the Z discs, as well as an enlarged endoplasmic reticulum, consistent with myofibrillar derangement. Hedberg-Oldfors et al. (2016) reported a 7.5-year-old girl, born of consanguineous Kurdish parents, with MFM7. After normal early psychomotor development, she presented around 3 years of age with walking difficulties due to muscle weakness and atrophy of the lower limbs and progressive equinus contractures of the feet. Achilles tendon elongation surgery at age 6.5 years resulted in improvement in her walking abilities; there was no progression of symptoms from 6.5 to 7.5 years of age. She was not able to walk on her heels, but could walk on her toes and run. She also had slightly increased lumbar lordosis, weak reflexes, and limited movement of the shoulders, elbows, hips, and ankles. Muscle imaging showed muscle atrophy and fatty replacement of the posterior calf muscles. Muscle biopsy showed increased variability of fiber size affecting type 1 and type 2 fibers, internalized nuclei, and small fibers. There was variable myofibrillar ATPase activity, and electron microscopy showed abnormal sarcomeres with Z-line thickening and formation of small nemaline rods. Cognitive function, fine motor skills, and respiratory and heart function were all normal. Inheritance The transmission pattern of MFM7 in the family reported by Straussberg et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 brothers, born of consanguineous Arab Israeli parents, with MFM7, Straussberg et al. (2016) identified a homozygous truncating mutation in the KY gene (Y135X; 605739.0001). The mutation, which was found by a combination of autozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. Immunostaining showed absence of the KY protein in patient muscle, consistent with a loss of function. In a 7.5-year-old girl, born of consanguineous Kurdish parents, with MFM7, Hedberg-Oldfors et al. (2016) identified a homozygous frameshift mutation in the KY gene (605739.0002). The mutation was found by whole-exome sequencing and segregated with the disorder in the family. Animal Model The kyphoscoliosis (ky) mouse mutant exhibits a primary degenerative myopathy preceding chronic thoracolumbar kyphoscoliosis. The histopathology of the ky mutant suggests that ky protein activity is crucial for normal muscle growth and function as well as the maturation and stabilization of the neuromuscular junction. Muscle hypertrophy in response to increasing demand is deficient in the ky mutant, whereas adaptive fiber type shifts take place (Blanco et al., 2001). INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Facial muscle weakness Mouth \- Atrophy of the lateral margins of the tongue SKELETAL Spine \- Kyphosis \- Lordosis \- Rigid spine Limbs \- Elbow contractures \- Achilles tendon contractures Feet \- Pes equinovarus MUSCLE, SOFT TISSUES \- Muscle weakness, primarily lower limbs \- Muscle weakness, upper limbs (in some patients) \- Muscle atrophy \- Difficulty walking \- Inability to walk on heels \- Fiber size variation seen on skeletal muscle biopsy \- Rounded fibers \- Atrophic fibers \- Internalized nuclei \- Myofibrillary changes \- Abnormal sarcomeres \- Z-disc streaming \- Z-disc thickening NEUROLOGIC Peripheral Nervous System \- Hyporeflexia LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Onset in early childhood \- Slowly progressive \- Three patients from 2 unrelated consanguineous families have been reported (last curated September 2016) MOLECULAR BASIS \- Caused by mutation in the kyphoscoliosis peptidase gene (KY, 605739.0001 ) ▲ 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-hydroxybutyric 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	MYOPATHY, MYOFIBRILLAR, 7	c4310711	24,670	omim	https://www.omim.org/entry/617114	2019-09-22T15:46:52	{"doid": ["0080098"], "omim": ["617114"], "orphanet": ["496686"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that primary coenzyme Q10 deficiency-2 (COQ10D2) is caused by homozygous mutation in the PDSS1 gene (607429) on chromosome 10p12. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of primary coenzyme Q10 deficiency, see COQ10D1 (607426). Clinical Features Mollet et al. (2007) reported 2 sibs, born of consanguineous Moroccan parents, in which CoQ10 deficiency was manifest as a multisystem disorder with early-onset deafness, optic atrophy, mild mental retardation, peripheral neuropathy, obesity, livedo reticularis, and cardiac valvulopathy. The patients were 22 and 14 years old at the time of the report. Enzymologic analysis showed low quinone-dependent oxidative phosphorylation activity in affected members, and CoQ10 deficiency was confirmed by restoration of oxidative phosphorylation activity after quinone addition. Patient fibroblasts showed low CoQ10 levels. Inheritance The transmission pattern of CoQ10 deficiency in the family reported by Mollet et al. (2007) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 Moroccan sibs with CoQ10 deficiency, Mollet et al. (2007) identified a homozygous mutation in the PDSS1 gene (D308E; 607429.0001). The mutation was found by homozygosity mapping followed by candidate gene analysis. Transformation of yeast lacking Coq1 with yeast Coq1 containing a mutation corresponding to human D308E resulted in defective growth on respiratory medium. INHERITANCE \- Autosomal recessive GROWTH Weight \- Obesity HEAD & NECK Head \- Macrocephaly Ears \- Deafness, early-onset Eyes \- Optic atrophy CARDIOVASCULAR Heart \- Valvulopathy \- Aortic regurgitation \- Mitral regurgitation Vascular \- Pulmonary artery hypertension SKIN, NAILS, & HAIR Skin \- Livedo reticularis MUSCLE, SOFT TISSUES \- Muscle biopsy shows mitochondrial aggregates \- Coenzyme Q10 deficiency \- Decreased respiratory complex I+III and II+III activity NEUROLOGIC Central Nervous System \- Mental retardation, mild Peripheral Nervous System \- Peripheral neuropathy \- Areflexia LABORATORY ABNORMALITIES \- Increased serum lactate MISCELLANEOUS \- Two sibs born of consanguineous Moroccan parents have been reported (last curated May 2012) MOLECULAR BASIS \- Caused by mutation in the prenyl diphosphate synthase, subunit 1 gene (PDSS1, 607429.0001 ) ▲ 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-hydroxybutyric 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	COENZYME Q10 DEFICIENCY, PRIMARY, 2	c3553354	24,671	omim	https://www.omim.org/entry/614651	2019-09-22T15:54:37	{"doid": ["0070239"], "omim": ["614651"], "orphanet": ["254898"], "synonyms": ["Hearing loss-encephaloneuropathy-obesity-valvulopathy syndrome"], "genereviews": ["NBK410087"]}
## Summary ### Clinical characteristics. PAX6-related aniridia occurs either as an isolated ocular abnormality or as part of the Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome. Aniridia is a pan ocular disorder affecting the cornea, iris, intraocular pressure (resulting in glaucoma), lens (cataract and lens subluxation), fovea (foveal hypoplasia), and optic nerve (optic nerve coloboma and hypoplasia). Individuals with aniridia characteristically show nystagmus and impaired visual acuity (usually 20/100 - 20/200); however, milder forms of aniridia with subtle iris architecture changes, good vision, and normal foveal structure do occur. Other ocular involvement may include strabismus and occasionally microphthalmia. Although the severity of aniridia can vary between and within families, little variability is usually observed in the two eyes of an affected individual. WAGR syndrome. The risk for Wilms tumor is 42.5%-77%; of those who develop Wilms tumor, 90% do so by age four years and 98% by age seven years. Genital anomalies in males can include cryptorchidism and hypospadias (sometimes resulting in ambiguous genitalia), urethral strictures, ureteric abnormalities, and gonadoblastoma. While females typically have normal external genitalia, they may have uterine abnormalities and streak ovaries. Intellectual disability (defined as IQ <74) is observed in 70%; behavioral abnormalities include attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, anxiety, depression, and obsessive-compulsive disorder. Other individuals with WAGR syndrome can have normal intellect without behavioral problems. ### Diagnosis/testing. The diagnosis of PAX6-related aniridia is established in a proband with one of the two following clinical and molecular genetic findings: * Isolated aniridia (i.e., without systemic involvement) and a heterozygous PAX6 pathogenic variant, ranging in size from a single nucleotide (e.g., those resulting in a nonsense, missense, or splice site variant or single-nucleotide deletion or duplication) to a partial- or whole-gene deletion (or in rare instances deletions telomeric to PAX6 that do not include PAX6); or * Aniridia and one or more additional findings of WAGR syndrome and a deletion of PAX6 and the upstream adjacent gene, WT1 ### Management. Treatment of manifestations: * Aniridia. Correction of refractive errors, use of tinted or photochromic lenses to reduce light sensitivity, occlusion therapy in childhood for amblyopia, use of low-vision aids. Treatment of severe cataracts requires attention to potential complications caused by poor zonular stability. Glaucoma: Initial treatment is usually topical anti-glaucoma medication; surgery is reserved for eyes that do not respond to medical therapy. Ocular surface disease: medical treatment (lubricants, mucolytics, and punctal occlusion) may help slow the progression of corneal opacification. When corneal opacification causes significant visual reduction, penetrating keratoplasty with limbal stem cell transplantation may be considered; however, this has a high risk of failure and possible lifelong systemic immunosuppression to prevent rejection. * WAGR syndrome. Wilms tumor, genital anomalies, and developmental delay / intellectual disability are managed as per standard practice. Surveillance: * Aniridia. Monitor children younger than age eight years every four to six months for refractive errors and detection and treatment of incipient or actual amblyopia; annual ophthalmology follow up of all individuals to detect problems such as corneal changes, raised intraocular pressure, and cataracts. * WAGR syndrome. Children with aniridia and a WT1 deletion require renal ultrasound examinations every three months and follow up by a pediatric oncologist until age eight years. Because of the increased risk for renal impairment in WAGR syndrome (especially in those with bilateral Wilms tumor), lifelong evaluation of renal function is recommended. Developmental progress and educational needs require regular monitoring. Behavioral assessment for anxiety, ADHD, and aggressive or self-injurious behavior as needed. Agents/circumstances to avoid: Intraocular surgery may increase the likelihood of (or exacerbate existing) keratopathy; repeated intraocular surgery predisposes to severe aniridic fibrosis syndrome. Evaluation of relatives at risk: Early clarification of the genetic status of infants who are offspring or sibs of an individual with PAX6-related isolated aniridia (by either an eye examination or molecular genetic testing for the PAX6 variant in the family) is recommended in order to identify those who would benefit from prompt treatment and surveillance of complications of aniridia. ### Genetic counseling. Isolated aniridia and WAGR syndrome are inherited in an autosomal dominant manner. * Isolated aniridia. ~70% of individuals have an affected parent; ~30% have a de novo PAX6 pathogenic variant or deletion of a regulatory region controlling PAX6 expression. Each child of an individual with isolated aniridia has a 50% chance of inheriting the causative genetic alteration and developing aniridia. In rare instances of mosaicism for the PAX6 pathogenic variant in the proband, the risk to offspring may be lower. * WAGR syndrome is associated with contiguous-gene deletions including PAX6 and WT1. If the proband has a de novo contiguous-gene deletion and neither parent has evidence of mosaicism for the deletion, the risk to sibs is no greater than that in the general population. When the PAX6 genetic alteration in a family is known, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis PAX6-related aniridia includes isolated aniridia without systemic involvement and the Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome. No formal diagnostic criteria have been published. ### Suggestive Findings PAX6-related isolated aniridia should be suspected in individuals who have the following clinical and imaging findings of aniridia with no other associated systemic abnormalities. Clinical findings * Aniridia. Complete or partial iris hypoplasia best seen on slit lamp examination. Iris translucency or abnormal architecture and pupillary abnormalities may also be seen. * Reduced visual acuity secondary to: * Absence of or reduction in the normal foveal architecture (usually [not always] observed) * Optic nerve abnormalities (e.g., optic nerve hypoplasia or coloboma) * Early-onset nystagmus (usually apparent by age 6 weeks) * Microphthalmia and ocular coloboma (iris, chorioretinal, and/or optic disc) Imaging findings * Optical coherence tomography (OCT) may be used to document foveal hypoplasia. Although OCT is difficult to perform in the presence of nystagmus, useful images can be obtained with persistence. This should be routinely performed to support a clinical diagnosis, especially where iris defects may be subtle. Anterior segment OCT can also be used to delineate the detailed anatomy of the anterior segment structures, even in those with corneal opacity [Majander et al 2012]. * Ultrasound B-scan should be performed routinely to assess axial length due to the association with microphthalmia. * High-frequency ultrasound biomicroscopy. In infants with corneal opacity or severe corneal edema resulting from associated congenital glaucoma, high-frequency anterior segment ultrasound examination, usually performed under anesthesia, can demonstrate iris hypoplasia and/or absence [Nischal 2007]. Note: Iris fluorescein angiography may identify subtle iris hypoplasia but is rarely used clinically. Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome should be suspected in individuals with aniridia and no family history of aniridia who also have at least one of the following findings: * Wilms tumor (also known as nephroblastoma), a childhood kidney malignancy. Of children with WAGR who develop Wilms tumor, 90% do so by age four years and 98% by age seven years (see Wilms Tumor Predisposition). * Genitourinary abnormalities. In males: cryptorchidism, hypospadias, ambiguous genitalia; in females: normal external female genitalia, but uterine abnormalities (heart-shaped bicornate uterus) and streak ovaries. In males and females: end-stage renal disease, ureteric abnormalities, and gonadoblastoma. * Intellectual disability and/or behavior abnormalities including depression, anxiety, ADHD, obsessive-compulsive disorder, and autism. * Childhood-onset obesity and pancreatitis ### Establishing the Diagnosis The diagnosis of PAX6-related aniridia is established in a proband with one of the two following clinical and molecular genetic findings (Table 1): * Isolated aniridia (i.e., without systemic involvement) and a heterozygous PAX6 pathogenic variant, ranging in size from a single nucleotide (e.g., those resulting in a nonsense, missense, or splice site variant or single-nucleotide deletion or duplication) to a partial or whole-gene deletion [Richardson et al 2016] Note: Deletions telomeric to PAX6 that do not include PAX6 have been reported. * A heterozygous variant in the ultraconserved PAX6 cis-regulatory element (SIMO) that resides 150 kb downstream from PAX6 in intron 9 of ELP4 (NM_001288726.1) causes isolated aniridia [Bhatia et al 2013]. * MLPA detected a 0.6-Mb deletion downstream of PAX6 on chromosome 11 that encompasses DCDC1, DPH4, IMMP1L, and ELP4 [Wawrocka et al 2012]. Coverage of these regions on chromosomal or gene-targeted arrays will vary [Blanco-Kelly et al 2017, Franzoni et al 2017]. * Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome and EITHER of the following: * A deletion of PAX6 and the upstream adjacent gene, WT1 Note: Reported deletions include the recurrent 11p13 deletion (see Table 1). * One or more additional findings of WAGR syndrome found on physical examination in individuals with aniridia. Note: If the child has not had genetic testing, the clinical diagnosis of WAGR syndrome usually cannot be established or ruled out until a child has passed through the age of risk for Wilms tumor, intellectual disability, and behavior abnormalities. Molecular genetic testing can establish the molecular basis of aniridia, and thus distinguish between isolated aniridia (no increased risk for Wilms tumor) and WAGR (markedly increased risk for Wilms tumor). In the following scenarios molecular genetic testing approaches are based on the individual's age, clinical findings, family history, and testing methods available. #### Scenario 1 The proband is an infant with aniridia who represents a simplex case (i.e., a single occurrence in the family). Option 1 1. Perform chromosomal microarray (CMA) (which may use array-based comparative genomic hybridization [aCGH] and/or a SNP genotyping array) to identify a contiguous-gene deletion that includes PAX6 and WT1. Note: (1) Although routine (genomic) CMA will detect an 11p13 WAGR deletion, other gene-targeted CMA designs may be used to identify either a PAX6-WT1 contiguous-gene deletion OR whole-gene or partial deletion of PAX6. (2) Deletions telomeric to PAX6 that do not include PAX6 have been reported [Wawrocka et al 2012, Blanco-Kelly et al 2017, Franzoni et al 2017]. Coverage of these regions (e.g., intron 9 of ELP4) on chromosomal or gene-targeted arrays will vary. 2. If a deletion involving PAX6 and WT1 is not identified, perform sequence analysis of PAX6. Note: Genome sequencing (GS) is likely to enable screening of intronic regions (e.g., the SIMO of ELP4) or chromosomal rearrangements (e.g., deletions in ELP4); however, individual genomic regions will need to be examined for coverage and quality of sequence. GS is not yet part of routine care in most centers. Option 2 1. Perform sequence analysis of PAX6. Note: The first three exons of PAX6 are noncoding. Variants in these noncoding exons have been associated with disease [Glaser et al 1992, Grønskov et al 1999]. 2. If a PAX6 pathogenic variant is not identified, perform CMA to identify a contiguous-gene deletion that includes PAX6 and WT1. Note: Although routine CMA will detect an 11p13 WAGR deletion, other gene-targeted CMA designs may be used to identify either a PAX6-WT1 contiguous-gene deletion OR whole-gene or partial deletion of PAX6. #### Scenario 2 The proband is thought to have isolated aniridia because (a) there is a positive family history of isolated aniridia or (b) the proband has exceeded the age of risk for Wilms tumor. 1. Perform PAX6 sequence analysis. Note: The first three exons of PAX6 are noncoding. Variants in these noncoding exons have been associated with disease [Glaser et al 1994, Grønskov et al 1999]. 2. If no PAX6 pathogenic variant is identified, perform CMA to investigate for any contiguous-gene deletions/duplications involving PAX6 or WT1; or consider sequence analysis and/or deletion/duplication analysis to also include the SIMO region of ELP4. #### Scenario 3 The proband is either an infant with aniridia and genital anomalies or an older individual with aniridia and intellectual disability and/or Wilms tumor and/or genital anomalies. Perform CMA to identify a contiguous-gene deletion that includes PAX6 and WT1. ### Table 1. Molecular Genetic Testing Used in PAX6-Related Aniridia View in own window DisorderProportion of ProbandsGenes 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method &Phenotype Isolated aniridia2/3 3PAX6Sequence analysis 4~85% 5, 6 Gene-targeted deletion/duplication analysis 7~15% 8 WAGR 9: ~700-kb heterozygous deletion at 11p13 10 ISCA-37401 111/3 3PAX6 & WT1CMA 12100% FISH 13, 14100% 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\. Grønskov et al [2001], Robinson et al [2008], Blanco-Kelly et al [2017], Vasilyeva et al [2017] 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, C-terminal extension (CTE) variants 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\. Redeker et al [2008], Bobilev et al [2016], Richardson et al [2016], Blanco-Kelly et al [2017], Sannan et al [2017], Vasilyeva et al [2017] 6\. In one individual a heterozygous single-nucleotide variant in the ultraconserved PAX6 cis-regulatory element (SIMO) (residing 150 kb downstream from PAX6 in intron 9 of ELP4) has been reported to cause isolated aniridia [Bhatia et al 2013]. 7\. 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. 8\. Leiden Open Variation Database (LOVD) and Chao et al [2003], Redeker et al [2008], Aradhya et al [2012], Lim et al [2012], Han et al [2013], Ansari et al [2016], Bobilev et al [2016], Blanco-Kelly et al [2017], Vasilyeva et al [2017]. Note: Many reported large deletions (encompassing PAX6 but not WT1 OR involving EPL4 and DCDC1 downstream of PAX6) would be detectable by CMA. 9\. Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome caused by deletion of PAX6 and WT1 10\. GRCh37/hg19 chr11:31,803,509-32,510,988: Genomic coordinates represent the minimum deletion size associated with the 11p13 recurrent deletion as designated by ClinGen. Deletion coordinates may vary slightly based on array design used by the testing laboratory. Note that the size of the deletion as calculated from these genomic positions may differ from the expected deletion size due to the presence of segmental duplications near breakpoints. 11\. Standardized clinical annotation and interpretation for genomic variants from the Clinical Genome Resource (ClinGen) project (formerly the International Standards for Cytogenomic Arrays [ISCA] Consortium) 12\. Chromosome microarray analysis (CMA) using oligonucleotide arrays (i.e., array comparative genomic hybridization) and/or SNP genotyping arrays. CMA designs in current clinical use target the 11p13 region. 13\. FISH is not appropriate as a diagnostic method for an individual in whom the 11p13 deletion syndrome was not detected by CMA designed to target this region. 