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A number sign (#) is used with this entry because familial cold autoinflammatory syndrome-1 (FCAS1) is caused by heterozygous mutation in the NLRP3 gene (606416), encoding cryopyrin, on chromosome 1q44. Description Familial cold autoinflammatory syndrome is characterized clinically by recurrent attacks of a maculopapular rash associated with arthralgias, myalgias, fever and chills, and swelling of the extremities after exposure to cold. Despite the first description of 'cold urticaria' (Kile and Rusk, 1940) the rash in most patients is nonpruritic and nonurticarial. Rarely, some patients may also develop late-onset renal amyloidosis (Hoffman et al., 2000). Overlapping syndromes also caused by mutation in the NLRP3 gene include Muckle-Wells syndrome (CAPS2; 191900), which has a high frequency of amyloidosis and late-onset sensorineural deafness, and chronic neurologic cutaneous and articular syndrome (CINCA, CAPS3; 607115), which shows earlier onset and a more severe phenotype. ### Genetic Heterogeneity of Familial Cold Autoinflammatory Syndrome See also FCAS2 (611762), caused by mutation in the NLRP12 gene (609648) on chromosome 19q13; FCAS3 (614468), caused by mutation in the PLCG2 gene (600220) on chromosome 16q23; and FCAS4 (616115), caused by mutation in the NLRC4 gene (606831) on chromosome 2p22. Clinical Features Kile and Rusk (1940) first described familial cold urticaria. The proband in their family developed urticarial wheals, pain and swelling of joints, chills, and fever after exposure to the cold. Witherspoon et al. (1948) also described familial urticaria resulting from cold exposure. Doeglas (1973) reported a large kindred with 10 affected individuals. One of the 10 had leukocytosis during an attack. Derbes and Coleman (1972) reviewed the literature on familial cold urticaria and described several similar disorders to provide a basis for differential diagnosis. Ormerod et al. (1993) studied 8 of 20 affected members from a 46-member affected family. Urticaria was maximal in early adult life. Three patients responded favorably to treatment with stanozolol. The authors suggested that this disorder, like hereditary angioedema (HAE; 106100), involves deficiency of an inhibitory factor. Zip et al. (1993) reported a large and extensively affected family. They found reports of 10 pedigrees, 7 from the United States and 1 each from Holland, France, and South Africa. Their own family showed transmission through 6 generations and by inference 8 generations. The onset of the disorder was in infancy. The onset of symptoms after cold challenge was delayed (one-half to 6 hours). Zip et al. (1993) tabulated the differences between idiopathic acquired cold urticaria and familial cold urticaria. In the familial form, the lesions tend to be erythematous rather than urticarial and to be accompanied by fever, chills, arthralgias, and stiffness. Leukocytosis is present, whereas it is absent in acquired cold urticaria, duration of the episodes is much longer, passive transfer is negative, and mast cell degranulation is absent. Mapping By analyzing 5 families with familial cold urticaria, Hoffman et al. (2000) identified linkage to 1q44. They found a 2-point maximum lod score of 8.13 at recombination fraction 0.0 for marker D1S2836; multipoint linkage identified a maximum lod score of 10.92 in the same region; and haplotype analysis defined a 10.5-cM region between D1S423 and D1S2682. Hoffman et al. (2000) suggested that familial cold urticaria and Muckle-Wells syndrome are allelic disorders. The linkage mapping by Hoffman et al. (2000) was consistent with that presented in abstract form by Jung et al. (1996) in 2 FCU families. Jung et al. (1996) had also suggested that familial cold urticaria and Muckle-Wells syndrome are probably allelic. Molecular Genetics In 3 unrelated families with familial cold autoinflammatory syndrome, Hoffman et al. (2001) found 3 missense mutations in exon 3 of the CIAS1 gene (606416.0001-606416.0003). The families had been described by Shepard (1971), Vlagopoulos et al. (1975), and Wanderer (1979), respectively. In 1 family with Muckle-Wells syndrome, Hoffman et al. (2001) found a mutation in the CIAS1 gene (606416.0004), demonstrating that these 2 syndromes are indeed allelic. Nomenclature Because of genetic evidence and phenotypic similarity to hereditary periodic fevers (e.g., familial Mediterranean fever, 249100), Hoffman et al. (2001) suggested 'familial cold autoinflammatory syndrome' as a more accurate and preferable name for the disorder previously referred to as 'familial cold urticaria.' INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Conjunctivitis GENITOURINARY Kidneys \- Renal amyloidosis, late-onset (uncommon) SKELETAL \- Arthralgia, episodic SKIN, NAILS, & HAIR Skin \- Maculopapular rash, episodic \- Rash may or may not be pruritic MUSCLE, SOFT TISSUES \- Myalgia, episodic \- Swelling of the extremities, episodic NEUROLOGIC Central Nervous System \- Headache, episodic METABOLIC FEATURES \- Fever, episodic LABORATORY ABNORMALITIES \- Polymorphonuclear leukocytosis, episodic \- Increased serum C-reactive protein, episodic MISCELLANEOUS \- Onset in infancy or early childhood \- Episodes occur 30 minutes to 3 hours after exposure to cold \- Episodes usually last 1 to 2 days \- See also Muckle-Wells syndrome ( 191900 ), an allelic disorder with overlapping features MOLECULAR BASIS \- Caused by mutation in the NLR family, pyrin-domain containing 3 gene (NLRP3, 606416.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	FAMILIAL COLD AUTOINFLAMMATORY SYNDROME 1	c0343068	26,900	omim	https://www.omim.org/entry/120100	2019-09-22T16:43:06	{"doid": ["0090062"], "mesh": ["D056587"], "omim": ["120100"], "icd-10": ["M04.2"], "orphanet": ["47045"], "synonyms": ["Alternative titles", "FCAS", "COLD HYPERSENSITIVITY", "COLD-INDUCED AUTOINFLAMMATORY SYNDROME, FAMILIAL", "COLD URTICARIA, FAMILIAL", "CRYOPYRIN-ASSOCIATED PERIODIC SYNDROME 1"]}
Acute, contagious viral disease of swine caused by swine vesicular disease virus Swine vesicular disease virus Virus classification (unranked): Virus Realm: Riboviria Kingdom: Orthornavirae Phylum: Pisuviricota Class: Pisoniviricetes Order: Picornavirales Family: Picornaviridae Genus: Enterovirus Species: Enterovirus B Strain: Swine vesicular disease virus Swine vesicular disease (SVD) is an acute, contagious viral disease of swine caused by swine vesicular disease virus, an Enterovirus.[1] It is characterized by fever and vesicles with subsequent ulcers in the mouth and on the snout, feet, and teats. The pathogen is relatively resistant to heat, and can persist for a long time in salted, dried, and smoked meat products.[2] Swine vesicular disease does not cause economically important disease, but is important due to its similarity to foot-and-mouth disease.[3] ## Contents * 1 Transmission * 2 Clinical signs * 3 Prevention and control * 4 History * 5 References ## Transmission[edit] Swine vesicular disease is most commonly brought into a herd by the introduction of a subclinically infected pig.[2] The disease can be transmitted in feed containing infected meat scraps,[4] or by direct contact with infected feces (such as in an improperly cleaned truck). ## Clinical signs[edit] After an incubation period up to 7 days, the signs associated with swine vesicular disease occur.[5] The first sign is a transient mild fever.[5] Other signs include: * Vesicles in the mouth and on the snout and feet * Lameness and an unsteady gait, shivering, and jerking–type leg movements * Ruptured vesicles can cause ulcers on limbs and feet, and foot pads may be loosened. Young animals are more severely affected. Recovery often occurs within a week. Mortality is negligible. Swine vesicular disease has the same clinical signs as foot-and-mouth disease, and can only be diagnosed by laboratory testing.[4] ## Prevention and control[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (July 2017) (Learn how and when to remove this template message) No vaccine exists for SVD. Prevention measures are similar to those for foot-and-mouth disease: controlling animals imported from infected areas, sanitary disposal of garbage from international aircraft and ships, and thorough cooking of garbage. Infected animals should be placed in strict quarantine. Eradication measures for the disease include quarantining infected areas, depopulation and disposal of infected and contact pigs, and cleaning and disinfecting contaminated premises. ## History[edit] Swine vesicular disease was first identified in Italy in 1966.[6] In 1971, an outbreak occurred in Hong Kong,[6] and the disease was subsequently found other countries in Europe and Asia.[4] ## References[edit] 1. ^ "Genus: Enterovirus" (html). International Committee on Taxonomy of Viruses. Retrieved 21 August 2019. "Swine vesicular disease virus is a variant of coxsackievirus B5 and causes a vesicular disease in pigs clinically indistinguishable from foot-and-mouth disease (genus Aphthovirus) and vesicular disease in pigs caused by Seneca Valley virus (genus Senecavirus)." 2. ^ a b "Technical disease card: Swine vesicular disease" (PDF). World Organisation for Animal Health. 2013. Retrieved 2017-07-16. 3. ^ Maclachlan, NJ; Dubovi, EJ, eds. (2010). "Swine vesicular disease virus". Fenner's Veterinary Virology (5th ed.). Academic Press. pp. 489–90. ISBN 9780128011706. 4. ^ a b c Murphy, FA; Gibbs, PJ; Horzinek, MC; Studdert, SJ (1999). "Swine vesicular disease". Veterinary virology (3rd ed.). San Diego: Academic Press. p. 523. ISBN 9780080552033. 5. ^ a b Quinn, PJ; Markey, BK; Leonard, FC; Hartigan, P; Fanning, S; Fitzpatrick, ES (2011). Veterinary Microbiology and Microbial Disease (2nd ed.). Hoboken: John Wiley & Sons. p. 685. ISBN 9781118251164. 6. ^ a b Mahy, Brian W.J. (2009). "Swine vesicular disease virus (SVDV)". The dictionary of virology (4th ed.). Amsterdam: Elsevier/Academic Press. p. 459. ISBN 9780080920368. Wikisource has original text related to this article: Diseases of Swine (8th edition)/Chapters 25 Taxon identifiers * Wikidata: Q47400772 * NCBI: 12075 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Swine vesicular disease	c0039010	26,901	wikipedia	https://en.wikipedia.org/wiki/Swine_vesicular_disease	2021-01-18T18:48:38	{"mesh": ["D013555"], "wikidata": ["Q662016"]}
A number sign (#) is used with this entry because of evidence that myopia-21 (MYP21) is caused by heterozygous mutation in the ZNF644 gene (614159) on chromosome 1p22. Description Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004). For a discussion of genetic heterogeneity of susceptibility to myopia, see 160700. Clinical Features Shi et al. (2011) studied 6 patients from a 5-generation Han Chinese family segregating autosomal dominant severe high myopia. (High myopia is defined as a spherical refractive error greater than or equal to -6.00 diopters.) Disease onset was at 3 to 4 years of age, with all affected individuals developing high myopia by age 7 years. Three elderly patients showed typical fundus features of high myopia, with thinning of the retinal pigment epithelium and the choriocapillaris that resulted in the so-called 'tigroid' or 'tessellated' appearance of the fundus. Inheritance The transmission pattern in the Han Chinese family segregating high myopia reported by Shi et al. (2011) was consistent with autosomal dominant inheritance. Molecular Genetics In a 5-generation Han Chinese family segregating autosomal dominant high myopia, Shi et al. (2011) performed exome sequencing and segregation analysis and identified a missense mutation in the ZNF644 gene (S672G; 614159.0001). A lod score of 3.19 was obtained (theta = 0.0) for autosomal dominant inheritance with full penetrance and 0.0001 for the disease allele frequency. Analysis of ZNF644 in an additional 300 unrelated sporadic Han Chinese patients with high myopia revealed 5 heterozygous mutations in 11 patients, respectively (see, e.g., 614159.0002-614159.0003), that were not found in 600 ethnically matched controls . By Sanger sequencing, Tran-Viet et al. (2012) screened for mutations in the ZNF644 gene in a cohort of 131 U.S. patients with high-grade myopia. In 2 individuals, one Caucasian and the other African American, they identified a heterozygous mutation (T242M and E274V, respectively). The variants were not found in 1,344 and 100 ethnically matched chromosomes, respectively; however, due to lack of additional family members for both individuals, segregation analysis was not possible. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- High myopia, severe \- Tigroid appearance of fundus (in some patients) \- Tesselated appearance of fundus (in some patients) \- Myopic conus (in some patients) MISCELLANEOUS \- Onset of disease before 7 years of age MOLECULAR BASIS \- Caused by mutation in the zinc finger protein 644 gene (ZNF644, 614159.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MYOPIA 21, AUTOSOMAL DOMINANT	c3279997	26,902	omim	https://www.omim.org/entry/614167	2019-09-22T15:56:15	{"omim": ["614167"]}
Aicardi syndrome is a disorder that occurs almost exclusively in females. It is characterized by three main features that occur together in most affected individuals. People with Aicardi syndrome have absent or underdeveloped tissue connecting the left and right halves of the brain (agenesis or dysgenesis of the corpus callosum). They have seizures beginning in infancy (infantile spasms), which tend to progress to recurrent seizures (epilepsy) that can be difficult to treat. Affected individuals also have chorioretinal lacunae, which are defects in the light-sensitive tissue at the back of the eye (retina). People with Aicardi syndrome often have additional brain abnormalities, including asymmetry between the two sides of the brain, brain folds and grooves that are small in size or reduced in number, cysts, and enlargement of the fluid-filled cavities (ventricles) near the center of the brain. Some have an unusually small head (microcephaly). Most affected individuals have moderate to severe developmental delay and intellectual disability, although some people with this disorder have milder disability. In addition to chorioretinal lacunae, people with Aicardi syndrome may have other eye abnormalities such as small or poorly developed eyes (microphthalmia) or a gap or hole (coloboma) in the optic nerve, a structure that carries information from the eye to the brain. These eye abnormalities may cause blindness in affected individuals. Some people with Aicardi syndrome have unusual facial features including a short area between the upper lip and the nose (philtrum), a flat nose with an upturned tip, large ears, and sparse eyebrows. Other features of this condition include small hands, hand malformations, and spinal and rib abnormalities leading to progressive abnormal curvature of the spine (scoliosis). They often have gastrointestinal problems such as constipation or diarrhea, gastroesophageal reflux, and difficulty feeding. The severity of Aicardi syndrome varies. Some people with this disorder have very severe epilepsy and may not survive past childhood. Less severely affected individuals may live into adulthood with milder signs and symptoms. ## Frequency Aicardi syndrome is a very rare disorder. It occurs in about 1 in 105,000 to 167,000 newborns in the United States. Researchers estimate that there are approximately 4,000 affected individuals worldwide. ## Causes The cause of Aicardi syndrome is unknown. Because it occurs almost exclusively in females, researchers believe that it is probably the result of a mutation in a gene on the X chromosome. People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Genes on these chromosomes are also involved in other functions in the body. Females typically have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY). Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, so that each X chromosome is active in about half the body's cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation. Skewed X-inactivation sometimes occurs when there is a severe gene mutation in one of the X chromosomes in each cell. Because the cells where this chromosome is active will not be able to survive as well, X-inactivation will appear to be skewed. Skewed X-inactivation has been identified in girls with Aicardi syndrome, further supporting the idea that the disorder is caused by a mutation in a gene on the X chromosome. However, this gene has not been identified, and it is unknown how the genetic change that causes Aicardi syndrome results in the various signs and symptoms of this disorder. ## Inheritance Pattern Nearly all known cases of Aicardi syndrome are sporadic, which means that they are not passed down through generations and occur in people with no history of the disorder in their family. The disorder is believed to result from new gene mutations. Aicardi syndrome is classified as an X-linked dominant condition. While the gene associated with this disorder is not known, it is believed to be located on the X chromosome. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell is nearly always lethal very early in development, so almost all babies with Aicardi syndrome are female. However, a few affected males with an extra copy of the X chromosome in each cell (47,XXY) have been identified. Males with a 47,XXY chromosome pattern also have a condition called Klinefelter syndrome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Aicardi syndrome	c0175713	26,903	medlineplus	https://medlineplus.gov/genetics/condition/aicardi-syndrome/	2021-01-27T08:25:23	{"gard": ["1535"], "mesh": ["D058540"], "omim": ["304050"], "synonyms": []}
Semantic dementia (SD) is a form of frontotemporal dementia (FTD; see this term), characterized by the progressive, amodal and profound loss of semantic knowledge (combination of visual associative agnosia, anomia, surface dyslexia or dysgraphia and disrupted comprehension of word meaning) and behavioral abnormalities, attributable to the degeneration of the anterior temporal lobes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Semantic dementia	c0338462	26,904	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100069	2021-01-23T17:14:58	{"gard": ["10792"], "mesh": ["D057180"], "omim": ["172700", "600274"], "umls": ["C0338462"], "icd-10": ["G31.0"], "synonyms": ["Semantic primary progressive aphasia", "Semantic variant PPA"]}
Mitochondrial neurogastrointestinal encephalopathy syndrome Other namesMNGIE syndrome Structure of thymidine phosphorylase enzyme, the main gene product of the TYMP gene. Mutations in the TYMP gene result in the loss of function of thymidine phosphorylase activity leading to the onset of MNGIE.[1] Mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) is a rare autosomal recessive mitochondrial disease.[2] It has been previously referred to as polyneuropathy, ophthalmoplegia, leukoencephalopathy, and POLIP syndrome.[3] The disease presents in childhood, but often goes unnoticed for decades.[2][4][5] Unlike typical mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations, MNGIE is caused by mutations in the TYMP gene, which encodes the enzyme thymidine phosphorylase.[2][5] Mutations in this gene result in impaired mitochondrial function, leading to intestinal symptoms as well as neuro-ophthalmologic abnormalities.[2][4] A secondary form of MNGIE, called MNGIE without leukoencephalopathy, can be caused by mutations in the POLG gene.[3] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Management * 5 References * 6 External links ## Signs and symptoms[edit] Like other mitochrondrial diseases, MNGIE is a multisystem disorder.[6] MNGIE primarily affects the gastrointestinal and neurological systems. Gastrointestinal symptoms may include gastrointestinal dysmotility, due to inefficient peristalsis, which may result in pseudo-obstruction and cause malabsorption of nutrients.[2][5] Additionally, gastrointestinal symptoms such as borborygmi, early satiety, diarrhea, constipation, gastroparesis, nausea, vomiting, weight loss, and diverticulitis may be present in MNGIE patients.[2] Neurological symptoms may include diffuse leukoencephalopathy, peripheral neuropathy, and myopathy.[2] Ocular symptoms may include retinal degeneration, ophthalmoplegia, and ptosis.[2][5] Those with MNGIE are often thin and experience continuous weight loss. The characteristic thinness of MNGIE patients is caused by multiple factors including inadequate caloric intake due to gastrointestinal symptoms and discomfort, malabsorption of food from bacterial overgrowth due to decreased motility, as well as an increased metabolic demand due to inefficient production of ATP by the mitochondria.[citation needed] ## Genetics[edit] A variety of mutations in the TYMP gene have been discovered that lead to the onset of mitochondrial neurogastrointestinal encephalopathy syndrome.[2] The TYMP gene is a nuclear gene, however, mutations in the TYMP gene affect mitochrondrial DNA and function.[2] Mutations in this gene result in a loss of thymidine phosphorylase activity.[2] Thymidine phosphorylase is the enzymatic product of the TYMP gene and is responsible for breaking down thymidine nucleosides into thymine and 2-deoxyribose 1-phosphate.[2] Without normal thymidine phosphorylase activity, thymidine nucleosides begin to build up in cells.[2] High nucleoside levels are toxic to mitochondrial DNA and cause mutations that lead to dysfunction of the respiratory chain, and thus, inadequate energy production in the cells.[2] These mitochondrial effects are responsible for the symptomatology associated with the disease.[2] ## Diagnosis[edit] Diverticula While the disease manifests early in life in most cases, diagnosis of the disease is often quite delayed.[2][4][5] The symptoms that affected patients present vary, but the most common presenting symptoms are gastrointestinal issues such as nausea, vomiting, abdominal pain, and diarrhea, and neurologic or ocular symptoms such as hearing loss, weakness, and peripheral neuropathy.[4] These gastrointestinal symptoms cause patients with MNGIE to be very thin and experience persistent weight loss and this often leads to MNGIE being misdiagnosed as an eating disorder.[2] These symptoms without presentation of disordered eating and warped body image warrant further investigation into the possibility of MNGIE as a diagnosis.[2] Presentation of these symptoms and lack of disordered eating are not enough for a diagnosis. Radiologic studies showing hypoperistalsis, large atonic stomach, dilated duodenum, diverticula, and white matter changes are required to confirm the diagnosis.[4] Elevated blood and urine nucleoside levels are also indicative of MNGIE syndrome.[2] Abnormal nerve conduction as well as analysis of mitochondria from liver, intestines, muscle, and nerve tissue can also be used to support the diagnosis.[2][4] ## Management[edit] A successful treatment for MNGIE has yet to be found, however, symptomatic relief can be achieved using pharmacotherapy and celiac plexus neurolysis.[4] Celiac plexus neurolysis involves interrupting neural transmission from various parts of the gastrointestinal tract. By blocking neural transmission, pain is relieved and gastrointestinal motility increases.[4] Stem cell therapies are currently being investigated as a potential cure for certain patients with the disease, however, their success depends on physicians catching the disease early before too much organ damage has occurred.[2] ## References[edit] 1. ^ "EMBL European Bioinformatics Institute". www.ebi.ac.uk. Retrieved 2015-12-03. 2. ^ a b c d e f g h i j k l m n o p q r s t u Garone, Caterina; Tadesse, Saba; Hirano, Michio (2011-11-01). "Clinical and genetic spectrum of mitochondrial neurogastrointestinal encephalomyopathy". Brain. 134 (11): 3326–3332. doi:10.1093/brain/awr245. ISSN 0006-8950. PMC 3212717. PMID 21933806. 3. ^ a b "OMIM Entry - # 603041 - MITOCHONDRIAL DNA DEPLETION SYNDROME 1 (MNGIE TYPE); MTDPS1". omim.org. Retrieved 2015-12-02. 4. ^ a b c d e f g h Teitelbaum, J.E. (September 2002). "Diagnosis and Management of MNGIE in Children: Case Report and Review of the Literature". Journal of Pediatric Gastroenterology and Nutrition. 35 (3): 377–83. doi:10.1097/00005176-200209000-00029. PMID 12352533. 5. ^ a b c d e Walia, Anuj (December 2006). "Mitochondrial neuro-gastrointestinal encephalopathy syndrome" (PDF). Indian Journal of Pediatrics. 73 (12): 1112–1114. doi:10.1007/BF02763058. PMID 17202642. S2CID 40345738. 6. ^ Bardosi, A (1987). "Myo-, Neuro-, Gastrointestinal Encephalopathy (MNGIE Syndrome) due to partial deficiency of cytochrome-C oxidase: A new mitochondrial multisystem disorder". Acta Neuropathologica. 74 (3): 248–58. doi:10.1007/BF00688189. PMID 2823522. S2CID 20379299. ## External links[edit] Classification D * ICD-9-CM: 277.87 * OMIM: 603041 * MeSH: C536350 * DiseasesDB: 32948 External resources * GeneReviews: Mitochondrial Neurogastrointestinal Encephalopathy Disease * Orphanet: 298 * v * t * e Mitochondrial diseases Carbohydrate metabolism * PCD * PDHA Primarily nervous system * Leigh disease * LHON * NARP Myopathies * KSS * Mitochondrial encephalomyopathy * MELAS * MERRF * PEO No primary system * DAD * MNGIE * Pearson syndrome Chromosomal * OPA1 * Kjer's optic neuropathy * SARS2 * HUPRA syndrome * TIMM8A * Mohr–Tranebjærg syndrome see also mitochondrial proteins * v * t * e Inborn error of purine–pyrimidine metabolism Purine metabolism Anabolism * Adenylosuccinate lyase deficiency * Adenosine Monophosphate Deaminase Deficiency type 1 Nucleotide salvage * Lesch–Nyhan syndrome/Hyperuricemia * Adenine phosphoribosyltransferase deficiency Catabolism * Adenosine deaminase deficiency * Purine nucleoside phosphorylase deficiency * Xanthinuria * Gout * Mitochondrial neurogastrointestinal encephalopathy syndrome Pyrimidine metabolism Anabolism * Orotic aciduria * Miller syndrome Catabolism * Dihydropyrimidine dehydrogenase deficiency [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Mitochondrial neurogastrointestinal encephalopathy syndrome	c0872218	26,905	wikipedia	https://en.wikipedia.org/wiki/Mitochondrial_neurogastrointestinal_encephalopathy_syndrome	2021-01-18T18:49:18	{"gard": ["9920"], "mesh": ["C536350", "C537477"], "umls": ["C0872218"], "icd-9": ["277.87"], "orphanet": ["298"], "wikidata": ["Q6881876"]}