14\. FISH, qPCR, or other quantitative methods of targeted deletion analysis can be used to identify the 11p13 deletion in at-risk relatives of the proband to help determine recurrence risk (see Genetic Counseling). ## Clinical Characteristics ### Clinical Description PAX6-related aniridia occurs either as an isolated ocular abnormality or as part of the Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome. Aniridia, a congenital eye anomaly, is usually detected at birth if fully penetrant. It is often the presenting feature of WAGR; children with WAGR are at significant risk of developing Wilms tumor during early childhood. #### Aniridia Aniridia is a pan ocular disorder affecting the cornea, iris, intraocular pressure, lens, fovea, and optic nerve. The phenotype is variable between and within families; however, affected individuals usually show little variability between the two eyes. Individuals with aniridia characteristically show nystagmus, impaired visual acuity (usually 20/100 - 20/200), and foveal hypoplasia. Milder forms of aniridia with subtle iris architecture changes, good vision, and normal foveal structure do occur [Hingorani et al 2009]. Other abnormalities include corneal changes, glaucoma, cataract, lens subluxation, strabismus, optic nerve coloboma and hypoplasia, and occasionally microphthalmia. The reduction in visual acuity is primarily caused by foveal hypoplasia, but cataracts, glaucoma, and corneal opacification are responsible for progressive visual failure. Most children with aniridia present at birth with an obvious iris or pupillary abnormality or in infancy with nystagmus (usually apparent by age 6 weeks). Congenital glaucoma rarely occurs in aniridia; in such cases, a large corneal diameter and corneal edema may be the presenting findings. Despite their many ocular problems, most individuals with aniridia can retain useful vision with appropriate ophthalmologic management. Iris. The most obvious ocular abnormality is iris hypoplasia. The severity varies from a nearly normal iris to almost complete iris absence, in which a small stump of residual iris tissue is visible on gonioscopy, anterior segment optical coherence tomography (OCT), or ultrasound biomicroscopy [Okamoto et al 2004]. In less extreme cases, the pupil size may be normal, but there may be loss of the iris surface architecture or the presence of iris transillumination [Hingorani et al 2009]. Other iris changes include partial iris defects (resembling a coloboma) or eccentric or misshapen pupils and iris ectropion [Nelson et al 1984, Willcock et al 2006]. Lens. Congenital lens opacities (especially polar) are common [Gramer et al 2012]. Often there is persistent vascularization of the anterior lens capsule (tunica vasculosa lentis) or remnants of the pupillary membrane. The lens opacities are rarely dense enough to require lens extraction in infancy, but visually significant lens opacities eventually develop in 50%-85% of affected individuals, often in the teens or early adulthood. Lens subluxation or dislocation occurs but is uncommon. Intraocular pressure. When elevated intraocular pressure is associated with loss of retinal ganglion cells resulting in visual field loss and optic nerve cupping, a diagnosis of glaucoma is made. Both elevated intraocular pressure and glaucoma are common in people with aniridia and may eventually occur in up to two thirds of individuals [Gramer et al 2012]. The onset of glaucoma is usually in later childhood or adulthood; glaucoma in infancy is rare [Gramer et al 2012]. Cornea. Keratopathy (corneal degeneration) is a relatively late manifestation with multifactorial causes including limbal stem cell abnormalities and abnormal wound healing [Ramaesh et al 2005]. Changes vary from mild peripheral vascularization to pan corneal vascularization, opacification, and keratinization. Inadequate tear production is common and exacerbates the ocular surface problems. Central corneal thickness is increased – a finding of uncertain clinical relevance, but which may result in undermeasurement of intraocular pressure on tonometry [Brandt et al 2004, Whitson et al 2005]. Rarely, those with aniridia may have microcornea and, extremely rarely, megalocornea [Lipsky & Salim 2011, Wang et al 2012]. Fovea. Foveal hypoplasia is usually (but not always) present. Findings include reduced foveal reflex, macular hypopigmentation, and crossing of the usual foveal avascular zone by retinal vessels. OCT images can clearly delineate the absence of normal foveal architecture. Optic nerve. Optic nerve hypoplasia (i.e., the optic nerve head appears abnormally small) may occur in up to 10% and there may be optic nerve colobomata [McCulley et al 2005]. Aniridic fibrosis syndrome. Individuals with aniridia who have a history of multiple ocular procedures (penetrating keratoplasty, intraocular lenses [IOLs], and drainage tube insertion) may rarely develop aniridic fibrosis syndrome in which a fibrotic retrolenticular and retrocorneal membrane arises from the root of the rudimentary iris tissue. This membrane may cause forward displacement of the IOLs, IOL entrapment, and corneal decompensation [Tsai et al 2005]. Retina. Retinal detachment may occur, probably as a consequence of a high myopia or previous intraocular surgery. Very rarely, primary retinal manifestations such as an exudative vascular retinopathy or chorioretinal degeneration may be seen [Hingorani et al 2009, Aggarwal et al 2011]. Other ocular manifestations. Affected individuals may have significant refractive errors and may develop a secondary strabismus (squint, eye misalignment). Some affected individuals have microphthalmia (manifest as decreased axial length on USS B-scan) and ocular coloboma (iris, chorioretinal, and/or optic disc). Central nervous system. Individuals with isolated aniridia may show reduced olfaction and cognition, behavioral problems, or developmental delay. Central nervous system abnormalities (including absence or hypoplasia of the anterior commissure; abnormalities of gray matter in the anterior cingulate cortex, cerebellum, and temporal and occipital lobes; white matter deficits in and reduced volume of the corpus callosum; absence of the pineal gland; and occasionally olfactory bulb hypoplasia) can be demonstrated on MRI [Sisodiya et al 2001, Free et al 2003, Mitchell et al 2003, Ellison-Wright et al 2004, Valenzuela & Cline 2004, Bamiou et al 2007, Abouzeid et al 2009, Grant et al 2017]. Hearing. Central auditory processing difficulties (from abnormal interhemispheric transfer) present in some individuals may cause hearing difficulties. This finding is particularly important in the context of associated visual impairment [Bamiou et al 2007]. #### Wilms Tumor-Aniridia-Genital Anomalies-Retardation (WAGR) Syndrome Individuals with molecularly confirmed deletions of 11p13 involving PAX6 and WT1 are diagnosed with WAGR syndrome [Clericuzio et al 2011, Blanco-Kelly et al 2017]. Aniridia is almost universally present in individuals with such a deletion and typically is complete. However, WAGR without aniridia has been described. Wilms tumor risk for children with a molecularly confirmed heterozygous contiguous-gene deletion of PAX6 and WT1 at chromosome 11p13 is between 42.5% and 77% [Fischbach et al 2005, Clericuzio et al 2011]. Of those who develop Wilms tumor, 90% do so by age four years and 98% by age seven years. Compared to children with isolated Wilms tumor, children with WAGR syndrome are more likely to develop bilateral tumors and to have an earlier age of diagnosis and more favorable tumor histology with a better prognosis [Halim et al 2012]. Wilms tumor, also known as a nephroblastoma, is a childhood kidney malignancy. Associated features include abdominal pain, fever, anemia, hematuria, and hypertension in up to 30% of affected children. See Wilms Tumor Predisposition. The risk of later end-stage renal disease (ESRD) is significant, relating to Wilms tumor and its surgery, focal segmental glomerulosclerosis, and occasionally renal malformation. The rate of ESRD is 36% with unilateral Wilms tumor and 90% with bilateral Wilms tumor. Approximately 25% of individuals with WAGR syndrome have proteinuria ranging from minimal to overt nephritic syndrome [Breslow et al 2005, Fischbach et al 2005]. Genitourinary abnormalities include ambiguous genitalia, urethral strictures, ureteric abnormalities, and gonadoblastoma. Males display cryptorchidism (most common feature, seen in 60%) and hypospadias. Females may have uterine abnormalities including bicornate uterus and streak ovaries; their external genitalia are usually normal [Fischbach et al 2005]. Intellectual disability and behavioral abnormalities in WAGR syndrome are highly variable: * Intellectual disability (defined as IQ <74) is seen in 70% of individuals with WAGR syndrome; other individuals with WAGR syndrome can have normal intellect without behavioral problems. * Behavioral abnormalities include attention deficit hyperactivity disorder, autism spectrum disorder, anxiety, depression, and obsessive-compulsive disorder. Neurologic abnormalities occur in up to one third of individuals with WAGR syndrome. Findings include hypertonia or hypotonia, epilepsy, enlarged ventricles, corpus callosum agenesis, and microcephaly. Obesity. The association of obesity in the WAGR spectrum, for which the acronym WAGRO has been suggested, has been confirmed [Brémond-Gignac et al 2005a]. Other. Affected individuals may also show craniofacial dysmorphism, hemihypertrophy, growth retardation, scoliosis, and kyphosis. Other anomalies reported on occasion include polydactyly and congenital diaphragmatic hernia [Nelson et al 1984, Brémond-Gignac et al 2005b, Manoukian et al 2005, Scott et al 2005] (see Congenital Diaphragmatic Hernia Overview). ### Genotype-Phenotype Correlations Isolated aniridia. PAX6 haploinsufficiency produces classic and severe aniridia with a high incidence of sight-reducing pathology including optic nerve malformations, glaucoma, cataract, and corneal changes [Kleinjan & van Heyningen 1998, Prosser & van Heyningen 1998, Grønskov et al 1999, Hanson et al 1999, Lauderdale et al 2000, van Heyningen & Williamson 2002, Chao et al 2003, Tzoulaki et al 2005, Dansault et al 2007, Hingorani et al 2009]. PAX6 pathogenic missense variants, particularly those that are in the paired domain and therefore likely to significantly reduce the DNA binding ability, tend to produce atypical/milder or variable-phenotype aniridia with better vision, more residual iris tissue, and a lower frequency of sight-reducing malformations and complications [Hingorani et al 2009]. C-terminal extension (CTE) pathogenic variants, which generate a longer protein product, are associated with a moderately severe aniridic phenotype with poor vision, keratopathy, and cataracts; however, individuals with CTE pathogenic variants are less likely to have glaucoma and are more likely to have preservation of iris tissue than individuals who have pathogenic null variants [Hingorani et al 2009, Aggarwal et al 2011]. For reasons that are not clear, the rare reports of significant non-foveal retinal abnormalities (exudative retinopathy, chorioretinal degeneration) are all associated with CTE pathogenic variants [Hingorani et al 2009, Aggarwal et al 2011]. ### Penetrance Isolated aniridia has almost complete penetrance. Aniridia in WAGR also has almost complete penetrance. The risk of Wilms tumor is up to 77%. ### Prevalence The prevalence of aniridia is 1:40,000 to 1:100,000. No racial or sexual differences are recognized. The prevalence of WAGR syndrome is approximately 1:500,000. ## Differential Diagnosis ### Individuals with Aniridia and No Identifiable PAX6 Pathogenic Variant Heterozygous pathogenic variants in the following genes are included in the differential diagnosis of PAX6-related aniridia: * FOXC1. Phenocopies exist and include dominant alleles of FOXC1, which can cause diagnostic difficulties [Khan et al 2008, Ito et al 2009]. * PITX2. Perveen et al [2000] * PITX3. Semina et al [1998] * Unknown. Ansari et al [2016] could not identify the cause of aniridia in 20 patients despite PAX6, FOXC1, and PITX2 sequence analysis, FISH, and aCGH, suggesting there may be further genetic heterogeneity with potentially new disease loci and/or novel mutational mechanisms. Rieger anomaly, a form of anterior segment mesenchymal dysgenesis, is characterized by severe iris atrophy, corectopia (displaced pupils), iris holes, and, frequently, childhood-onset glaucoma. Rieger anomaly may be distinguished from aniridia by the presence of posterior embryotoxon (visible Schwalbe's line seen as a white line just inside the corneal limbus) with attached iris strands, relatively good visual acuity, and the absence of nystagmus or foveal abnormality. Iris coloboma is a developmental defect resulting in a focal absence of the iris and a keyhole-shaped pupil; the rest of the iris is normal. Chorioretinal coloboma may be associated. Most iris colobomas are not associated with reduced visual acuity or nystagmus unless accompanied by a large posterior coloboma that involves the optic nerve and fovea; such large chorioretinal colobomas are apparent on fundoscopic examination. Gillespie syndrome (OMIM 206700), characterized by partial iris hypoplasia, cerebellar ataxia, and intellectual disability, can be distinguished from aniridia by a characteristic iris configuration in Gillespie syndrome showing a scalloped pupillary edge with iris strands extending onto the anterior lens surface [Nelson et al 1997]. In five simplex cases of Gillespie syndrome (i.e., a single occurrence in a family), three were found to have biallelic ITPR1 pathogenic variants and two were found to have a de novo heterozygous ITPR1 pathogenic variant [Gerber et al 2016]. Oculocutaneous albinism (OCA) and ocular albinism typically present in early infancy with nystagmus but a structurally complete iris, typical diffuse iris transillumination (resulting from reduced pigment in the iris pigment epithelium), hypopigmented fundus, and, in the case of OCA, skin and hair hypopigmentation, which distinguish these disorders from aniridia (see Oculocutaneous Albinism Type 4 and X-Linked Ocular Albinism). The other causes of nystagmus and poor vision in infancy (e.g., retinal dysplasia, retinal dystrophy, congenital cataracts, optic nerve hypoplasia, congenital infections) lack the iris changes seen in aniridia. Causes of partial or complete absence of iris tissue in adults include trauma, prior ocular surgery, and the iridocorneal endothelial syndromes. The age at onset, medical history, and absence of other ocular features in aniridia should prevent diagnostic confusion with aniridia. ## Management ### Evaluation Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with aniridia (whether isolated or part of WAGR syndrome), the following are recommended: * Evaluation of visual acuity (not easily performed in infants) and documentation of the degree of iris tissue deficiency, and the presence of foveal and optic nerve hypoplasia in order to predict future visual function. * Evaluation for the degree of involvement of the cornea and lens and measurement of intraocular pressure, as they are potentially treatable causes of further visual reduction; however, treatable changes may not appear until later in life. * Consultation with a clinical geneticist and/or genetic counselor To establish the extent of disease and needs in an individual diagnosed with Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome, the following are recommended: * Evaluation by a pediatrician to assess growth and feeding * Evaluation for Wilms tumor * Evaluation by a urologist for urogenital abnormalities * Developmental assessment ### Treatment of Manifestations Aniridia. Simple measures are often the most important: * Regular eye examinations and correction of refractive errors. Refractive errors range from high myopia through emmetropia to high hypermetropia. Spectacle correction of refractive errors is usually recommended as use of contact lenses can be difficult in the presence of keratopathy and reduced tear production. * Tinted or photochromic lenses to reduce light sensitivity associated with the large pupillary aperture. Colored, tinted, or artificial pupil contact lenses may reduce light sensitivity or restore a more normal appearance to the eye but, as above, may be difficult to wear because of a poor ocular surface and tear film. * Occlusion therapy in childhood for anisometropic amblyopia or strabismic amblyopia * Optical low-vision aids and other devices such as closed-circuit television systems to help adults and children of school age * Advice and help with schooling * Social support Note: Corrective surgery for strabismus can be undertaken to improve alignment and appearance but will not result in improved visual function. Lens. Cataract extraction can significantly improve visual acuity in those with severe lens opacities. It should be remembered that in aniridia visual improvement after surgery is limited by foveal hypoplasia; thus, mild to moderate lens opacities may not require surgery: * Children rarely require surgery (lensectomy). * In adults, phacoemulsification and intraocular lens implantation can improve visual function if the cataract is severe. Note: (1) A significant number of individuals with aniridia have poor zonular stability, which increases the risk for intraoperative complications and influences the choice of surgical technique and options for intraocular lens (IOL) implantation [Schneider et al 2003]. (2) The use of various types of black diaphragm aniridic IOLs may reduce glare or light sensitivity but are associated with a higher rate of surgical complications [Reinhard et al 2000, Menezo et al 2005, Pozdeyeva et al 2005]. Intraocular pressure * Glaucoma is usually initially treated with topical anti-glaucoma medication. * Surgery is reserved for eyes that do not respond to medical therapy: * Trabeculectomy with or without antimetabolites (e.g., 5-fluorouracil, mitomycin C) is often used but is associated with a higher risk of treatment failure than that seen in patients with primary glaucoma who undergo the same treatment. * Drainage tube surgery (with or without antimetabolites) or cyclodiode laser treatment may be necessary in refractory cases; however, this treatment is increasingly being undertaken as a primary procedure [Khaw 2002, Kirwan et al 2002, Arroyave et al 2003, Lee et al 2010]. Note: (1) Glaucoma presenting in infancy is more difficult to treat. Medical treatment is generally ineffective and surgery is required. Goniotomy and trabeculotomy have a low success rate, but trabeculectomy with or without antimetabolites is often successful [Nelson et al 1984, Okada et al 2000, Khaw 2002]. (2) While goniosurgery has been suggested as a preventive measure, glaucoma never develops in a significant proportion of those with aniridia [Swanner et al 2004]. Cornea * Ocular surface disease can be treated medically using lubricants, mucolytics, and punctal occlusion, which may help slow the progression of sight-threatening corneal changes. Note: Drops without preservatives are often required to avoid preservative-related ocular surface toxicity. * When corneal opacification causes significant visual reduction, penetrating keratoplasty (PK) may be considered; however, in the presence of the significant limbal stem cell deficiency observed in aniridia, PK alone has a poor prognosis [Tiller et al 2003]. * Limbal stem cell transplantation alone, preceding or concurrent with keratoplasty, may be undertaken but requires an allograft as both eyes are usually affected. This may take the form of a cultured stem cell sheet or a limbal tissue transplant [Lee et al 2008, Pauklin et al 2010]. However, this therapy is associated with a high risk of failure, and lifelong systemic immunosuppression may be required to prevent rejection. Whether the use of cultured oral mucous membrane cells may have a beneficial role is as yet uncertain. Aniridic fibrosis syndrome. Surgical intervention is recommended at the first sign of aniridic fibrosis syndrome [Tsai et al 2005]. Wilms tumor. See Wilms Tumor Predisposition overview. Genital abnormalities. This may need specialist care for functional and cosmetic management including endocrine therapy and surgical correction (e.g., hypospadias repair). There may be fertility issues that require support or active management. Developmental delay / intellectual disability. There are a range of developmental, intellectual, psychiatric, and behavioral issues, as well as the challenges of visual impairment. Children may require: * Special educational support including extra or different teaching resources and a specialized educational setting, specialist teachers of the visually impaired, educational psychologists, and formal statements of educational needs; * Involvement of a pediatrician and sometimes a pediatric psychiatrist. #### Developmental Delay / Intellectual Disability Management Issues The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country. Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the US, early intervention is a federally funded program available in all states. Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed. Ages 5-21 years * In the US, an IEP based on the individual's level of function should be developed by the local public school district. Affected children are permitted to remain in the public school district until age 21. * Discussion about transition plans including financial, vocation/employment, and medical arrangements should begin at age 12 years. Developmental pediatricians can provide assistance with transition to adulthood. All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life. Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. In the US: * Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. * Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. #### Social/Behavioral Concerns Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and is typically performed one on one with a board-certified behavior analyst. Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary. Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist. ### Surveillance #### Aniridia Amblyopia and refractive error. Children younger than age eight years should be monitored every four to six months for refractive errors and detection and treatment of incipient or actual amblyopia (strabismic, refractive, or sensory). Glasses and other visual aids should be provided to optimize access to educational materials. Detection of later-onset eye pathology. Individuals with aniridia should have an annual ophthalmology review to detect problems such as corneal changes, raised intraocular pressure, and cataracts. Glaucoma. Individuals with aniridia should undergo annual glaucoma screening throughout life including: * Measurement of intraocular pressure; * Optic disc examination; * Visual field assessment when possible. Note: Assessment of the optic disc and visual field may be difficult in the presence of media opacities and nystagmus. Optic disc photography is a useful method of monitoring optic disc changes. Aniridic fibrosis syndrome. Individuals with aniridia with a history of multiple ocular procedures (penetrating keratoplasty, IOLs, and drainage tube insertion) should be monitored for aniridic fibrosis syndrome [Tsai et al 2005]. #### WAGR Syndrome Wilms tumor. Children with aniridia and a WT1 deletion require renal ultrasound examinations every three months and follow up by a pediatric oncologist until they reach age eight years. See Wilms Tumor Predisposition. (Those without deletion of the WT1 locus are at very low risk for Wilms tumor and do not require such screening [Grønskov et al 2001, Muto et al 2002].) Urogenital abnormalities require follow up as per the treating urologist and/or endocrinologist. Renal function. Because of the increased risk for renal impairment in WAGR syndrome, lifelong evaluation of renal function is recommended for those with WAGR syndrome, especially those with bilateral Wilms tumor [Breslow et al 2005], by annual monitoring of blood pressure and urinalysis for proteinuria beginning in early adolescence. Note that this monitoring is not necessary for individuals in whom genetic testing has excluded a WT1 deletion. Hearing. Children with WAGR syndrome and isolated aniridia may have abnormal hearing despite a normal audiogram; thus, detailed audiologic evaluation is recommended [Bamiou et al 2007]. Developmental progress and educational needs require regular monitoring. Provide behavioral assessment for anxiety, ADHD, and aggressive or self-injurious behavior as needed. ### Agents/Circumstances to Avoid It has been suggested that intraocular surgery may increase the likelihood of (or exacerbate existing) keratopathy [Edén et al 2010], and repeated intraocular surgery does predispose to the rare but severe aniridic fibrosis syndrome. Patients should therefore be counseled about these risks before undertaking such surgery. ### Evaluation of Relatives at Risk Early clarification of the genetic status of infants who are offspring or sibs of an individual with PAX6-related isolated aniridia (by either an eye examination or molecular genetic testing for the PAX6 variant in the family) is recommended in order to identify those who would benefit from prompt treatment and surveillance of complications of aniridia. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Ongoing research is investigating the role and success of limbal stem cell transplantation and ocular mucous membrane cell transplantation for keratopathies associated with limbal stem cell failure, including aniridia [Menzel-Severing et al 2013, Polisetti & Joyce 2013]. A Phase II randomized, double-masked, placebo-controlled study of ataluren in patients with aniridia caused by pathogenic nonsense variants in PAX6 is under way (ClinicalTrials.gov Identifier: NCT02647359). This is based on preclinical evidence that the small-molecule drug ataluren can effectively suppress the nonsense mutation in the Pax6 mouse model, generating full-length functional protein that reversed the developmental defect following postnatal drug administration [Gregory-Evans et al 2014, Wang et al 2017]. 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-hydroxybutyric 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	PAX6-Related Aniridia	None	24,672	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1360/	2021-01-18T21:06:20	{"synonyms": []}
Achondroplasia with severe combined immunodeficiency is an extremely rare type of SCID. The condition is characterized by the classic signs of SCID, including severe and recurrent infections, diarrhea, failure to thrive, and absence of T and B lymphocytes along with skeletal anomalies like short stature, bowing of the long bones and other abnormalities affecting the ends of the long bones (metaphyseal abnormalities). Children with this condition have a shortened life expectancy, generally surviving only into early childhood. Achondroplasia with severe combined immunodeficiency is inherited in an autosomal recessive manner. [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-hydroxybutyric 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	Short-limb skeletal dysplasia with severe combined immunodeficiency	c1860168	24,673	gard	https://rarediseases.info.nih.gov/diseases/2988/short-limb-skeletal-dysplasia-with-severe-combined-immunodeficiency	2021-01-18T17:57:43	{"mesh": ["C565984"], "omim": ["200900"], "umls": ["C1860168"], "orphanet": ["935"], "synonyms": ["SLSD with SCID", "Achondroplasia so-called and severe combined immunodeficiency", "Achondroplasia-SCID syndrome", "Achondroplasia-severe combined immunodeficiency syndrome", "Achondroplasia-Swiss type agammaglobulinemia syndrome", "Immunodeficiency-short limb dwarfism syndrome", "Short limb skeletal dysplasia with SCID"]}
Intermediate anorectal malformation is a rare, genetic, non-syndromic subtype of anorectal malformation, resulting from a developmental defect during embryogenesis, characterized by a wide spectrum of anorectal anomalies lying between the pubococcygeal line and the ischial tuberosity (e.g., rectovestibular and rectovaginal fistulas in the female, rectobulbar fistula in the male, and anal agenesis). Patients may present with failure to pass meconium, failure to thrive, and recurrent urinary tract infections. [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-hydroxybutyric 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	Intermediate isolated anorectal malformation	None	24,674	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171208	2021-01-23T17:37:20	{"icd-10": ["Q42.0", "Q42.1"]}
A rare, systemic amyloidosis characterized by slowly progressive renal dysfunction, increased serum creatinine, mostly normal urine analysis with no significant proteinuria and associated heart disease. Cardiac involvement presents as hypertrophic obstructive cardiomyopathy, left ventricular outflow tract obstruction, coronary artery disease and conduction system abnormalities. Histology reveals renal tubular atrophy, interstitial fibrosis, glomerular sclerosis, and medullar amyloid deposits. [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-hydroxybutyric 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	AApoAIV amyloidosis	None	24,675	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=439232	2021-01-23T19:00:31	{"icd-10": ["E85.8"], "synonyms": ["Apolipoprotein A-IV amyloidosis"]}
Potentially fatal overhydration Not to be confused with Hydrocephalus, volume overload, or hypervolemia. Water intoxication Other namesWater overload[1] SpecialtyToxicology, critical care medicine Water intoxication, also known as water poisoning, hyperhydration, overhydration, or water toxemia, is a potentially fatal disturbance in brain functions that results when the normal balance of electrolytes in the body is pushed outside safe limits by excessive water intake.[2] Under normal circumstances, accidentally consuming too much water is exceptionally rare. Nearly all deaths related to water intoxication in normal individuals have resulted either from water-drinking contests, in which individuals attempt to consume large amounts of water or from long bouts of exercise during which excessive amounts of fluid were consumed.[3] In addition, water cure, a method of torture in which the victim is forced to consume excessive amounts of water, can cause water intoxication. Water, just like any other substance, can be considered a poison when over-consumed in a brief period of time. Water intoxication mostly occurs when water is being consumed in a high quantity without adequate electrolyte intake.[4] Excess of body water may also be a result of a medical condition or improper treatment; see "hyponatremia" for some examples. Water is considered one of the least toxic chemical compounds, with an LD50 of over 150 ml/kg in rats.[5] ## Contents * 1 Risk factors * 1.1 Low body mass (infants) * 1.2 Endurance sports * 1.3 Overexertion and heat stress * 1.4 Psychiatric conditions * 1.5 Iatrogenic * 2 Pathophysiology * 3 Prevention * 4 Treatment * 5 Notable cases * 6 See also * 7 References ## Risk factors[edit] ### Low body mass (infants)[edit] It can be very easy for children under one year old (especially those under nine months) to absorb too much water. Because of their small body mass, it is easy for them to take in a large amount of water relative to body mass and total body sodium stores.[6] ### Endurance sports[edit] Marathon runners are susceptible to water intoxication if they drink too much while running. This is caused when sodium levels drop below 135 mmol/L when athletes consume large amounts of fluid. This has been noted to be the result of the encouragement of excessive fluid replacement by various guidelines. This has largely been identified in marathon runners as a dilutional hyponatremia.[7] A study conducted on runners completing the 2002 Boston Marathon found that thirteen percent finished the race with hyponatremia. The study concluded that the strongest predictor of hyponatremia was weight gain while racing (over-hydration), and hyponatremia was just as likely to occur in runners who chose sports drinks as those who chose water.[7] Medical personnel at marathon events are trained to suspect water intoxication immediately when runners collapse or show signs of confusion. ### Overexertion and heat stress[edit] Any activity or situation that promotes heavy sweating can lead to water intoxication when water is consumed to replace lost fluids. Persons working in extreme heat and/or humidity for long periods must take care to drink and eat in ways that help to maintain electrolyte balance. People using drugs such as MDMA (often referred to colloquially as "Ecstasy") may overexert themselves, perspire heavily, feel increased thirst, and then drink large amounts of water to rehydrate, leading to electrolyte imbalance and water intoxication – this is compounded by MDMA use increasing the levels of antidiuretic hormone (ADH), decreasing the amount of water lost through urination.[8] Even people who are resting quietly in extreme heat or humidity may run the risk of water intoxication if they drink large amounts of water over short periods for rehydration. ### Psychiatric conditions[edit] Psychogenic polydipsia is the psychiatric condition in which patients feel compelled to drink large quantities of water, thus putting them at risk of water intoxication. This condition can be especially dangerous if the patient also exhibits other psychiatric indications (as is often the case), as the care-takers might misinterpret the hyponatremic symptoms.[9] ### Iatrogenic[edit] When an unconscious person is being fed intravenously (for example, total parenteral nutrition) or via a nasogastric tube, the fluids given must be carefully balanced in composition to match fluids and electrolytes lost. These fluids are typically hypertonic, and so water is often co-administered. If the electrolytes are not monitored (even in an ambulatory patient), either hypernatremia or hyponatremia may result.[10] Some neurological/psychiatric medications (Oxcarbazepine, among others) have been found to cause hyponatremia in some patients.[11] Patients with diabetes insipidus are particularly vulnerable due to rapid fluid processing.[12] ## Pathophysiology[edit] At the onset of this condition, fluid outside the cells has an excessively low amount of solutes, such as sodium and other electrolytes, in comparison to fluid inside the cells, causing the fluid to move into the cells to balance its concentration. This causes the cells to swell. In the brain, this swelling increases intracranial pressure (ICP), which leads to the first observable symptoms of water intoxication: headache, personality changes, changes in behavior, confusion, irritability, and drowsiness. These are sometimes followed by difficulty breathing during exertion, muscle weakness & pain, twitching, or cramping, nausea, vomiting, thirst, and a dulled ability to perceive and interpret sensory information. As the condition persists, papillary and vital signs may result including bradycardia and widened pulse pressure. The cells in the brain may swell to the point where blood flow is interrupted resulting in cerebral edema. Swollen brain cells may also apply pressure to the brain stem causing central nervous system dysfunction. Both cerebral edema and interference with the central nervous system are dangerous and could result in seizures, brain damage, coma or death.[13] ## Prevention[edit] Water intoxication can be prevented if a person's intake of water does not grossly exceed their losses. Healthy kidneys are able to excrete approximately 800 millilitres to 1 litre of fluid water (0.84–1.04 quarts) per hour.[14] However, stress (from prolonged physical exertion), as well as disease states, can greatly reduce this amount.[14] ## Treatment[edit] Mild intoxication may remain asymptomatic and require only fluid restriction. In more severe cases, treatment consists of: * Diuretics to increase urination, which are most effective for excess blood volume. * Vasopressin receptor antagonists ## Notable cases[edit] * 1991, Andy Warhol: Five years after his death, Warhol's family publicly accused the hospital where he had his gallbladder removed of causing his death by water intoxication administered post-operatively. A claimed autopsy weight of 68 kg (150 lb), with his weight being 58 kg (128 lb) when admitted, was cited as evidence that too much fluid had been given.[15] * October 24, 1995: Anna Wood, a 15-year-old Australian schoolgirl, died from the effects of water intoxication secondary to use of MDMA (commonly known as ecstasy). * November 16, 1995: Leah Betts, an English schoolgirl, died as the result of drinking too much water, though in the media her death was mistakenly attributed to taking an ecstasy tablet at her 18th birthday party.[16] * 2003: British actor Anthony Andrews survived a case of water intoxication. He was performing as Henry Higgins in a revival of the musical My Fair Lady at the time, and consumed up to eight litres of water a day. He was unconscious and in intensive care for three days.[17][18] * February 2, 2005: Matthew Carrington, a student at Chico State University in Chico, California, died as a direct result of a fraternity hazing ritual involving forced water intoxication. * January 12, 2007: Jennifer Strange died after drinking nearly 2 gallons (7.6 liters) of water in an attempt to win a Nintendo Wii.[19] The KDND radio station's morning show, the Morning Rave, held an on-air contest entitled "Hold Your Wee for a Wii," in which contestants were asked to drink as much water as they could without urinating. The DJs were made aware of the dangers but did not inform the contestants. KDND's parent company, Entercom Sacramento LLC, was subsequently ordered to pay $16,577,118 in damages to Jennifer's family.[20][21] * March 11, 2020: Zachary Sabin, an 11-year-old child, died after being forced to drink almost three liters of water in just four hours by his parents. They thought his urine was too dark, so they made him drink water until he threw up.[22] ## See also[edit] * Water portal * Dehydration * Drowning * Hyperkalemia / Hypokalemia * Hypermagnesemia / Hypomagnesemia * Hypernatremia / Hyponatremia * Gastroenteritis * Oral rehydration therapy * Polydipsia * Water urticaria * Dihydrogen monoxide hoax * Electrolyte imbalance * List of unusual deaths * Potomania * The dose makes the poison ## References[edit] 1. ^ Prowle, JR; Echeverri, JE; Ligabo, EV; Ronco, C; Bellomo, R (2010). "Fluid balance and acute kidney injury". Nature Reviews. Nephrology. 6 (2): 107–15. doi:10.1038/nrneph.2009.213. ISSN 1759-5061. PMID 20027192. S2CID 19548988. "...fluids are widely administered to patients who have, or are at risk of, acute kidney injury (AKI). However, deleterious consequences of overzealous fluid therapy are increasingly being recognized. Salt and water overload can predispose to organ dysfunction..." 2. ^ Peechakara, BV; Gupta, M (2020), "article-36749", Water Toxicity, Treasure Island (FL): StatPearls Publishing, PMID 30725916, retrieved 2020-11-24 3. ^ Noakes TD, Speedy DB (July 2006). "Case proven: exercise associated hyponatraemia is due to overdrinking. So why did it take 20 years before the original evidence was accepted?". British Journal of Sports Medicine. 40 (7): 567–72. doi:10.1136/bjsm.2005.020354. PMC 2564296. PMID 16799109. 4. ^ Farrell DJ, Bower L (Oct 2003). "Fatal water intoxication". Journal of Clinical Pathology. 56 (10): 803–804. doi:10.1136/jcp.56.10.803-a. PMC 1770067. PMID 14514793. 5. ^ [1] — see to Section 11: Toxicological Information for the LD50 verification 6. ^ "Water Intoxication in Infants". Retrieved 31 August 2015. 7. ^ a b Almond CS, Shin AY, Fortescue EB, et al. (April 2005). "Hyponatremia among runners in the Boston Marathon". The New England Journal of Medicine. 352 (15): 1550–6. doi:10.1056/NEJMoa043901. PMID 15829535. S2CID 42909509. 8. ^ Timbrell, John (2005). The Poison Paradox: Chemicals as Friends and Foes. OUP Oxford. ISBN 978-0-19-280495-2. 9. ^ Zerbe, Robert L.; Robertson, Gary L. (1981-12-24). "A Comparison of Plasma Vasopressin Measurements with a Standard Indirect Test in the Differential Diagnosis of Polyuria". New England Journal of Medicine. 305 (26): 1539–1546. doi:10.1056/NEJM198112243052601. ISSN 0028-4793. PMID 7311993. 10. ^ Schwaderer AL, Schwartz GJ (April 2005). "Treating hypernatremic dehydration". Pediatrics in Review. 26 (4): 148–50. doi:10.1542/pir.26-4-148. PMID 15805238. 11. ^ "Oxcarbazepine". Retrieved 31 August 2015. 12. ^ What Is Diabetes Insipidus? 13. ^ Moreau, David (2008). Fluids & Electrolytes Made Incredibly Easy! (4th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 75–77. ISBN 978-1582555652. 14. ^ a b Coco Ballantyne. "Strange but True: Drinking Too Much Water Can Kill". Retrieved 31 August 2015. 15. ^ "Care Faulted In the Death Of Warhol". NYT. Retrieved 27 October 2013. 16. ^ "Hyponatremia ("Water Intoxication")". The DEA.org. Retrieved May 10, 2007. 17. ^ Grice, Elizabeth (August 21, 2003). "My battle with the bottle". The Daily Telegraph. London. 18. ^ Valentine Low; Evening Standard (3 July 2003). "Actor tells of water overdose". Evening Standard. Retrieved 31 August 2015. 19. ^ "Woman dies after being in water-drinking contest". LA Times. 2007-01-14. Archived from the original on 2020-04-19. Retrieved 2020-04-19. 20. ^ "Ten Fired After Radio Contest Tragedy". www.cbsnews.com. Retrieved 2019-02-02. 21. ^ "$16M Awarded In Water Drinking Death". ABC News. 2009-11-02. Retrieved 2019-02-02. 22. ^ https://www.ctvnews.ca/world/couple-accused-of-killing-son-by-forcing-him-to-drink-water-1.4989133 Classification D * ICD-10: E87.7 * ICD-9-CM: 276.69 * MeSH: D014869 * DiseasesDB: 29222 * v * t * e Acid–base disorders Acidosis Metabolic * High anion gap * Ketoacidosis * Diabetic ketoacidosis * Alcoholic ketoacidosis * Lactic * Normal anion gap * Hyperchloremic * Renal tubular Respiratory * Respiratory Alkalosis * Metabolic * Contraction alkalosis * Respiratory Other * Mixed disorder of acid-base balance * Acid–base homeostasis Authority control * NDL: 01202638 [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-hydroxybutyric 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	Water intoxication	c0392689	24,676	wikipedia	https://en.wikipedia.org/wiki/Water_intoxication	2021-01-18T18:33:06	{"mesh": ["D014869"], "umls": ["C0392689"], "icd-9": ["276.69"], "icd-10": ["E87.7"], "wikidata": ["Q1144913"]}
In mother and daughter and probably in the mother's father, Minas and Podos (1968) observed open angle glaucoma with elevated episcleral venous pressure, manifested by dilated episcleral veins. Eyes \- Open angle glaucoma \- Elevated episcleral venous pressure \- Dilated episcleral veins 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-hydroxybutyric 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	GLAUCOMA WITH ELEVATED EPISCLERAL VENOUS PRESSURE	c1842030	24,677	omim	https://www.omim.org/entry/137700	2019-09-22T16:40:42	{"mesh": ["C564235"], "omim": ["137700"]}