A number sign (#) is used with this entry because of evidence that this severe primary immunodeficiency, characterized by the absence of major histocompatibility complex (MHC) class II gene expression, results from defects in at least 4 different transacting regulatory genes required for transcription of MHC class II genes. There are at least 4 complementation groups: group A with a defect in the MHC2TA gene (600005); group C with a defect in the RFX5 gene (601863); group D with a defect in the RFXAP gene (601861); and group B with a defect in the RFXANK gene (603200). A fifth complementation group, group E, also results from a mutation in the RFX5 gene. The disorder is inherited as an autosomal recessive. The bare lymphocyte syndrome type II is a member of the relatively heterogeneous class of SCID, or severe combined immunodeficiency. It is associated with, and probably results from, the lack of expression of HLA antigens on some cells of hematopoietic origin (Touraine et al., 1978). In addition to being of interest in its own right as a 'cause' of SCID, BLS provides insight into the role of MHC determinants in lymphocyte differentiation. In France, Touraine et al. (1980) reported 2 affected brothers, and a family in the Netherlands was reported by Schuurman et al. (1979, 1980). In the French family, 4 other sibs had died in infancy. BLS lymphocytes lacked HLA-A, -B, and -C antigens; they also lacked beta-2-microglobulin (109700) to a degree approaching that of the Daudi cell line which has a deletion of chromosome 15. Schuurman et al. (1980) reported studies of 2 unrelated families, 1 Turkish, the other Algerian. Consanguinity was likely in the former and certain in the latter. The affected children were of both sexes. First symptoms presented after the age of 3 or 4 months. All children had severe and persistent diarrhea, mucocutaneous candidiasis, interstitial pneumonia and various bacterial infections but no proved systemic viral infections. The findings of special studies supported the important role of class I HLA antigens in antigen recognition by T lymphocytes. It seemed that the abnormality in this syndrome might lie in the HLA genes or the B2M gene. Marcadet et al. (1985) reported BLS in a 5-year-old girl born of first-cousin parents who had had repeated infections of the upper and lower respiratory tract, protracted diarrhea, and malabsorption for several years. The organisms included Hemophilus influenzae, Candida albicans, herpes simplex, cytomegalovirus, and adenovirus. Despite normal numbers of T and B lymphocytes, there were no delayed hypersensitivity reactions in vivo; panhypogammaglobulinemia was present, and antigen-induced lymphocyte proliferation and cell-mediated lymphocytotoxicity were absent in vitro. They also reported the disorder in a 4-year-old girl born of presumably unrelated parents of Algerian descent; 2 sisters and 1 brother had died of severe infections before age 4 years. In these 2 patients, Marcadet et al. (1985) showed by molecular genetic techniques that the HLA genes, although poorly expressed, were in fact present. Furthermore, therapeutic decisions concerning bone marrow transplantation were possible. In a family with 2 affected sibs, Sullivan et al. (1985) investigated the molecular basis of this syndrome by means of cDNA probes for both beta-2-microglobulin and class I MHC genes. Southern blots showed no gross internal defect in either. Northern blot analysis also showed no qualitative difference between affected and unaffected family members. In contrast, quantitation of transcripts demonstrated that both B2M and class I MHC were decreased and decreased in a coordinate fashion. The authors interpreted this to mean that BLS represents a pretranslational regulatory defect of expression of 2 genes. Baxter-Lowe et al. (1989) used in vitro amplification of the HLA genes and sequence-specific oligonucleotide probe hybridization (SSOPH) to investigate the HLA status of an infant with HLA-deficient severe combined immunodeficiency. The technology used permitted detection of HLA polymorphism at the level of single amino acid differences and eliminated the requirement for HLA expression. After determining the patient's haplotypes by this method, they selected a donor for bone marrow transplantation with a successful result. As of 1985, 2 types of BLS had been identified: in type I (604571), the defect concerns only HLA class I molecules (Touraine et al., 1978; Schuurman et al., 1979), whereas in type II, both HLA class I and class II molecules are affected (Griscelli et al., 1980). In the latter disease, also called HLA class II-negative SCID, the abnormal expression of HLA molecules has been shown to be secondary to defective synthesis (Lisowska-Grospierre et al., 1985) due in turn to an abnormal transacting regulatory gene located outside the major histocompatibility complex (Marcadet et al., 1985; de Preval et al., 1985). The transacting regulatory factor, known as RF-X, binds to class II promoters and is defective in hereditary HLA deficiency type II, otherwise known as the 'bare lymphocyte syndrome.' The failure of HLA expression leads to immunodeficiency affecting both cellular and humoral responses to antigens. Death due to chronic diarrhea and repeated bacterial and viral infections frequently occurs in childhood. Lisowska-Grospierre et al. (1985) studied patients with an autosomal recessive combined immunodeficiency and an HLA-negative phenotype of activated T and B lymphocytes. The synthesis of the HLA-A, -B, and -C heavy chain was markedly decreased, whereas beta-2-microglobulin was made in normal amounts. No mRNA for either alpha or beta chains of HLA-DR was found. The Ii-chain, the invariant polypeptide associated intracellularly with HLA-DR, and its mRNA were made in normal amounts. Since the structural genes coding for class II polypeptides seemed to be unaffected, the genetic defect in these patients must have concerned the regulation of the expression of the HLA-DR genes. There appeared to be a transactive pleiotropic MHC-regulating gene located perhaps outside the MHC region. Will et al. (1990) described an offspring of healthy consanguineous Tunisian parents who had type II bare lymphocyte syndrome with the additional feature of neutropenia and neutrophil dysfunction (defective spontaneous migration and chemotaxis). Prenatal diagnosis was performed by Durandy et al. (1987) in 6 fetuses at risk for the disease, using membrane immunofluorescence on blood lymphocytes and monocytes. Two pregnancies were found to be affected. Not only do the BLS trait and the MHC locus segregate independently (de Preval et al., 1985), but class II gene expression can be restored by fusion to a class II MHC-positive cell (Accolla et al., 1985). Several complementation groups have been defined by fusion studies (Hume and Lee, 1989). By studies of a panel of class II MHC-negative regulatory mutants, Kara and Glimcher (1991) demonstrated at least 2 distinct defects that affected gene expression by mechanisms other than direct promoter mutations. Some BLS cells had protein-promoter interactions, both in vitro and in vivo, suggesting a defect in gene activation. A mutation in an activation domain of a transcription factor or in a coactivator protein that does not directly contact DNA could be responsible. In other cases of BLS, Kara and Glimcher (1991) found no promoter interactions in vivo, despite the observation that such interactions occur in vitro. This finding suggested that the defect in these instances may involve promoter accessibility and, thus, chromatin structure. A mutation affecting a factor that interacts with a common locus activation region could prevent the organization of closed chromatin into an open domain. Alternatively, the defect might reside in a common transcription factor that serves not only to activate transcription but also to displace or reorganize nucleosomes locally. By the fusion complementation assay, using a relatively large number of class II-defective patient cell lines and mutant B-lymphoblastoid cell lines, Benichou and Strominger (1991) showed that genetic defects in at least 3, and probably 4, transactivating factors can lead to this phenotype, a failure to transcribe and express class II genes. Several specific DNA binding factors that bind to various class II gene promoters had been cloned. Lisowska-Grospierre et al. (1994) performed fusion experiments with B-cell and fibroblast cell lines from 22 HLA class II-deficient patients, representing two-thirds of all known cases. They found that 2 complementation groups accounted for 20 of the 22 cases. These 2 complementation groups corresponded closely to 2 ethnic groups: most patients of north African origin were classified into one group, while all patients originating from Spain were classified into a second main group. In a comprehensive review, Mach et al. (1994) pointed to 2 general types of defects in BLS, which is a disease of gene regulation: in complementation group A, the defect resides in the C2TA gene, RFX binding is normal in vitro, and HLA class II promoter occupancy is normal in vivo. All patients in complementation groups B and C are defective in RFX binding in vitro and exhibit unoccupied class II promoters in vivo. Mach et al. (1994) noted that only a small number of patients had been assigned to complementation group A. Wolf et al. (1995) reported the cases of identical twin brothers with a defect in constitutive and inducible surface expression of MHC class II molecules on B cells, monocytes, and activated T cells. Unlike previously reported patients, the 2 infants did not have a regulatory defect in the coordinated control of MHC class II gene transcription. Low levels of HLA-DR alpha-chain and beta-chain protein (142860) were detected and, most surprisingly, cellular and humoral immune responses were induced in both infants after tetanus vaccination. For 18 months after birth up until the time of report, the 2 boys had had a benign clinical course. Douhan et al. (1996) concluded that the twin brothers in the study by Wolf et al. (1995) belonged to a previously unrecognized complementation group of MHC class II deficiency. In contrast to patients belonging to complementation groups A through D, the twin brothers showed a relatively benign clinical symptomatology and were able to mount MHC class II dependent T-cell responses and T-dependent antibody responses after vaccination, e.g., with tetanus toxoid (Wolf et al., 1995). However, similar to all other patients, MHC class II expression was undetectable on the surface of peripheral blood B cells, monocytes, and activated T cells, so that the cell type responsible for antigen presentation in the patients remained to be defined. Wolf et al. (2001) investigated MHC class II expression on epidermal Langerhans cells, monocyte-derived dendritic cells, dermal microvascular endothelial cells and fibroblasts compared with B cells, peripheral blood monocytes, and activated T cells in order to search for antigen-presenting cells that might be responsible for the cellular and humoral immune responses observed in the twins. The results showed residual surface membrane expression of functional MHC class II molecules on epidermal Langerhans cells and monocyte-derived dendritic cells, but not on B cells, monocytes, or activated T cells, indicating a cell-specific defect of MHC class II expression. Thus, the defect encountered in these patients was not expressed to the same extent in different cell lineages, which is relevant to the understanding of the patients' phenotype, and also illustrated that only small amounts of MHC class II are needed to mount a functional cellular immune response in vivo. Nekrep et al. (2002) identified an arg149-to-gln mutation (R149Q; 601863.0005) in the DNA-binding domain of RFX5 in cell lines (termed 'Ker' cell lines) derived from the histoidentical twins lacking MHC class II transcription reported by Wolf et al. (1995) and Douhan et al. (1996). Functional and structural modeling analyses indicated that the mutant protein was incapable of binding the X box of the HLA-DRA promoter, whereas expression of wildtype RFX5 in the Ker cell lines rescued MHC class II expression. Kovats et al. (1995) demonstrated that the function of antigen-presenting cells is deficient in multiple genetic complementation groups of BLS type II. They demonstrated this by studying antigen-presenting cell (APC) function in DR-transfected BLS cells derived from multiple complementation groups. Each BLS cell line displayed the same defective APC phenotype: an inability to mediate class II-restricted presentation of exogenous protein antigens and structurally altered class II alpha/beta dimers. Expression of the HLA class II-like genes DMA (142855) and DMB (142856), previously implicated in antigen presentation, was reduced or absent in the BLS cells. Fusion of BLS cells with a cell line that has a genomic deletion of HLA class II genes coordinately restored class II structural gene and DM gene expression and a wildtype APC phenotype. Thus, each of the molecular defects that silences class II structural gene transcription also results in a defective APC phenotype, providing strong evidence for coregulation of these 2 functionally linked pathways. DeSandro et al. (1999) reviewed the molecular bases of the several forms of BLS. According to a review by de la Salle et al. (1999), 3 types of HLA deficiency, types I, II, and III, resulting from the absence of HLA class I molecules, class II molecules, and both class I and class II molecules, respectively, had been described. A review of the HLA class I deficiencies was provided by de la Salle et al. (1999) and of the class II deficiencies by Reith et al. (1999). Only 9 well-documented cases of HLA class I deficiency with normal expression of class II molecules were found by de la Salle et al. (1999). Contrary to types II and III bare lymphocyte syndrome, which are characterized by the early onset of severe combined immunodeficiency, class I deficiencies are not accompanied by particular pathologic manifestations during the first years of life, although chronic lung disease develops in late childhood. In contrast to type II or type III bare lymphocyte syndrome, pathology of the gut (diarrhea) is not observed. Systemic infections have not been described in HLA class I-deficient patients. Chronic bacterial infections, often beginning in the first decade of life, are restricted to the respiratory tract and extend from the upper to the lower airway. Most authors report bronchiectasis, emphysema, panbronchiolitis, and bronchial obstruction. High frequency of involvement of the nasal sinuses and of nasal polyps, uncommon in non-cystic fibrosis children, was noted. Some cases of type I bare lymphocyte syndrome have deficiency in the TAP2 gene (170261). Reith et al. (1999) stated that approximately 70 patients from 57 unrelated families had been reported worldwide. Most of the patients were of North African origin (Algeria, Tunisia, Morocco). There was a high incidence of consanguinity in the affected families. In patient FZA with bare lymphocyte syndrome type II, complementation group B, Nagarajan et al. (2000) identified homozygosity for a missense mutation (L195P; 603200.0005) in the RFXANK gene. The patient's unaffected parents were heterozygous for the mutation. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive RESPIRATORY Airways \- Upper respiratory tract infections \- Lower respiratory tract infections ABDOMEN Liver \- Progressive liver disease \- Viral hepatitis Biliary Tract \- Pseudosclerosing cholangitis \- Bacterial cholangitis Gastrointestinal \- Protracted diarrhea \- Malabsorption \- Variable degree of villous atrophy \- Intraepithelial infiltration by lymphocytes, macrophages, plasma cells \- Severe colitis GENITOURINARY \- Recurrent urinary tract infections SKIN, NAILS, & HAIR Skin \- Mucocutaneous candidiasis NEUROLOGIC Central Nervous System \- Meningoencephalitis \- Chronic lymphocytic meningitis \- Poliomyelitis HEMATOLOGY \- Neutropenia \- Severe autoimmune cytopenia IMMUNOLOGY \- Absence of humoral and cellular immune response to foreign antigens \- Frequent bacterial, viral, protozoan, and fungal infections \- Susceptible to vaccine-induced polio LABORATORY ABNORMALITIES \- Normal number of T and B lymphocytes \- Reduced CD4+ count and proportionally increased CD8+ count \- Panhypogammaglobulinemia or agammaglobulinemia \- Absence of delayed hypersensitivity skin test MISCELLANEOUS \- Majority of children die between 6 months and 5 yrs MOLECULAR BASIS \- Caused by mutation in the MHC class II transactivator gene (MHC2TA, 600005.0001 ) \- Caused by mutation in the regulatory factor X-associated protein gene (RFXAP, 601861.0001 ) \- Caused by mutation in the regulatory factor X, 5 gene (RFX5, 601863.0001 ) \- Caused by mutation in the regulatory factor X, ankyrin repeat-containing gene (RFXANK, 603200.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	BARE LYMPHOCYTE SYNDROME, TYPE II	c2931418	26,906	omim	https://www.omim.org/entry/209920	2019-09-22T16:30:33	{"doid": ["5812"], "mesh": ["C537079"], "omim": ["209920"], "orphanet": ["572"], "synonyms": ["Alternative titles", "BLS, TYPE II", "BARE LYMPHOCYTE SYNDROME", "SEVERE COMBINED IMMUNODEFICIENCY, HLA CLASS II-NEGATIVE", "SCID, HLA CLASS II-NEGATIVE"]}
Deletion 5q35 refers to the different congenital malformation syndromes resulting from deletions of variable extent of the terminal part of the long arm of chromosome 5 (5q), spanning the region from 5q35.1 to 5q35.3 . The most significant anomaly is a recurring deletion in 5q35.2 comprising the NSD1 gene that causes Sotos syndrome that is characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty. Subtelomeric deletions of the terminal 3.5 Mb region on 5q35.3 are very rare, characterized by prenatal lymphedema with increased nuchal translucency, pronounced muscular hypotonia in infancy, borderline intelligence, postnatal short stature due to growth hormone deficiency, and a variety of minor anomalies such as mildly bell-shaped chest, minor congenital heart defects and a distinct facial gestalt. Larger deletions including bands 5q35.1, 5q35.2 and 5q35.3 cause a more severe phenotype that associates severe developmental delay with microcephaly, and significant cardiac defects (e.g. atrial septal defect with/without atrioventricular conduction defects, Ebstein anomaly, tetralogy of Fallot) linked to haploinsufficiency of NKX2.5 (5q35.1). Various combinations of signs may result from deletions of variable extent depending on the genes comprised in the deleted segment. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Deletion 5q35	c2931574	26,907	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1627	2021-01-23T18:51:38	{"mesh": ["C537647"], "icd-10": ["Q93.5"], "synonyms": ["Del (5)(q35)", "Del (5)(qter)", "Distal 5q deletion", "Monosomy 5q35", "Telomeric deletion 5q"]}
Steroid rosacea SpecialtyDermatology Steroid-induced rosacea is an iatrogenic condition (induced by the physician or patient) from the use of either systemic steroid or topical steroids. It is nearly identical to steroid induced acne from the standpoint of etiology.[1] Topical Steroid induced rosacea (left); after steroid withdrawal and photobiomodulation therapy (right). ## Contents * 1 Cause * 2 Prevention * 3 Treatment * 4 See also * 5 References * 6 External links ## Cause[edit] Steroid-induced rosacea can be caused by the prolonged used of a topical steroid on the face. Topical steroid comes in 7 different strengths (Some countries use 4 categories). Class I is super potent, and class VII is very weak. Usually, any categories of steroids over class VI can induce rosacea with prolonged use. The typical presentation is inflammatory acne lesions consisting of pustules, papules, and cysts. The patient often admits to the daily use of a topical steroid, often being under the advisement of a physician. Examination of the pustules often revealed inflammatory cells, and in many cases, numerous motile demodex mites. ## Prevention[edit] Physicians need to be aware of the danger of topical steroids. Only mild steroids should be applied to the face. The use of the topical steroid should be limited to the condition. Alternate week therapy or 3 consecutive days a week therapy is better than continuous therapy in preventing steroid-induced rosacea. Only the mildest topical steroid should be used on the face if a condition warrants such use. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) does not necessary prevent steroid induced rosacea. Similar conditions have been seen with both Elidel and Protopic, possibly from immunosuppression and Demodex or bacterial growth. ## Treatment[edit] Treatment often involves the gradual weaning off the topical steroid, and the use of a systemic anti-inflammatory antibiotic. If the patient is using a strong topical steroid, he or she is weaned to a weaker class VI or VII steroid. Usually, they are to use the substitute steroid daily, then only on weekends, then stop completely. The facial dermatitis and discomfort often worsen when they stop the offending steroid. The oral antibiotic will decrease the inflammatory nature of the lesions. The antibiotic of choice is usually a tetracycline antibiotic. Additionally, tacrolimus combined with oral antibiotics has proven to speed up the recovery process.[2] ## See also[edit] * Rosacea * List of cutaneous conditions ## References[edit] 1. ^ http://dermnetnz.org/acne/steroid-rosacea.html 2. ^ http://dermnetnz.org/acne/steroid-rosacea.html ## External links[edit] * Steroid Rosacea [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Steroid rosacea	c1274978	26,908	wikipedia	https://en.wikipedia.org/wiki/Steroid_rosacea	2021-01-18T18:58:02	{"umls": ["C1274978"], "wikidata": ["Q7611610"]}
Spastic paraplegia-precocious puberty syndrome is a complex form of hereditary spastic paraplegia characterized by the onset of progressive spastic paraplegia associated with precocious puberty (due to Leydig cell hyperplasia) in childhood (at the age of 2 years). Moderate intellectual disability was also reported. There have been no further descriptions in the literature since 1983. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Spastic paraplegia-precocious puberty syndrome	c1866850	26,909	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2826	2021-01-23T17:02:53	{"gard": ["4918"], "mesh": ["C536874"], "omim": ["182820"], "umls": ["C1866850"]}
Logopenic progressive aphasia (lv-PPA) is a form of primary progressive aphasia (PPA; see this term), characterized by impaired single-word retrieval and naming and impaired repetition with spared single-word comprehension and object knowledge. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Logopenic progressive aphasia	c4274665	26,910	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=250831	2021-01-23T17:33:42	{"gard": ["10791"], "icd-10": ["G31.0"], "synonyms": ["LPA", "Logopenic primary progressive aphasia", "Logopenic variant PPA"]}
A rare ophthalmic disorder characterized by the unilateral or bilateral occurrence of a tonic pupil (showing sectorial denervation of the sphincter pupillae, so that the pupil constricts poorly to light, while the response to near is present but abnormally prolonged), in association with the absence of deep tendon reflexes. In some patients, patchy hypo- or anhidrosis may also be present (a variant known as Ross syndrome). The condition typically occurs in young adults, with a female preponderance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Holmes-Adie syndrome	c0001519	26,911	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=454718	2021-01-23T18:21:16	{"gard": ["5749"], "mesh": ["D000270"], "omim": ["103100"], "umls": ["C0001519"], "icd-10": ["H57.0"], "synonyms": ["Adie syndrome", "Tonic pupil-tendon areflexia syndrome"]}
A number sign (#) is used with this entry because of evidence that craniofacial anomalies and anterior segment dysgenesis syndrome is caused by heterozygous mutation in the VSX1 gene (605020) on chromosome 20p11. One such family has been reported. Clinical Features Mintz-Hittner et al. (2004) studied 7 members of a 3-generation African American family, 4 of whom had abnormal craniofacial features and anterior segment developmental anomalies. Clinical features demonstrated extremely variable expressivity, but all affected individuals had wide interpupillary distance, abnormal corneal endothelium, and unusual pinnae. Other features included partially to completely empty sella turcica, posterior fossa cyst, anterior encephalocele, and/or hydrocephalus. Electrophysiologic examination provided evidence for abnormal cone bipolar cells (on visual evoked response and electroretinogram) in affected adult patients and for abnormal auditory bipolar cells (on audiogram and audio-evoked brainstem response) in the propositus. Molecular Genetics In affected members of an African American family with abnormal craniofacial features and anterior segment developmental anomalies, Mintz-Hittner et al. (2004) found a heterozygous G-to-T transversion at codon 256 in the CVC domain of the VSX1 protein that resulted in a change of an alanine to serine (A256S; 605020.0004). The A256S mutation segregated with the 4 patients and was not found in 624 control chromosomes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CRANIOFACIAL ANOMALIES AND ANTERIOR SEGMENT DYSGENESIS SYNDROME	c3280099	26,912	omim	https://www.omim.org/entry/614195	2019-09-22T15:56:12	{"omim": ["614195"]}
Central core disease (CCD) is an inherited neuromuscular disorder characterised by central cores on muscle biopsy and clinical features of a congenital myopathy. ## Epidemiology Prevalence is unknown. ## Clinical description CCD typically presents in infancy with hypotonia and motor developmental delay and is characterized by predominantly proximal weakness, pronounced in the hip girdle. Orthopaedic complications are common and malignant hyperthermia susceptibility (MHS) is a frequent complication. ## Etiology CCD and MHS are allelic conditions, both caused by (predominantly dominant) mutations in the skeletal muscle ryanodine receptor (RYR1) gene, encoding the principal skeletal muscle sarcoplasmic reticulum calcium release channel (RyR1). Altered excitability and/or changes in calcium homeostasis within muscle cells due to mutation-induced conformational changes in the RyR protein are considered to be the main pathogenetic mechanism(s). ## Diagnostic methods The diagnosis of CCD is based on the presence of suggestive clinical features and central cores on muscle biopsy. Muscle MRI may show a characteristic pattern of selective muscle involvement and aid the diagnosis in cases with equivocal histopathological findings. Mutational analysis of the RYR1 gene may provide genetic confirmation of the diagnosis. ## Management and treatment Management is mainly supportive and has to anticipate susceptibility to potentially life-threatening reactions to general anaesthesia. Further evaluation of the underlying molecular mechanisms may provide the basis for future rational pharmacological treatment. ## Prognosis In the majority of patients, weakness is static or only slowly progressive, with a favourable long-term outcome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Central core disease	c0751951	26,913	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=597	2021-01-23T18:26:55	{"gard": ["6014"], "mesh": ["D020512"], "omim": ["117000"], "umls": ["C0751951"], "icd-10": ["G71.2"]}
A number sign (#) is used with this entry because of evidence that punctate palmoplantar keratoderma type IA (PPKP1A) is caused by heterozygous mutation in the AAGAB gene (614888) on chromosome 15q23. Description Punctate palmoplantar keratoderma type I, also called keratosis punctate palmoplantaris type Buschke-Fisher-Brauer, is a rare autosomal dominant hereditary skin disease characterized by multiple hyperkeratotic centrally indented papules that develop in early adolescence or later and are irregularly distributed on the palms and soles. In mechanically irritated areas, confluent plaques can be found. Interfamilial and intrafamilial severity shows broad variation. There have been reports of an association between PPKP and the development of early- and late-onset malignancies, including squamous cell carcinoma (summary by Giehl et al., 2012). Another form of PPKP type I has been mapped to chromosome 8q24 (PPKP1B; 614936). Other forms of punctate palmoplantar keratoderma include a porokeratotic type (PPKP2; 175860) and focal acrohyperkeratosis (PPKP3; 101850). For a general phenotypic description and a discussion of genetic heterogeneity of palmoplantar keratoderma (PPK), see epidermolytic PPK (144200). Clinical Features In 14 families with keratosis palmoplantaris papulosa reported by Schirren and Dinger (1965), direct transmission was observed. Females were less severely affected. Salamon et al. (1982) studied a family with 8 cases including instances of male-to-male transmission. Onset in the proband was at age 20 years. Useful clinical photographs were provided. Comparison of the histologic findings with those reported by others suggested to Salamon et al. (1982) that keratodermia palmoplantaris papulosa is genetically heterogeneous. Stevens et al. (1994, 1996) reported a large family in which 38 persons in 4 generations had keratosis punctata. Ten of 34 affected adults developed different malignancies (Hodgkin disease and renal, breast, pancreatic, and colonic adenocarcinomas). In 5 persons malignancies developed before the age of 50. Stevens et al. (1994) proposed that in this family mutation in the type I acidic keratin gene cluster at 17q12-q21 (see, e.g., KRT9, 607606) might be related to pathology of tumor suppressor gene(s) in the region of 17q21 (see, e.g., BRCA1, 113705). In a Table, Stevens et al. (1996) stated that the characteristics in this family were onset between ages 12 and 30 years, multiple tiny punctate keratoses over the entire palmoplantar surfaces, coalescence of the punctate keratoses into a more diffuse pattern over the pressure points of the soles, and variable nail changes. In 3 ethnically diverse, 4-generation families segregating punctate palmoplantar keratoderma type I (PPKP1), Martinez-Mir et al. (2003) found that all affected family members had typical features without nail involvement. No increased prevalence of cancer was found in the families. Giehl et al. (2012) studied 3 families with PPKP, 2 of Croatian origin and 1 of German origin. In the 14 affected individuals, keratoses on the soles were more severe than those on the palms, especially over pressure points. Histology showed marked hyperkeratosis with focal parakeratosis and prominent hypergranulosis, consistent with PPKP1. Phenotypic variability was observed between as well as within the families. Pohler et al. (2012) studied a collection of 18 PPKP1 kindreds from Scotland, Ireland, Japan, and Tunisia, 11 of which had a family history consistent with autosomal dominant inheritance. In all families the onset was typically in the first to second decades of life, with the appearance of small circumscribed lesions on the palms and soles that consistently increased in number with advancing age and later coalesced to form larger lesions. However, there was considerable phenotypic variation between families, with lesions remaining subtle in some, whereas in others the phenotype resembled human papillomavirus (HPV)-induced lesions and was much more severe, painful, and debilitating. Histology of affected palmar epidermis from 3 unrelated kindreds of different ethnicities showed very similar findings, involving a well-defined central epidermal depression associated with hypergranulosis and a prominent layer of overlying orthokeratosis. Immunohistochemical staining for the cell proliferation marker Ki67 showed continuous staining of the proliferative basal cell compartment of the epidermis beneath the hyperkeratotic lesions, indicative of a hyperproliferative form of hyperkeratosis rather than a retention hyperkeratosis due to defective desquamation. Ultrastructural analysis of affected plantar skin showed mild acanthosis, a reduction in the granular cell layer, and compact orthokeratosis. In basal keratinocytes, there was a large increase in the number of small vesicles close to the cell membrane and prominent dilatation of the Golgi apparatus in affected epidermis compared to control skin. Pohler et al. (2012) noted that the ultrastructural findings were compatible with a defect in vesicle transport. Mapping In 3 ethnically diverse, 4-generation families segregating punctate palmoplantar keratoderma type I, Martinez-Mir et al. (2003) found linkage of the disorder to a 9.98-cM interval flanked by markers D15S534 and D15S818 on chromosome 15q22-q24 (maximum 2-point lod score of 4.93 at theta = 0.0 for D15S988). In a large 7-generation Tunisian PPKP kindred that originated from Saudi Arabia and was previously reported by El Amri et al. (2010), Pohler et al. (2012) found linkage to the previously reported 15q22 locus, obtaining a maximum 2-point lod score of 8.18 at theta = 0.0 for the marker D15S983. A 6.24-Mb critical interval was defined by recombination events. ### Exclusion Studies Kelsell et al. (1995) excluded linkage of a form of PPKP to the keratin gene clusters on 12q and 17q. Molecular Genetics In 2 Croatian families and a German family with PPKP1, Giehl et al. (2012) performed whole-exome sequencing followed by filtering and identified 2 heterozygous nonsense mutations in the AAGAB gene, R161X (614888.0001) and R124X (614888.0002), that segregated fully with disease in the respective families. Haplotype analysis of the 2 Croatian families indicated that the R161X mutation was inherited by descent from a common ancestor. By whole-exome sequencing in the proband from a 4-generation Scottish family with PPKP1, Pohler et al. (2012) identified heterozygosity for the R161X mutation in the AAGAB gene, which was confirmed by conventional sequencing to segregate with disease in the family and was not found in the current dbSNP or 1000 Genomes databases. Sequencing of AAGAB in a large 7-generation Tunisian pedigree with PPKP mapping to 15q22 revealed a heterozygous 2-bp deletion (614888.0003) that segregated with disease in the family, as well as in 2 additional Tunisian families. Sequencing of another 14 PPKP kindreds of Scottish, Irish, Japanese, and Tunisian backgrounds, respectively, revealed another 6 mutations in the AAGAB gene, including 1 splice site, 1 nonsense, and 4 frameshift mutations (see, e.g., 614888.0004-614888.0006). INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Disseminated hyperkeratotic papules on palms and soles (especially over pressure points) Skin Histology \- Hyperproliferative hyperkeratoses \- Acanthosis, mild \- Reduced granular layer \- Compact orthohyperkeratosis Electron Microscopy \- Cytoskeletal disruption seen on TEM of suprabasal and/or basal keratinocytes \- Numerous mitochondria \- Prominent distended Golgi apparatus \- Abnormal abundance of membrane-bound vesicles MISCELLANEOUS \- Inter- and intrafamilial phenotypic variability (subtle to painful and debilitating) \- Onset in first to second decade \- Keratoses on soles tend to be more severe \- Lesions increase in number with advancing age and coalesce to form larger lesions MOLECULAR BASIS \- Caused by mutation in the alpha- and gamma-adaptin-binding protein gene (AAGAB, 614888.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PALMOPLANTAR KERATODERMA, PUNCTATE TYPE IA	c1835662	26,914	omim	https://www.omim.org/entry/148600	2019-09-22T16:39:11	{"doid": ["0080214"], "mesh": ["C536161"], "omim": ["148600"], "orphanet": ["79501"], "synonyms": ["Alternative titles", "KERATOSIS PALMOPLANTARIS PAPULOSA", "PPKP1", "PALMOPLANTAR KERATODERMA, PUNCTATE TYPE I", "KERATODERMIA PALMOPLANTARIS PAPULOSA, BUSCHKE-FISCHER-BRAUER TYPE", "KPPP1", "Buschke-Fischer-Brauer syndrome", "Keratodermia palmoplantaris papulosa, Buschke-Fischer-Brauer type"]}
A number sign (#) is used with this entry because polymorphisms in the IL2RA (147730) region correlated with lower concentrations of soluble IL2RA have been associated with susceptibility to type 1 diabetes. One of the regions identified in a type I diabetes (see 222100) genomewide linkage scan extended from D10S197 to D10S220 across the centromere of chromosome 10 (Davies et al., 1994). Reed et al. (1997) undertook large scale, high resolution, multipoint affected sib pair linkage and single point transmission disequilibrium test (TDT) linkage analyses of 10p11-q11 in U.K., U.S., Norwegian, Sardinian, and Italian type I diabetic Caucasian populations. Linkage to 2 markers in this region was indicated by TDT. An allele at D10S588 was positively associated in a U.K. case-control study and was neutrally transmitted in CEPH families. By using a haplotype tag SNP approach, Vella et al. (2005) tested type I diabetes sample collections consisting of 7,457 cases and controls and of 725 multiplex families. Tag SNPs were analyzed using a multilocus test to provide a regional test for association. They found strong statistical evidence in the case-control collection for a type I diabetes locus in the CD25 (IL2RA; 147730) region of chromosome 10p15 and replicated the association in the family collection. Vella et al. (2005) recognized that association might not be with CD25 itself, but rather with a causal variant in linkage disequilibrium with CD25. In an analysis of up to 5,312 individuals with type 1 diabetes and 6,855 controls, Lowe et al. (2007) localized the type 1 diabetes association in the IL2RA gene region to 2 independent groups of SNPs, spanning overlapping regions of 14 and 40 kb, encompassing IL2RA intron 1 and the 5-prime regions of IL2RA and flanking gene RBM17 (606935) (odds ratio = 2.04; p = 10(-28)). IL2RA type 1 diabetes susceptibility genotypes were associated with lower circulating levels of soluble IL2RA (p = 6.28 x 10(-28)), suggesting that an inherited lower immune responsiveness predisposes to type 1 diabetes. Endocrine \- Diabetes mellitus, insulin-dependent Inheritance \- Autosomal locus and allelic heterogeneity ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DIABETES MELLITUS, INSULIN-DEPENDENT, 10	c1866040	26,915	omim	https://www.omim.org/entry/601942	2019-09-22T16:14:09	{"mesh": ["C566602"], "omim": ["601942"], "synonyms": ["Alternative titles", "INSULIN-DEPENDENT DIABETES MELLITUS 10"]}
Thyroid disease in women is an autoimmune disease that affects the thyroid in women. This condition can have a profound effect during pregnancy and on the child. It also is called Hashimoto's thyroiditis (theye-royd-EYET-uhss). During pregnancy, the infant may be seriously affected and have a variety of birth defects. Many women with Hashimoto's disease develop an underactive thyroid. They may have mild or no symptoms at first, but symptoms tend to worsen over time. If a woman is pregnant and has symptoms of Hashimoto's disease, the clinician will do an exam and order one or more tests.[1][2][3] The thyroid is a small gland in the front of the neck. The thyroid makes hormones called T3 and T4 that regulate how the body uses energy. Thyroid hormone levels are controlled by the pituitary gland, which is a pea-sized gland in the brain. It makes thyroid stimulating hormone (TSH), which triggers the thyroid to make thyroid hormone.[1] In thyroid disease the immune system makes antibodies that damage thyroid cells and interfere with their ability to make thyroid hormone. Over time, thyroid damage can cause thyroid hormone levels to be too low. This is called an underactive thyroid or hypothyroidism (heye-poh-THEYE-royd-ism). An underactive thyroid causes every function of the body to slow down, such as heart rate, brain function, and the rate your body turns food into energy. Hashimoto's disease is the most common cause of an underactive thyroid. It is closely related to Graves' disease, another autoimmune disease affecting the thyroid.[1] ## Contents * 1 Effects of hormone * 2 Testing * 3 Disease prior to pregnancy * 4 Treatment during pregnancy * 5 Breastfeeding * 6 References ## Effects of hormone[edit] Normal hormone changes during pregnancy cause thyroid hormone levels to increase. The thyroid may enlarge slightly in healthy women during pregnancy, but not enough to be felt. These changes do not affect the pregnancy or unborn baby. Yet, untreated thyroid problems can threaten pregnancy and the growing baby. Symptoms of normal pregnancy, like fatigue, can make it easy to overlook thyroid problems in pregnancy.[1] Thyroid hormone is vital during pregnancy. The unborn baby's brain and nervous system need thyroid hormone to develop. During the first trimester, the baby depends on the mother's supply of thyroid hormone. At 10 to 12 weeks of pregnancy, the baby's thyroid begins to work on its own. But the baby still depends on the mother for iodine, which the thyroid uses to make thyroid hormone. Pregnant women need about 250 micrograms (mcg) of iodine a day. Some women might not get all the iodine they need through the foods they eat or prenatal vitamins. Using iodized salt — salt that has had iodine added to it over plain table salt is recommended. Prenatal vitamins that contain iodine are also recommended.[1] Some women develop thyroid problems in the first year after giving birth. This is called postpartum thyroiditis. It often begins with symptoms of an overactive thyroid, which last 2 to 4 months. Mild symptoms might be overlooked. Affected women then develop symptoms of an underactive thyroid, which can last up to a year. An underactive thyroid needs to be treated. In most cases, thyroid function returns to normal as the thyroid heals.[1] ## Testing[edit] Experts have not reached agreement on whether all pregnant women should be routinely screened for thyroid problems. But, if an underactive thyroid with or without symptoms is found during pregnancy it will be treated to lower the risk of pregnancy problems. An underactive thyroid without symptoms occurs in 2 to 3 in every 100 pregnancies. Women can request thyroid screening.[1] ## Disease prior to pregnancy[edit] Women being treated for Hashimoto's disease can become pregnant. It is recommended that thyroid function be well-controlled before getting pregnant.[1] Untreated or poorly treated underactive thyroid can lead to problems for the mother, such as: * Preeclampsia * Anemia * Miscarriage * Placental abruption * High cholesterol * Postpartum bleeding[1] It also can cause serious problems for the baby, such as: * Preterm birth * Low birth weight * Stillbirth * Birth defects * Thyroid problems[1] ## Treatment during pregnancy[edit] Main article: thyroid disease in pregnancy During pregnancy, women may want to see both an OB/GYN and an endocrinologist, a doctor who treats people with hormone problems. Levothyroxine is safe to use during pregnancy and necessary for the health of the baby.[4] Women with Hashimoto's disease or an underactive thyroid who are taking levothyroxine before pregnancy may need a higher dose to maintain normal thyroid function. Clinicians may check thyroid function every 6 to 8 weeks during pregnancy. After delivery, hormone levels usually go back to the pre-pregnancy level.[1] ## Breastfeeding[edit] Levothyroxine does pass through breast milk. It is not likely to cause problems for the baby. In some cases, an underactive thyroid may inhibit the production of breast milk.[1] ## References[edit] 1. ^ a b c d e f g h i j k l "Thyroid Disease & Pregnancy". Office on Women’s Health, U.S. Department of Health and Human Services. 1 February 2017. Retrieved 20 July 2017. This article incorporates text from this source, which is in the public domain. 2. ^ "Thyroid disease". 2016-12-15. 3. ^ "Postpartum Thyroiditis" (PDF). American Thyroid Association. 2014. Retrieved 20 July 2017. 4. ^ Carney, Leo A.; Quinlan, Jeffrey D.; West, Janet M. (2014-02-15). "Thyroid Disease in Pregnancy". American Family Physician. 89 (4): 273–8. ISSN 0002-838X. PMID 24695447. Classification D * ICD-10: E03.9 * ICD-9-CM: 244.9 * MeSH: D007037 * DiseasesDB: 6558 External resources * MedlinePlus: 000353 * eMedicine: med/1145 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Thyroid disease in women	None	26,916	wikipedia	https://en.wikipedia.org/wiki/Thyroid_disease_in_women	2021-01-18T19:01:14	{"wikidata": ["Q39055819"]}