A chronic and rare endocrine disorder due to autoimmune destruction of the adrenal cortex and resulting in a glucocorticoid and mineralocorticoid deficiency. Properly speaking, it designates autoimmune adrenalitis, but it is a term commonly used to describe any form of chronic primary adrenal insufficiency (CPAI). ## Epidemiology The prevalence of AD is 1/9,000-1/6,900 in the developed countries. ## Clinical description Disease onset peaks around 40 but it can occur at any age. It presents insidiously with nonspecific symptoms that can be mistaken for other more prevalent conditions. Common manifestations include fatigue, loss of energy, malaise, weight loss, nausea, anorexia (failure to thrive in children), muscle and joint pain. Pigmentation of skin and mucous membranes (darkening of the skin especially in the palmar creases, knuckles, scars, oral mucosa and sites of friction) is a cardinal sign of AD. Symptoms of postural hypotension and hypoglycemia are late manifestations. Patients may also crave salt. Vitiligo and alopecia areata are often present. AD also causes dehydroepiandrosterone deficiency causing additional symptoms seen only in women (loss of axillary/pubic hair, absence of pubarch in children, reduced libido and dry skin). Acute primary adrenal insufficiency (AAI; see this term), also called an adrenal crisis, can occur if treatment is not followed or during precipitating illnesses and is a life threatening medical emergency. ## Etiology AD results from autoimmune destruction of the adrenal cortex and can be isolated or seen as part of an autoimmune disorder (autoimmune polyendocrine syndrome type 1, 2 or 4, see these terms). ## Diagnostic methods Biochemical tests are needed to diagnose AD. Early morning serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels are measured. Plasma ACTH is much higher in individuals with AD (>22 pmol/L) and morning serum cortisol levels are usually low (<83nmol/L) but can fluctuate. A stimulation test observing the cortisol response to exogenous ACTH is a useful tool in confirming a diagnosis. In healthy subjects serum cortisol concentrations increase (>500 nmol/L) after exogenous ACTH administration but no increase is seen in AD patients. Raised plasma ACTH levels confirm AD diagnosis. ## Differential diagnosis Secondary adrenal insufficiency needs to be eliminated. Causes include pituitary tumors, lymphatic hypophystitis, pituitary tuberculosis and sarcoidosis, all of which are differential diagnoses. Infiltrative disorders and other causes of CPAI should be excluded and include tuberculosis (see this term), fungal infections and AIDS-associated opportunistic infections. Genetic disorders, tumors, and treatment with certain drugs are other less common causes of CPAI. ## Management and treatment Management is life-long and requires a multidisciplinary team. Glucocorticoid replacement with oral hydrocortisone (10-25 mg daily taken in 2-3 doses) is given to mimic physiological cortisol secretion patterns. Oral fludrocortisone is given to replace mineralocorticoid hormones. Dehydroepiandrosterone replacement is optional. Glucocorticoid levels can be adjusted during times of stress to prevent AAI. The dose of hydrocortisone is maintained on the basis of clinical assessment and responses, taking into account a patient's well-being and presence of signs of over-replacement or under-replacement. An assessment of plasma renin activity is helpful in optimizing the dose of fludrocortisone. Growth and development in children must be monitored. Patients should carry a ready to inject hydrocortisone preparation and carry a medical alert card, in case of adrenal crisis. ## Prognosis There is no cure for AD but with proper treatment and care taken to prevent AAI there is no decrease in life expectancy. AD is only life threatening when ignored. [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-hydroxybutyric 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	Addison disease	c0001403	24,678	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85138	2021-01-23T18:26:45	{"gard": ["5740"], "mesh": ["D000224"], "omim": ["103230", "240200"], "umls": ["C0001403", "C0271737"], "icd-10": ["E27.1"], "synonyms": ["Autoimmune Addison disease", "Autoimmune adrenalitis", "Classic Addison disease", "Primary Addison disease"]}
Papillary renal cell carcinoma SpecialtyOncology SymptomsHematuria, flank pain, palpable abdominal mass Diagnostic methodMedical Image Test (ultrasound, computed tomography, magnetic resonance imaging) TreatmentNephrectomy, partial nephretocmy, targeted molecular therapy Prognosis82-90% for five-year survival rate Papillary renal cell carcinoma (PRCC) is a malignant, heterogeneous tumor originating from renal tubular epithelial cells of the kidney, which comprises approximately 10-15% of all kidney neoplasms.[1] Based on its morphological features, PRCC can be classified into two main subtypes, which are type 1 (basophilic) and type 2 (eosinophilic).[2] As with other types of renal cell cancer, most cases of PRCC are discovered incidentally without showing specific signs or symptoms of cancer.[3] In advanced stages, hematuria, flank pain, and abdominal mass are the three classic manifestation.[4] While a complete list of the causes of PRCC remains unclear, several risk factors were identified to affect PRCC development, such as genetic mutations, kidney-related disease, environmental and lifestyle risk factors.[5] For pathogenesis, type 1 PRCC is mainly caused by MET gene mutation while type 2 PRCC is associated with several different genetic pathways.[6] For diagnosis, PRCC is detectable through computed tomography (CT) scans or magnetic resonance imaging (MRI), which commonly present a small homogeneous hyposvascular tumor.[7] Nephrectomy or partial nephrectomy is usually recommended for PRCC treatment, often accompanied with several targeted molecular therapies to inhibit metastatic spread.[8][9] PRCC patients are predominantly male with a mean age of 52-66 years.[10] When compared to conventional clear cell renal cell carcinoma (RCC), the prognosis of non-metastatic PRCC is more favorable, whereas a relatively worse outcome was reported in patients with metastatic disease.[11] Globally, the incidence of PRCC ranges between 3,500 to 5,000 cases, while it greatly varies depending on gender, age, and race/ethnicity.[12] ## Contents * 1 Classification * 1.1 Type 1 Papillary Renal Cell Carcinoma * 1.2 Type 2 Papillary renal cell carcinoma * 2 Signs and Symptoms * 3 Causes * 4 Pathogenesis * 5 Diagnosis * 5.1 Computed tomography (CT) * 5.2 Magnetic resonance imaging (MRI) * 5.3 Grading System * 6 Treatment * 6.1 Surgery * 6.2 Targeted Therapy * 7 Prognosis * 8 Epidemiology * 9 References * 10 External Links ## Classification[edit] A micrograph of Type 1 PRCC, illustrating features of small basophilic cells with scarce cytoplasm. A single layer of cells are surrounding the basal membrane.[13] In 2014, PRCC was first acknowledged as a renal tumor subtype by the World Health Organization (WHO) considering its distinct genetic, molecular and histologic characteristics.[10] It is further divided into type 1 and type 2 based on morphological features.[14] ### Type 1 Papillary Renal Cell Carcinoma[edit] A micrograph of Type 2 PRCC, showing cells containing abundant eosinophilic granular cytoplasm with prominent nucleoli.[13] Type 1 PRCC, also known as a renal tumor caused by a genetic predisposition of hereditary papillary renal cancer syndrome, compromises approximately 25% of all PRCCs.[15][16] In the perspective of immunochemistry, it has a profile of strong CK7 and alpha-methyl acyl-CoA racemase (AMACR) expression at most focal CA-IX expression.[17] Histologically, its epithelium is composed of relatively small-sized simple cuboidal cells lined in a single layer.[18] These cells are well-characterized by basophilic cytoplasm.[19] Due to its solid growth, an extremely compact papillary architecture is often observed.[17] Other morphological characteristics include intracellular hemosiderin and foamy macrophages placed inside of papillary fibrovascular cores or psammoma bodies.[20] In general, the nuclei of type 1 PRCC belong to grade 1-2 of the Fuhrman system.[17] ### Type 2 Papillary renal cell carcinoma[edit] Accounting for 25% of PRCCs, type 2 PRCC is the pathological subtype that is most commonly associated with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome.[15][16] When compared to type 1, it shows more variation in protein expression mostly by loss of CK7.[17] In a gross examination, it shows papillae covered by large cells abundant in eosinophilic cytoplasm.[19] Its large spherical nuclei on papillary cores are arranged in a pseudo-stratified manner.[17] Unlike type 1 PRCC, foamy macrophages and psammoma bodies are less common in case of type 2.[16] The majority of type 2 PRCC has high Fuhrman grade nuclei with prominent nucleoli.[17] ## Signs and Symptoms[edit] Due to its asymptomatic nature, PRCC is often undetectable, and the majority of cases are incidentally diagnosed during the radiological workup of unrelated diseases.[3][8] Its clinical manifestations are similar to those of clear cell RCC, which are the classical triad of renal cell carcinoma (hematuria, flank pain and palpable abdominal mass; only 6-10% of patients) or even nonspecific symptoms including fatigue, weight loss, fever, and anorexia.[4][10][21] Since early diagnosis is relatively uncommon, PRCC patients may experience symptoms caused by the metastatic spread to secondary sites. Specifically, metastasis occurs most frequently in the lungs followed by bone and the brain, exhibiting a wide range of symptoms including bone pain to a persistent cough.[8][21] ## Causes[edit] Currently, the exact cause of PRCC remains unclear. Possible risk factors have been identified that contribute to PRCC development, which include genetic mutations, hereditary syndrome, renal injuries, and lifestyle factors. Germline mutation of c-MET oncogene and fumarate hydratase gene elevates the risk of type 1 and type 2 PRCC respectively through distinct signaling pathways.[22][23] Regarding hereditary conditions, patients with hereditary papillary renal cancer syndrome showed a greater risk of type 1 PRCC, whereas those with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome have an increased risk of type 2 PRCC.[24][5] Moreover, patients who experienced chronic kidney diseases or acute kidney injury exhibited a higher incidence of PRCC.[25][26] Additionally, other risk factors such as smoking, obesity, and high blood pressure can influence the pathogenesis of PRCC.[5] ## Pathogenesis[edit] An overview of the MET molecular pathway in PRCC[6] Different molecular mechanisms are involved in PRCC development, which further result in distinct histologic features and clinical outcomes. Type 1 PRCC is caused by a genetic mutation or a gain in chromosome 7 where the MET gene is positioned, resulting in the promotion of oncogenic pathways in renal epithelial cells.[6] Typically, the MET gene is upregulated for renal tissue repair and regeneration by encoding the receptor tyrosine kinase c-MET of hepatocyte growth factor.[6] However, activation of the oncogenic pathway in the MET gene will manifest invasion, anti-apoptosis, angiogenesis, and metastasis.[6] Type 2 PRCC is associated with irregularity of several signaling pathways, which includes CDKN2A silencing, mutation in chromatin-modifying genes, and a GpG island methylator phenotype (CIMP).[27] CDKN2A is a tumor suppressor gene, while loss of its expression results in enhanced tumorigenesis and metastasis.[27][28] Moreover, mutation of gene involved in chromatin remodeling (SETD2, BAP1, or PBRM) may lead to higher rate of TFE3/TFEB fusion.[27] Additionally, CIMP papillary renal cell carcinoma tumors exhibited somatic FH gene mutation, which is closely associated with HLRCC syndrome.[29] ## Diagnosis[edit] Currently, cross-sectional imaging with computed tomography (CT) and magnetic resonance imaging (MRI) is known as the best option for diagnosing papillary renal tumors.[30] Unenhanced (left) and nephrographic phase (right) CT scans display a 1-cm low-attenuation PRCC tumor (arrow) in the right renal cortex[8] ### Computed tomography (CT)[edit] Contrast-enhanced computed tomography (CT) is most commonly used to identify the subtypes of RCC. PRCC can be differentiated from other types of RCC due to its distinguishing features, displaying a small hypovascular renal tumor on T2 weighted images.[7] Typically, PRCC tends to appear homogeneous while clear cell RCC is likely to be in a heterogeneous form when the tumor is less than 3cm in diameter.[31] Comparatively, in cases of tumors larger than 3cm in diameter, PRCC is generally heterogeneous with areas of necrosis and hemorrhage compared to chromophobe RCC.[8][32] Solid, small PRCC tumors (<3cm in diameter) are more easily viewed on nephrographic, excretory phase images rather than on unenhanced, corticomedullary phase images.[8] ### Magnetic resonance imaging (MRI)[edit] Magnetic resonance imaging (MRI) is recommended instead of CT for patients with an allergy to iodinated contrast materials.[8] As some renal tumors do not enhance significantly on CT, MRI examination is required to be performed with more sensitive contrast enhancement.[7] On MRI, the distinct features of PRCC are fibrous capsules and homogeneously low single intensity on both T1- and T2-weighted images.[8][33] Specifically, PRCC exhibits hypointensity due to its dense collagenous matrix or deposition of calcium and hemosiderin within the tumor.[34] Such visual features help PRCC to be differentiated from clear cell RCC, which has heterogeneously higher single intensity shown on T2-weighted images.[8][33] PRCC displays the smallest tumor-to-cortex enhancement at corticomedullary and nephrographic phases when juxtaposed with clear cell and chromophobe RCCs.[33] ### Grading System[edit] The Fuhrman system is one of the most widely accepted grading system for RCCs; however, it was either not applicable or has not been validated for new subtypes of renal carcinoma.[35] Regarding such issues, the International Society of Urologic Pathologists (ISUP) suggested a novel histological tumor grading system as a prognostic parameter of renal cell carcinoma in 2012 to diagnose tumor grades based on nucleolar prominence.[36] Currently recommended by the WHO, this four-tiered WHO/ISUP grading system has also been validated for PRCC.[36] Fuhrman System for Papillary Renal Cell Carcinoma (PRCC) Grading[37] Grade Definition 1 Nucleoli are absent or inconspicuous and basophilic at × {\displaystyle \times } 400 magnification. 2 Nucloeli are conspicuous and eosinophilic at × {\displaystyle \times } 400 magnification and visible but not prominent at × {\displaystyle \times } 100 magnification. 3 Nucleoli are conspicuous and eosinophilic at × {\displaystyle \times } 100 magnification 4 There is extreme nuclear pleomorphism, multinucleate giants cells, and/or rhabdoid an/or sarcomatoid differentiation ## Treatment[edit] First-line treatment for metastatic PRCC has not been standardized. Thus, similar treatment approaches for clear cell RCC have been used for PRCC, even though it has a distinct tumor histology.[9][38] ### Surgery[edit] Nephrectomy or nephron-sharing partial nephrectomy is widely recommended to reduce the risk of metastasis by eliminating all or part of the kidney.[8] Surgery procedures for PRCC depend on the patient's status and are very similar to procedures performed on RCC patients. ### Targeted Therapy[edit] Several medications that target molecular pathways in RCC have been possible options for advanced and metastatic PRCC.[9] Among different medications, tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors are effective in inhibiting angiogenesis, blocking growth and suppressing spread of the tumor.[39] Sunitinib, sorafenib, and axitinib are TKIs with anti-vascular endothelial growth factor (VEGF), which inhibit cellular signaling by targeting multiple receptor tyrosine kinase.[39][40][41][42] Everolimus and temsirolimus are used in deregulating the mTOR pathway.[43][44] Specifically, mTOR inhibitors have crucial roles in regulating cell growth, cell proliferation and metabolism of highly active tumor cells.[39] Other targeted agents such as MET inhibitors, epidermal growth factor receptor (EGFR) inhibitors, and monoclonal antibodies, are also promising treatment approaches for PRCC.[9] Foretinib is one example of a multikinase inhibitor targeting c-MET.[45] Considering that MET gene mutation is one oncogenic pathway of PRCC, MET inhibitors like tivantinib and volitinib are currently being investigated as a new targeted therapy option.[9][45] ## Prognosis[edit] The five-year survival rate of PRCC has been reported as 82-90%, which is slightly higher than that of other kidney cancers.[46] The reduced survival rate has been positively correlated to several factors, which are high nuclear grade and stage, vascular invasion, DNA aneuploidy, and more.[47] Patients with type 1 PRCC have significantly improved survival rates than those with type 2, which is a reflection of its lower TNM stage with a well-encapsulated tumor.[48] Compared to other common types of RCC, PRCC exhibits a relatively lower risk of tumor recurrence and cancer-related death after nephrectomy.[49] Specifically, the cancer-specific survival rate at five years following surgery with PRCC has reached up to 91%, while clear cell RCC and chromophobe RCC were 72% and 88%, respectively.[47] ## Epidemiology[edit] Among different histologic subtypes of RCC, PRCC is the second most predominant type and accounts for 10-15% of all renal tumors.[50] In the case of the United States, it is estimated that the incidence of PRCC will rise to 3,500 to 5,000 cases annually.[12] Generally, PRCC is more prevalent among men than women, while the reported sex ratio (M: F) varies from 1.8:1 to 3.8:1.[51] The mean age at presentation is identified as 52-66 years old; however, no statistically significant difference was found in the incidence of PRCC between the younger (< 40 years) and older adult groups (>40 years).[10][52] In terms of racial variation, several studies have proven that people with African or Afro-Caribbean ancestry tend to have higher chances of being diagnosed with PRCC. According to the National Cancer Database, PRCC was more common in the Non-Hispanic Black population (38.9%) when compared to other races – Asian American (18.0%), Non-Hispanic White (13.2%), and Hispanic White populations (6.1%).[53] ## References[edit] 1. ^ Cairns P (2011). "Renal cell carcinoma". Cancer Biomarkers. 9 (1–6): 461–73. doi:10.3233/CBM-2011-0176. PMC 3308682. PMID 22112490. 2. ^ Lee J, Chae HK, Lee W, Nam W, Lim B, Choi SY, et al. (2018-12-28). "Comparison of Prognosis in Types 1 and 2 Papillary Renal Cell Carcinoma and Clear Cell Renal Cell Carcinoma in T1 Stage". The Korean Journal of Urological Oncology. 16 (3): 119–125. doi:10.22465/kjuo.2018.16.3.119. 3. ^ a b Encyclopedia of Cancer. Academic Press. 2018-10-12. ISBN 978-0-12-812485-7. 4. ^ a b Courthod G, Tucci M, Di Maio M, Scagliotti GV (October 2015). "Papillary renal cell carcinoma: A review of the current therapeutic landscape". Critical Reviews in Oncology/Hematology. 96 (1): 100–12. doi:10.1016/j.critrevonc.2015.05.008. hdl:2318/1564896. PMID 26052049. 5. ^ a b c "Risk Factors for Kidney Cancer". www.cancer.org. Retrieved 2020-04-08. 6. ^ a b c d e Rhoades Smith KE, Bilen MA (November 2019). "A Review of Papillary Renal Cell Carcinoma and MET Inhibitors". Kidney Cancer. 3 (3): 151–161. doi:10.3233/KCA-190058. PMC 6918905. PMID 31867475. 7. ^ a b c Couvidat C, Eiss D, Verkarre V, Merran S, Corréas JM, Méjean A, Hélénon O (November 2014). "Renal papillary carcinoma: CT and MRI features". Diagnostic and Interventional Imaging. 95 (11): 1055–63. doi:10.1016/j.diii.2014.03.013. PMID 25443332. 8. ^ a b c d e f g h i j Vikram R, Ng CS, Tamboli P, Tannir NM, Jonasch E, Matin SF, et al. (2009-05-01). "Papillary renal cell carcinoma: radiologic-pathologic correlation and spectrum of disease". Radiographics. 29 (3): 741–54, discussion 755-7. doi:10.1148/rg.293085190. 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"Enhancement characteristics of papillary renal neoplasms revealed on triphasic helical CT of the kidneys". AJR. American Journal of Roentgenology. 178 (2): 367–72. doi:10.2214/ajr.178.2.1780367. PMID 11804895. 32. ^ Kim JK, Kim TK, Ahn HJ, Kim CS, Kim KR, Cho KS (June 2002). "Differentiation of subtypes of renal cell carcinoma on helical CT scans". AJR. American Journal of Roentgenology. 178 (6): 1499–506. doi:10.2214/ajr.178.6.1781499. PMID 12034628. 33. ^ a b c Gurel S, Narra V, Elsayes KM, Siegel CL, Chen ZE, Brown JJ (2013-03-11). "Subtypes of renal cell carcinoma: MRI and pathological features". Diagnostic and Interventional Radiology. 19 (4): 304–11. doi:10.5152/dir.2013.147. PMID 23439256. 34. ^ Hiraki Y, Okamoto D, Nishie A, Asayama Y, Ishigami K, Ushijima Y, et al. (August 2019). "Papillary renal cell carcinoma with massive hematoma mimicking hemangioma". Radiology Case Reports. 14 (8): 1003–1006. doi:10.1016/j.radcr.2019.05.025. PMC 6556879. PMID 31198484. 35. ^ Warren AY, Harrison D (December 2018). "WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies". World Journal of Urology. 36 (12): 1913–1926. doi:10.1007/s00345-018-2447-8. PMC 6280811. PMID 30123932. 36. ^ a b Moch H (July 2016). "[The WHO/ISUP grading system for renal carcinoma]". Der Pathologe. 37 (4): 355–60. doi:10.1007/s00292-016-0171-y. PMID 27271258. S2CID 8644427. 37. ^ Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM (July 2016). "The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours". European Urology. 70 (1): 93–105. doi:10.1016/j.eururo.2016.02.029. PMID 26935559. 38. ^ Liu K, Ren Y, Pang L, Qi Y, Jia W, Tao L, et al. (2015-07-01). "Papillary renal cell carcinoma: a clinicopathological and whole-genome exon sequencing study". International Journal of Clinical and Experimental Pathology. 8 (7): 8311–35. 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PMID 31509346. ## External Links[edit] Classification D * ICD-10: C64[1] * MeSH: C538614 * v * t * e Tumors of the urinary and genital systems Kidney Glandular and epithelial neoplasm * Renal cell carcinoma * Renal oncocytoma Mixed tumor * Wilms' tumor * Mesoblastic nephroma * Clear-cell sarcoma of the kidney * Angiomyolipoma * Cystic nephroma * Metanephric adenoma by location * Renal medullary carcinoma * Juxtaglomerular cell tumor * Renal medullary fibroma Ureter * Ureteral neoplasm Bladder * Transitional cell carcinoma * Squamous-cell carcinoma * Inverted papilloma Urethra * Transitional cell carcinoma * Squamous-cell carcinoma * Adenocarcinoma * Melanoma Other * Malignant fibrous histiocytoma * v * t * e Glandular and epithelial cancer Epithelium Papilloma/carcinoma * Small-cell carcinoma * Combined small-cell carcinoma * Verrucous carcinoma * Squamous cell carcinoma * Basal-cell carcinoma * Transitional cell carcinoma * Inverted papilloma Complex epithelial * Warthin's tumor * Thymoma * Bartholin gland carcinoma Glands Adenomas/ adenocarcinomas Gastrointestinal * tract: Linitis plastica * Familial adenomatous polyposis * pancreas * Insulinoma * Glucagonoma * Gastrinoma * VIPoma * Somatostatinoma * Cholangiocarcinoma * Klatskin tumor * Hepatocellular adenoma/Hepatocellular carcinoma Urogenital * Renal cell carcinoma * Endometrioid tumor * Renal oncocytoma Endocrine * Prolactinoma * Multiple endocrine neoplasia * Adrenocortical adenoma/Adrenocortical carcinoma * Hürthle cell Other/multiple * Neuroendocrine tumor * Carcinoid * Adenoid cystic carcinoma * Oncocytoma * Clear-cell adenocarcinoma * Apudoma * Cylindroma * Papillary hidradenoma Adnexal and skin appendage * sweat gland * Hidrocystoma * Syringoma * Syringocystadenoma papilliferum Cystic, mucinous, and serous Cystic general * Cystadenoma/Cystadenocarcinoma Mucinous * Signet ring cell carcinoma * Krukenberg tumor * Mucinous cystadenoma / Mucinous cystadenocarcinoma * Pseudomyxoma peritonei * Mucoepidermoid carcinoma Serous * Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma Ductal, lobular, and medullary Ductal carcinoma * Mammary ductal carcinoma * Pancreatic ductal carcinoma * Comedocarcinoma * Paget's disease of the breast / Extramammary Paget's disease Lobular carcinoma * Lobular carcinoma in situ * Invasive lobular carcinoma Medullary carcinoma * Medullary carcinoma of the breast * Medullary thyroid cancer Acinar cell * Acinic cell carcinoma [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-hydroxybutyric 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	Papillary renal cell carcinoma	c1306837	24,679	wikipedia	https://en.wikipedia.org/wiki/Papillary_renal_cell_carcinoma	2021-01-18T18:36:08	{"gard": ["9575", "9572"], "mesh": ["D002292", "C538614"], "umls": ["C1306837", "C1336078"], "orphanet": ["319298"], "wikidata": ["Q16877679"]}