A number sign (#) is used with this entry because of evidence that thoracic aortic aneurysm-8 (AAT8) is caused by heterozygous mutation in the PRKG1 gene (176894) on chromosome 10q11. Clinical Features Tran-Fadulu et al. (2006) described 3 families with autosomal dominant inheritance of thoracic aortic aneurysms leading to either type A or type B dissections and a young age of onset of aortic dissections in both men and women. One family (TAA216) was a large 6-generation pedigree in which the second-generation matriach died suddenly at 35 years of age from rupture of the ascending aorta, with cystic medial necrosis noted on pathology. One of her daughters died suddenly at 18 years of age due to type A aortic dissection with rupture; a second daughter died of type A dissection at 45 years of age, with medial degeneration noted on pathology. A third daughter had type A aortic dissection at 37 years of age, and underwent repair, but died a year later of unknown causes. The second daughter had 12 children, half of whom had aortic disease: in addition to thoracic aortic aneurysms, 2 also had abdominal aortic aneurysms, 2 had aneurysms of the interatrial septum, 1 had mild tortuosity of the ascending aorta, and 1 had a subcutaneous arteriovenous aneurysm of the hand. Mapping Tran-Fadulu et al. (2006) studied 3 families segregating autosomal dominant thoracic aortic aneurysms (AAT) with a young age of onset of dissection. Genetic analysis of 1 of the families (TAA216) excluded linkage to known AAT loci (see 607086) and the FBN1 gene (134797). The authors hypothesized that the other 2 families would also be distinct from known loci based on their phenotypic similarity to the larger pedigree. In 4 families with thoracic aortic aneurysm and dissection, 1 of which was the large 6-generation family previously studied by Tran-Fadulu et al. (2006), Guo et al. (2013) performed 2-point linkage analysis of disease with a variant in the PRKG1 gene (see MOLECULAR GENETICS) and obtained a combined lod score of 7.88. Molecular Genetics By exome sequencing in a large 6-generation family segregating autosomal dominant thoracic aortic aneurysm and dissection, originally described by Tran-Fadulu et al. (2006) (family TAA216), Guo et al. (2013) excluded mutations in known genes associated with familial thoracic aortic disease and identified a heterozygous missense mutation in the PRKG1 gene (R177Q; 176894.0001). Analysis of exome data from 55 unrelated AAT probands identified heterozygosity for the same R177Q variant in the probands from 2 more families (TAA508 and TAA690), and Sanger sequencing of PRKG1 in another 307 probands identified R177Q in a fourth family (TAA292). The mutation segregated with disease in each family, and thoracic aortic disease was fully penetrant in family members over 18 years of age. Acute aortic dissection occurred as young as 17 years of age and was equally penetrant in men and women. Review of patient records for additional vascular disease revealed the presence of enlargement of the descending thoracic aorta, abdominal aorta, and other arteries in some patients. In family TAA508, 1 affected individual also had a giant coronary artery aneurysm and another had a spontaneous coronary artery dissection and ectatic coronary arteries. Tortuosity of the thoracic aorta was noted in 2 patients from family TAA216 and in 1 patient from family TAA292. Guo et al. (2013) stated that none of the mutation-positive patients who were examined by a clinical geneticist had features of Marfan syndrome (see 154700) or any other genetic syndrome associated with thoracic aortic disease (see, e.g., 609192). Pathogenesis Guo et al. (2013) examined aortic tissue from affected individuals from families TAA216 and TAA292 and observed the typical pathology associated with thoracic arotic disease, including increased proteoglycan accumulation, decreased smooth muscle cells, and elastic fiber loss and fragmentation. There was a substantial increase in small arteries in the medial layer from the vasa vasorum in PRKG1-mutation-positive individuals compared to controls. Guo et al. (2013) noted that similar invasion of the vasa vasorum into the medial layer had previously been seen in the aortas of individuals with MYH11 (160745) and MYLK (600922) mutations (Pannu et al., 2007; Wang et al., 2010). INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Aneurysm of interatrial septum (in some patients) Vascular \- Thoracic aortic aneurysm \- Thoracic aortic dissection \- Tortuosity of thoracic aorta (in some patients) \- Abdominal aortic aneurysm (in some patients) \- Coronary artery aneurysm (in some patients) \- Coronary artery dissection (in some patients) \- Small vessel cerebrovascular disease (rare) MISCELLANEOUS \- Aortic dissection may occur in second decade of life MOLECULAR BASIS \- Caused by mutation in the cGMP-dependent regulatory protein kinase, type 1 gene (PRKG1, 176894.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	AORTIC ANEURYSM, FAMILIAL THORACIC 8	c3809513	26,917	omim	https://www.omim.org/entry/615436	2019-09-22T15:52:08	{"doid": ["14004"], "omim": ["615436"], "orphanet": ["91387"], "synonyms": ["Familial TAAD"]}
White sponge nevus is a condition characterized by the formation of white patches of tissue called nevi (singular: nevus) that appear as thickened, velvety, sponge-like tissue. The nevi are most commonly found on the moist lining of the mouth (oral mucosa), especially on the inside of the cheeks (buccal mucosa). Affected individuals usually develop multiple nevi. Rarely, white sponge nevi also occur on the mucosae (singular: mucosa) of the nose, esophagus, genitals, or anus. The nevi are caused by a noncancerous (benign) overgrowth of cells. White sponge nevus can be present from birth but usually first appears during early childhood. The size and location of the nevi can change over time. In the oral mucosa, both sides of the mouth are usually affected. The nevi are generally painless, but the folds of extra tissue can promote bacterial growth, which can lead to infection that may cause discomfort. The altered texture and appearance of the affected tissue, especially the oral mucosa, can be bothersome for some affected individuals. ## Frequency The exact prevalence of white sponge nevus is unknown, but it is estimated to affect less than 1 in 200,000 individuals worldwide. ## Causes Mutations in the KRT4 or KRT13 gene cause white sponge nevus. These genes provide instructions for making proteins called keratins. Keratins are a group of tough, fibrous proteins that form the structural framework of epithelial cells, which are cells that line the surfaces and cavities of the body and make up the different mucosae. The keratin 4 protein (produced from the KRT4 gene) and the keratin 13 protein (produced from the KRT13 gene) partner together to form molecules known as intermediate filaments. These filaments assemble into networks that provide strength and resilience to the different mucosae. Networks of intermediate filaments protect the mucosae from being damaged by friction or other everyday physical stresses. Mutations in the KRT4 or KRT13 gene disrupt the structure of the keratin protein. As a result, keratin 4 and keratin 13 are mismatched and do not fit together properly, leading to the formation of irregular intermediate filaments that are easily damaged with little friction or trauma. Fragile intermediate filaments in the oral mucosa might be damaged when eating or brushing one's teeth. Damage to intermediate filaments leads to inflammation and promotes the abnormal growth and division (proliferation) of epithelial cells, causing the mucosae to thicken and resulting in white sponge nevus. ### Learn more about the genes associated with White sponge nevus * KRT13 * KRT4 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell can be sufficient to cause the disorder. However, some people who have a mutation that causes white sponge nevus do not develop these abnormal growths; this phenomenon is called reduced penetrance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	White sponge nevus	c1721005	26,918	medlineplus	https://medlineplus.gov/genetics/condition/white-sponge-nevus/	2021-01-27T08:25:22	{"gard": ["8501"], "mesh": ["D053529"], "omim": ["193900", "615785"], "synonyms": []}
A group of neurodegenerative disorders characterized by mostly pure cerebellar syndromes with occasional non-cerebellar signs (e.g. pyramidal signs, peripheral neuropathy, writer's cramp) and includes spinocerebellar ataxia (SCA) type 5 (SCA5), SCA6, SCA11, SCA26, SCA30, and SCA31. ## Epidemiology The prevalence is unknown but varies within populations and between geographical locations. SCA6 is the most common form of this group with an estimated prevalence of less than 1/100,000. SCA31 is the second most common form and is found mainly in Japan while the other forms of ACDA type III are rarer. ## Clinical description Age of onset for these disorders is variable but is usually in adulthood. This group of disorders is characterized by mainly pure cerebellar signs such as dysarthria and gait and limb ataxia (starting with difficulty walking and loss of balance/coordination and progressing to loss of mobility and dysphagia). A spectrum of oculomotor dysfunction is also present in most patients and can include nystagmus as well as impaired vestibulo-ocular reflex and smooth pursuit. Non-cerebellar signs are less common but can include pyramidal signs (SCA11), peripheral neuropathy (SCA6), and writer's cramp (SCA5). The vast majority of these diseases have a slowly progressive course. ## Etiology Causal mutations of ACDA type III have been reported in several genes: CACNA1A (19p13) in SCA6, SPTBN2 (11q13.2) in SCA5, TTBK2 (15q15.2) in SCA11, BEAN1 (16q21) in SCA31. The causal gene of SCA30 has not yet been discovered. ## Diagnostic methods Diagnosis is based on characteristic clinical findings, molecular genetic testing and magnetic resonance imaging (MRI) findings. Cerebellar atrophy with Purkinje cell degeneration is the common finding seen in all types of ACDA type III. ## Differential diagnosis Differential diagnosis includes other forms of rare hereditary ataxias, in particular other types of autosomal dominant cerebellar ataxia (see this term). ## Antenatal diagnosis Prenatal diagnosis is possible in families with a known disease causing mutation. ## Genetic counseling This group of diseases is inherited in an autosomal dominant manner and genetic counseling is possible. ## Management and treatment There is no cure for ADCA type III and treatment is supportive. Physical and occupational therapy is essential for maintaining activity along with the use of walking aids, canes and wheelchairs when necessary. Computer devices can help patients with dysarthria. Dysphagia should be monitored to decrease the risk of aspiration pneumonia. In those with vertigo, vestibular suppressants may be beneficial. Consultation with an ophthalmologist is recommended and prism glasses can help with nystagmus. Annual neurological examinations are recommended to monitor disease progression. ## Prognosis The majority of patients with ACDA type III eventually become disabled and cannot walk unassisted. Life-expectancy is slightly reduced (average age of death being 65 years or older). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Autosomal dominant cerebellar ataxia type III	None	26,919	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=94148	2021-01-23T18:26:43	{"icd-10": ["G11.8"], "synonyms": ["ADCA3", "ADCAIII", "Autosomal dominant cerebellar ataxia type 3", "Pure cerebellar syndrome-mild pyramidal signs syndrome"]}
Colobomatous microphthalmia is a developmental disorder of the eye characterized by unilateral or bilateral microphthalmia associated with ocular coloboma. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Colobomatous microphthalmia	c2931501	26,920	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98938	2021-01-23T18:28:45	{"gard": ["3644"], "mesh": ["C537463"], "omim": ["251505", "300345", "601186", "605738", "610092", "611638", "613703", "614497", "615145", "616428"], "umls": ["C2931501"], "icd-10": ["Q11.2"], "synonyms": ["MAC", "Microphthalmia with colobomatous cyst", "Microphthalmia-anophthalmia-coloboma syndrome"]}
Primary effusion lymphoma SpecialtyHematology, oncology, virology CausesChronic viral infection with KSHV/HHV8 or HIV PrognosisGuarded Primary effusion lymphoma (PEL) is classified as a diffuse large B cell lymphoma. It is a rare malignancy of plasmablastic cells that occurs in individuals that are infected with the Kaposi's sarcoma-associated herpesvirus (i.e. KSHV/HHV8). Plamsmablasts are immature plasma cells, i.e. lymphocytes of the B-cell type that have differentiated into plasmablasts but because of their malignant nature do not differentiate into mature plasma cells but rather proliferate excessively and thereby cause life-threatening disease.[1] In PEL, the proliferating plasmablastoid cells commonly accumulate within body cavities to produce effusions (i.e. accumulations of fluid), primarily in the pleural, pericardial, or peritoneal cavities, without forming a contiguous tumor mass.[2] In rare cases of these cavitary forms of PEL, the effusions develop in joints, the epidural space surrounding the brain and spinal cord, and underneath the capsule (i.e. tightly-woven collagen fibers) which forms around breast implants.[1] Less frequently, individuals present with extracavitary primary effusion lymphomas, i.e., solid tumor masses not accompanied by effusions.[3] The extracavitary tumors may develop in lymph nodes, bone, bone marrow, the gastrointestinal tract, skin, spleen, liver, lungs, central nervous system, testes, paranasal sinuses, muscle, and, rarely, inside the vasculature and sinuses of lymph nodes.[1] As their disease progresses, however, individuals with the classical effusion-form of PEL may develop extracavitary tumors and individuals with extracavitary PEL may develop cavitary effusions.[4] PEL typically occurs in individuals who are immunocompromised, i.e. individuals whose immune system is weakened and therefore less able to fight infectious agents and cancers. This weakening is ascribed to KSHV/HHV8 infection that is commonny further promoted by concurrent human immunodeficiency virus (i.e. HIV) infection, prior organ transplantation,[4] the decline in immunity that develops with aging,[1] and/or cirrhosis of the liver due to hepatitis B or C virus.[5] The plasmacytoid cells in PEL are also commonly infected with the Epstein-Barr virus (i.e. EBV). EBV is a known cause of various Epstein-Barr virus-associated lymphoproliferative diseases including various B-cell lymphomas. However, the role of this virus in the development of PEL is not clear,[4] although some studies suggest that EBV infection cooperates with KSHV/HHV8 infection to promote the development and/or progression of this disease.[3] Formally, PEL is defined by the World Health Organization, 2016 as a KSHV/HHV8-positive[6] and KSHV/HHV8-driven large B-cell lymphoma. This lymphoma also belongs to a group of lymphoid neoplasms with plasmablastic differentiation that involve malignant plasmablasts but differ from PEL in the types of tissues where they accumulate, the gene abnormalities they carry, and/or the predisposing conditions involved in their development.[1] More than 50, 30, and 60% of all PEL cases, respectively, develop in individuals who already have KSHV/HHV8-positive Karposi's sarcoma, human herpesvirus 8-associated multicentric Castleman disease,[7] and/or (especially in HIV-positive individuals) evidence of bearing EBV-infected plasmsmablasts.[2] Primary effussion lymphoma is an extremely aggressive cancer that is highly resistant to various chemotherapy treatments. It has carried a median survival time of ~5 months,[8] with overall survival rates at 1, 3, and 5 year of only 30, 18, and 17%, respectively. In many cases, however, this high mortality reflects, at least in part, the lethality of its underlying predisposing diseases, particularly HIV/AIDS in HIV-infected individuals. New treatment strategies, including those directed at its underlying predisposing diseases, may improve the prognosis of PEL.[9] ## Contents * 1 History * 2 Pathophysiology * 3 Presentation * 4 Diagnosis * 5 KSHV/HHV8-negative primary effusion lymphoma * 6 Treatment and prognosis * 7 See also * 8 References * 9 External links ## History[edit] PEL was first described in 1989 as a malignant B cell-derived non-Hodgkin lymphoma that developed in three individuals afflicted with HIV/AIDS.[10] In 1995, a group of researchers found DNA sequences that identified KSHV/HHV8 sequences in 8 lymphomas in the malignant cells of patients infected with the HIV; all 8 patients had effusions containing malignant cells in their pleural, pericardial, or peritoneal spaces and had malignant cells in their effusions that evidenced the Epstein-Barr viral genome.[11] Nadir and colleagues termed this syndrome of findings pulmonary effusion lymphoma in 1996.[12] During the years following these initial reports, several cases of PEL were found to be KSHV/HHV8-negative, i.e. occurring in individuals with no evidence of being infected with KSHV/HHV8, or to be manifested by solid tumors that were not associated with effusions, i.e. cases of extracavitary PEL.[13] ## Pathophysiology[edit] PEL develops in patients that have predisposing diseases that reduce the immune systems ability to attack precancerous and cancerous cells. Initially, KSHV/HHV8 viruses infect plasmablasts to establish a latency state in which the viruses express malignancy-promoting genes (see KSHV/HHV8 genes). Products of these viral genes include: 1) LANA-1, which inhibits host cells' p53 protein thereby reducing these cells' apoptosis (i.e. programmed cell death) response to injury, and also inhibits the activity of host cells' retinoblastoma protein thereby increasing these cells' proliferation; 2) vcylin, an analog of host cell cyclin, which binds RB to increase these cells' proliferation; 3) vFLIP, which inhibits host cell's apoptosis and activates these cells' NF-κB signaling pathway to prolong their survival; 4) various protein isoforms of kaposin which stimulate host cells to release cytokines (e.g., GM-CSF and IL-6) that act back on these cells to stimulate their growth;[4] 5) vIL6, a viral analog of host cells' IL-6 which, while not often expressed,[8] induces these cells to produce VEGF, a cytokine that feeds back on these cells to inhibit their apoptosis and to increase the permeability of nearby blood vessels thereby promoting the formation of effusions;[14] 6) K1 protein which promotes the malignancy of host cells; 7) G-protein coupled receptor protein which promotes host cells' proliferation and survival; and 8) several viral microRNAs that promote host cells to proliferate, inhibit these cells' apoptosis, and stimulate the vascularization of nearby small blood vessel to promote effusions.[9] While HIV/AIDS is associated with a wide range of cancers, including those involving B-cells such as plasmablastic lymphoma, the development of these cancers is commonly attributed to co-infection with oncogenic viruses (e.g. KSHV/HHV8, EBV): the direct role of HIV/AIDS in promoting PEL is unclear.[15] Finally, some studies suggest that EBV cooperates with KSHV/HHV8 to cause PEL, perhaps by enhancing the ability of KSHV/HHV8 to establish their pro-malignant latency phase in infected cells.[3] As a probable result of their excessive proliferation, prolonged survival, and ability to avoid attack by a weakened immune system, the malignant cells in PEL exhibit a high degree of genomic instability, i.e. alterations in the structure and/or expression of their genetic material which are associated with the development and/or progression of PEL. These alterations include mutations (i.e. changes in nucleic acid sequences), chromosomal rearrangements (i.e. deletions, duplications, inversions, translocations), aneuploidy (i.e. increases or decreases in the number of chromosomes), and the abnormal expression of genes that may or may not be a result of the preceding structural gene changes. Potentially important examples include: 1) overexpression of the APOBEC3B gene whose protein product (termed "probable DNA dC->dU-editing enzyme APOBEC-3B") contributes to the regulation of cell growth; 2) missense mutations in the IRAK1 gene which causes overactivation of its product protein, interleukin-1 receptor-associated kinase 1, and thereby overactivation of the NF-κB signaling pathway that regulates cell proliferation and survival;[4] 3) overexpression of the AQP3 gene whose protein product, aquaporin 3, is a water channel that when overexpressed is thought to promote the progression and spread of various types of cancers;[16] 4) overexpression of the P-selectin glycoprotein ligand-1 gene whose protein product promotes cell attachment to vascular endothelium; 5) overexpressin of the MUC1 gene whose product, the Mucin 1, cell surface associated protein, binds with P53 to inhibit cell death and interacts with beta-catenin to promote the tissue-invasiveness of cancer cells; and 6) overexpression of the MYC gene, whose product, c-Myc, is the cancer-causing MYC proto-oncogene although this overexpression, unlike the c-Myc overexession occurring in other B-cell lymphomas, is usually not associated with structural abnormalities in its gene[4] but rather is often overexpressed due to the action of the LANA-1 protein made by KSHV/HHV8.[2] The identification of these changes in tissue samples can assist in making the diagnosis of PEL.[4] ## Presentation[edit] Individuals diagnosed with PEL most commonly (>33% of all cases) present with advanced Stage III or IV disease.[5] They are predominately males with a median age of 42 years if they are infected with HIV and 73 years if they are not so infected. Some one-third to one-half of these individuals have a history of Karposi's sarcoma, less commonly of multicentric Castleman disease, and/or rarely of immune deficiency due to organ transplantation, hepatitis complicated by cirrhosis caused by hepatitis B or C viral infection, or of old age. PEL occurring in the elderly generally occurs in EBV-negative individuals residing in the Mediterranean region. Individuals with the cavitary form of PEL present with symptoms due to effusions in the pleural cavity (e.g. shortness of breath), pericardium (e.g. chest pain/discomfort, hypotension, shortness of breath), peritoneal cavity (e.g. abdominal swelling), or, much less often, joints (e.g. swelling), the epidural space (e.g. central nervous system symptoms), or breast implants (e.g. breast swelling/pain/malformation). While most cases of classical PEL involve one cavitary site, some individuals present with two or more sites of cavitary involvement.[4] Individuals with extracavitary PEL present with lesions in the lung, central nervous system, gastrointestinal tract,[4] and/or lymph nodes.[5] Gastrointestinal track lesions often occur as multiple lymphoid polyps in the large intestine.[1] At diagnosis, more than 50% of individuals afflicted with either cavitary or extracavitary PEL have or report a history of B symptoms (i.e. fever, weight loss, night sweat).[7] Laboratory examination in all PEL cases often show anemia, low blood levels of platelets, high serum levels of IL6, and high levels of circulating KSHV/HHV8.[8] ## Diagnosis[edit] In classical cavitary cases, the diagnosis of PEL may be suspected based on its presentation as effusions in one or more bodily cavities in individuals with a history of the immunodeficiencies cited above. The diagnosis is supported by microscopic examination of cytologic smears taken from these effusions. These smears typically show plasmablasts and, in some cases, other malignant cells that have the morphology of anaplasts (i.e.large pleomorphic cells) or the Reed-Sternberg cells associated with Hodgkin disease.[1] As detected by immunostaining methods, the malignant cells typically express molecular marker proteins such as CD45 (which is not expressed on mature plasma cells) as well as activation and plasma cell marker proteins such as CD30, MUC1, CD38, syndecan 1, and IRF4/MUM1; they do not express B-cell molecular marker proteins such as PAX5, CD19, CD29, or CD79a. The cells may also express many of the structural and non-structural gene abnormalities cited in the Pathophysiology section.[1] By definition, individuals with PEL are infected by Kaposi's sarcoma-associated herpesvirus (HHV-8 or KSHV/HHV8)[17][18] and therefore evidence malignant cells that express products of this virus such as LANA1.[1] In most cases, these individuals are also infected with EBV[19] and therefore evidence malignant cells that express products of this virus such as EBER1/2 nuclear RNA's.[1] Cases associated with HIV/AIDS test positive for antibodies directed against this virus.[1] (PEL occurs in the absence of HHV-8 and HIV, although this is rare.[20]) Individuals with PEL that is associated with cirrosis due to hepatitis evidence positive serum tests for the hepatitis virus B antigen (HBsAg) or one of the various tests for hepatitis C antigen.[5] Extracavitary PEL is diagnosed based on findings that their mass lesions contain the same or very similar types of malignant cells and the same set of blood and serum findings as those that are found in cavitary PEL.[3] ## KSHV/HHV8-negative primary effusion lymphoma[edit] Effusion-based lymphoma, KSHV/HHV8-negative (also termed Type II PEL) has been described by some researchers. These cases closely resemble KSHV/HHV8-positive (also termed Type I PEL) but have yet to be defined by the World Health Organization (2017). Compared to Type I PEL, Type II PEL occurs more often in older individuals, is less often associated with EBV, and more often afflicts individuals who lack evidence of being immunocompromised.[1] That is, the majority of HHV-8-negative EBL cases do not evidence a potentially PEL causative agent, such as HIV, EBV, HCV, or iatrogenic immunodeficiency, except for old age and, in 20% to 40% of cases, the presence of hepatitis C virus infection.