This article may be too technical for most readers to understand. Please help improve it to make it understandable to non-experts, without removing the technical details. (September 2015) (Learn how and when to remove this template message) Rasmussen syndrome SpecialtyDermatology/oncology Rasmussen syndrome is a condition characterized by multiple trichoepitheliomas.[1][2] ## See also[edit] * List of cutaneous neoplasms associated with systemic syndromes * List of cutaneous conditions ## References[edit] 1. ^ Bolognia, Jean L.; et al. (2007). Dermatology. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ James, William D.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. This oncology 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-hydroxybutyric 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	Rasmussen syndrome	c0393484	24,680	wikipedia	https://en.wikipedia.org/wiki/Rasmussen_syndrome	2021-01-18T18:42:11	{"mesh": ["D004660"], "wikidata": ["Q7295137"]}
A crush fetish is a fetish and a paraphilia in which sexual arousal is associated with observing objects being crushed or being crushed oneself. The crushed objects vary from inanimate items (e.g. food), to injurious and/or fatal crushing of invertebrates (e.g. insects, snails, worms, spiders), or vertebrates (e.g. birds, reptiles, mammals).[1][2] In the most severe cases, crushing has involved homicide[3] or extended torture until death of restrained animals including dogs, cats, pigs, and monkeys. Animal welfare organisations, such as the Humane Society of the United States, condemn this practice and consider it extremely disturbing.[2] The motivation for these acts may be the production of a film recording the events, which is sold on the Internet to crush fetishists who find the content sexually gratifying; a tailored genre known as 'crush film'. There are currently no laws specifically forbidding the crushing of animals, but the production or trade of crush erotica involving live vertebrates is illegal in many countries, including the United States and the United Kingdom.[4] In the United States, interstate commerce in [hard] crush videos has been illegal since 2010,[5] and many other countries also have banned them.[6] ## Contents * 1 Classification * 2 Crush films * 2.1 General * 2.2 Legal status * 2.2.1 United States * 2.2.2 United Kingdom * 2.2.3 China * 3 See also * 4 References * 5 External links ## Classification[edit] Crush fetishists have used terms to classify crushing, on the basis of the object subjected to the crushing: * 'Soft crush' – crushing of inanimate objects and invertebrates. This is the most common form. Most exclusive soft crush fetishists prefer to distinguish themselves from other crush fetishists, believing that other crush fetishists give them an unduly negative reputation.[7] * 'Hard crush' – crushing of non-human vertebrates. This is considered more cruel than soft crush as vertebrates are generally believed to have a greater capacity to suffer pain.[8] * 'Trample fetish' – crushing of humans.[9] This is not to be confused with the similarly potentially dangerous practice of erotic asphyxiation, where the stimulus of arousal is oxygen deprivation, not necessarily involving crushing. ## Crush films[edit] Play media Example of a soft crush fetish film using kiwifruits ### General[edit] Crush films are videos produced for sexual gratification of crush fetishists.[10][11][12][2] In crush films, the crushing agent is typically a woman, who will concentrate her body weight upon her feet to compress the object against the floor. The feet are typically dressed in sexually suggestive dominatrix-like footwear, such as high-heels and lace stockings, but other footwear or bare feet may be used. This recalls elements of both foot fetishism and BDSM culture.[2] Jeff Vilencia is one known director of crush films, such as Smush![13] Vilencia, along with many other fetishists, has loved to see invertebrates crushed since a young age; he claims that when he was 2–3 years old, he repeatedly attempted to get people to step on him.[14] ### Legal status[edit] The legality of crush films and the actual practice of crushing varies by region; however, many have been posted on web sites and are available for download via the Internet, making the control of their distribution difficult. The production or trade of crush erotica involving vertebrates is condemned by opponents of animal cruelty and is illegal in many countries including the United States.[15] #### United States[edit] In 1999, the United States Congress enacted a statute affecting the legality of crush films which criminalized the creation, sale, and possession of depictions of animal cruelty, though with an exception for "any depiction that has serious religious, political, scientific, educational, journalistic, historical, or artistic value."[16] In 2008, the United States Court of Appeals for the Third Circuit invalidated the ban on the sale and possession of such films (if not otherwise obscene) as a violation of the Constitution's guarantee for freedom of speech.[17] The United States Supreme Court affirmed the Third Circuit's decision in United States v. Stevens, finding the law unconstitutional because the law was so broad and vague that it included any portrayal of an animal in or being harmed such as by hunting or disease.[18] On November 28, 2010, bill H.R. 5566, which prohibits interstate commerce in animal crush films, was passed by the House of Representatives and the Senate, and on December 9, the bill was signed by President Obama becoming the Animal Crush Video Prohibition Act of 2010.[5] On September 8, 2015, a Houston woman pleaded guilty in the nation's first federal animal crush video case.[19][20] On November 25, 2019, President Donald Trump signed the Preventing Animal Cruelty and Torture Act (PACT Act) into law, making animal “crushing” and sexual abuse of animals a federal felony if the offense is in or affecting foreign or interstate commerce, or if it is committed on federally owned property, such as national parks, federal prisons, and military bases. While the law does not supersede state or local ordinance, a PACT conviction does provide for federal fines and imprisonment of up to seven years. The PACT act defines animal crushing as when "one or more living non-human mammals, birds, reptiles or amphibians is purposely crushed, burned, drowned, suffocated, impaled or otherwise subjected to serious bodily injury."[21] #### United Kingdom[edit] Although the majority of films are thought to originate in the United States, the first arrest in the UK was made in 2002 of Craig Chapman, Christine Besford, Sarah Cooke, and Theraza Smallwood. The industry is estimated to generate hundreds of thousands of pounds' worth of sales.[22] #### China[edit] In 2006 an Internet crush video surfaced in which a woman stomps on a kitten with stiletto high-heels. Eventually the woman drives her heel into the kitten's eye and penetrates the eye socket, leading to loss of blood and the death of the kitten.[23] Internet users discovered and revealed the identity of the woman as Wang Jue (simplified Chinese: 王珏; traditional Chinese: 王玨; pinyin: Wáng Jué), a nurse, and revealed that the cameraman was a provincial television employee. Wang Jue posted an apology on the Luobei city government website, claiming that she was susceptible to persuasion to crush the kitten, being despondent from her recent divorce.[24] Both Wang Jue and the cameraman lost their jobs as a result of the incident, although their actions were not illegal under the country's animal cruelty laws.[25] ## See also[edit] * Human sexuality portal * Erotica and pornography portal * Animal abuse * Footjob * Macrophilia * Paraphilia * Shock video * Vorarephilia * Zoosadism ## References[edit] 1. ^ G.A. Pearson. (1997). Digest Cultural Entomology. Fourth issue. Crush Fetishists 2. ^ a b c d Nancy, Perry (15 September 2010). "Animal Crush Videos: Senate Committee Testimony". The Humane Society of the United States. Retrieved 9 May 2020. 3. ^ "Love Crushed Sex". Darwin Awards. 1999. Retrieved 10 May 2020. 4. ^ "Crush fetish". www.ehrfurcht.com. Archived from the original on 2017-01-22. Retrieved 2014-03-03. 5. ^ a b H.R. 5566: Animal Crush Video Prohibition Act of 2010. www.govtrack.us 6. ^ DeMello, Margo (September 2009). Feet and Footwear: A Cultural Encyclopedia. Santa Barbara, California: Greenwood Publishing Group. ISBN 9780313357145. Retrieved March 3, 2014. 7. ^ Thoswal. (March 2014). Hear A Crush Fetishist Out Archived 2014-12-14 at the Wayback Machine 8. ^ Dr. Mark Griffiths, (May 17, 2012). A Beginner's Guide To Crush Fetishism 9. ^ Reischel, Julia (April 20, 2006). "Crush Me, Kill Me". New Times Broward-Palm Beach. 10. ^ Third Circuit Rejects Proposed New "Depiction of Animal Cruelty" First Amendment Exception The Volokh Conspiracy, July 18, 2008 11. ^ A. S. Hamrah. (2000) A Better Mousetrap. Hermenaut.com (accessed 2006-05-04) 12. ^ G.A. Pearson. (1997). Digest Cultural Entomology. Fourth issue. Insects as Sexual Fetish Objects . North Carolina State University. 13. ^ IMDB. Smush. (accessed 2006-05-04) 14. ^ Lex Appeal Animal Cruelty, Crush Videos and the First Amendment. 15. ^ Hearing before the subcommittee on crime, of the committee on the judiciary (United States) House of Representatives. Punishing Depictions of Animal Cruelty and the Federal Prisoner Health Care Co-Payment Act of 1999. (accessed 2006-05-04) 16. ^ § 48. Depiction of animal cruelty. United States Code: Title 18, Part I, Chapter 3, § 48. Cornell University Law School 17. ^ United States v. Stevens - Protecting Animals no Justification for First Amendment Amputation, The Legal Satyricon, 20-07-2008 18. ^ Adam Liptak (April 20, 2010), "Justices Reject Ban on Videos of Animal Cruelty", The New York Times 19. ^ Dart, Tom (9 September 2015). "Houston woman convicted of making 'animal crush' fetish porn videos" – via The Guardian. 20. ^ "Houston Woman Convicted of Producing and Distributing Animal Crush Videos". Federal Bureau of Investigation. 21. ^ "'A major step to end animal abuse': Trump signs bill making animal cruelty a felony". USA Today. 26 November 2019. 22. ^ Tony Thompson (May 18, 2002). "'Crush videos' plumb depths of perversion". The Guardian. 23. ^ "The meow murderess brought to heel". Daily News and Analysis. 2006-03-18. Retrieved 2010-08-30. 24. ^ "High-heeled kitten killer apologizes". China Daily. 2006-03-16. Retrieved 2010-08-30. 25. ^ Robinson, Jill (7 Apr 2014). "China's Rapidly Growing Animal Welfare Movement". Huffington Post. Retrieved 15 July 2014. ## External links[edit] Wikimedia Commons has media related to Crush fetish. * US Supreme Court to hear cruelty video case * News article on Crush Film Ban * Mickey Rooney, supporting a ban on Crush Films * Court Voids Law Aimed at Animal Cruelty Videos * v * t * e Paraphilias List * Abasiophilia * Acrotomophilia * Agalmatophilia * Algolagnia * Apotemnophilia * Autassassinophilia * Biastophilia * Capnolagnia * Chremastistophilia * Chronophilia * Coprophagia * Coprophilia * Crurophilia * Crush fetish * Dacryphilia * Dendrophilia * Emetophilia * Eproctophilia * Erotic asphyxiation * Erotic hypnosis * Erotophonophilia * Exhibitionism * Formicophilia * Frotteurism * Gerontophilia * Homeovestism * Hybristophilia * Infantophilia * Kleptolagnia * Klismaphilia * Lactaphilia * Macrophilia * Masochism * Mechanophilia * Microphilia * Narratophilia * Nasophilia * Necrophilia * Object sexuality * Odaxelagnia * Olfactophilia * Omorashi * Paraphilic infantilism * Partialism * Pedophilia * Podophilia * Plushophilia * Pyrophilia * Sadism * Salirophilia * Scopophilia * Somnophilia * Sthenolagnia * Tamakeri * Telephone scatologia * Transvestic fetishism * Trichophilia * Troilism * Urolagnia * Urophagia * Vorarephilia * Voyeurism * Zoophilia * Zoosadism See also * Other specified paraphilic disorder * Erotic target location error * Courtship disorder * Polymorphous perversity * Sexual fetishism * Human sexual activity * Perversion * Sexology * Book * 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-hydroxybutyric 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	Crush fetish	None	24,681	wikipedia	https://en.wikipedia.org/wiki/Crush_fetish	2021-01-18T18:34:32	{"wikidata": ["Q1142083"]}
Carnitine-acylcarnitine translocase (CACT) deficiency is a life-threatening, inherited disorder of fatty acid oxidation which usually presents in the neonatal period with severe hypoketotic hypoglycemia, hyperammonemia, cardiomyopathy and/or arrhythmia, hepatic dysfunction, skeletal muscle weakness, and encephalopathy. ## Epidemiology The prevalence is unknown. Less than 60 cases have been reported worldwide to date. ## Clinical description Most patients with CACT deficiency have a severe phenotype presenting within the first 48 hours of life as hypoketotic hypoglycemia, hyperammonemia, cardiomyopathy and arrhythmias, skeletal muscle damage, liver dysfunction and hypothermia. Neurological involvement with encephalopathy, epilepsy and developmental delay are also noted. Some patients present as a sudden infant death. A rare milder phenotype presenting in infancy/early childhood is also described which manifests with episodes of hypoketotic hypoglycemia and hyperammonemia often precipitated by fasting and/or intercurrent illness. ## Etiology Mutations in the SLC25A20 gene (3p21.31) are responsible for CACT deficiency. CACT is located in the inner mitochondrial membrane and operates a carnitine/acylcarnitine exchange across this membrane. It is an essential component of the carnitine cycle that regulates the transport of long chain fatty acids into the mitochondria where fatty acid oxidation takes place. The milder phenotype results from significant mutant protein activity. ## Diagnostic methods Patients with CACT deficiency present with a non-specific dicarboxylic aciduria. Blood acylcarnitine analysis shows a very high acyl fraction with marked increase in C16, C18, and C18:1 species. Free carnitine is very low. Specific enzyme analysis in cultured fibroblasts or lymphocytes will confirm a diagnosis as will the demonstration of two pathogenic mutations in the SLC25A20 gene. Newborn screening for CACT deficiency is available in Austria, Czech Republic, Germany, Hungary, Iceland, Portugal and Spain. ## Differential diagnosis The neonatal and severe infantile forms of carnitine palmitoyl transferase II (CPT II) deficiency (see this term) need to be excluded as they have an identical acylcarnitine profile to CACT. Clinically these two disorders are virtually indistinguishable, although congenital abnormalities are not reported in CACT and only sometimes in CPT II. ## Antenatal diagnosis Prenatal diagnosis is possible by mutation analysis of chorionic villus tissue when two pathogenic mutations have been established in a family. Specific enzyme analysis is also available for cultured chorionic villus cells. ## Genetic counseling CACT is an autosomal recessive condition and genetic counseling is available. ## Management and treatment Strict avoidance of fasting along with the institution of a low long-chain fat diet and medium chain triglyceride (MCT) supplementation is necessary. However, the MCT formula should be as low as possible in C10 and C12 fatty acids as high dietary intake of these can lead to decompensation. Carnitine supplementation is also recommended. During an acute episode, intravenous glucose is administered in order to inhibit lipolysis. ## Prognosis Severe CACT deficiency generally has a poor prognosis, with most patients dying before the age of 3 months, although a few infants treated early on in the neonatal period have had a favorable outcome in the medium term. Patients with a mild phenotype generally have a good prognosis given adherence to the treatment regimen. [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-hydroxybutyric 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	Carnitine-acylcarnitine translocase deficiency	c0342791	24,682	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=159	2021-01-23T19:01:03	{"gard": ["1123"], "mesh": ["C562812"], "omim": ["212138"], "umls": ["C0342791"], "icd-10": ["E71.3"], "synonyms": ["CACT deficiency"]}
Congenital muscular dystrophy type 1A (MDC1A) belongs to a group of neuromuscular disorders that beings at birth or infancy and is characterized mainly by hypotonia, muscle weakness and muscle wasting. Other signs and symptoms include rigidity of the spine; scoliosis; and delayed, limited motor development, with most individuals needing assistive devices for mobility. Respiratory problems, feeding disorders and seizures may also occur. With time, affected individuals may develop an elongated face and ophthalmoplegia disorders (paralysis or weakness in muscles of the eye). Intellectual development is typically normal. The prognosis is poor, as many affected children do not reach adolescence. It is caused by mutations in the LAMA2 gene and is inherited in an autosomal recessive manner. Treatment is generally symptomatic and includes a multidisciplinary approach. [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-hydroxybutyric 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	Congenital muscular dystrophy type 1A	c1263858	24,683	gard	https://rarediseases.info.nih.gov/diseases/3843/congenital-muscular-dystrophy-type-1a	2021-01-18T18:01:08	{"mesh": ["C537384"], "omim": ["607855"], "umls": ["C1263858"], "orphanet": ["258"], "synonyms": ["Merosin-negative congenital muscular dystrophy", "Merosin-deficient congenital muscular dystrophy", "Muscular dystrophy, congenital, merosin-deficient", "MDC1A", "Laminin alpha-2 deficiency", "LAMA2-related muscular dystrophy"]}
Corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome is a rare, genetic, corneal dystrophy disorder characterized by corneal opacification and dyskeratosis (which may cause visual impairment), associated with systemic features including palmoplantar hyperkeratosis, laryngeal dyskeratosis, pruritic hyperkeratotic scars, chronic rhintis, dyshidrosis and/or nail thickening. [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-hydroxybutyric 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	Corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome	c3808876	24,684	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=352662	2021-01-23T16:58:19	{"omim": ["615225"], "icd-10": ["Q82.8"]}