[13] Type II PEL also tends to involve malignant plasmablasts, anaplasts, and/or Reed-Sternberg-like cells that have somewhat different expression patters of protein markers (e.g. the malignant cells in Type II PEL frequently express CD20 but often do not express CD30) and gene abnormalities (e.g. the malignant cells in Type II PEL more commonly evidence rearrangements in their Myc, BCL2, and BCL6 genes) than the malignant cells in Type I PEL. The response to treatment and prognosis of Type II PEL is poor[1] but may be somewhat better than the treatment-responsiveness and prognosis of Type I PEL.[13] One factor that appears to improve the treatment of Type II PEL is the addition of rituximab (a monoclonal antibody directed against and killing CD20-bearing cell) to the intensive chemotherapy regimens used to treat Type I PEL: the malignant cells in Type II PEL commonly express CD20 whereas the malignant cells in Type I PEL rarely express this cell surface marker. However, there are several cases of KSHV/HHV8-negative EBL that presented with pericardial effusions without evidence of more extensive disease that have experienced complete responses and favorable prognoses without chemotherapy or other cancer treatment (including rituximab) after simple drainage of the effusion. These cases suggest that, in addition to the presence of rituximab-sensitive CD20-bearing malignant cells, Type II PEL may be a less severe disease than Type I PEL, at lease in certain cases.[13] ## Treatment and prognosis[edit] PEL is generally resistant to cancer chemotherapy drugs that are active against other B-cell lymphomas and therefore carries a poor prognosis.[21] Overall median and 1 year survival rates in a series of 28 patients treated with chemotherapy for PEL were 6.2 months and 39.3%, respectively. In this study, the complete response rate (presumed to be temporary) to a standard CHOP chemotherapeutic regimen (i.e. cyclophosphamide doxorubicin, vincristine, and prednisone) was only 10% whereas a more intensive CHO chemotherapy regimen which included high dose methotrexate and bleomycin achieved a compete response rate (presumed temporary) of 70%. A second study using CHOP-like regimens or one of these regimens plus methotrexate also produced better results with the latter regimens: 5 year survival rates for the CHOP-like and CHOP-like plus methotrexate regimens were 34.4% and 45.7%, respectively.[4] A review of 105 PEL cases reported median survival times, 1 year, 3 year, and 5 year survival rates of 4.8 months, 30%, 18%, and 17%, respectively. In this study, patients with advanced Ann Arbor Stage III or IV disease had a particularly poor survival rate at 1 year of 25%; this compared to a rate of 42% for patients with stage I or II disease.[5] Anti-viral drugs directed against Cytomegalovirus (i.e. cidofovir, ganciclovir, and valganciclovir) have been reported to produce complete presumed temporary responses in individual cases of PEL while drugs directed against HIV in patients with HIV+ PEL have achieved presumed temporary median response and 5 year survival rates of 0.7 months and 28%, respectively. The National Comprehensive Cancer Network (NCCN) guideline recommends treating HIV/AIDS-related PEL with antiviral therapy in combination with aggressive chemotherapy regimens such as DA-EPOCH, cyclophosphamide, doxorubicin, and etoposide, or CHOP. Rituximab, a monoclonal antibody directed against and killing CD20-expressing cells, appears to improve the efficacy of chemotherapy regimens in treating cases of PEL that evidence CD20-positve malignant cells such as Type II PEL. It has been suggested that regimens that include rituximab might improve the treatment of not only CD+ Type II PEL but also the uncommon cases of CD20+ Type I PEL and all cases of CD- PEL. The efficacy of rituximab in CD- PEL may be due to the ability of this antibody to kill non-malignant CD+ 20 lymphocytes and thereby their potential to promote the disease.[8][22][23] A National Cancer Institute-sponsored clinical study is in its recruiting phase to study the efficacy of DA-EPOCH (which includes rituximab) plus lenalidomide in treating PEL.[24] Current studies are also examining the effects of drug-based inhibition of the signaling pathways that are overactive in the malignant plasmablasts in PEL (see Pathophysiology section) for their therapeutic effectiveness.[4] ## See also[edit] * List of hematologic conditions ## References[edit] 1. ^ a b c d e f g h i j k l m Chen BJ, Chuang SS (March 2020). "Lymphoid Neoplasms With Plasmablastic Differentiation: A Comprehensive Review and Diagnostic Approaches". Advances in Anatomic Pathology. 27 (2): 61–74. doi:10.1097/PAP.0000000000000253. PMID 31725418. 2. ^ a b c Korkolopoulou P, Vassilakopoulos T, Milionis V, Ioannou M (July 2016). "Recent Advances in Aggressive Large B-cell Lymphomas: A Comprehensive Review". Advances in Anatomic Pathology. 23 (4): 202–43. doi:10.1097/PAP.0000000000000117. PMID 27271843. 3. ^ a b c d Rezk SA, Zhao X, Weiss LM (September 2018). "Epstein-Barr virus (EBV)-associated lymphoid proliferations, a 2018 update". Human Pathology. 79: 18–41. doi:10.1016/j.humpath.2018.05.020. PMID 29885408. 4. ^ a b c d e f g h i j k Shimada K, Hayakawa F, Kiyoi H (November 2018). "Biology and management of primary effusion lymphoma". Blood. 132 (18): 1879–1888. doi:10.1182/blood-2018-03-791426. PMID 30154110. 5. ^ a b c d e El-Fattah MA (December 2017). "Clinical characteristics and survival outcome of primary effusion lymphoma: A review of 105 patients". Hematological Oncology. 35 (4): 878–883. doi:10.1002/hon.2372. PMID 27859456. 6. ^ Zanelli M, Zizzo M, Bisagni A, Froio E, De Marco L, Valli R, Filosa A, Luminari S, Martino G, Massaro F, Fratoni S, Ascani S (April 2020). "Germinotropic lymphoproliferative disorder: a systematic review". Annals of Hematology. doi:10.1007/s00277-020-04024-3. PMID 32307569. 7. ^ a b Sukswai N, Lyapichev K, Khoury JD, Medeiros LJ (January 2020). "Diffuse large B-cell lymphoma variants: an update". Pathology. 52 (1): 53–67. doi:10.1016/j.pathol.2019.08.013. PMID 31735345. 8. ^ a b c d Gonçalves PH, Uldrick TS, Yarchoan R (September 2017). "HIV-associated Kaposi sarcoma and related diseases". AIDS (London, England). 31 (14): 1903–1916. doi:10.1097/QAD.0000000000001567. PMC 6310482. PMID 28609402. 9. ^ a b Arora N, Gupta A, Sadeghi N (July 2017). "Primary effusion lymphoma: current concepts and management". Current Opinion in Pulmonary Medicine. 23 (4): 365–370. doi:10.1097/MCP.0000000000000384. PMID 28399009. 10. ^ Knowles DM, Inghirami G, Ubriaco A, Dalla-Favera R (February 1989). "Molecular genetic analysis of three AIDS-associated neoplasms of uncertain lineage demonstrates their B-cell derivation and the possible pathogenetic role of the Epstein-Barr virus". Blood. 73 (3): 792–9. PMID 2537119. 11. ^ Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM (May 1995). "Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas". The New England Journal of Medicine. 332 (18): 1186–91. doi:10.1056/NEJM199505043321802. PMID 7700311. 12. ^ Nador RG, Cesarman E, Chadburn A, Dawson DB, Ansari MQ, Sald J, Knowles DM (July 1996). "Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus". Blood. 88 (2): 645–56. PMID 8695812. 13. ^ a b c d Kubota T, Sasaki Y, Shiozawa E, Takimoto M, Hishima T, Chong JM (December 2018). "Age and CD20 Expression Are Significant Prognostic Factors in Human Herpes Virus-8-negative Effusion-based Lymphoma". The American Journal of Surgical Pathology. 42 (12): 1607–1616. doi:10.1097/PAS.0000000000001168. PMID 30273194. 14. ^ Narkhede M, Arora S, Ujjani C (2018). "Primary effusion lymphoma: current perspectives". OncoTargets and Therapy. 11: 3747–3754. doi:10.2147/OTT.S167392. PMC 6029609. PMID 29988764. 15. ^ Rubinstein PG, Aboulafia DM, Zloza A (February 2014). "Malignancies in HIV/AIDS: from epidemiology to therapeutic challenges". AIDS (London, England). 28 (4): 453–65. doi:10.1097/QAD.0000000000000071. PMC 4501859. PMID 24401642. 16. ^ Marlar S, Jensen HH, Login FH, Nejsum LN (October 2017). "Aquaporin-3 in Cancer". International Journal of Molecular Sciences. 18 (10). doi:10.3390/ijms18102106. PMC 5666788. PMID 28991174. 17. ^ Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM (May 1995). "Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas". N. Engl. J. Med. 332 (18): 1186–91. doi:10.1056/NEJM199505043321802. PMID 7700311. 18. ^ Staudt MR, Kanan Y, Jeong JH, Papin JF, Hines-Boykin R, Dittmer DP (July 2004). "The tumor microenvironment controls primary effusion lymphoma growth in vivo". Cancer Res. 64 (14): 4790–9. doi:10.1158/0008-5472.CAN-03-3835. PMID 15256448. 19. ^ Fan W, Bubman D, Chadburn A, Harrington WJ, Cesarman E, Knowles DM (January 2005). "Distinct subsets of primary effusion lymphoma can be identified based on their cellular gene expression profile and viral association". J. Virol. 79 (2): 1244–51. doi:10.1128/JVI.79.2.1244-1251.2005. PMC 538532. PMID 15613351. 20. ^ Youngster I, Vaisben E, Cohen H, Nassar F (January 2006). "An unusual cause of pleural effusion". Age Ageing. 35 (1): 94–6. doi:10.1093/ageing/afj009. PMID 16364944. 21. ^ Chen YB, Rahemtullah A, Hochberg E (May 2007). "Primary effusion lymphoma". Oncologist. 12 (5): 569–76. doi:10.1634/theoncologist.12-5-569. PMID 17522245. 22. ^ Shin J, Lee JO, Choe JY, Bang SM, Lee JS (January 2017). "Human Herpesvirus 8-Unrelated Primary Effusion Lymphoma-Like Lymphoma in an Elderly Korean Patient with a Good Response to Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone". Cancer Research and Treatment. 49 (1): 274–278. doi:10.4143/crt.2016.076. PMC 5266403. PMID 27283030. 23. ^ Horiuchi M, Nakao T, Tsutsumi M, Nakaya Y, Fuseya H, Yoshida M, Yoshimura T, Hayashi Y, Fukushima H, Inoue T, Yamane T (2019). "[Human herpes virus 8-negative primary effusion lymphoma-like lymphoma recurring as a tumor adjacent to the left atrium]". [Rinsho Ketsueki] the Japanese Journal of Clinical Hematology (in Japanese). 60 (3): 218–222. doi:10.11406/rinketsu.60.218. PMID 31068519. 24. ^ https://clinicaltrials.gov/ct2/show/NCT02911142?term=rituximab&cond=Primary+Effusion+Lymphoma&draw=2&rank=1 ## External links[edit] Classification D * ICD-O: M9678/3 * MeSH: D054685 * DiseasesDB: 33904 * SNOMED CT: 713516007 External resources * Orphanet: 48686 * v * t * e Leukaemias, lymphomas and related disease B cell (lymphoma, leukemia) (most CD19 * CD20) By development/ marker TdT+ * ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ * naive B cell (CLL/SLL) * mantle zone (Mantle cell) CD22+ * Prolymphocytic * CD11c+ (Hairy cell leukemia) CD79a+ * germinal center/follicular B cell (Follicular * Burkitt's * GCB DLBCL * Primary cutaneous follicle center lymphoma) * marginal zone/marginal zone B-cell (Splenic marginal zone * MALT * Nodal marginal zone * Primary cutaneous marginal zone lymphoma) RS (CD15+, CD30+) * Classic Hodgkin lymphoma (Nodular sclerosis) * CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma) PCDs/PP (CD38+/CD138+) * see immunoproliferative immunoglobulin disorders By infection * KSHV (Primary effusion) * EBV * Lymphomatoid granulomatosis * Post-transplant lymphoproliferative disorder * Classic Hodgkin lymphoma * Burkitt's lymphoma * HCV * Splenic marginal zone lymphoma * HIV (AIDS-related lymphoma) * Helicobacter pylori (MALT lymphoma) Cutaneous * Diffuse large B-cell lymphoma * Intravascular large B-cell lymphoma * Primary cutaneous marginal zone lymphoma * Primary cutaneous immunocytoma * Plasmacytoma * Plasmacytosis * Primary cutaneous follicle center lymphoma T/NK T cell (lymphoma, leukemia) (most CD3 * CD4 * CD8) By development/ marker * TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) * prolymphocyte (Prolymphocytic) * CD30+ (Anaplastic large-cell lymphoma * Lymphomatoid papulosis type A) Cutaneous MF+variants * indolent: Mycosis fungoides * Pagetoid reticulosis * Granulomatous slack skin aggressive: Sézary disease * Adult T-cell leukemia/lymphoma Non-MF * CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma * Pleomorphic T-cell lymphoma * Lymphomatoid papulosis type B * CD30+: CD30+ cutaneous T-cell lymphoma * Secondary cutaneous CD30+ large-cell lymphoma * Lymphomatoid papulosis type A Other peripheral * Hepatosplenic * Angioimmunoblastic * Enteropathy-associated T-cell lymphoma * Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma) * Subcutaneous T-cell lymphoma By infection * HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) * Aggressive NK-cell leukemia * Blastic NK cell lymphoma T or NK * EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma) * Large granular lymphocytic leukemia Lymphoid+ myeloid * Acute biphenotypic leukaemia Lymphocytosis * Lymphoproliferative disorders (X-linked lymphoproliferative disease * Autoimmune lymphoproliferative syndrome) * Leukemoid reaction * Diffuse infiltrative lymphocytosis syndrome Cutaneous lymphoid hyperplasia * Cutaneous lymphoid hyperplasia * with bandlike and perivascular patterns * with nodular pattern * Jessner lymphocytic infiltrate of the skin General * Hematological malignancy * leukemia * Lymphoproliferative disorders * Lymphoid leukemias [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Primary effusion lymphoma	c1292753	26,921	wikipedia	https://en.wikipedia.org/wiki/Primary_effusion_lymphoma	2021-01-18T18:48:14	{"gard": ["9247"], "mesh": ["D054685"], "umls": ["C1292753"], "icd-10": ["C83.8"], "orphanet": ["48686"], "wikidata": ["Q3832899"]}
A number sign (#) is used with this entry because hypogonadotropic hypogonadism-17 with or without anosmia (HH17) can be caused by heterozygous mutation in the SPRY4 gene (607984) on chromosome 5q31, sometimes in association with mutations in other genes, e.g., FGFR1 (136350) and DUSP6 (602748). Description Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' For a discussion of genetic heterogeneity of hypogonadotropic hypogonadism with or without anosmia as well as a discussion of oligogenicity of this disorder, see 147950. Molecular Genetics In a cohort of 386 unrelated individuals with congenital hypogonadotropic hypogonadism (CHH), 199 of whom were anosmic and 187 normosmic, many of whom were known to harbor mutations in previously identified HH-associated genes, Miraoui et al. (2013) analyzed 7 genes involved in the FGF8 (600483)-FGFR1 (136350) network and identified 14 HH probands with heterozygous missense mutations in the SPRY4 gene (see, e.g., 607984.0001-607984.0004). In 3 of the patients, their SPRY4 mutation was accompanied by a heterozygous missense mutation in another HH-associated gene, including FGFR1 (136350.0027; see HH2, 147950) and DUSP6 (602748.0002, 602748.0003; see HH19, 615269). Additional features present in the 14 probands with SPRY4 mutations included low bone mass in 4 patients, hearing loss in 3, and abnormal dentition in 2. Miraoui et al. (2013) concluded that mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH. INHERITANCE \- Autosomal dominant (see MISCELLANEOUS below) HEAD & NECK Ears \- Hearing loss (in some patients) Nose \- Hyposmia/anosmia (in some patients) Teeth \- Abnormal dentition (in some patients) GENITOURINARY \- Delayed or absent puberty SKELETAL \- Osteopenia or osteoporosis (in some patients) \- Fractures (in some patients) NEUROLOGIC Central Nervous System \- Hyposmia/anosmia (in some patients) ENDOCRINE FEATURES \- Delayed or absent puberty MISCELLANEOUS \- Phenotypic variability within families and among patients carrying the same mutation appears to be due to the oligogenic nature of the disorder, with some patients having mutations in more than 1 neuroendocrine-related gene MOLECULAR BASIS \- Caused by mutation in the SPRY domain containing 4 gene (SPRY4, 607984.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HYPOGONADOTROPIC HYPOGONADISM 17 WITH OR WITHOUT ANOSMIA	c0162809	26,922	omim	https://www.omim.org/entry/615266	2019-09-22T15:52:44	{"doid": ["0090079"], "mesh": ["D017436"], "omim": ["615266"], "orphanet": ["432", "478"], "synonyms": ["Gonadotropic deficiency", "Isolated congenital gonadotropin deficiency", "Normosmic idiopathic hypogonadotropic hypogonadism", "nIHH"], "genereviews": ["NBK1334"]}
CMV polyradiculomyelopathy SpecialtyNeurology CMV polyradiculomyelopathy (PRAM) is one of the five distinct neurological syndromes caused by CMV in HIV/AIDS. It causes subacute ascending lower extremity weakness with paresthesias and radicular pain, hyporeflexia or areflexia,[1] and urinary retention.[2] It has been suggested that CMV polyradiculomyelopathy should be treated with both ganciclovir and foscarnet in patients who develop the disease while taking either of these drugs.[3] ## References[edit] 1. ^ Cohen, B. A.; McArthur, J. C.; Grohman, S.; Patterson, B.; Glass, J. D. (1 March 1993). "Neurologic prognosis of cytomegalovirus polyradiculomyelopathy in AIDS". Neurology. 43 (3, Part 1): 493–9. doi:10.1212/WNL.43.3_Part_1.493. PMID 8383823. 2. ^ Guiot, HM; Pita-García, IL; Bertrán-Pasarell, J; Alfonso, G (December 2006). "Cytomegalovirus polyradiculomyelopathy in AIDS: a case report and review of the literature". Puerto Rico Health Sciences Journal. 25 (4): 359–62. PMID 17550105. 3. ^ Reiss, Carol (2008). Neurotropic Viral Infections. 355: Cambridge University Press. ISBN 9781139474160.CS1 maint: location (link) This article about a medical condition affecting the nervous system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CMV polyradiculomyelopathy	c1696682	26,923	wikipedia	https://en.wikipedia.org/wiki/CMV_polyradiculomyelopathy	2021-01-18T19:02:53	{"umls": ["C1696682"], "wikidata": ["Q5013043"]}
Disorder of motivation, curiosity and affect Athymhormia SpecialtyNeurology, Psychiatry Athymhormia is a disorder of motivation, one of that class of neuro-psychiatric conditions marked by abnormalities or deficiencies in motivation. Symptoms include the loss or reduction of desire and interest toward previous motivations, loss of drive and the desire for satisfaction, curiosity, the loss of tastes and preferences, and flat affect. In athymhormia, however, these phenomena are not accompanied by the characterizing features of depression nor by any notable abnormality in intellectual or cognitive function. ## Contents * 1 Origin of diagnostic category * 2 Cause * 3 See also * 4 References * 5 Further reading * 6 External links ## Origin of diagnostic category[edit] The diagnostic category was coined in 1922 by the French psychiatrists Dide and Guiraud, originally in reference to the behavior identified in some schizophrenic patients. ## Cause[edit] The cause of this condition has been hypothesized to derive from abnormalities in the limbic frontal cortex, the striatum, globus pallidus, and dorso-medial thalamic nucleus. In the context of the theory of those who propose the existence of a distinct neural pathway for mood and interest, or the "hormothymic" system, athymhormia may be a disorder of this system. ## See also[edit] * Aboulia * Amotivational syndrome * Anhedonia * Athymhormic syndrome * Avolition ## References[edit] ## Further reading[edit] * Patrick Verstichel and Pascale Larrouy. "Drowning Mr. M." Scientific American Mind. April 2005. ## External links[edit] Classification D * Habib M, Poncet M (1988). "[Loss of vitality, of interest and of the affect (athymhormia syndrome) in lacunar lesions of the corpus striatum]". Rev. Neurol. (Paris) (in French). 144 (10): 571–7. PMID 3194605. * Carota A, Staub F, Bogousslavsky J (February 2002). "Emotions, behaviours and mood changes in stroke". Curr. Opin. Neurol. 15 (1): 57–69. doi:10.1097/00019052-200202000-00010. PMID 11796952. * Bogousslavsky J (April 2003). "William Feinberg lecture 2002: emotions, mood, and behavior after stroke". Stroke. 34 (4): 1046–50. doi:10.1161/01.STR.0000061887.33505.B9. PMID 12649523. * Habib M (2004). "Athymhormia and disorders of motivation in Basal Ganglia disease". J Neuropsychiatry Clin Neurosci. 16 (4): 509–24. doi:10.1176/jnp.16.4.509. PMID 15616180. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Athymhormia	c4049569	26,924	wikipedia	https://en.wikipedia.org/wiki/Athymhormia	2021-01-18T18:43:31	{"umls": ["C4049569"], "wikidata": ["Q2869281"]}
Charcot-Marie-Tooth disease type 4B2 (CMT4B2) is a subtype of Charcot-Marie-Tooth type 4 characterized by a severe, early childhood-onset of demyelinating sensorimotor neuropathy, early-onset glaucoma, focally folded myelin sheaths in the peripheral nerves, severely reduced nerve conduction velocities, and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, sensory loss, and frequent pes cavus). Severe visual impairment leading to visual loss has 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Charcot-Marie-Tooth disease type 4B2	c1858278	26,925	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99956	2021-01-23T18:07:38	{"gard": ["9200"], "mesh": ["C535421"], "omim": ["604563"], "umls": ["C1858278"], "icd-10": ["G60.0"], "synonyms": ["CMT4B2"]}
A number sign (#) is used with this entry because the phenotype can be caused by homozygous or compound heterozygous mutation in the RAG1 (179615) or RAG2 (179616) genes. This disorder is allelic to B cell-negative, T cell-negative, NK cell-negative SCID (601457), which has a more severe phenotype. Clinical Features Schuetz et al. (2008) reported 3 unrelated girls with combined cellular and humoral deficiencies and multiple granulomas. The first patient presented at age 2.5 years with multiple facial papulonodular lesions composed of epithelioid cells with a strong lymphocytic infiltrate. She was originally diagnosed with a T-cell lymphoma, but there was a poor response to chemotherapy. Extensive laboratory evaluation showed profound hypogammaglobulinemia, decreased T cells, and defective T-cell function. Bone marrow transplant was successful. The second patient developed severe infections in infancy and later developed skin, tongue, and lung lesions consistent with noninfectious granulomas. Immunophenotyping showed low numbers of B and T cells. Bone marrow transplant was successful. The third patient presented at age 10 years with a history of severe infections and massive splenomegaly. She was found to have hypogammaglobulinemia and defective T-cell function. Noninfectious granulomas were present in the spleen and lungs. None of the patients had a thymus visible on ultrasonography. Schuetz et al. (2008) noted that the phenotype in these patients was distinct from classic SCID and from Omenn syndrome (603554). The relatively late onset and lack of repeated life-threatening infections suggested that the T-cell repertoire was sufficient to offer some residual protection. Perks and Petheram (1978) reported a brother and sister of Maltese ancestry who had recurrent respiratory infections. Investigations showed combined cellular and humoral immune defects and noncaseating granulomas in lungs, liver, lymph nodes, and skin. The brother presented at age 16 years with iritis and died at age 25 from gram-negative septicemia. The sister presented at age 25 with pulmonary complaints. Progressive deterioration of pulmonary and hepatic function was observed in both. The phenotype in these patients resembled that described by Schuetz et al. (2008). ### Clinical Variability De Ravin et al. (2010) reported a 14-year-old boy who presented with destructive midline granulomatous disease of the head and neck. The patient had a complicated medical history. He had a history of myasthenia gravis with thymectomy at age 10 years, and a history of recurrent ear and sinus infections. The thymus showed dysplastic features and absence of autoimmune regulator, indicating a defect in thymocyte maturation. Laboratory studies showed a decrease of IgG subclasses 2 and 4 and mild CD8+ T cell lymphopenia, whereas CD3+ T cells, CD19+ B cells, and NK cells were normal. He was treated for Wegener granulomatosis with chemotherapeutic agents, but developed severe lymphopenia and continued to have relapses of noninfectious granulomas. In vitro studies showed dysregulated cellular inflammatory responses to various stimuli, including increased production of IL1B (147720) and IL8 (146930). An older sister had autoimmune cytopenias and antinuclear antibody-positive collagen vascular disease, with death at age 5 years. Molecular analysis of the proband identified compound heterozygous mutations in the RAG1 gene: W522C (179615.0024), which retained about 50% residual activity, and a null mutation (1621delC; 179615.0025). De Ravin et al. (2010) concluded that the proband had a phenotypic variant of RAG1 deficiency, with some residual enzyme activity being responsible for the later presentation and milder phenotype. The authors suggested a dysregulation of the inflammatory response to environmental antigens in this patient. Molecular Genetics In 2 unrelated patients with childhood onset of cellular and humoral deficiencies associated with granuloma formation, Schuetz et al. (2008) identified compound heterozygous mutations in the RAG1 gene (179615.0018-179615.0021). A third affected child had compound heterozygous mutations in the RAG2 gene (179616.0009 and 179616.0010). INHERITANCE \- Autosomal recessive IMMUNOLOGY \- Granulomas, non-infectious \- Granulomas can appear on skin, tongue, lungs, or other tissues \- Hypogammaglobulinemia \- Lack of thymus on ultrasound \- Decreased numbers of B cells \- Decreased numbers of T cells \- Defective T cell function \- Residual RAG1 and RAG2 activity MISCELLANEOUS \- Onset in infancy or early childhood \- Allelic disorder to T cell-negative, B cell-negative, NK cell- negative SCID ( 601457 ), which is more severe MOLECULAR BASIS \- Caused by mutation in the recombination-activating gene 1 (RAG1, 179615.0018 ) \- Caused by mutation in the recombination-activating gene 2 (RAG2, 179616.0009 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	COMBINED CELLULAR AND HUMORAL IMMUNE DEFECTS WITH GRANULOMAS	c2673536	26,926	omim	https://www.omim.org/entry/233650	2019-09-22T16:27:22	{"mesh": ["C567115"], "omim": ["233650"], "orphanet": ["157949"]}
For a phenotypic description and a discussion of genetic heterogeneity of Fuchs endothelial corneal dystrophy, see FECD1 (136800). Nomenclature This disorder, a late-onset form of Fuchs endothelial corneal dystrophy mapping to chromosome 9p24.1-p22.1, is referred to in OMIM as FECD7. Some references in the literature (e.g., Riazuddin et al., 2010) use the designation 'FCD4 locus' to refer to the genetic locus for FECD on chromosome 9. Mapping In a large pedigree with late-onset FECD, Riazuddin et al. (2010) identified a Q840P mutation in the ZEB1 gene (189909.0004) in 7 of 12 affected individuals (see FECD6, 613270). A genomewide scan in the pedigree identified an additional locus for FECD on chromosome 9p24.1-p22.1, with a maximum 2-point lod score of 3.48 at D9S256 (theta = 0.00), in 10 of the 12 affected individuals. Three of the 5 individuals carrying both the Q840P mutation and the disease-transmitting haplotype on 9p were over 70 years of age and had a severe FECD phenotype; all 3 had undergone corneal transplantation. Riazuddin et al. (2010) suggested that mutations either in ZEB1 or at the 9p locus are sufficient for disease, and that genetic interaction between the 2 loci can lead to a more severe form of the disease. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CORNEAL DYSTROPHY, FUCHS ENDOTHELIAL, 7	c0016781	26,927	omim	https://www.omim.org/entry/613271	2019-09-22T15:59:07	{"doid": ["11555"], "mesh": ["D005642"], "omim": ["613271"], "orphanet": ["98974"], "synonyms": ["Alternative titles", "FCD4 LOCUS", "CORNEAL DYSTROPHY, FUCHS ENDOTHELIAL, LATE-ONSET"]}
In a pedigree strongly supportive of X-linked recessive inheritance, Myhre et al. (1982) described 5 males with severe congenital mixed hearing loss and primary hypogonadism. The affected males also showed antisocial and immature behavior. An isolated case was observed in an unrelated family. Partial heterochromia iridis occurred in both affected and unaffected members of the large pedigree. It is not clear from the article whether the 'unaffected' persons with heterochromia iridis were carrier females. Audiograms in carrier females showed no hearing loss. Brunner et al. (1991) suggested that this phenotype represents a contiguous gene syndrome. Evidence supporting that was presented by Bach et al. (1992): in a study with molecular probes of 13 unrelated male probands with Gusher-associated, X-linked mixed deafness (DFN3; 304400), they found microdeletions in 2. One of these, from the family of Myhre et al. (1982), had the more extensive deletion, suggesting a locus for hypogonadism in the vicinity of the DFN3 gene. It was stated that the proband, TD, had a fixed stapes and gusher with progressive mixed deafness. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DEAFNESS-HYPOGONADISM SYNDROME	c1844680	26,928	omim	https://www.omim.org/entry/304350	2019-09-22T16:18:26	{"mesh": ["C564435"], "omim": ["304350"], "orphanet": ["90646"], "synonyms": ["Alternative titles", "DHS"]}
A number sign (#) is used with this entry because of evidence that ectodermal dysplasia-14 with or without hypohidrosis (ECTD14) is caused by homozygous or compound heterozygous mutation in the TSPEAR gene (612920) on chromosome 21q22. Description Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Ectodermal dysplasia-14 of the hair/tooth type is primarily characterized by scalp hypotrichosis and hypodontia. Some patients have decreased sweating, and some show subtle facial dysmorphism (Peled et al., 2016). Clinical Features Peled et al. (2016) studied 5 patients with ectodermal dysplasia from 3 consanguineous families, 2 of Arab Muslim origin and 1 Jewish Ashkenazi family. All affected individuals displayed hypodontia with conical teeth, as well as various degrees of scalp hypotrichosis that was most prominent on the anterior scalp. One individual exhibited hypertrichosis over the chest and another showed hypotrichosis of the lower extremities. Patients in 2 families had decreased sweating. Patients also shared subtle dysmorphic features, including a long oval face, square chin, downslanting palpebral fissures, low insertion of columella, and thick lips. Follicular accentuation was observed and was most marked over bony prominences. Patient scalp biopsy showed a paucity of hair follicles, and scanning electron microscopy of patient hair revealed abnormal structure of the follicular cuticle, with flattened and partially absent cuticular scales. The status of the patients' nails was not reported. Audiometry, performed in 3 patients from 2 families, was normal. Molecular Genetics In 2 cousins of Arab Muslim origin and an unrelated man with ectodermal dysplasia, who were negative for mutation in 2 genes associated with similar ectodermal phenotypes, Peled et al. (2016) performed whole-exome sequencing and identified homozygosity for 2 adjacent variants in the TSPEAR gene (612920.0001) in the 2 cousins, and compound heterozygosity for the same pair of variants and a 4-bp deletion in TSPEAR (612920.0002) in the male patient. In an unrelated female patient with ectodermal dysplasia, analysis of the TSPEAR gene revealed compound heterozygosity for 2 missense mutations (Y618N, 612920.0003 and D639N, 612920.0004). INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Hypotrichosis of scalp, especially anteriorly Face \- Long oval face \- Square chin Ears \- Normal hearing Eyes \- Downslanting palpebral fissures Nose \- Low insertion of columella Mouth \- Thick lips Teeth \- Hypodontia \- Conical teeth SKIN, NAILS, & HAIR Skin \- Follicular accentuation, especially over bony prominences \- Hypohidrosis (in some patients) Skin Histology \- Paucity of scalp hair follicles Electron Microscopy \- Flattened and partially absent cuticular scales Hair \- Hypotrichosis of scalp, especially anteriorly \- Hypertrichosis of chest (in 1 patient) \- Hypotrichosis of lower extremities (in 1 patient) MISCELLANEOUS \- Variable degree of scalp hypotrichosis MOLECULAR BASIS \- Caused by mutation in the thrombospondin-type laminin G domain and EAR repeats gene (TSPEAR, 612920.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	ECTODERMAL DYSPLASIA 14, HAIR/TOOTH TYPE WITH OR WITHOUT HYPOHIDROSIS	None	26,929	omim	https://www.omim.org/entry/618180	2019-09-22T15:43:18	{"omim": ["618180"]}
Late infantile neuronal ceroid lipofuscinoses (LINCLs) are a genetically heterogeneous group of neuronal ceroid lipofuscinoses (NCLs; see this term) typically characterized by onset during infancy or early childhood with decline of mental and motor capacities, epilepsy, and vision loss through retinal degeneration. ## Epidemiology LINCLs have been reported in populations with diverse ethnic origins with the highest prevalence being reported in Finland (around 1/385,000), estimates of below 1/1,000,000 in other Scandinavian counties and an annual incidence at birth of at least 1/200,000 in Germany. ## Clinical description The initial clinical symptoms are motor or/and cognitive decline or epilepsy but the mean age of onset and speed of progression may vary depending on the underlying genetic defect. Patients with classic LINCL generally present with a standstill of mental development or the onset of severe epilepsy around the third year of life. The disorder progresses to complete loss of almost all motor and mental capacities before school age. As visual loss is not a prominent finding in the early stages of the disease course, it is frequently not recognized. Several variant forms have also been described in the literature (vLINCL) in which the mean ages of onset generally vary from 2-7 years and which commonly manifest with severe epilepsy followed by cognitive and motor decline and vision loss. ## Etiology LINCLs are transmitted in an autosomal recessive manner and mutations in the following genes may result in LINCL with a classic and/or variant phenotype: PPT1 (designated CLN1; 1p32), TPP1 (11p15; designated CLN2 and responsible for the majority of cases of cLINCL), CLN5 (13q22), CLN6 (15q21), MFSD8 (designated CLN7), CLN8 (8p23) and CTSD (designated CLN10; 11p15.5). ## Diagnostic methods The diagnostic strategy for patients presenting with LINCL should include enzymatic testing for deficiencies in palmitoyl-protein thioesterase 1, tripeptidyl-peptidase 1 and cathepsin D, present in patients with PPT1, TPP1 and CTSD mutations, respectively. When these tests are negative, skin biopsy material should be examined by electron microscopy to search for the presence of storage material with autofluorescent ceroid lipopigments. If these pigments are present, molecular genetic analysis can be used to identify rare mutations in the other disease-causing genes and confirm the diagnosis. ## Differential diagnosis The differential diagnosis should include inborn errors of metabolism and inflammatory brain diseases. ## Antenatal diagnosis Prenatal diagnosis is possible on the basis of enzymatic analysis or molecular genetic testing if the mutation in the family has already been identified. ## Genetic counseling Genetic counseling should be provided to affected families. ## Management and treatment There is no curative treatment. Management consists of palliative care including administration of anticonvulsive drugs, treatment of spasticity with muscular relaxants and gastronomy feeding in the later stages of the disease. Stem cell therapy may provide an alternative treatment for some forms of LINCL in the future. ## Prognosis The prognosis is poor with most children becoming severely disabled by mid-childhood. Most patients do not survive to reach 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Late infantile neuronal ceroid lipofuscinosis	c0022340	26,930	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=168491	2021-01-23T18:34:18	{"mesh": ["D009472"], "omim": ["204500", "256730", "256731", "600143", "601780", "610127", "610951"], "umls": ["C0022340"], "icd-10": ["E75.4"], "synonyms": ["Jansky-Bielschowsky disease", "LINCL", "Late infantile NCL"]}
## Clinical Features Savarirayan et al. (2000) reported 2 unrelated, sporadic cases of a mesomelic dysplasia characterized by absence of fibulas and severely hypoplastic, triangular-shaped tibias. Moderate mesomelic shortness was present in the upper limbs with proximal widening of the ulnas. An abnormal pelvis and marked bilateral glenoid hypoplasia were other skeletal abnormalities. The authors believed that these cases represented a distinct form of mesomelic dysplasia. Nakamura et al. (2007) described a father-son pair with a severe form of mesomelic dysplasia that shared many features of the Savarirayan and Nievergelt (163400) types. Radiographs of the son at 6 months of age showed mild mesomelic shortening of the arms with proximal radius hypoplasia and broadening of the distal radius and proximal ulna. The lower limbs showed greater involvement with markedly short, broad tibia and absent fibular ossification. Rudimentary distal ossification occurred with age. The father demonstrated identical abnormalities of the tibia and fibula but had broader radii and ulnae with interosseous bridging on the left. The triad of severely deformed tibia, rudimentary fibula, and mildly affected radius and ulna in the son resembled that of the Savarirayan type. The broad, trapezoidal radius in the father showed greater similarity to the Nievergelt type. Nakamura et al. (2007) suggested that the Savarirayan and Nievergelt types may be allelic autosomal dominant disorders. Yasui et al. (2000) reported 2 unrelated patients with bilateral partial deficiencies of the tibia and fibula associated with apparently intact femur and tarsal bones, teratologic dislocation of the hips, and subluxation of the radial head. Ultrasound and MRI studies suggested the presence of cartilaginous remnants of the tibia and fibula. Cytogenetics Ladinsky et al. (2014) reported a male infant with hypereosinophilic syndrome (607685), lower extremity hemimelia with mesomelic shortening, and sensorineural hearing loss. At birth he had plagiocephaly, upslanting palpebral fissures, depressed nasal bridge, long philtrum, high anteriorly arched palate, and posteriorly rotated ears with over-folded helices. He also had left hip dysplasia and left undescended testicle. Echocardiogram showed a patent foramen ovale versus small secundum atrial septal defect, which closed spontaneously. Renal ultrasound revealed mild bilateral nonprogressive pelviectasis. Computed tomography demonstrated malformed bilateral semicircular canals resulting in sensorineural hearing loss. He had bilateral tibial and fibular hemimelia and significant lower extremity mesomelia. At 3 months of age, the child developed eczematous patches on his cheeks, scalp, and upper extremities. By 10 months of age, the rash had spread over both lower extremities. Skin biopsy of the rash showed superficial dermatitis with perivascular infiltration of both lymphocytes and eosinophils. Bone marrow examination performed at 11 months of age was hypercellular with active and progressive trilineage maturation and marked eosinophilia. Array comparative genomic hybridization studies showed a heterozygous 1.76-Mb deletion on chromosome 6p22.3 that was not identified in the parents by FISH analysis. Flottmann et al. (2015) performed array comparative genomic hybridization in 3 unrelated patients with mesomelic dysplasia of the Savarirayan type, including patient 1 described by Yasui et al. (2000) and patient 2 described by Savarirayan et al. (2000) and identified 2 Mb overlapping de novo microdeletions on chromosome 6p22.3. The deletions encompass 4 known genes: MBOAT1 (611732), E2F3 (600427), CDKAL1 (611259) and SOX4 (184430). All patients showed mesomelia of the lower limbs with hypoplastic tibiae and fibulae. Flottmann et al. (2015) identified a fourth patient with an overlapping, slightly larger de novo deletion that also encompassed the flanking gene ID4 (600581); this patient had intellectual disability and no skeletal abnormalities. The authors stated that the DECIPHER database listed 4 other patients with no significant skeletal abnormalities and overlapping, but much larger, deletions, and the ClinVar database listed only one overlapping 12-Mb deletion in a patient with developmental delay (dbVar:nsv530892). Flottmann et al. (2015) suggested that the deletion identified in the patients with mesomelic dysplasia removes 2 regulatory boundaries and brings several potential limb enhancers into close proximity of ID4 resulting in the aberrant activation and misexpression of ID4 in the limb bud, thereby causing the mesomelic dysplasia. Molecular Genetics Steichen-Gersdorf et al. (2008) reported a female infant with mesomelic dysplasia characterized by bilateral fibular absence and short, dysplastic, triangulated tibiae. The femurs were of normal size. The radii and ulnae were slightly short, and the radial heads were subluxed. The feet were in a marked equinovalgus position with postaxial reduction on the right side and abnormally spaced toes on the left. She had respiratory insufficiency and myoclonic jerks, and died at age 4 months. Postmortem examination showed malrotation of the colon, a horseshoe kidney, and ambiguous genitalia. The findings were similar to those described by Savarirayan et al. (2000), with the addition of central nervous system manifestations and urogenital anomalies, but the phenotype was also reminiscent of a severe form of Nievergelt syndrome. Array comparative genomic hybridization studies showed a heterozygous 500-kb deletion on chromosome 2q11.2 containing the LAF4 gene (601464). In situ hybridization studies in mouse embryos showed expression of Laf4 in the developing brain and limb buds. Kraft et al. (2015) reevaluated the patient reported by Steichen-Gersdorf et al. (2008) and determined that she had a 353-kb intragenic deletion in the LAF4 gene encompassing only 9 exons of the gene and resulting in a truncated 850-residue protein lacking a domain predicted to be involved in transcription activation. Homozygous knockout of the Laf1 gene in mice did not result in a recognizable phenotype. However, mice with either the heterozygous or homozygous 353-kb deletion had a short zeugopod in the upper limb as well as lower limb abnormalities that recapitulated part of the human phenotype, including small, triangular ossification center of the tibia and severe hypoplasia of the fibula. The mice also had polydactyly of the feet with incomplete penetrance. Kraft et al. (2015) suggested that the phenotype in the patient was a Nievergelt-like syndrome, and concluded that the truncated protein exerts a dominant-negative effect leading to the abnormalities of bone formation. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Head \- Delayed closure of anterior fontanelle CHEST Ribs Sternum Clavicles & Scapulae \- Hypoplastic glenoid SKELETAL Pelvis \- Dislocated hips \- Hypoplastic acetabular roof \- Widened sacro-sciatic notch \- Tall, narrow ilia Limbs \- Mesomelic limb shortening (lower limb greater than upper limb) \- Proximal widening of ulna \- Dislocation of radial head \- Hypoplastic tibia \- Oval or triangular-shaped tibia \- Absent fibula Hands \- Normal hands Feet \- Equinovalgus \- Normal tarsal \- Normal metatarsals \- Normal phalanges NEUROLOGIC Central Nervous System \- Developmental delay ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MESOMELIC DYSPLASIA, SAVARIRAYAN TYPE	c1854470	26,931	omim	https://www.omim.org/entry/605274	2019-09-22T16:11:26	{"mesh": ["C565349"], "omim": ["605274"], "orphanet": ["85170"], "synonyms": ["Alternative titles", "MESOMELIC DYSPLASIA WITH ABSENT FIBULAS AND TRIANGULAR TIBIAS"]}
Pterygium of the conjunctiva and cornea is a benign (non-cancerous) pink lesion that grows from the conjunctiva onto the cornea. They typically start from on the inner surface of the eye, and grow toward the the pupil. Long term exposure to ultraviolet light has been associated with causing this condition. Depending on the size of the pterygium, a person can experience vision problems. Surgical removal of the pterygium is often not needed unless it is causing irritation or vision loss. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Pterygium of the conjunctiva and cornea	c1867441	26,932	gard	https://rarediseases.info.nih.gov/diseases/4569/pterygium-of-the-conjunctiva-and-cornea	2021-01-18T17:58:04	{"mesh": ["C566740"], "omim": ["178000"], "umls": ["C1867441"], "synonyms": []}
For a discussion of genetic heterogeneity of alopecia-mental retardation syndrome, see APMR1 (203650). Clinical Features Wali et al. (2007) reported a consanguineous Pakistani family with autosomal recessive mental retardation associated with generalized alopecia. Affected individuals had complete absence of scalp hair at birth and showed lack of eyebrows, eyelashes, and axillary and pubic hair. Teeth, nails, sweating, and hearing were normal. All affected individuals were severely mentally retarded (IQ from 25 to 30) and had behavioral issues. Heterozygous carriers had normal hair and were unaffected. Mapping By genomewide linkage analysis of a Pakistani family with autosomal recessive alopecia and mental retardation, Wali et al. (2007) identified a locus, which they termed APMR3, on chromosome 18q11.2-q12.2 (maximum 2-point lod score of 3.03 with D18S1102). Multipoint linkage analysis resulted in maximum lod score of 4.03 with several markers in the candidate region. The size of the candidate region was 10.9 cM (12.7 Mb) between D18S866 and D18S811. Sequence analysis of 9 candidate genes in this interval did not reveal any pathogenic mutations. INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Hair \- Alopecia, complete NEUROLOGIC Central Nervous System \- Mental retardation, severe MISCELLANEOUS \- Onset at birth ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	ALOPECIA-MENTAL RETARDATION SYNDROME 3	c2931280	26,933	omim	https://www.omim.org/entry/613930	2019-09-22T15:57:01	{"mesh": ["C536660"], "omim": ["613930"], "orphanet": ["2850"]}
Van Bogaert (1953) and Hozay (1953) described a form of acroosteolysis with facial abnormalities in a brother and sister, aged 27 and 28, respectively. The parents were distantly related. The fingers and toes appeared infantile. The distal end of the ulna was underdeveloped. The facies were characterized by flat nasal bridge, thickened cheeks, deformed ears, micrognathia with abnormal dental position, and absent beard. Myopia and astigmatism were present. The male was mildly retarded; the female had done well in school. Ludo van Bogaert (1897-1989) lived and worked all his life in Antwerp, Belgium. As a neurologist and neuropathologist, he was a master of clinicopathologic correlation (Karcher, 1990). Hair \- Absent beard Skel \- Acroosteolysis Limbs \- Small fingers and toes \- Hypoplastic distal ulna Neuro \- Mild mental retardation Facies \- Flat nasal bridge \- Thickened cheeks \- Micrognathia Teeth \- Abnormal dental position Inheritance \- Autosomal recessive Eyes \- Myopia \- Astigmatism Ears \- Deformed ears ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	VAN BOGAERT-HOZAY SYNDROME	c1848598	26,934	omim	https://www.omim.org/entry/277150	2019-09-22T16:21:24	{"mesh": ["C536526"], "omim": ["277150"]}