## Description Idiopathic scoliosis is a structurally fixed lateral curvature of the spine with a rotatory component. There is at least a 10 degree curvature as demonstrated by upright spine roentgenograms by the Cobb method (Weinstein, 1994). Scoliosis may occur secondary to other hereditary disorders including Marfan syndrome (154700), dysautonomia (223900), neurofibromatosis (see 162200), Friedreich ataxia (see 229300), and muscular dystrophies. ### Genetic Heterogeneity of Susceptibility to Isolated Scoliosis Loci for isolated scoliosis have been mapped to chromosome 19 (IS1), chromosome 17 (IS2; 607354), chromosome 8 (IS3; 608765), chromosome 9q31-q34 (IS4; 612238), and chromosome 17q25-qter (IS5; 612239). Inheritance De George and Fisher (1967) could not find evidence for operation of simple genetic factors for scoliosis. High concordance in both monozygotic and dizygotic twins and an excess of propositi born to older mothers suggested to these workers that maternal factors predominate. Wynne-Davies (1968) favored either dominant or multifactorial inheritance. Dominant inheritance was suggested by Faber (1936), by Garland (1934) who observed the condition in 5 generations, and by Gilly et al. (1963). Male-to-male transmission is apparently rare and was specifically absent in 17 families studied by Cowell et al. (1972), who suggested X-linked dominant inheritance. The 8 to 1 ratio of females to males supports this conclusion. Connor et al. (1987) did a systematic study of 87 families with early-onset scoliosis. Bell and Teebi (1995) described a French Canadian family in which a father and 2 daughters had idiopathic scoliosis. The parents were not known to be related. Axenovich et al. (1999) performed segregation analysis on 101 pedigrees ascertained through a proband with idiopathic scoliosis, using a model with age and gender effects. When they analyzed the pedigrees defining affected status as persons with a Cobb angle of more than 5 degrees, they detected no significant major gene effect. However, when the affected status was assigned only to persons with pronounced forms of disease (a curve of at least 11 degrees), a significant contribution of a major causal gene could be established and inheritance could be described according to a dominant major gene diallele model, assuming incomplete sex- and age-dependent penetrance of genotypes. Inoue et al. (1998) studied idiopathic scoliosis in 21 pairs of twins in whom DNA fingerprinting was used to establish monozygosity in 13 and dizygosity in 8. There was concordance for idiopathic scoliosis in 92.3% of monozygotic and 62.5% of dizygotic twins. Of the 12 pairs of monozygotic twins concordant for idiopathic scoliosis, 6 showed discordant curve patterns. In a study of 69 extended Utah families with a history of adolescent idiopathic scoliosis, including a total of 247 affected individuals with disease confirmed by x-rays and medical records, Ward et al. (2010) concluded that the condition is polygenic and multifactorial. Excluding all probands and assuming autosomal dominant inheritance, 1,260 individuals over the age of 16 years were determined to be at risk because they had a parent with AIS. Assuming 50% of those individuals carried the allele, estimated penetrance in at-risk males was approximately 9%, whereas that for at-risk females was approximately 29%. The lowest recurrence risk calculated, for third-degree relatives, was still an average of 9%, well above the general population's risk. Onset of AIS appeared to be inherited separately from curve pattern and severity. In a study of phenotypes in 36 of the families, affected individuals were consistent in either curve severity or curve pattern, but not both. The authors stated that it was unclear whether severity or pattern was more heritable, but that the location of the curve on the spine might be the most heritable trait of the phenotype. Ward et al. (2010) concluded that AIS is genetically complex, with low penetrance of cumulative alleles and variable expression. Mapping Chan et al. (2002) studied 7 unrelated multiplex families of Chinese descent with adolescent idiopathic scoliosis, comprising 25 affected members, and performed a genomewide scan with more than 400 fluorescent microsatellite markers. Multipoint linkage analysis revealed significant linkage to the distal short arm of chromosome 19, with both a maximum multipoint lod score and a nonparametric lod score of 4.93. Two-point linkage analysis gave a lod score of 3.63 at a recombination fraction of 0.00 at D19S216. Refinement placed the locus in a region spanning 5.2 cM on the sex-averaged genetic map on 19p13.3. ### Associations Pending Confirmation In 5 families with at least 2 individuals with scoliosis, one of whom in each family had 'triple-curve' scoliosis, in which affected individuals had 3 distinct scoliotic curves that each measured at least 10 degrees, Marosy et al. (2010) performed genomewide linkage analysis and identified the most significant values for D6S1065 on chromosome 6q (p less than 2.0 x 10(-10)) and for D10S677 on chromosome 10q (p less than 5.0 x 10(-7)). Fine mapping with SNPs narrowed the loci to a 1.0-Mb interval on chromosome 6q and a 7.0-Mb interval on chromosome 10q (p less than 0.001). Molecular Genetics ### Associations Pending Confirmation Ogura et al. (2015) performed a genomewide association study (GWAS) of 2,109 affected subjects with adolescent idiopathic scoliosis compared with 11,140 control subjects. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, Ogura et al. (2015) identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 x 10 (13), OR = 1.21, 95% CI 1.15-1.27). The most significantly associated SNPs were in intron 3 of BNC2 (608669), which encodes the zinc finger transcription factor basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs had the potential to regulate BNC2 transcription activity and that susceptibility alleles increased BNC2 expression. Ogura et al. (2015) identified a functional SNP, rs10738445, in BNC2 whose susceptibility allele showed both higher binding to a transcription factor, YY1 (600013), and higher BNC2 enhancer activity than the nonsusceptibility allele. Finally, Ogura et al. (2015) showed that BNC2 overexpression produced body curvature in developing zebrafish in a gene dosage-dependent manner. Ogura et al. (2015) concluded that increased BNC2 expression is implicated in the etiology of adolescent idiopathic scoliosis. For discussion of a possible association between scoliosis and variation in the POC5 gene, see 617880. Animal Model Opsahl et al. (1984) showed an inverse relationship between the amount of copper in the diet and the severity and incidence of scoliosis in scoliosis-prone chickens. Spine \- Scoliosis Inheritance \- Autosomal dominant vs. multifactorial ▲ 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-hydroxybutyric 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	SCOLIOSIS, ISOLATED, SUSCEPTIBILITY TO, 1	c2700406	24,685	omim	https://www.omim.org/entry/181800	2019-09-22T16:34:53	{"omim": ["181800"], "synonyms": ["Alternative titles", "ADOLESCENT ISOLATED SCOLIOSIS", "ADOLESCENT IDIOPATHIC SCOLIOSIS"]}
North Asian tick typhus Other namesNorth Asian tick fever SpecialtyInfectious disease North Asian tick typhus also known as Siberian tick typhus, is a condition characterized by a maculopapular rash.[1][2] It is associated with Rickettsia sibirica.[3] ## See also[edit] * Flinders Island spotted fever * Queensland tick typhus * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1130. ISBN 978-1-4160-2999-1. 2. ^ Parola P, Paddock CD, Raoult D (2005). "Tick-Borne Rickettsioses around the World: Emerging Diseases Challenging Old Concepts". Clinical Microbiology Reviews. 18 (4): 719–756. doi:10.1128/CMR.18.4.719-756.2005. PMC 1265907. PMID 16223955. 3. ^ Lewin MR, Bouyer DH, Walker DH, Musher DM (October 2003). "Rickettsia sibirica infection in members of scientific expeditions to northern Asia". Lancet. 362 (9391): 1201–2. doi:10.1016/S0140-6736(03)14515-1. PMID 14568744. ## External links[edit] Classification D * ICD-10: A77.2 * ICD-9-CM: 082.2 * DiseasesDB: 33146 * v * t * e Proteobacteria-associated Gram-negative bacterial infections α Rickettsiales Rickettsiaceae/ (Rickettsioses) Typhus * Rickettsia typhi * Murine typhus * Rickettsia prowazekii * Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus Spotted fever Tick-borne * Rickettsia rickettsii * Rocky Mountain spotted fever * Rickettsia conorii * Boutonneuse fever * Rickettsia japonica * Japanese spotted fever * Rickettsia sibirica * North Asian tick typhus * Rickettsia australis * Queensland tick typhus * Rickettsia honei * Flinders Island spotted fever * Rickettsia africae * African tick bite fever * Rickettsia parkeri * American tick bite fever * Rickettsia aeschlimannii * Rickettsia aeschlimannii infection Mite-borne * Rickettsia akari * Rickettsialpox * Orientia tsutsugamushi * Scrub typhus Flea-borne * Rickettsia felis * Flea-borne spotted fever Anaplasmataceae * Ehrlichiosis: Anaplasma phagocytophilum * Human granulocytic anaplasmosis, Anaplasmosis * Ehrlichia chaffeensis * Human monocytotropic ehrlichiosis * Ehrlichia ewingii * Ehrlichiosis ewingii infection Rhizobiales Brucellaceae * Brucella abortus * Brucellosis Bartonellaceae * Bartonellosis: Bartonella henselae * Cat-scratch disease * Bartonella quintana * Trench fever * Either B. henselae or B. quintana * Bacillary angiomatosis * Bartonella bacilliformis * Carrion's disease, Verruga peruana β Neisseriales M+ * Neisseria meningitidis/meningococcus * Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia M− * Neisseria gonorrhoeae/gonococcus * Gonorrhea ungrouped: * Eikenella corrodens/Kingella kingae * HACEK * Chromobacterium violaceum * Chromobacteriosis infection Burkholderiales * Burkholderia pseudomallei * Melioidosis * Burkholderia mallei * Glanders * Burkholderia cepacia complex * Bordetella pertussis/Bordetella parapertussis * Pertussis γ Enterobacteriales (OX−) Lac+ * Klebsiella pneumoniae * Rhinoscleroma, Pneumonia * Klebsiella granulomatis * Granuloma inguinale * Klebsiella oxytoca * Escherichia coli: Enterotoxigenic * Enteroinvasive * Enterohemorrhagic * O157:H7 * O104:H4 * Hemolytic-uremic syndrome * Enterobacter aerogenes/Enterobacter cloacae Slow/weak * Serratia marcescens * Serratia infection * Citrobacter koseri/Citrobacter freundii Lac− H2S+ * Salmonella enterica * Typhoid fever, Paratyphoid fever, Salmonellosis H2S− * Shigella dysenteriae/sonnei/flexneri/boydii * Shigellosis, Bacillary dysentery * Proteus mirabilis/Proteus vulgaris * Yersinia pestis * Plague/Bubonic plague * Yersinia enterocolitica * Yersiniosis * Yersinia pseudotuberculosis * Far East scarlet-like fever Pasteurellales Haemophilus: * H. influenzae * Haemophilus meningitis * Brazilian purpuric fever * H. ducreyi * Chancroid * H. parainfluenzae * HACEK Pasteurella multocida * Pasteurellosis * Actinobacillus * Actinobacillosis Aggregatibacter actinomycetemcomitans * HACEK Legionellales * Legionella pneumophila/Legionella longbeachae * Legionnaires' disease * Coxiella burnetii * Q fever Thiotrichales * Francisella tularensis * Tularemia Vibrionaceae * Vibrio cholerae * Cholera * Vibrio vulnificus * Vibrio parahaemolyticus * Vibrio alginolyticus * Plesiomonas shigelloides Pseudomonadales * Pseudomonas aeruginosa * Pseudomonas infection * Moraxella catarrhalis * Acinetobacter baumannii Xanthomonadaceae * Stenotrophomonas maltophilia Cardiobacteriaceae * Cardiobacterium hominis * HACEK Aeromonadales * Aeromonas hydrophila/Aeromonas veronii * Aeromonas infection ε Campylobacterales * Campylobacter jejuni * Campylobacteriosis, Guillain–Barré syndrome * Helicobacter pylori * Peptic ulcer, MALT lymphoma, Gastric cancer * Helicobacter cinaedi * Helicobacter cellulitis 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-hydroxybutyric 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	North Asian tick typhus	c0549160	24,686	wikipedia	https://en.wikipedia.org/wiki/North_Asian_tick_typhus	2021-01-18T18:58:13	{"mesh": ["D000073605"], "umls": ["C0549160"], "wikidata": ["Q7053975"]}
Fanconi anemia (FA) affects the way genetic information (DNA) is copied and repaired. FA leads to bone marrow failure, skeletal abnormalities, and an increased risk for cancer. People with FA have a decreased number of red blood cells, white blood cells, and platelets leading to anemia, frequent infections, and excessive bleeding. In addition, people with FA may have limb, kidney, eye, skin, and genitourinary tract abnormalities. FA occurs due to variations in one of at least 22 genes. It is usually inherited in an autosomal recessive pattern, but it may also be inherited in an autosomal dominant or X-linked recessive pattern. FA can be diagnosed based on the symptoms, clinical exam, laboratory testing. The diagnosis may be confirmed by genetic testing. Treatment is focused on managing the symptoms. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for the blood problems associated with this condition. [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-hydroxybutyric 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	Fanconi anemia	c0015625	24,687	gard	https://rarediseases.info.nih.gov/diseases/6425/fanconi-anemia	2021-01-18T18:00:32	{"mesh": ["D005199"], "omim": ["227650"], "umls": ["C0015625"], "orphanet": ["84"], "synonyms": ["Fanconi pancytopenia", "Fanconi's anemia"]}
See also: Food security in Mexico Overview of obesity in Mexico Obesity in Mexico is a relatively recent phenomenon, having been widespread since the 1980s with the introduction of processed food into much of the Mexican food market. Prior to that, dietary issues were limited to under and malnutrition, which is still a problem in various parts of the country. Following trends already ongoing in other parts of the world, Mexicans have been foregoing traditional whole grains and vegetables in favor of a diet with more animal products and processed foods. It has seen dietary energy intake and rates of overweight and obese people rise with seven out of ten at least overweight and a third clinically obese. ## Contents * 1 History * 1.1 Undernutrition vs. overnutrition * 1.2 Nutrition transition * 1.3 Socioeconomic factors of obesity * 1.4 Rates of obesity and consequences * 2 Efforts to combat the problem * 3 See also * 4 References * 5 Further reading ## History[edit] ### Undernutrition vs. overnutrition[edit] Until the late 20th century, dietary issues in Mexico were solely a question of undernutrition or malnutrition, generally because of poverty and distribution issues.[1][2] For this reason, obesity was associated with wealth and health, the latter especially in children.[3][4] Despite changes in the Mexican diet and food distribution, malnutrition still remains problematic in various parts of the country.[5] ### Nutrition transition[edit] By the 1980s, Latin American populations began to experience widespread changes in their diet, away from produce and grains toward processed food in a manner similar to what had previously occurred in developed countries.[6] The main reason for this shift is the dominance of transnational food companies in the Mexican market, following a trend seen in other parts of the world.[7][8] This shift was toward the consumption of high-energy -sugar, -fat, and -salt food featuring various types of sweeteners and animal products and a decrease in whole grains and vegetables.[1][7] Animal proteins replaced vegetable, with a 50% increase in prevalence from the 1960s to the 1990s.[6] The total cholesterol availability in Mexico surpasses the US guidelines for daily intake, at over 300 mg per day, a result of the increased availability of saturated fats.[6] The change was initially limited to more affluent urban groups that could afford processed foods and these groups showed an increase in health conditions associated with this diet, including obesity.[6] These foods are easier and less time-consuming to prepare.[1][7] With easier access to fast food and supermarkets, more affluent households also tend to buy more meat and less oils and grains, while poorer urban households tend to choose foods that exceed their energy needs and lack essential vitamins and minerals.[9] In a survey of 650 urban school lunches, none were graded as healthy and only one percent graded as adequate.[10] Since the 1980s, rural diets, that had consisted primarily of vegetables and very little animal or saturated fats, have shown declines in fruit and vegetable intake.[6] In Northern Mexico, rural populations who transitioned from their traditional diets to more processed diets also experienced a dramatic increase in obesity and diabetes.[9] In addition to dietary changes, modern life has also made the Mexican population more sedentary. Traditional labor-intensive jobs in farming, factories and mining have given way to desk jobs. In addition, most people use motorized transportation instead of walking or biking.[2] About 40% of Mexicans do not exercise.[4] ### Socioeconomic factors of obesity[edit] Since the 1980s, many studies have been carried out intending to identify the one nutrient, food, or beverage that leads to weight gain and obesity. Sugar, fat, fast food, soft drinks, and the list goes on - all of them were suspect of being the reason for the worldwide increasing overweight and obesity rates and yet none of them could essentially be made responsible. However, the studies did prove that "each of [the examined dietary elements ] is associated with either obesity or weight gain" (Drewnowski, 2007). Furthermore, these elements have one characteristic in common which is their relative inexpensiveness (as opposed to fruits, vegetables, fresh juice etc.) and also, they are preferably bought by lower-income consumers (Drewnowski).[citation needed] A review of studies (Dinsa et al.) analyzing the association between socioeconomic status (SES) and obesity among men, women, and children in developing countries found that in upper-middle-income countries like Mexico (Mexico is categorized as upper middle income (The World Bank) and middle HDI (UNDP)) obesity is highly prevalent. Middle-income and medium HDI countries showed a negative association between SES and obesity among women, i.e. the prevalence of obesity rises with decreasing income. The negative association becomes even clearer in countries growing into the high-income category. Among men, results have been mixed and the studies on children all revealed a positive association between SES and obesity.[citation needed] First, an explanation for the positive association among children could be a shift in free time activity based on their family's affluence, e.g. children of more affluent families are more likely to have access to and probably spend more time with playing video games whereas children of less affluent families cannot afford such luxury goods and predominantly stick to more active free time activities and therefore have a higher energy expenditure that compensates for their energy intake. Second, the negative association among middle-income women in consideration of the above-mentioned expensiveness of most healthy products raises the question of whether the easier access to unhealthy, energy-dense and less expensive food is the crucial point to explain the high prevalence of obesity in Mexico (Dinsa et al.).[citation needed] What Drewnowski describes as the "economics of food choice" is the fact that people have to manage their often scarce resources in a way that all basic expenditures (food, housing, clothing, school fees) are covered. Consequently, the kind of food people consume also, or primarily, depends on food prices (Dinsa et al., Drewnowski, Lozada et al.). While energy-dense products, rich in sugar and fats, cost less in relation to the energy they provide, low-energy healthy food like fruits and vegetables is more expensive in this respect (Drewnowski, 166). Furthermore, fruits and vegetables are now twice as expensive than 20 years ago whereas the costs of added sugar and fats did not change (Drewnowski, 162). To sum up, "foods, beverages, snacks, or diets said to promote obesity [are], in every case, inexpensive. In contrast, more costly dietary patterns [are] associated with leanness, weight maintenance, or greater weight loss" (Drewnoski, 166). In conclusion, low-income can be seen as an obstacle to a healthier diet as the consumption of "good" products may wear out the available budget.[citation needed] Another aspect that deserves attention is that people of lower SES usually live in less secure neighborhoods where walking around might present a danger. In addition, these places, in general, do not show a lot of establishments that offer healthy food. As a study conducted in New York found, the "walkability" of one's neighborhood and the lack of availability of healthy food establishments are also predictors of obesity (Muñez Oliveira, 23).[citation needed] Finally, although today Mexico shows a lower level of undernourishment, many of the now young adults used to suffer from nutritional stunting in early life, which is also considered to increase the risk of becoming overweight or obese later in life (Food and Agriculture Organization of the United Nations).[citation needed] All in all, the socioeconomic factor as a determinant for food choice, living conditions, and possible indicators of past undernourishment has been proved to be a predictor of obesity and weight gain. Therefore, future policies countering obesity should aim at increasing the accessibility of healthy food alternatives for the less affluent population, e.g. by subsidizing fruits, vegetables, and fiber-rich whole grains. However, the creation of consciousness about the importance of healthy eating and physical activity among the population, and particularly among children, remains an essential measure as well.[citation needed] ### Rates of obesity and consequences[edit] After the widespread introduction of processed foods, obesity rates began to rise in the country. As of 2000, individual dietary energy intake has been speculated to be approximately 2,500–3,060 calories (10,500–12,800 kJ) per day, 30% more than in 1962.[1][7] A 1999 survey found 24% of Mexican women were obese and an additional 35% were overweight; 55% men were either obese or overweight.[5] In a survey conducted by National Health Survey in 2000, it was found that the prevalence of obesity in the sample population was 67% in women and 61% in men. A similar survey in 2003 targeting obesity from rural, low-income communities showed that around 60% of women and 50% of men were considered either overweight or obese with respect to the Body Mass Index.[11] By 2010, seven out of ten Mexicans were overweight with a third clinically obese.[1][12] Mexico ranks the most obese country in the world in adult obesity (as of 2013), and first for childhood obesity with about 4.5 million children diagnosed as such. Mexico passed the United States as the most obese country in the world.[4] The prevalence of overweight and obesity is 16.7% in preschool children, 26.2% in school children, and 30.9% in adolescents. For adults, the prevalence of overweight and obesity is 39.7 and 29.9%, respectively.[13] Since the 1990s, fat has become the principal source of energy in the Mexican diet and it is assumed that the consumption of highly processed food will continue increasing.[8] As a consequence, Mexico has seen the same kind of health issues that have affected other countries with overweight populations. Standardized mortality rates (SMR) for diabetes, acute myocardial infarction (AMI), and hypertension have increased dramatically.[14] As of 2012, diabetes \- associated with obesity - was the largest single killer of Mexicans.[15] As of 2016, it was responsible for over 100,000 premature deaths in the country.[16] Economically, the rising obesity rate in Mexico is also taking a toll on its health care system. According to a study published by Cambridge University Press, cost of treatment for obesity related diseases is projected to grow from an estimated $806 million in 2010 to $1.2 billion in 2030 and $1.7 billion in 2050.[17] Recent efforts have been made by the Mexican government to address the issue of obesity as a reduction of 1% in mean BMI would reduce the cost by $43 million in 2030 and $85 million in 2050 respectively. Through initiatives that focus on the narrative of a healthier lifestyle, the government aims to reduce the projected obesity prevalence. However, not much is known about the effectiveness of those programs. ## Efforts to combat the problem[edit] There have been efforts to combat obesity in the country, with the federal government investing about seven percent of its budget to various nutritional programs.