Epulis SpecialtyOral medicine Epulis (Greek: ἐπουλίς; plural epulides) is any tumor like enlargement (i.e. lump) situated on the gingival or alveolar mucosa.[1][2] The word literally means "(growth) on the gingiva",[3][4] and describes only the location of the mass and has no further implications on the nature of the lesion.[5] There are three types: fibromatous, ossifying and acanthomatous.[medical citation needed] The related term parulis (commonly called a gumboil) refers to a mass of inflamed granulation tissue at the opening of a draining sinus on the alveolus over (or near to) the root of an infected tooth.[2] Another closely related term is gingival enlargement, which tends to be used where the enlargement is more generalized over the whole gingiva rather than a localized mass. ## Contents * 1 Epulis fissuratum * 2 Pyogenic granuloma * 3 Pregnancy epulis * 4 Fibrous epulis * 5 Ossifying fibroid epulis * 6 Giant cell epulis * 7 Epulis granulomatosa * 8 Congenital epulis * 9 References * 10 External links ## Epulis fissuratum[edit] Main article: epulis fissuratum This is a fibrous hyperplasia of excess connective tissue folds that takes place in reaction to chronic trauma from an ill fitting denture. It usually occurs in the mandibular labial sulcus. The clinical appearance of these lesions can vary, from erythematous mucosa that is prone to bleeding (a manifestation of hyperaemia), to lesions of more dense connective tissue, appearing more pale and firm.[6] Sometimes the term epulis is used synonymously with epulis fissuratum,[2] but this is technically incorrect as several other lesions could be described as epulides. This condition typically affects middle-aged and elderly patients. It is causes when a denture irritates the mucosa forming an ulcer. In time, this ulcer may develop into an elongated fibro-epithelial enlargement. Several leaflets may develop.[7] Management of this condition includes trimming the denture flange or areas causing irritation to the mucosa. Should modification of the denture not cause the lesion to decrease in size after 2–3 weeks, the swelling should be biopsied and examined histologically.[7] ## Pyogenic granuloma[edit] Main article: pyogenic granuloma This type of epulis is neither pyogenic ("pus producing") nor a true granuloma, but it is a vascular lesion. About 75% of all pyogenic granulomas occur on the gingiva,[2] growing beneath the gingival margin,[8] although they may also occur elsewhere in the mouth or other parts of the body (where the term epulis is inappropriate). This common oral lesion is thought to be a reaction to recurrent trauma or a response to non-specific infection.[9] It is more common in younger people and in females, and appears as a red-purple nodular swelling and bleeds easily. Small lesions can vary from a few millimetres up to two or three centimetres. Larger lesions can be attached to the gingiva with or without a stalk.[10] This type of epulis may also penetrate interdentally and present as bilobular, i.e. present both buccally and lingually.[8] ## Pregnancy epulis[edit] Also termed a "pregnancy tumor" or "granuloma gravidarum",[2] this lesion is identical to a pyogenic granuloma in all respects apart from the fact that it occurs exclusively in pregnant females.[3] Hormonal changes during pregnancy causes an increased inflammatory response to plaque and other irritants, which in turn causes the development of the epulis.[9] There is usually pregnancy gingivitis also.[3] Pregnancy epulis commonly occurs during the third trimester of pregnancy.[11] ## Fibrous epulis[edit] In adults, this type of epulis is characterised as a firm, pink mass that is not inflamed. It seems to grow from below the free gingival margin/interdental papilla.[8] This epulis most commonly occurs on the gingiva near the front of the mouth between two teeth.[3] When gingival hyperplasia is confined to one area of the jaw, this is when it is termed an epulis fibrosa, caused by an increase in collagenous tissue with varying cellularity.[12] It may be sessile or pedunculated and is composed of fibrosed granulation tissue. Fibrous epulides are firm and rubbery, and pale pink in color. Over time, bone may form within the lesion at which point the term peripheral ossifying fibroma may be used (in some parts of the world), despite having no relation to the ossifying fibroma of bone and it is not a fibroma.[13]:315 This type of epulis is most often painless, but pain may be associated due to secondary trauma, via brushing, flossing or chewing.[8] Diagnosis of a fibrous epulis is based firstly upon clinical features. A variety of common presentations exist including: painless, round and pedunculated swelllings, rarely exceeding 2 cm in diameter, swelling sometimes next to areas of irritation, rarely involve attached gingiva and they can be red or pale. The diagnosis is confirmed by an excisional biopsy.[14] ## Ossifying fibroid epulis[edit] Main article: peripheral ossifying fibroma Not to be confused with ossifying fibroma. This is a long-standing fibrous epulis in which bone has begun to form. It is believed that irritants and trauma cause the growth. Dental appliances, poor restorations and subgingival plaque and calculus are all examples of possible causes. It is seen most commonly in young adults and teenagers but can occur at any age, with the majority of cases occurring in females. In a clinical point of view, they are sessile or pedunculated, typically ulcerated and erythematous or are similar to the surrounding gingiva in colour. they are usually <2 cm in size. Ossifying fibroid epulis should be excised and examined make a definitive diagnosis. However, recurrences are common.[15] ## Giant cell epulis[edit] Main article: peripheral giant cell granuloma This epulis contains giant cells and is usually found on the gum margin between teeth which are anterior to the permanent molars.[13]:317 The development of a giant cell epulis may be related to the recent loss of baby teeth, extraction or trauma.[13]:319 The swelling is round, soft and commonly maroon or purplish in colour.[13]:317 It is also termed peripheral giant cell granuloma. Children are typically mainly affected, with females being affected more than males[16] Diagnosis of giant cell epulis usually requires a biopsy and radiographs should be taken of the area.[17] ## Epulis granulomatosa[edit] An epulis granulomatosa is a granuloma which grows from an extraction socket (the hole left after a tooth has been removed), and as such can be considered to be a complication of healing after oral surgery.[18] ## Congenital epulis[edit] Main article: congenital epulis This rare epulis (also called granular cell tumor, congenital gingival granular cell tumor or Neumann's tumor) presents at birth, and is not acquired,[19] in contrast to most other epulides which tend to be reactive lesions to tissue irritation. Congenital epulides mainly affect females and every so often, the growth is so large that it can obstruct breathing and feeding.[13]:322 On rare occasion, it may arise on the tongue, or be multifocal. Clinically, congenital epuli are usually found on the alveolar ridge, and are typically pink, pedunculated, firm, have a smooth or lobulated surface and the size varies from a few to 9 mm. They are usually found in solitary with multiple growths only in 10% of cases. It is commonly a pedunculated lesion in the incisor region. A diagnoses can usually be made based on clinical findings.[20] Histologically, congenital epuli are benign and thought to have a mesenchymal origin. When examined, cells with abundant granular eosinophilic and small eccentric nuclei are found. A delicate fibrovascular network can be found between the cells. It has an unusual resemblance to granular cell myoblastoma and is more common in the maxilla than the mandible.[21] A congenital Epulis can potentially involute, therefore, if it is not interfering with feeding and breathing, monitoring the lesion is advised. Otherwise, the lesion is removed with a simple excision and it does not have a tendency to recur.[20] Diagnosis is typically based upon clinical features but a biopsy confirms this.[22] ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 2. ^ a b c d e Neville BW, Damm DD, Allen CA, Bouquot JE (2002). Oral & maxillofacial pathology (2nd ed.). Philadelphia: W.B. Saunders. pp. 440–442, 447–448. ISBN 978-0721690032. 3. ^ a b c d Cawson RA, Odell EW (2002). Cawson's essentials of oral pathology and oral medicine (7th ed.). Edinburgh: Churchill Livingstone. pp. 275–278. ISBN 978-0443071065. 4. ^ ἐπουλίς. Liddell, Henry George; Scott, Robert; A Greek–English Lexicon at the Perseus Project. 5. ^ Newman MG, Takei HH, Klokkevold PR, Carranza FA, eds. (2012). Carranza's clinical periodontology (11th ed.). St. Louis, Mo.: Elsevier/Saunders. pp. 93. ISBN 978-1-4377-0416-7. 6. ^ Cutright, Duane E. (1974-03-01). "The histopathologic findings in 583 cases of epulis fissuratum". Oral Surgery, Oral Medicine, Oral Pathology. 37 (3): 401–411. doi:10.1016/0030-4220(74)90113-3. ISSN 0030-4220. PMID 4591192. 7. ^ a b Scully, Crispian (1999). Handbook of Oral Disease. London: Martin Dunitz. pp. 120–121. 8. ^ a b c d Agrawal, Amit Arvind (September 2015). "Gingival enlargements: differential diagnosis and review of literature". World Journal of Clinical Cases. 3 (9): 779–788. doi:10.12998/wjcc.v3.i9.779. PMC 4568527. PMID 26380825. 9. ^ a b Mitchell, David; Mitchell, Laura (July 2014). Oxford Handbook of Clinical Dentistry. Oxford University Press. doi:10.1093/med/9780199679850.001.0001. ISBN 9780199679850. 10. ^ R Pramod, John (2014). Textbook of Oral Medicine. doi:10.5005/jp/books/12196. ISBN 9789350908501. 11. ^ Rabinerson, D; Kaplan, B; Dicker, D; Dekel, A (September 2002). "[Epulis during pregnancy]". Harefuah. 141 (9): 824–6, 857, 856. PMID 12362490. 12. ^ Slootweg, Pieter. J (2013). Dental pathology: a practical introduction. Springer. p. 91. ISBN 9783642367137. 13. ^ a b c d e Cawson, RA; Odell, EW (2008). Cawson's essentials of oral pathology and oral medicine (8th ed.). Edinburgh: Churchill Livingstone. ISBN 9780702040016. 14. ^ Scully, Crispian (1999). Handbook of Oral Disease. London: Martin Dunitz. p. 285. 15. ^ Azher, U.; Das, U. M. (2009-01-01). "Peripheral ossifying fibroma". Journal of Indian Society of Pedodontics and Preventive Dentistry. 27 (1): 49–51. doi:10.4103/0970-4388.50818. ISSN 0970-4388. PMID 19414975. 16. ^ Scully, Crispian (1999). Handbook of Oral Disease. London: Martin Dunitz. p. 286. 17. ^ Scully, Crispian (1999). Handbook of Oral Disease. Martin Dunitz Ltd. p. 287. 18. ^ Leong, R; Seng, GF (May–Jun 1998). "Epulis granulomatosa: extraction sequellae". General Dentistry. 46 (3): 252–5. PMID 9693538. 19. ^ Eghbalian, F; Monsef, A (March 2009). "Congenital epulis in the newborn, review of the literature and a case report". Journal of Pediatric Hematology/Oncology. 31 (3): 198–9. doi:10.1097/mph.0b013e31818ab2f7. PMID 19262247. 20. ^ a b Küpers, A. Marlijn; Andriessen, Peter; van Kempen, Muriel J. P.; van der Tol, Ignaz G. H.; van der Waal, Isaäc; Baart, Jacques A.; Dumans, Antoine G. (Feb 2009). "Congenital epulis of the jaw: a series of five cases and review of literature". Pediatric Surgery International. 25 (2): 207–210. doi:10.1007/s00383-008-2304-8. hdl:1871/23572. PMID 19082830. 21. ^ Bosanquet, David; Roblin, Graham (November 2009). "Congenital Epulis: A Case Report and Estimation of Incidence". International Journal of Otolaryngology. 2009: 508780. doi:10.1155/2009/508780. PMC 2809329. PMID 20130770. 22. ^ Scully, Crispian (1999). Handbook of Oral Disease. London: Martin Dunitz. p. 280. ## External links[edit] Classification D * ICD-10: K06.8 * ICD-9-CM: 523.8 * DiseasesDB: 4410 * SNOMED CT: 71708001 * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Epulis	c0266919	26,935	wikipedia	https://en.wikipedia.org/wiki/Epulis	2021-01-18T19:06:31	{"mesh": ["D005882"], "umls": ["C0266919"], "icd-9": ["523.8"], "icd-10": ["K06.8"], "wikidata": ["Q841989"]}
Rare neurodegenerative disease whose symptoms include slowly progressive muscle wasting Spinal muscular atrophy with progressive myoclonic epilepsy Other namesHereditary myoclonus-progressive distal muscular atrophy syndrome This condition is inherited in an autosomal recessive manner SpecialtyNeurology Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), sometimes called Jankovic–Rivera syndrome, is a very rare neurodegenerative disease whose symptoms include slowly progressive muscle wasting (atrophy), predominantly affecting proximal muscles, combined with denervation and myoclonic seizures.[1] Only 12 known families are described in scientific literature to have SMA-PME.[2] SMA-PME is associated with a missense mutation (c.125C→T) or deletion in exon 2 of the ASAH1 gene and is inherited in an autosomal recessive manner.[3] SMA-PME is closely related to a lysosomal disorder disease called Farber lipogranulomatosis.[4] As with many genetic disorders, there is no known cure to SMA-PME. The condition was first described in 1979 by American researchers Joseph Jankovic and Victor M. Rivera.[5] ## Contents * 1 ASAH1 Gene * 2 See also * 3 References * 4 Further reading * 5 External links ## ASAH1 Gene[edit] The ASAH1 Gene codes for acid ceramidase which is an enzyme found in lysosomes. The lysosome breaks down acid ceramidase and the fatty acid component [6] is then used to produce myelin. Myelin is a coating around the nerves in the body which help transfer signals from nerve cell to nerve cell and increase transmission rate.[7] In patients with SMA-PME, the cermidase function is reduced to only be 33.33% effective.[2] The lack of myelin resulting from the lack of acid ceramidase break down leads to nerve cell damage. ## See also[edit] * Spinal muscular atrophies * Progressive myoclonus epilepsy ## References[edit] 1. ^ Haliloglu, G.; Chattopadhyay, A.; Skorodis, L.; Manzur, A.; Mercuri, E.; Talim, B.; Akçören, Z.; Renda, Y.; Muntoni, F.; Topaloğlu, H. (2002). "Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy: Report of New Cases and Review of the Literature". Neuropediatrics. 33 (6): 314–319. doi:10.1055/s-2002-37087. PMID 12571787. 2. ^ a b Reference, Genetics Home. "Spinal muscular atrophy with progressive myoclonic epilepsy". Genetics Home Reference. Retrieved 2018-09-24. 3. ^ Zhou, J.; Tawk, M.; Tiziano, F. D.; Veillet, J.; Bayes, M.; Nolent, F.; Garcia, V.; Servidei, S.; Bertini, E.; Castro-Giner, F.; Renda, Y.; Carpentier, S. P.; Andrieu-Abadie, N.; Gut, I.; Levade, T.; Topaloglu, H.; Melki, J. (2012). "Spinal Muscular Atrophy Associated with Progressive Myoclonic Epilepsy is Caused by Mutations in ASAH1". The American Journal of Human Genetics. 91 (1): 5–14. doi:10.1016/j.ajhg.2012.05.001. PMC 3397266. PMID 22703880. 4. ^ Gan, Joanna J.; Garcia, Virginie; Tian, Jane; Tagliati, Michele; Parisi, Joseph E.; Chung, Jeffrey M.; Lewis, Richard; Baloh, Robert; Levade, Thierry; Pierson, Tyler Mark (2015-12-01). "Acid ceramidase deficiency associated with spinal muscular atrophy with progressive myoclonic epilepsy". Neuromuscular Disorders. 25 (12): 959–963. doi:10.1016/j.nmd.2015.09.007. ISSN 0960-8966. PMID 26526000. 5. ^ Jankovic, J.; Rivera, V. M. (1979). "Hereditary myoclonus and progressive distal muscular atrophy". Annals of Neurology. 6 (3): 227–231. doi:10.1002/ana.410060309. PMID 534421. 6. ^ Park, Jae-Ho; Schuchman, Edward H. (December 2006). "Acid ceramidase and human disease". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1758 (12): 2133–2138. doi:10.1016/j.bbamem.2006.08.019. ISSN 0006-3002. PMID 17064658. 7. ^ Morell, Pierre; Quarles, Richard H. (1999). "The Myelin Sheath". Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th Edition. ## Further reading[edit] * National Institutes of Health (December 2013). "Genetics Home Reference: Spinal muscular atrophy with progressive myoclonic epilepsy". ## External links[edit] Classification D * ICD-10: G25.3 * OMIM: 159950 * MeSH: C537563 External resources * Orphanet: 2590 * 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]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Spinal muscular atrophy with progressive myoclonic epilepsy	c1834569	26,936	wikipedia	https://en.wikipedia.org/wiki/Spinal_muscular_atrophy_with_progressive_myoclonic_epilepsy	2021-01-18T18:57:13	{"gard": ["3044"], "mesh": ["C537563"], "umls": ["C1834569"], "orphanet": ["2590"], "wikidata": ["Q7577468"]}
## Clinical Features In 2 sibs, Johnson et al. (1997) described an apparently 'new' syndrome of spondylospinal thoracic dysostosis with a short, curved spine and fusion of the spinous processes, short thorax with 'crab-like' configuration of the ribs, pulmonary hypoplasia, severe arthrogryposis and multiple pterygia, and hypoplastic maxilla and mandible. The disorder was thought to be an autosomal recessive lethal trait. The first sib was born at 32 to 34 weeks' gestation following induced labor and forceps extraction because of intrauterine fetal death presumed to have occurred at approximately 7 months in a pregnancy complicated by weak fetal movements. The second sib was born at term by cesarean section. She was found to have malformations similar to those of her sister; she died soon after birth. The parents were nonconsanguineous. Johnson et al. (1997) concluded that the disorder differed from the Jarcho-Levin syndrome (277300) because in their patients there was clearly a primary bone fusion of the spinus processes of the spinal column with secondary small chest cage; hence, their use of the term spondylospinal thoracic dysostosis. Nomenclature The term 'spondylospinal' seems redundant (VAM). Johnson et al. (1997) appeared to be using 'spondylo-' to mean vertebra and 'spinal' to refer specifically to the spinus process of the vertebrae. Skel \- Spondylospinal thoracic dysostosis \- Short, curved spine \- Fused spinous processes Lung \- Pulmonary hypoplasia Skull \- Hypoplastic maxilla \- Hypoplastic mandible Skin \- Multiple pterygia Joints \- Severe arthrogryposis Inheritance \- Autosomal recessive lethal Misc \- Weak fetal movements Thorax \- Short thorax \- 'Crab-like' configuration of ribs ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SPONDYLOSPINAL THORACIC DYSOSTOSIS	c1866184	26,937	omim	https://www.omim.org/entry/601809	2019-09-22T16:14:13	{"mesh": ["C566622"], "omim": ["601809"]}
A number sign (#) is used with this entry because of evidence that hypomyelinating leukodystrophy-9 (HLD9) is caused by compound heterozygous mutation in the RARS gene (107820) on chromosome 5q34. Description Hypomyelinating leukodystrophy-9 is an autosomal recessive neurologic disorder characterized by onset of delayed psychomotor development, spasticity, and nystagmus in the first year of life. Additional neurologic features such as ataxia and abnormal movements may also occur. Brain imaging shows diffuse hypomyelination affecting all regions of the brain (summary by Wolf et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. Clinical Features Wolf et al. (2014) reported 4 patients from the Netherlands, 2 sisters and 2 unrelated patients, with severe neurologic impairment apparent in the first year of life. One of the sisters presented at age 1 year with stagnation of motor development associated with increased tone in the legs and difficulty walking; she achieved unsupported walking at age 2 years. At age 6 years, she had severe spasticity of the legs, mild intention tremor, dysmetria, dysarthria, and nystagmus. Her younger sister presented with nystagmus at age 5 months. At age 4 years, she had severe spasticity of the legs and mild ataxia. An unrelated patient presented with delayed motor development and spasticity and never achieved supported walking. At age 20 years, he had severe lower limb spasticity, pseudobulbar palsy, mild ataxia, lack of smooth pursuit, and mild mental retardation. Mild generalized atrophy with white matter volume loss was present on MRI. These 3 patients had mild mental retardation; they also had mild spasticity of the upper limbs. The other unrelated patient had a more severe phenotype, with microcephaly and delayed psychomotor development apparent at age 2 months. At age 2 years, she did not fix or follow, had axial hypotonia with poor head control, some dystonic movements, and an extrapyramidal syndrome with increased reflexes. A low level of cognition and lack of visual contact in this patient were consistent with early severe atrophy present at brain imaging. Brain imaging of all 4 patients was compatible with a severe lack of myelin affecting the supra- and infratentorial regions. Nafisinia et al. (2017) described a sister and brother, born to unrelated Maltese parents, and a male patient, born to first-cousin Turkish parents, with a hypomyelinating disorder similar to Pelizaeus-Merzbacher disease (312080). All 3 patients had developmental delay, nystagmus, brisk deep tendon reflexes in the lower extremities, ankle clonus, and cognitive impairment. The 2 who were able to walk had an ataxic gait. One of the patients had intractable focal occipital epilepsy. Brain MRI, performed in 2 of the 3 patients, showed hypomyelination and hypoplastic corpus callosum. The sibs' father was unaffected; their mother had normal intellect, but had fluttering eye movements with rapid changes in fixation and was found to have multiple small foci of abnormal high signal intensity in the deep white matter on brain MRI. The Turkish patient had 2 aunts and an uncle in the paternal line who had severe, incompletely characterized neurologic disorders and died between 2 months and 12 years without having learned to walk or speak. Inheritance The transmission pattern of HLD9 in the families reported by Wolf et al. (2014) was consistent with autosomal recessive inheritance. Molecular Genetics In 4 patients from 3 unrelated families from the Netherlands with hypomyelinating leukodystrophy, Wolf et al. (2014) identified compound heterozygous mutations in the RARS gene (107820.0001-107820.0005). Mutations in 2 of the families were found by whole-exome sequencing and confirmed by Sanger sequencing. All patients carried 1 missense mutation and a mutation predicted to result in the loss of a functional protein in trans; functional studies of the variants were not performed. In a sister and brother with hypomyelinating leukodystrophy-9, who were born to unrelated Maltese parents, Nafisinia et al. (2017) identified homozygosity for one of the mutations in the RARS gene (D2G; 107820.0001) previously reported in affected sisters by Wolf et al. (2014). The mutation, found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Using Sanger sequencing of all 15 exons of the RARS gene, Nafisinia et al. (2017) screened a cohort of 45 patients with a hypomyelinating disorder who did not have a genetic diagnosis and identified a male patient, born to first-cousin Turkish parents, with compound heterozygous mutations in the RARS gene (107820.0006-107820.0007). Using patient fibroblast extracts, Nafisinia et al. (2017) found that levels of RARS protein and the multi-RNA synthetase complex into which it assembles were significantly reduced. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly (1 patient) Eyes \- Nystagmus \- Poor smooth pursuit \- Poor visual fixation (1 patient) MUSCLE, SOFT TISSUES \- Hypertonicity of the lower limbs NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mental retardation, mild to severe \- Spasticity, more apparent in the lower limbs \- Ataxia \- Dysmetria \- Dysarthria \- Extrapyramidal syndrome \- Poor or absent independent walking \- Hyperreflexia \- Intention tremor \- Brain imaging shows hypomyelination \- Thin corpus callosum \- Global cerebral atrophy, mild (in some patients) \- Epilepsy, focal occipital (in 1 patient) MISCELLANEOUS \- Onset in the first year of life \- Variable severity \- Six patients from 5 families have been reported (last curated November 2018) MOLECULAR BASIS \- Caused by mutation in the arginyl-tRNA synthetase 1 gene (RARS1, 107820.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	LEUKODYSTROPHY, HYPOMYELINATING, 9	c4015323	26,938	omim	https://www.omim.org/entry/616140	2019-09-22T15:49:48	{"doid": ["0060791"], "omim": ["616140"], "orphanet": ["438114"], "synonyms": []}
17q12 microdeletion syndrome is a rare chromosomal anomaly syndrome resulting from the partial deletion of the long arm of chromosome 17 characterized by renal cystic disease, maturity onset diabetes of the young type 5, and neurodevelopmental disorders, such as cognitive impairment, developmental delay (particularly of speech), autistic traits and autism spectrum disorder. Müllerian aplasia in females, macrocephaly, mild facial dysmorphism (high forehead, deep set eyes and chubby cheeks) and transient hypercalcaemia 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	17q12 microdeletion syndrome	c3281138	26,939	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261265	2021-01-23T19:10:14	{"omim": ["614527"], "icd-10": ["Q93.5"], "synonyms": ["Del(17)(q12)", "Monosomy 17q12"]}