[4] Both public and private money has been spent on various campaigns aimed at modern eating habits. Mexico’s government has created nutrition programs, to deal with nutritional issues such as obesity; especially in vulnerable people and low-income sectors.[18] These include food distribution among low-income communities, micronutrient supplementation, and fortification of food.[18] All of this is made to fight the deficiency of vitamins and minerals. Some programs, as the distribution ones, try to achieve the objective by dispensing food coupons on marginalized communities.[18] One of these initiatives is implemented by the Mexican Institute of Social Security (IMSS).[18] This program is known as "Preven-IMSS" (Prevent-IMSS). It integrates nutritional and physical activities as components, to combat diabetes, obesity, and high blood pressure.[18] Another government initiative is with Mexico’s Health Ministry called "Oportunidades" (Opportunities) and "Liconsa". Opportunidades has the aim to support low-income and extremely poor families with health services and food.[18] This is reached by offering nutrition education with which families can develop their capacities to sustenance health and nutrition care.[18] In 2008, the Mexican Secretariat of Health and PepsiCo launched a health campaign for children. The program is aimed at elementary school-age children and encourages active participation in exercise activities and adopting a healthy lifestyle by using a computer game. In this game, the "nutrin," as the figure is called, needs help making decisions on what foods to eat, what sports to play, and when it should go to the doctor for a check-up.[19][full citation needed] "Wrestling vs obesity" was a campaign to promote to wrestling (lucha libre) fans to have an active way of life taking advantage of one of the most popular sports of Mexico. This campaign spanned from August 5 to November 19 of 2012 in Mexico City, State of Mexico, Hidalgo, Puebla, Tamaulipas, San Luis Potosí, Guanajuato and Morelos. "El Elegio" (A Mexican wrestler) was the official image for this campaign. He appeared in a pre-fight video talking about obesity and how to avoid it. During these events, both health/nutrition information was distributed along with application forms for government health care.[20] Voit, a sport brand, with the cooperation of the Mexican Football Federation and the health secretary of Mexico, released a new campaign with the name of "Measure yourself and activate". For this campaign Voit produced a special orange match ball with the name of "Xacte midete 2012" (Measure yourself exactly 2012) for professional football games in Mexico. This new ball is aimed at promoting the sport in children and reducing childhood obesity. Decio de Maria Serrano, the president of the Mexican soccer federation, said: "We are excited with this new campaign. All the people that are involved in this amazing sport have to contribute to combat childhood obesity it is a big responsibility because it is a big problem in this country. (Mexico) It is a task that deserves support" [21] Congress's lower house of Congress passed a special tax on junk food that is seen as potentially the broadest of its kind, part of an ambitious Mexican government effort to contain runaway rates of obesity and diabetes. The House passed the proposed measure to charge a 5% tax on packaged food that contains 275 calories (1,150 kJ) or more per 100 grams, on grounds that such high-energy items typically contain large amounts of salt and sugar and few essential nutrients.[22] Subsequent studies have indicated that the one peso per liter tax rate has only led to a small reduction in soft drink consumption, and the fall in calorie consumption was described as "nothing compared to the drop in calories people needed to consume in order to not be obese".[23] The effectiveness of the tax on junk food was subject to debate.[citation needed] ## See also[edit] * List of countries by Body Mass Index (BMI) ## References[edit] 1. ^ a b c d e Popkin, Barry (2004). "La transición nutricional y el cambio mundial hacia la obesidad" (PDF). Diabetes y Sociedad. 49 (3): 38–40. Archived from the original (PDF) on 31 October 2014. Retrieved 19 April 2013. 2. ^ a b Rivera, Juan; Barquera, Simon (2004). "Nutrition Transition in Mexico and in other Latin American Countries". Nutrition Reviews. 62 (7): 149–157. doi:10.1301/nr.2004.jul.s149-s157. PMID 15387482. 3. ^ The nutrition transition and obesity: Food and Agricultural Order of the United Nations. 4. ^ a b c d Sobrepeso y obesidad, Gobierno Del Distrito Federal, April 2013, http://www.who.int/topics/obesity/en/index.html. 5. ^ a b "Fat Mexico - Obesity on the rise in Mexico", The Economist. 6. ^ a b c d e Bermudez, Odilia I.; Tucker, Katherine L. (2003). "Trends in dietary patterns of Latin American populations". Cadernos de Saúde Pública. 19: S87–S99. doi:10.1590/S0102-311X2003000700010. PMID 12886439. 7. ^ a b c d Hawkes, Corinna (2004). "The role of foreign direct investment in the nutrition transition". Public Health Nutrition. 8 (4): 357–368. doi:10.1079/PHN2004706. PMID 15975180. 8. ^ a b Popkin, Barry; Adair, Linda (2012). "NOW AND THEN: The Global Nutrition Transition: The Pandemic of Obesity in Developing Countries". Nutr Rev. 70 (1): 3–21. doi:10.1111/j.1753-4887.2011.00456.x. PMC 3257829. PMID 22221213. 9. ^ a b Uauy, Ricardo; Monteiro, Carlos Augusto (2004). "The Challenge of Improving Food and Nutrition in Latin America". Food and Nutrition Bulletin. 25 (2): 175–82. doi:10.1177/156482650402500211. PMID 15214264. 10. ^ Vargas, Lilian; Jiménez-Cruz, Arturo; Bacardí-Gascón, Montserrat (2013). "Unhealthy and Healthy Food Consumption Inside and Outside of the School by Pre-school and Elementary School Mexican Children in Tijuana, Mexico". Journal of Community Health. 38 (6): 1166–74. doi:10.1007/s10900-013-9729-2. PMID 23864428. 11. ^ Fernald, L. C.; Gutierrez, J. P.; Neufeld, L. M.; Olaiz, G; Bertozzi, S. M.; Mietus-Snyder, M; Gertler, P. J. (2004). "High Prevalence of Obesity Among the Poor in Mexico" (PDF). JAMA. 291 (21): 2544–5. doi:10.1001/jama.291.21.2544. PMID 15173143. 12. ^ "One taco too many". The Economist. Oct 21, 2010. Retrieved 22 April 2013. 13. ^ Barquera Cervera, Simón; Campos-Nonato, Ismael; Rojas, Rosalba; Rivera, Juan (November 2010). "[Obesity in Mexico: epidemiology and health policies for its control and prevention]". Gaceta Medica de Mexico. 146 (6): 397–407. ISSN 0016-3813. PMID 21384636. 14. ^ Rivera, Juan; Barquera, Simon (2002). "Epidemiological and nutritional transition in Mexico: rapid increase of non-communicable chronic diseases and obesity" (PDF). Public Health Nutrition. 5 (1A): 113–122. doi:10.1079/PHN2001282. PMID 12027273. Retrieved 19 April 2013. 15. ^ Gillette, Hope (February 18, 2013). "Mexico continues to battle serious diabetes, obesity epidemic". VOXXI. Retrieved 22 April 2013. 16. ^ Sonja Peteranderl (13 March 2018). "Sugar crisis in Mexico". D+C, development and cooperation. Retrieved 20 March 2018. 17. ^ Rtveladze, Ketevan; Marsh, Tim; Barquera, Simon; Sanchez Romero, Luz Maria; Levy, David; Melendez, Guillermo; Webber, Laura; Kilpi, Fanny; McPherson, Klim; Brown, Martin (2013). "Obesity prevalence in Mexico: Impact on health and economic burden". Public Health Nutrition. 17 (1): 233–9. doi:10.1017/S1368980013000086. PMID 23369462. 18. ^ a b c d e f g Rome (2006). Case studies from six developing countries. FAO Food and Nutrition Papers. ISBN 978-9251054895. Retrieved 24 April 2013. 19. ^ Tuckman, 2008 20. ^ Lucha libre vs Obesidad, April 2013, http://www.seguro-popular.gob.mx/index.php?option=com_content&view=article&id=547&Itemid=472. 21. ^ CAMPAÑA "MÍDETE Y ACTÍVATE, April 2013, http://www.cns.salud.gob.mx/contenidos/midete.html. 22. ^ Mexico Tries Taxes to Combat Obesity, https://www.wsj.com/articles/SB10001424052702304864504579141462546165166 23. ^ editor, Denis Campbell Health policy (2016-03-17). "Sugar tax: financially regressive but progressive for health?". The Guardian. ISSN 0261-3077. Retrieved 2016-08-10.CS1 maint: extra text: authors list (link) ## Further reading[edit] * World's Fattest Countries * "High Prevalence of Obesity Among the Poor in Mexico". JAMA. * "US lifestyles blamed for obesity epidemic sweeping Mexico". The Guardian. * "Mexico Confronts Sudden Surge in Obesity". New York Times. * Report Of Mexican Obesity Rates - Brief Article - Statistical Data Included". Nutrition Research Newsletter, June, 2000. * "Pepsi tackles childhood obesity with videogames in Mexico". The Guardian. * v * t * e Obesity in North America Sovereign states * Antigua and Barbuda * Bahamas * Barbados * Belize * Canada * Costa Rica * Cuba * Dominica * Dominican Republic * El Salvador * Grenada * Guatemala * Haiti * Honduras * Jamaica * Mexico * Nicaragua * Panama * Saint Kitts and Nevis * Saint Lucia * Saint Vincent and the Grenadines * Trinidad and Tobago * United States Dependencies and other territories * Anguilla * Aruba * Bermuda * Bonaire * British Virgin Islands * Cayman Islands * Curaçao * Greenland * Guadeloupe * Martinique * Montserrat * Puerto Rico * Saint Barthélemy * Saint Martin * Saint Pierre and Miquelon * Saba * Sint Eustatius * Sint Maarten * Turks and Caicos Islands * United States Virgin Islands [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-hydroxybutyric 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	Obesity in Mexico	None	24,688	wikipedia	https://en.wikipedia.org/wiki/Obesity_in_Mexico	2021-01-18T18:52:51	{"wikidata": ["Q7074859"]}
Symptoms of psychological disturbance exhibited by officers in military units that suffer heavy casualties The term old sergeant’s syndrome is used to describe symptoms of psychological disturbance exhibited by officers in military units that suffer heavy casualties. It is most common in cohesive military squads that have strong interpersonal relationships among officers.[1] The term was first introduced in a study published by Sobel in 1947.[2] Sobel described soldiers who were “burnt out” and “worn out.” These soldiers were previously highly dedicated and very efficient. However, after prolonged, continuous exposure to combat, they began to exhibit negative psychological symptoms such as difficulty making decisions, being reluctant to accept responsibility for others, and preferring routine, simple tasks over more challenging ones. More serious symptoms included a loss of self-confidence, anxiety, depression and a tendency to make self-deprecatory remarks. They also had difficulty making friends and were reluctant to interact with new recruits. According to Sobel, the soldiers’ ability to carry out their duties deteriorated to the point that they became a handicap to their units, but their motivation to carry out the assigned mission remained strong. Ninety percent of men that developed this type of battle reaction were infantry foot soldiers. These men were either original members of the division or had been with it for extended periods of time, with an average overseas service of 23 months. Hence, they were the last “old men” in their platoon or company.[2] The cohesiveness of the unit likely initially provided psychological support for the individual. However, the loss of comrades during battle causes severe distress. When the unit is reinforced with replacements, many soldiers are reluctant to establish emotional ties with the newcomers, mainly in fear of the pain they recently experienced. As a result, they become isolated from the group.[1] In many respects, old sergeant’s syndrome is similar to the phenomenon of burnout as the term has since evolved in the civilian literature .[3] ## References[edit] 1. ^ a b Forsyth, Donelson R. (2018-01-01). Group Dynamics. Cengage Learning. ISBN 978-1-337-40885-1 – via Google Books. 2. ^ a b Sobel, Raymond (1947-08-01). "The "Old Sergeant" Syndrome". Psychiatry. 10 (3): 315–321. doi:10.1080/00332747.1947.11022649. ISSN 0033-2747. PMID 20264030. 3. ^ Wilcox, Victoria L. (1994). Zajtchuk, Brigadier General Russ, MC, U.S. Army (ed.). Military Psychiatry: Preparing in Peace for War (PDF). Falls Church, Virginia: Office of The Surgeon General, Department of the Army, United States of America. ## Additional reading[edit] * Horwitz, Tony. "Did Civil War Soldiers Have PTSD?". Smithsonian Magazine. Retrieved 17 April 2020. [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-hydroxybutyric 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	Old sergeant's syndrome	None	24,689	wikipedia	https://en.wikipedia.org/wiki/Old_sergeant%27s_syndrome	2021-01-18T18:59:42	{"wikidata": ["Q96397282"]}
Granulomatous rosacea is a type of rosacea, a long-term (chronic) skin condition involving inflammation of the cheeks, nose, chin, forehead, or eyelids. Rosacea causes redness and pimples, mainly across the face. Granulomatous rosacea is a type of rosacea that occurs mainly around the cheeks, eyes, and mouth. The symptoms include yellowish-brown or pink bumps (papules) on the skin, thickening of the skin, and patchy redness. The cause of granulomatous rosacea is unknown, but both genetic and non-genetic factors contribute to this condition. Granulomatous rosacea can look like other skin conditions and may be difficult to diagnose. The diagnosis is usually made based on the symptoms and characteristic findings seen from a skin biopsy. Granulomatous rosacea usually occurs in adults, primarily in middle-aged women. Treatment is based on controlling the symptoms using medications, antibiotics, light therapy and other treatments. The long-term outlook for people with granulomatous rosacea depends on the severity of symptoms and the response to treatment. The main complications of this condition is social isolation, depression and low self-esteem. This type of rosacea is rare, but the exact prevalence is unknown. [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-hydroxybutyric 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	Granulomatous rosacea	c1275718	24,690	gard	https://rarediseases.info.nih.gov/diseases/6548/granulomatous-rosacea	2021-01-18T18:00:12	{"mesh": ["D012393"], "umls": ["C1275718"], "synonyms": []}
A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome. Clinical Features Pirola et al. (1998) described a 9-month-old girl who had hydrocephalus noted on fetal ultrasonography and was born with marked muscular hypotonia and dysmorphic features including dolichocephaly, high-arched and occult submucous cleft palate, low-set ears, relatively long distal phalanges of fingers, and an anteriorly placed anus. CT scan of the head revealed agenesis of the corpus callosum (see ACC, 217990) and dilation of both lateral ventricles; MRI revealed the presence of Probst bundles. Bisgaard et al. (2006) reported a 6.5-year-old girl with short stature that was not explained by hormone analyses and stimulation tests and a 3-year delay in bone age. Failure to thrive had followed repair of a ventricular septal defect (VSD) in infancy. She had slightly delayed psychomotor development and facial dysmorphism that included almond-shaped eyes, short nose, full cheeks, smooth philtrum, thin upper lip, low-set ears, and a protruding, dysplastic left ear. Caselli et al. (2007) described an 8-year-old girl who had neonatal persistence of fetal circulation and respiratory distress, in whom tricuspid insufficiency, right ventricular dilation, patent ductus arteriosus, atrial septal defect (ASD), and increased pulmonary resistance were detected. She had delayed psychomotor development with mild mental retardation. Examination at the age of 8 years, 2 months revealed short stature, mild facial asymmetry, medial flare eyebrows, short palpebral fissures, dysmorphic helix of the right ear, cup-shaped left ear, anteverted nares, thin upper lip, long and smooth philtrum, and high-arched palate. She had small hands and small, flat feet with increased distance between the first and second toes. Echocardiogram showed an atrial septal defect with minimal shunt; MRI of brain, EEG, auditory and visual evoked responses, and abdominal ultrasound were all normal. Caselli et al. (2007) noted that the phenotype of the patient described by Bisgaard et al. (2006) was 'remarkably similar' to this patient. Nowaczyk et al. (2008) studied 3 unrelated patients with de novo paternal interstitial deletions of 6q24.3. Although the 3 patients had deletions of different sizes with different breakpoints, 2 of the patients shared a 2.5-Mb region of overlap and strikingly similar facial features, including a triangular face, frontal bossing with metopic prominence, short and upward-slanting palpebral fissures, asymmetry of upper eyelids, hooded eyelids, shallow orbits, prominent inferior orbital crease, wide mouth, and long and flat philtrum. They both had congenital heart defects, with dysplastic tricuspid and pulmonary valves with mild regurgitation, mitral valve prolapse, and premature ventricular contractions in 1 patient and left axial displacement of the heart chambers and a large patent foramen ovale with a secundum atrial septal defect in the other patient. Additional features in common included redundant skin, joint laxity, a small thorax, and early developmental delay. The smallest region of overlap between all 3 patients was a less than 1-Mb deletion interval; all 3 patients had a history of intrauterine growth retardation (IUGR) and postnatal short stature without overt radiologic skeletal anomalies. The third patient, who had only IUGR and short stature, had previously been studied by Kumar et al. (1999). Nagamani et al. (2009) reported 4 patients with interstitial deletions involving chromosome 6q25, all of whom had microcephaly, developmental delay, dysmorphic features, and hearing loss; 2 patients also had agenesis of the corpus callosum. Cytogenetics In a 9-month-old girl with agenesis of the corpus callosum with Probst bundles, born of healthy parents, Pirola et al. (1998) detected a de novo unbalanced karyotype with an approximately 8-cM interstitial deletion on chromosome 6q25 between D6S1496 and D6S437; the final karyotype was 46,XX,del(6)(q25.1q25.3) and the deletion was determined to have arisen on the paternal chromosome 6. Kumar et al. (1999) studied a 3.3-year-old girl with intrauterine growth retardation and short stature who was otherwise developmentally normal, who had a karyotype of 46,XX,del(6)(q23.3q24.2). FISH analysis showed that the approximately 4- to 5-Mb deletion breakpoints lay between markers WI-5023 and D6S1024. Microsatellite analysis demonstrated that the de novo deletion was paternal in origin. In a 6.5-year-old girl with VSD, short stature, facial dysmorphism, and psychomotor delay, Bisgaard et al. (2006) detected an apparently balanced paracentric inversion of chromosome 4 inherited from the father (46,XX,inv(4)(q11.2q13)pat); metaphase CGH revealed a de novo interstitial deletion of chromosome 6q25, with a real-time PCR estimate of 6.88 to 7.21 Mb. In an 8-year-old girl with ASD, short stature, facial dysmorphism, and psychomotor delay, Caselli et al. (2007) performed array CGH and detected an approximately 2.6-Mb chromosome 6 interstitial deletion (46,XX,del(6)(q24.3q25.1)), with the proximal breakpoint located between 148.70 Mb and 148.78 Mb and the distal breakpoint between 151.28 Mb and 151.35 Mb. Noting the phenotypic similarities between this patient and the girl previously reported by Bisgaard et al. (2006) with a 7-Mb overlapping deletion, Caselli et al. (2007) concluded that this may represent a specific new 6q25 interstitial deletion syndrome. Caselli et al. (2007) stated that the overlapping critical deleted region contained 22 genes. Osoegawa et al. (2008) analyzed DNA samples from individuals born with cleft lip and cleft palate and identified a nonsyndromic patient with unilateral right cleft lip and cleft palate who had a de novo 3.2-Mb deletion at chromosome 6q25.1-q25.2. The proximal breakpoint of the deletion was within a 43-kb region between markers rs17855719 and rs851997, and the distal breakpoint was localized to a 120-kb region between rs1106753 and rs2273898. The microdeletion was determined to have arisen on the paternal chromosome 6. Osoegawa et al. (2008) noted that there were 11 genes in the deleted region. In 3 patients with intrauterine growth retardation and short stature who had de novo paternally derived interstitial deletions of chromosome 6q, Nowaczyk et al. (2008) performed FISH analysis and narrowed the region of common deletion to a 1-Mb interval between 145.9 and 146.9 Mb from the 6p telomere at 6q24.3, a segment containing 5 described genes, none of which had known function involving pre- or postnatal growth. Two of the patients, who exhibited the additional findings of early developmental delay, congenital heart defects, and a facial appearance that was strikingly similar, had deletions that extended more distally than that of the third patient, who had previously been studied by Kumar et al. (1999). In 4 patients with microcephaly, developmental delay, dysmorphic features, and hearing loss, 2 of whom also had agenesis of the corpus callosum, Nagamani et al. (2009) performed array CGH followed by high-resolution nucleotide array and detected deletions ranging from 3.77 to 13.81 Mb on chromosome 6q. The commonly deleted 3.52-Mb interval on 6q25.2-q25.3 contains 12 protein-coding genes, all but 1 of which are expressed in the brain. Nagamani et al. (2009) compared the deleted regions in the 2 patients with ACC to those of previously reported patients with ACC and 6q deletions, including the patient described by Pirola et al. (1998), and delimited a critical 3.3-Mb interval for ACC on 6q25.2-q25.3. Thienpont et al. (2010) reviewed the genotype and phenotype data from 12 patients with a chromosomal deletion on 6q, including patients previously reported by Pirola et al. (1998), Kumar et al. (1999), Bisgaard et al. (2006), Caselli et al. (2007), Nowaczyk et al. (2008), and Nagamani et al. (2009), and delineated an 850-kb critical region for congenital heart disease on chromosome 6q25.1. Bioinformatics prioritization of the 5 candidate genes at this locus identified the TAB2 gene (605101) as the top-ranking candidate for a role in congenital heart disease. Molecular Genetics Thienpont et al. (2010) analyzed the TAB2 gene in 402 patients with cardiac outflow tract defects and identified heterozygosity for missense mutations (605101.0001 and 605101.0002) in 2 patients with multiple types of congenital heart disease (614980); neither mutation was found in 658 ethnically matched control chromosomes. In addition, in a family with congenital aortic stenosis and cardiac arrhythmias segregating with a balanced t(2;6)(q21;q25) translocation, previously reported by Bache et al. (2006), Thienpont et al. (2010) performed FISH analysis that localized the 2q21 breakpoint to a 14.2-kb region disrupting the POTEE gene (608914) and the 6q25 breakpoint to a 17-kb region within the first intron, first exon, or promoter region of TAB2. Noting that POTEE is not expressed in the human heart and is variable in copy number in the normal human population, Thienpont et al. (2010) concluded that perturbations and mutations of TAB2 cause congenital heart defects. [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-hydroxybutyric 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	CHROMOSOME 6q24-q25 DELETION SYNDROME	c3150215	24,691	omim	https://www.omim.org/entry/612863	2019-09-22T16:00:27	{"doid": ["0060424"], "omim": ["612863"], "orphanet": ["251056"], "synonyms": ["Del(6)(q25)", "Monosomy 6q25"]}
Kearns-Sayre syndrome (KSS) is a neuromuscular disorder defined by the triad of onset before age 20 years, pigmentary retinopathy (a "salt-and-pepper" pigmentation in the retina that can affect vision, but often leaves it intact), and progressive external ophthalmoplegia (PEO). In addition, affected individuals have at least one of the following: cardiac conduction block, cerebrospinal fluid protein concentration greater than 100 mg/dL, or cerebellar ataxia. Kearns-Sayre syndrome is a mitochondrial DNA (mtDNA) deletion syndrome. It results from abnormalities in the DNA of mitochondria - small rod-like structures found in every cell of the body that produce the energy that drives cellular functions. This and other mitochondrial diseases correlate with specific DNA mutations that cause problems with many of the organs and tissues in the body, resulting in multisystem effects. Treatment for this slowly progressive disorder is generally symptomatic and supportive. [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-hydroxybutyric 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	Kearns-Sayre syndrome	c0022541	24,692	gard	https://rarediseases.info.nih.gov/diseases/6817/kearns-sayre-syndrome	2021-01-18T17:59:37	{"mesh": ["D007625"], "omim": ["530000"], "orphanet": ["480"], "synonyms": ["KSS", "Ophthalmoplegia, pigmentary degeneration of retina, and cardiomyopathy", "Oculocraniosomatic syndrome", "Ophthalmoplegia plus syndrome", "Mitochondrial cytopathy", "Ophthalmoplegia, progressive external, with ragged red fibers", "Chronic progressive external ophthalmoplegia with myopathy", "CPEO with myopathy", "CPEO with ragged red fibers"]}
Macrophagic myofasciitis Other namesMMF SpecialtyHistopathology Pseudomedical diagnosis Macrophagic myofasciitis Pseudomedical diagnosis RisksNocebo This article is part of a series on Alternative medicine General information * Alternative medicine * Alternative veterinary medicine * Quackery (Health fraud) * History of alternative medicine * Rise of modern medicine * Pseudoscience * Antiscience * Skepticism * Skeptical movement * National Center for Complementary and Integrative Health * Terminology of alternative medicine * Therapeutic nihilism Fringe medicine and science * Acupressure * Acupuncture * Alkaline diet * Anthroposophic medicine * Apitherapy * Applied kinesiology * Aromatherapy * Auriculotherapy * Bates method * Black salve * Bodywork * Bonesetter * Bowen technique * Breathwork * Fake COVID-19 treatments * Cancer treatments * Charcoal cleanse * Chiropractic * Chiropractic treatment techniques * Vertebral subluxation * Christian Science * Chromotherapy * Colon cleansing * Coffee enema * Colorpuncture * Colloidal silver * Craniosacral therapy * Crystal healing * Cupping therapy * Dental amalgam controversy * Detoxification * Foot detox * Ear candling * Energy medicine * Esoteric energy * Therapeutic touch * Fabunan Antiviral Injection * Facilitated communication * Feldenkrais Method * Functional medicine * Hair analysis * Herbal medicine * Holistic dentistry * Hologram bracelet * Homeopathy * Bach flower remedies * Biological terrain assessment * Hypnotherapy * Iridology * Ionized jewelry * Jilly Juice * Lightning Process * Lymphotherapy * Medical intuitive * Mesmerism * Magnet therapy * Manual therapy * Megavitamin therapy * Mind–body interventions * MMS * Myofascial release * NAET * Naturopathy * Oil pulling * Orgone * Orthomolecular medicine * Orthopathy * Osteomyology * Osteopathy * Ozone therapy * Parapsychology * Phrenology * Psychic surgery * Psychodermatology * Radionics * Rapid prompting method * RBOP * Reiki * Reflexology * Rolfing * Scientific racism * ThetaHealing * Thought Field Therapy * Urophagia * Vaginal steaming * Vision therapy * Vitalism * Young blood transfusion * Zero balancing Conspiracy theories (list) * Big Pharma conspiracy theory * HIV/AIDS denialism * OPV AIDS hypothesis * Anti-vaccination * Vaccines and autism * MMR vaccine and autism * Water fluoridation controversy * GMO conspiracy theories * Misinformation related to the COVID-19 pandemic Classifications * Alternative medical systems * Mind–body intervention * Biologically-based therapy * Manipulative methods * Energy therapy Traditional medicine * African * Muti * Southern Africa * Ayurveda * Ayurvedic acupressure * Dosha * Maharishi Vedic Approach to Health * Balneotherapy * Brazilian * Bush medicine * Cambodian * Chinese * Blood stasis * Chinese herbology * Dit Da * Gua sha * Gill plate trade * Meridian * Moxibustion * Pressure point * Qi * San Jiao * Tui na * Zang-fu * Chumash * Curandero * Faith healing * Iranian * Jamu * Kambo * Japanese * Korean * Mien Shiang * Mongolian * Prophetic medicine * Shamanism * Shiatsu * Siddha * Sri Lankan * Thai massage * Tibetan * Unani * Vietnamese Diagnoses * Adrenal fatigue * Aerotoxic syndrome * Candida hypersensitivity * Chronic Lyme disease * Electromagnetic hypersensitivity * Heavy legs * Leaky gut syndrome * Multiple chemical sensitivity * Wilson's temperature syndrome * v * t * e Macrophagic myofasciitis (MMF) is a histopathological finding involving inflammatory microphage formations with aluminium-containing crystal inclusions and associated microscopic muscle necrosis in biopsy samples of the deltoid muscle. Based on the presence of aluminium and the common practice of administering vaccines into the deltoid, it has been proposed that the abnormalities are a result of immunisation with aluminium adjuvant-containing vaccines. The findings were observed in a minority of persons being evaluated for "diffuse myalgias, arthralgias or muscle weakness" who underwent deltoid muscle biopsies. The individuals had a history of receiving aluminium-containing vaccines, administered months to several years prior to observation of MMF histopathology, however this link is tenuous and unsustainable. [1][2] It has been subsequently proposed that macrophagic myofasciitis is in fact a systemic disorder where various diseases develop in association and as consequence of vaccination with aluminium-containing vaccines in susceptible individuals, however, the World Health Organization has concluded that "[t]here is no evidence to suggest that MMF is a specific illness", and that "[t]he current evidence neither establishes nor excludes a generalized disorder affecting other organs."[1][2] ## Description[edit] MMF was first described in 1998 by a consortium of French myopathologists as an emerging condition of unknown cause characterised by a defining lesion observed upon muscle biopsy. MMF was identified in patients affected by myalgia and fatigue. MMF was judged a consequence of a switch to intramuscular injection and the deltoid muscle being the preferred site of both vaccine injection and biopsy in France (while other sites were preferred for biopsy in other countries) and the commencement of HBV vaccination in French adults. Similar lesions could be detected in babies and children upon biopsy of the quadriceps as this is the site of vaccine administration in this group. MMF could also be experimentally reproduced in animals, with regression over time. It has been proposed that in a small portion of the population, vaccination results in persistence of aluminium-compound particles in macrophages in association with myalgia, fatigue, and cognitive dysfunction. A MMF disorder has been compared to autoimmune/inflammatory syndrome induced by adjuvants.[3][4] A case-controlled study in France found those with MMF were more likely to have received aluminium-containing vaccines. MMF was also associated with fatigue “and related functional limitations", with fatigue more common in the beginning of the malady that led to the biopsy. However, neither myalgia, arthralgia, nor any other symptoms or risk factors were identified as specific to those with MMF.[2] Many of those with MMF had previously been treated for malaria with chloroquine or hydroxychloroquine.[5] As of 2009, with few exceptions, MMF had only been reported in France.[1] ## References[edit] 1. ^ a b c "WHO \| Macrophagic myofasciitis and aluminium-containing vaccines". WHO. Retrieved 2019-08-14. 2. ^ a b c "WHO \| Questions and Answers about macrophagic myofasciitis (MMF)". WHO. Retrieved 2019-08-16. 3. ^ Gherardi RK, Authier FJ (February 2012). "Macrophagic myofasciitis: characterization and pathophysiology". Lupus. 21 (2): 184–9. doi:10.1177/0961203311429557. PMC 3623725. PMID 22235051. 4. ^ "WHO \| Questions and Answers about macrophagic myofasciitis (MMF)". WHO. Retrieved 2019-08-16. 5. ^ medicinenet.com, "Definition of Macrophagic myofasciitis". Accessed August 22, 2013. This muscle 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-hydroxybutyric 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	Macrophagic myofasciitis	c2931639	24,693	wikipedia	https://en.wikipedia.org/wiki/Macrophagic_myofasciitis	2021-01-18T18:41:22	{"gard": ["176"], "mesh": ["C537829"], "umls": ["C2931639"], "orphanet": ["592"], "wikidata": ["Q3331434"]}
Neonatal acne Other namesAcne infantum, Acne neonatorum,[1] and Neonatal cephalic pustulosis[2] An infant with neonatal acne on the face, especially the forehead SpecialtyDermatology Neonatal acne, often called neonatal cephalic pustulosis, (not to be confused with "Benign cephalic histiocytosis") is an acneiform eruption that occurs in newborns or infants, and is often seen on the nose and adjacent portions of the cheeks.[3] The main cause of this condition is not known, but it could be due to the increased sensitivity of the infant's sebaceous glands to maternal hormones during pregnancy which also leads to a variety of skin conditions in the newborn.[medical citation needed] Typically, it peaks at around 2 months and rarely needs treatment. Sometimes gels or ointments are given.[4] ## See also[edit] * Acne aestivalis * Infantile acne * List of cutaneous conditions ## References[edit] 1. ^ Holm EA, Jemec GB (December 2000). "[Acne neonatorum/acne infantum]". Ugeskrift for Læger (in Danish). 162 (50): 6856–7. PMID 11187144. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.[page needed] 3. ^ Freedberg, Irwin M.; Eisen, Arthur Z.; Wolff, Klauss; Austen, K. Frank; Goldsmith, Lowell A.; Katz, Stephen, eds. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. p. 648. ISBN 978-0-07-138076-8. 4. ^ "Hormonal effects in newborns: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2018-11-20. ## Further reading[edit] * Katsambas AD, Katoulis AC, Stavropoulos P (February 1999). "Acne neonatorum: a study of 22 cases". Int. J. Dermatol. 38 (2): 128–30. doi:10.1046/j.1365-4362.1999.00638.x. PMID 10192162. * O'Connor NR, McLaughlin MR, Ham P (January 2008). "Newborn skin: Part I. Common rashes". Am Fam Physician. 77 (1): 47–52. PMID 18236822. 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-hydroxybutyric 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	Neonatal acne	c0263437	24,694	wikipedia	https://en.wikipedia.org/wiki/Neonatal_acne	2021-01-18T18:51:05	{"umls": ["C0263437"], "icd-10": ["L70.4"], "wikidata": ["Q342001"]}
Since the early 1980s, a resurgence of severe, invasive infections by group A streptococci (GAS; Streptococcus pyogenes) has occurred. The reemergence of streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) has been reported in several countries. Both are rapidly progressive invasive diseases that are associated with high mortality rate, ranging from 30 to 80% despite prompt antibiotic therapy and debridement. A particular subclone of the M1 serotype (M1T1) has persisted for more than 20 years as the most prevalent strain isolated from these infections. Release of inflammatory cytokines triggered by streptococcal superantigens has a pivotal role in invasive streptococcal disease. However, individuals infected with the same strain can develop different manifestations. Kotb et al. (2002) reported that the immunogenetics of the host influence the outcome of invasive streptococcal infection. They found that specific human leukocyte antigen (HLA) class II haplotypes conferred strong protection from severe systemic disease, whereas others increased the risk of severe disease. Patients with the DRB11501 (142857)/DQB10602 (604305) haplotype mounted significantly reduced responses and were less likely to develop severe systemic disease. Kotb et al. (2002) proposed that class II HLA allelic variation contributes to differences in the severity of invasive streptococcal infections through the ability of distinct HLA alleles/haplotypes to regulate cytokine responses triggered by streptococcal superantigens. [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-hydroxybutyric 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	STREPTOCOCCUS, GROUP A, SEVERITY OF INFECTION BY	c1846298	24,695	omim	https://www.omim.org/entry/607395	2019-09-22T16:09:18	{"omim": ["607395"]}
Genetic factors have been shown to be important in differences in the red cell-plasma lithium concentration ratio (Dorus et al., 1975). Ostrow et al. (1978) concluded that one group of manic-depressive patients have a heritable disorder of lithium transport across red cell membranes. Specifically, they concluded that the defect is in lithium-sodium counterflow. In 1 family that they diagrammed in a pedigree, the father and a son and 2 daughters from a sibship of 8 showed the defect. Neuro \- Manic-depressive illness subset Lab \- Red cell-plasma lithium transport 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-hydroxybutyric 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	LITHIUM TRANSPORT	c1835356	24,696	omim	https://www.omim.org/entry/152420	2019-09-22T16:38:48	{"omim": ["152420"]}
A number sign (#) is used with this entry because of evidence that spastic paraplegia-33 (SPG33) is caused by heterozygous mutation in the ZFYVE27 gene (610243) on chromosome 10q24. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600). Clinical Features Mannan et al. (2006) described a 5-generation German family with hereditary spastic paraplegia. Clinical features of affected members suggested that theirs was a pure form of SPG. The index patient had had pes equinus for many years when she noticed a gait disorder at age 50 years. She then manifested hyperreflexia and spasticity of the lower limbs, a positive Babinski sign, and ankle clonus. Sensitivity was normal. She later required a wheelchair and ultimately became bedridden. Her daughter and son also had pes equinus, spasticity of the legs, and gait disorder. Cognitive deficits or additional neurologic symptoms were not present. Molecular Genetics In affected members of German family segregating spastic paraplegia, Mannan et al. (2006) identified a heterozygous missense mutation in the ZFYVE27 gene (G191V; 610243.0001). The ZFYVE27 gene encodes a FYVE-finger domain protein that interacts with spastin (604277), the protein mutant in spastic paraplegia-4 (182601). An in vivo immunoprecipitation assay showed that interaction of the mutant ZFYVE27 protein with spastin was severely impaired. Two spastic paraplegia loci map in the vicinity of the ZFYVE27 gene on 10q24.2: SPG9 (601162) on 10q23.3-q24.2, and SPG27 (609041) within 10q22.1-q24.1. Mannan et al. (2006) excluded the ZFYVE27 gene from both of these loci. Thus, the subtype of spastic paraplegia caused by mutation in the ZFYVE27 gene was designated SPG33. Martignoni et al. (2008) commented that they found no difference in the ability of wildtype or G191V mutant protrudin to extend neurites in cellular functional expression studies. The G191V-mutant protein was also found to interact with Rab11-GDP (605570) and spastin (604277), indicating that the mutation did not lead to loss of function. They stated that G191V (rs35077384) had been identified as a SNP in several populations, with an allele frequency ranging from 0.008 to 0.067, thus casting doubt on its pathogenicity. Martignoni et al. (2008) proposed that SPG33 be removed from the list of SPG genes. Mannan (2008) replied that their study showed a decreased interaction between G191V-mutant protrudin and spastin and explained that discrepancies could be due to the different assays used or the variable effect of G191V-mutant protrudin in different ethnic populations. INHERITANCE \- Autosomal dominant SKELETAL Feet \- Pes equinus NEUROLOGIC Central Nervous System \- Lower limb spasticity \- Lower limb weakness \- Spastic gait \- Hyperreflexia \- Extensor plantar responses \- Ankle clonus MISCELLANEOUS \- Adult onset of gait abnormalities MOLECULAR BASIS \- Caused by mutation in the zinc finger FYVE-domain containing protein-27 gene (ZFYVE27, 610243.0001 ) ▲ 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-hydroxybutyric 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	SPASTIC PARAPLEGIA 33, AUTOSOMAL DOMINANT	c1853251	24,697	omim	https://www.omim.org/entry/610244	2019-09-22T16:04:48	{"mesh": ["C565214"], "omim": ["610244"]}
Cerebral laceration SpecialtyNeurosurgery A cerebral laceration is a type of traumatic brain injury that occurs when the tissue of the brain is mechanically cut or torn.[1] The injury is similar to a cerebral contusion; however, according to their respective definitions, the pia-arachnoid membranes are torn over the site of injury in laceration and are not torn in contusion.[2][3] Lacerations require greater physical force to cause than contusions,[1] but the two types of injury are grouped together in the ICD-9 and ICD-10 classification systems. ## Contents * 1 Signs and symptoms * 1.1 Associated injuries * 2 Diagnosis * 3 Prognosis * 4 References * 5 External links ## Signs and symptoms[edit] A fifth of people with cerebral lacerations have a lucid interval and no significant changes in level of consciousness.[2] The level of consciousness decreases as the laceration bleeds and blood begins to build up within the skull.[2] ### Associated injuries[edit] Cerebral lacerations usually accompany other brain injuries and are often found with skull fractures on both sides of the head.[2] Frequently occurring in the same areas as contusions, lacerations are particularly common in the inferior frontal lobes and the poles of the temporal lobes.[1] When associated with diffuse axonal injury, the corpus callosum and the brain stem are common locations for laceration.[1] Lacerations are very common in penetrating and perforating head trauma and frequently accompany skull fractures; however, they may also occur in the absence of skull fracture.[1] Lacerations, which may result when brain tissue is stretched, are associated with intraparenchymal bleeding (bleeding into the brain tissue).[1] ## Diagnosis[edit] This section is empty. You can help by adding to it. (November 2018) ## Prognosis[edit] A cerebral laceration with large amounts of blood apparent on a CT scan is an indicator of poor prognosis.[2] The progression and course of complications (health effects that result from but are distinct from the injury itself) do not appear to be affected by a cerebral laceration's location or a mass effect it causes.[2] ## References[edit] 1. ^ a b c d e f Hardman JM, Manoukian A (2002). "Pathology of Head Trauma". Neuroimaging Clinics of North America. 12 (2): 175–187, vii. doi:10.1016/S1052-5149(02)00009-6. PMID 12391630. 2. ^ a b c d e f Granacher RP (2007). Traumatic Brain Injury: Methods for Clinical & Forensic Neuropsychiatric Assessment, Second Edition. Boca Raton: CRC. p. 26. ISBN 0-8493-8138-X. Retrieved 2008-07-06. 3. ^ Gennarelli GA, Graham DI (2005). "Neuropathology". In Silver JM, McAllister TW, Yudofsky SC (eds.). Textbook Of Traumatic Brain Injury. Washington, DC: American Psychiatric Association. p. 29. ISBN 1-58562-105-6. Retrieved 2008-06-10. ## External links[edit] Classification D * ICD-10: S06.2, S06.3 * ICD-9-CM: 851 * 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-hydroxybutyric 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	Cerebral laceration	c0272945	24,698	wikipedia	https://en.wikipedia.org/wiki/Cerebral_laceration	2021-01-18T18:48:32	{"mesh": ["D001930"], "umls": ["C0272945"], "icd-9": ["851"], "icd-10": ["S06.3", "S06.2"], "wikidata": ["Q5064100"]}
Mosaic trisomy 9 is a rare chromosomal anomaly syndrome, with a highly variable phenotype, principally characterized by intellectual disability, growth and developmental delay, facial dysmorphism (incl. microphthalmia, deep-set eyes, low-set, malformed ears, bulbous nose, high-arched palate, micrognathia) and congenital heart defects (e.g. ventricular septal defect), as well as urogenital (e.g. hypoplastic genitalia, cryptorchidism), skeletal (congenital joint dislocations or hyperflexion, scoliosis/kyphosis) and central nervous system anomalies (hydrocephalus, Dandy-Walker malformation). Pigmentary mosaic skin lesions along the lines of Blaschko are also frequently 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-hydroxybutyric 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	Mosaic trisomy 9	c2930908	24,699	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99776	2021-01-23T17:17:47	{"gard": ["43"], "mesh": ["C535454"], "umls": ["C2930908"], "icd-10": ["Q92.1"], "synonyms": ["Mosaic trisomy chromosome 9", "Trisomy 9 mosaicism"]}

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