Placenta accreta Types of placenta accreta SpecialtyObstetrics Placenta accreta occurs when all or part of the placenta attaches abnormally to the myometrium (the muscular layer of the uterine wall). Three grades of abnormal placental attachment are defined according to the depth of attachment and invasion into the muscular layers of the uterus: * Accreta – chorionic villi attach to the myometrium, rather than being restricted within the decidua basalis. * Increta – chorionic villi invade into the myometrium. * Percreta – chorionic villi invade through the perimetrium (uterine serosa). Because of abnormal attachment to the myometrium, placenta accreta is associated with an increased risk of heavy bleeding at the time of attempted vaginal delivery. The need for transfusion of blood products is frequent, and surgical removal of the uterus (hysterectomy) is sometimes required to control life-threatening bleeding.[1] Rates of placenta accreta are increasing. As of 2016, placenta accreta affects an estimated 1 in 272 pregnancies.[2] ## Contents * 1 Risk factors * 2 Pathogenesis * 3 Diagnosis * 4 Complications * 5 Treatment * 6 Epidemiology * 7 References * 8 External links ## Risk factors[edit] An important risk factor for placenta accreta is placenta previa in the presence of a uterine scar. Placenta previa is an independent risk factor for placenta accreta. Additional reported risk factors for placenta accreta include maternal age and multiparity, other prior uterine surgery, prior uterine curettage, uterine irradiation, endometrial ablation, Asherman syndrome, uterine leiomyomata, uterine anomalies, hypertensive disorders of pregnancy[citation needed], and smoking. The condition is increased in incidence by the presence of scar tissue i.e. Asherman's syndrome usually from past uterine surgery, especially from a past dilation and curettage,[3] (which is used for many indications including miscarriage, termination, and postpartum hemorrhage), myomectomy,[4] or caesarean section. A thin decidua can also be a contributing factor to such trophoblastic invasion. Some studies suggest that the rate of incidence is higher when the fetus is female.[5] Other risk factors include low-lying placenta, anterior placenta, congenital or acquired uterine defects (such as uterine septa), leiomyoma, ectopic implantation of placenta (including cornual pregnancy).[6][7][8] Pregnant women above 35 years of age who have had a Caesarian section and now have a placenta previa overlying the uterine scar have a 40% chance of placenta accreta.[9] ## Pathogenesis[edit] The placenta forms an abnormally firm and deep attachment to the uterine wall. There is absence of the decidua basalis and incomplete development of the Nitabuch's layer.[10] There are three forms of placenta accreta, distinguishable by the depth of penetration. Type Fraction Description Placenta accreta 75–78% The placenta attaches strongly to the myometrium, but does not penetrate it. This form of the condition accounts for around 75% of all cases. Placenta increta 17% Occurs when the placenta penetrates the myometrium. Placenta percreta 5–7% The highest-risk form of the condition occurs when the placenta penetrates the entire myometrium to the uterine serosa (invades through entire uterine wall). This variant can lead to the placenta attaching to other organs such as the rectum or urinary bladder. ## Diagnosis[edit] When the antepartum diagnosis of placenta accreta is made, it is usually based on ultrasound findings in the second or third trimester. Sonographic findings that may be suggestive of placenta accreta include: 1. Loss of normal hypoechoic retroplacental zone 2. Multiple vascular lacunae (irregular vascular spaces) within placenta, giving "Swiss cheese" appearance 3. Blood vessels or placental tissue bridging uterine-placental margin, myometrial-bladder interface, or crossing the uterine serosa 4. Retroplacental myometrial thickness of <1 mm 5. Numerous coherent vessels visualized with 3-dimensional power Doppler in basal view Unfortunately, the diagnosis is not easy and is affected by a significant interobserver variability.[11] In doubtful cases it is possible to perform a nuclear magnetic resonance (MRI) of the pelvis, which has a very good sensitivity and specificity for this disorder.[12] MRI findings associated with placenta accreta include dark T2 bands, bulging of the uterus, and loss of the dark T2 interface.[13] Although there are isolated case reports of placenta accreta being diagnosed in the first trimester or at the time of abortion <20 weeks' gestational age, the predictive value of first-trimester ultrasound for this diagnosis remains unknown. Women with a placenta previa or "low-lying placenta" overlying a uterine scar early in pregnancy should undergo follow-up imaging in the third trimester with attention to the potential presence of placenta accreta. ## Complications[edit] * Damage to local organs (e.g., bowel, bladder,uterus and neurovascular structures in the retroperitoneum and lateral pelvic sidewalls from placental implantation and its removal; * Postoperative bleeding requiring repeated surgery; * Amniotic fluid embolism; * Complications (such as dilutional coagulopathy, consumptive coagulopathy, acute transfusion reactions, transfusion-associated lung injury, acute respiratory distress syndrome, and electrolyte abnormalities) caused by transfusion of large volumes of blood products, crystalloids, and other volume expanders; * Postoperative thromboembolism, infection, multisystem organ failure, and maternal death. The exact incidence of maternal mortality related to placenta accreta and its complications is unknown, but it is significant,[14] especially if the urinary bladder is involved[15] ## Treatment[edit] Treatment may be delivery by caesarean section and abdominal hysterectomy if placenta accreta is diagnosed before birth.[16][17] Oxytocin and antibiotics are used for post-surgical management.[18] When there is partially separated placenta with focal accreta, best option is removal of placenta. If it is important to save the woman's uterus (for future pregnancies) then resection around the placenta may be successful. Conservative treatment can also be uterus sparing but may not be as successful and has a higher risk of complications.[17] Techniques include: * Leaving the placenta in the uterus and curettage of uterus. Methotrexate has been used in this case.[18] * Intrauterine balloon catheterisation to compress blood vessels * Embolisation of pelvic vessels * Internal iliac artery ligation * Bilateral uterine artery ligation In cases where there is invasion of placental tissue and blood vessels into the bladder, it is treated in similar manner to abdominal pregnancy and manual placental removal is avoided. However, this may eventually need hysterectomy and/or partial cystectomy.[10] If the patient decides to proceed with a vaginal delivery, blood products for transfusion and an anesthesiologist are kept ready at delivery.[19] ## Epidemiology[edit] The reported incidence of placenta accreta has increased from approximately 0.8 per 1000 deliveries in the 1980s to 3 per 1000 deliveries in the past decade. Incidence has been increasing with increased rates of Caesarean deliveries, with rates of 1 in 4,027 pregnancies in the 1970s, 1 in 2,510 in the 1980s, and 1 in 533 for 1982–2002.[20] In 2002, ACOG estimated that incidence has increased 10-fold over the past 50 years.[8] The risk of placenta accreta in future deliveries after Caesarian section is 0.4-0.8%. For patients with placenta previa, risk increases with number of previous Caesarean sections, with rates of 3%, 11%, 40%, 61%, and 67% for the first, second, third, fourth, and fifth or greater number of Caesarean sections.[21] ## References[edit] 1. ^ Smith, Zachary L.; Sehgal, Shailen S.; Arsdalen, Keith N. Van; Goldstein, Irwin S. (2014). "Placenta Percreta With Invasion into the Urinary Bladder". Urology Case Reports. 2 (1): 31–32. doi:10.1016/j.eucr.2013.11.010. PMC 4733000. PMID 26955539. 2. ^ Society of Gynecologic Oncology; American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine; Cahill, Alison G.; Beigi, Richard; Heine, R. Phillips; Silver, Robert M.; Wax, Joseph R. (2018-12-01). "Placenta Accreta Spectrum". American Journal of Obstetrics and Gynecology. 219 (6): B2–B16. doi:10.1016/j.ajog.2018.09.042. ISSN 1097-6868. PMID 30471891. 3. ^ Capella-Allouc, S.; Morsad, F; Rongières-Bertrand, C; Taylor, S; Fernandez, H (1999). "Hysteroscopic treatment of severe Asherman's syndrome and subsequent fertility". Human Reproduction. 14 (5): 1230–3. doi:10.1093/humrep/14.5.1230. PMID 10325268. 4. ^ Al-Serehi, A; Mhoyan, A; Brown, M; Benirschke, K; Hull, A; Pretorius, DH (2008). "Placenta accreta: An association with fibroids and Asherman syndrome". Journal of Ultrasound in Medicine. 27 (11): 1623–8. doi:10.7863/jum.2008.27.11.1623. PMID 18946102. S2CID 833810. 5. ^ American Pregnancy Association (January 2004) 'Placenta Accreta Archived 2006-01-16 at the Wayback Machine'. Accessed 16 October 2006 6. ^ Arulkumaran, edited by Richard Warren, Sabaratnam (2009). Best practice in labour and delivery (1st ed., 3rd printing. ed.). Cambridge: Cambridge University Press. pp. 108, 146. ISBN 978-0-521-72068-7.CS1 maint: extra text: authors list (link) 7. ^ Shimonovitz, S; Hurwitz, A; Dushnik, M; Anteby, E; Geva-Eldar, T; Yagel, S (September 1994). "Developmental regulation of the expression of 72 and 92 kd type IV collagenases in human trophoblasts: a possible mechanism for control of trophoblast invasion". American Journal of Obstetrics and Gynecology. 171 (3): 832–8. doi:10.1016/0002-9378(94)90107-4. PMID 7522400. 8. ^ a b ACOG Committee on Obstetric, Practice (January 2002). "ACOG Committee opinion. Number 266, January 2002 : placenta accreta". Obstetrics and Gynecology. 99 (1): 169–70. doi:10.1016/s0029-7844(01)01748-3. PMID 11777527. 9. ^ Hobbins, John C. (2007). Obstetric ultrasound : artistry in practice. Oxford: Blackwell. p. 10. ISBN 978-1-4051-5815-2. 10. ^ a b Steven G. Gabbe; Jennifer R. Niebyl; Joe Leigh Simpson, eds. (2002). Obstetrics: normal and problem pregnancies (4. ed.). New York, NY [u.a.]: Churchill Livingstone. p. 519. ISBN 9780443065729. 11. ^ Bowman ZS, Eller AG, Kennedy AM, Richards DS, Winter TC, Woodward PJ, Silver RM (December 2014). "Interobserver variability of sonography for prediction of placenta accreta". Journal of Ultrasound in Medicine. 33 (12): 2153–8. doi:10.7863/ultra.33.12.2153. PMID 25425372. S2CID 22246937. 12. ^ D'Antonio F, Iacovella C, Palacios-Jaraquemada J, Bruno CH, Manzoli L, Bhide A (July 2014). "Prenatal identification of invasive placentation using magnetic resonance imaging: systematic review and meta-analysis". Ultrasound in Obstetrics & Gynecology. 44 (1): 8–16. doi:10.1002/uog.13327. PMID 24515654. S2CID 9237117. 13. ^ Balcacer, Patricia; Pahade, Jay; Spektor, Michael; Staib, Lawrence; Copel, Joshua A.; McCarthy, Shirley (2016). "Magnetic Resonance Imaging and Sonography in the Diagnosis of Placental Invasion". Journal of Ultrasound in Medicine. 35 (7): 1445–1456. doi:10.7863/ultra.15.07040. ISSN 0278-4297. PMID 27229131. 14. ^ Selman AE (April 2016). "Caesarean hysterectomy for placenta praevia/accreta using an approach via the pouch of Douglas". BJOG : An International Journal of Obstetrics and Gynaecology. 123 (5): 815–9. doi:10.1111/1471-0528.13762. PMC 5064651. PMID 26642997. 15. ^ Washecka R, Behling A (April 2002). "Urologic complications of placenta percreta invading the urinary bladder: a case report and review of the literature". Hawaii Medical Journal. 61 (4): 66–9. PMID 12050959. 16. ^ Johnston, T A; Paterson-Brown, S (January 2011). Placenta Praevia, Placenta Praevia Accreta and Vasa Praevia: Diagnosis and Management. Green-top Guideline No. 27. Royal College of Obstetricians and Gynecologists. 17. ^ a b Oyelese, Yinka; Smulian, John C. (2006). "Placenta Previa, Placenta Accreta, and Vasa Previa". Obstetrics & Gynecology. 107 (4): 927–41. doi:10.1097/01.AOG.0000207559.15715.98. PMID 16582134. S2CID 22774083. 18. ^ a b Turrentine, John E. (2008). Clinical protocols in obstetrics and gynecology (3rd ed.). London: Informa Healthcare. p. 286. ISBN 9780415439961. 19. ^ Committee On Obstetric, Practice (2002). "Placenta accreta Number 266, January 2002 Committee on Obstetric Practice". International Journal of Gynecology & Obstetrics. 77 (1): 77–8. doi:10.1016/S0020-7292(02)80003-0. PMID 12053897. S2CID 42076480. 20. ^ Committee on Obstetric Practice. "Placenta Accreta". American College of Obstetricians and Gynecologists. Archived from the original on 2016-11-23. Retrieved 2014-08-22. 21. ^ Silver, R.M.; Landon, M.B.; Rouse, D.J.; Leveno, K.J.; Spong, C.Y.; Thom, E.A.; Moawad, A.H.; Caritis, S. N.; Harper, M; Wapner, R. J.; Sorokin, Y; Miodovnik, M; Carpenter, M; Peaceman, A. M.; O'Sullivan, M. J.; Sibai, B; Langer, O; Thorp, J. M.; Ramin, S. M.; Mercer, B. M.; National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network; et al. (2006). "Maternal morbidity associated with multiple repeat cesarean deliveries". Obstet Gynecol. 107 (6): 1226–32. doi:10.1097/01.AOG.0000219750.79480.84. PMID 16738145. S2CID 257455. ## External links[edit] Classification D * ICD-10: O43.2 * ICD-10-CM: O43.21 * ICD-9-CM: 667.0 * MeSH: D010921 * DiseasesDB: 10091 * SNOMED CT: 70129008 * National Accreta Foundation * Interactive graphic explaining placenta accreta / Stanford Medical School Magazine article (right side) * v * t * e Pathology of pregnancy, childbirth and the puerperium Pregnancy Pregnancy with abortive outcome * Abortion * Ectopic pregnancy * Abdominal * Cervical * Interstitial * Ovarian * Heterotopic * Embryo loss * Fetal resorption * Molar pregnancy * Miscarriage * Stillbirth Oedema, proteinuria and hypertensive disorders * Gestational hypertension * Pre-eclampsia * HELLP syndrome * Eclampsia Other, predominantly related to pregnancy Digestive system * Acute fatty liver of pregnancy * Gestational diabetes * Hepatitis E * Hyperemesis gravidarum * Intrahepatic cholestasis of pregnancy Integumentary system / dermatoses of pregnancy * Gestational pemphigoid * Impetigo herpetiformis * Intrahepatic cholestasis of pregnancy * Linea nigra * Prurigo gestationis * Pruritic folliculitis of pregnancy * Pruritic urticarial papules and plaques of pregnancy (PUPPP) * Striae gravidarum Nervous system * Chorea gravidarum Blood * Gestational thrombocytopenia * Pregnancy-induced hypercoagulability Maternal care related to the fetus and amniotic cavity * amniotic fluid * Oligohydramnios * Polyhydramnios * Braxton Hicks contractions * chorion / amnion * Amniotic band syndrome * Chorioamnionitis * Chorionic hematoma * Monoamniotic twins * Premature rupture of membranes * Obstetrical bleeding * Antepartum * placenta * Circumvallate placenta * Monochorionic twins * Placenta accreta * Placenta praevia * Placental abruption * Twin-to-twin transfusion syndrome Labor * Amniotic fluid embolism * Cephalopelvic disproportion * Dystocia * Shoulder dystocia * Fetal distress * Locked twins * Nuchal cord * Obstetrical bleeding * Postpartum * Pain management during childbirth * placenta * Placenta accreta * Preterm birth * Postmature birth * Umbilical cord prolapse * Uterine inversion * Uterine rupture * Vasa praevia Puerperal * Breastfeeding difficulties * Low milk supply * Cracked nipples * Breast engorgement * Childbirth-related posttraumatic stress disorder * Diastasis symphysis pubis * Postpartum bleeding * Peripartum cardiomyopathy * Postpartum depression * Postpartum psychosis * Postpartum thyroiditis * Puerperal fever * Puerperal mastitis Other * Concomitant conditions * Diabetes mellitus * Systemic lupus erythematosus * Thyroid disorders * Maternal death * Sexual activity during pregnancy * Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Placenta accreta spectrum	c0032044	26,940	wikipedia	https://en.wikipedia.org/wiki/Placenta_accreta_spectrum	2021-01-18T18:57:48	{"mesh": ["D010921"], "umls": ["C0032044"], "icd-9": ["667.0"], "wikidata": ["Q517856"]}
For a discussion of genetic heterogeneity of X-linked spinocerebellar ataxia (SCAX), see SCAX1 (302500). Clinical Features Farlow et al. (1987) described a large kindred in which males of 3 generations connected through females showed an apparently X-linked syndrome comprising ataxia, pyramidal tract signs and adult-onset dementia. Initial signs, manifested by 2 to 3 years of age, were delayed walking and tremor. During their teens, the patients would develop mild but progressive ataxia and pyramidal signs. Memory problems in the third decade initiated a progressive dementia, leading to death in the sixth decade. Laboratory investigations failed to disclose an abnormality. Preliminary linkage studies using RFLPs suggested that Xq26-qter and much of the short arm could be excluded as sites for the gene. Neuro \- Ataxia \- Delayed walking \- Tremor \- Pyramidal tract signs \- Adult-onset dementia Inheritance \- X-linked ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SPINOCEREBELLAR ATAXIA, X-LINKED 4	c1844933	26,941	omim	https://www.omim.org/entry/301840	2019-09-22T16:18:45	{"mesh": ["C537316"], "omim": ["301840"], "orphanet": ["85292"], "synonyms": ["Alternative titles", "SCAX4", "ATAXIA-DEMENTIA SYNDROME, X-LINKED"]}
A number sign (#) is used with this entry because hereditary retinoblastoma is caused by a heterozygous germline mutation on one allele and a somatic mutation on the other allele of the RB1 gene (614041) on chromosome 13q14. See also the chromosome 13q14 deletion syndrome (613884) in which retinoblastoma is a feature. Description Retinoblastoma (RB) is an embryonic malignant neoplasm of retinal origin. It almost always presents in early childhood and is often bilateral. Spontaneous regression ('cure') occurs in some cases. The retinoblastoma gene (RB1) was the first tumor suppressor gene cloned. It is a negative regulator of the cell cycle through its ability to bind the transcription factor E2F (189971) and repress transcription of genes required for S phase (Hanahan and Weinberg, 2000). Clinical Features Connolly et al. (1983) reported a 4-generation family with 3 patterns of expression of the retinoblastoma gene: frank retinoblastoma, unilateral or bilateral; retinoma; and no visible retinal pathology except for 'normal degeneration' with age. ('Paving stone degeneration' of the type observed in 2 of 3 RB carriers, aged 49 and 59, is said by Duane (1980) to occur in about 20% of the adult population.) In a review, Balmer et al. (2006) noted that the most common presenting signs of retinoblastoma are leukocoria (a late sign) and strabismus (an early sign), but that many other ocular or general signs have been observed. Although the malignant tumor is curable with early treatment, there remains in the heritable form a major risk of second nonocular primary tumors. ### Retinoma Gallie and Phillips (1982) described benign lesions in the retina in retinoblastoma patients. The distinctive characteristics of these lesions, referred to by the authors as retinomas, included a translucent, grayish retinal mass protruding into the vitreous, 'cottage-cheese' calcification in 75%, and retinal pigment epithelial migration and proliferation in 60%. They suggested that retinomas represent not the heterozygous state postulated by the Knudson 2-stage model of carcinogenesis but rather the homozygous state occurring in differentiated cell(s). Gallie et al. (1982) suggested that retinomas represent either spontaneous regression of a retinoblastoma or a benign manifestation of the RB gene. ### Trilateral Retinoblastoma Brownstein et al. (1984) described 3 children with bilateral retinoblastoma and a morphologically similar neoplasm in the region of the pineal. They referred to this as trilateral retinoblastoma. The pineal gland has sometimes been referred to as 'the third eye.' Lueder et al. (1991) described a fourth case of pinealoma associated with bilateral retinoblastoma. The patient was one of 56 with heritable RB. Amoaku et al. (1996) reported 5 patients with trilateral retinoblastoma (including 2 previously reported), diagnosed among 146 consecutive patients with retinoblastoma in the West Midlands Health Authority Region in England between 1957 and 1994. This represented an incidence of 3%. There were 4 patients with pineoblastoma, only 1 of whom had a positive family history. The mean age at diagnosis of RB in the entire series was 6 months, whereas the patients with pineoblastoma were diagnosed at a mean age of 2 years. The tumors were not evident on the initial computed tomographic (CT) scans. One child presented with a calcified suprasellar mass 13 months before bilateral sporadic retinoblastoma was identified. Death occurred within 1 month of diagnosis of the intracranial tumor in 3 patients who received no treatment. In the other 2 patients, who were treated, death occurred at 15 months and 2 years, respectively, after diagnosis of intracranial tumor. Kivela (1999) performed a metaanalysis of trilateral retinoblastoma by reviewing the literature systematically and contacting authors to obtain missing information. Data from 106 children were used to determine frequency and Kaplan-Meier survival curves. No sex predilection was found. Median age at diagnosis of retinoblastoma was 5 months (range, 0 to 29 months); age at diagnosis was younger among 47 children (47%) with familial retinoblastoma compared with age at diagnosis among 52 children (53%) with sporadic retinoblastoma (2 vs 6.5 months; P less than 0.0001). Trilateral retinoblastoma usually affected the second or third generation with retinoblastoma. Median time from retinoblastoma to trilateral retinoblastoma was 21 months (range, 6 months before to 141 months after); time to trilateral retinoblastoma was longer for 78 (77%) pineal tumors compared with 23 (23%) suprasellar tumors (32 vs 6.5 months; P less than 0.0001). The size and prognosis of pineal and suprasellar tumors were similar. Screening by neuroimaging improved outcome. The cure rate was improved when the tumors were at or below 15 mm at the time of detection. Karatza et al. (2006) reported a pineal cyst simulating pineoblastoma in 11 children with retinoblastoma (2 familial and 9 sporadic). ### Second Primary Tumors The risk of osteogenic sarcoma is increased 500-fold in bilateral retinoblastoma patients, the bone malignancy being at sites removed from those exposed to radiation treatment of the eye tumor (Abramson et al., 1976). Francois (1977) concluded that there is a special predisposition to osteogenic sarcoma, both radiogenic and nonradiogenic, in retinoblastoma patients and possibly in their relatives. Matsunaga (1980) estimated that the relative risk of development of nonradiogenic osteosarcoma in persons with the retinoblastoma gene is 230. That osteosarcoma is a direct effect of the genomic change that underlies retinoblastoma is indicated by the cases of osteosarcoma without retinoblastoma but with genomic changes like those of retinoblastoma. Chauveinc et al. (2001) reviewed retinoblastoma survivors who subsequently developed osteosarcoma. They found that osteosarcomas occurred 1.2 years earlier inside than outside the radiation field in patients who had undergone external beam irradiation. Also, the latency between radiotherapy and osteosarcoma was 1.3 years shorter inside than outside the radiation field. Bimodal distribution of latency periods was observed for osteosarcomas arising inside but not outside the radiation field: 40% occurred after a short latency, while the latency for the remaining 60% was comparable to that of osteosarcoma arising outside the radiation field. The authors suggested that different mechanisms may be involved in the radiocarcinogenesis. They hypothesized that a radiation-induced mutation of the second RB1 allele may be the cause of osteosarcomas occurring after a short delay, while other genes may be responsible for osteosarcomas occurring after a longer delay. To understand why the RB protein is specifically targeted in osteosarcoma, Thomas et al. (2001) studied its function in osteogenesis. Loss of RB but not p107 (116957) or p130 (180203) blocked late osteoblast differentiation. RB physically interacted with the osteoblast transcription factor, CBFA1 (600211), and associated with osteoblast-specific promoters in vivo in a CBFA1-dependent fashion. Association of RB with CBFA1 and promoter sequences resulted in synergistic transactivation of an osteoblast-specific reporter. This transactivation function was lost in tumor-derived RB mutants, underscoring a potential role in tumor suppression. Thus, RB functions as a direct transcriptional coactivator promoting osteoblast differentiation, which may contribute to the targeting of RB in osteosarcoma. Friend et al. (1987) found that the same DNA segment that they had isolated from 13q14 and showed to have attributes of the retinoblastoma gene is additionally the target of somatic mutations in mesenchymal tumors among patients having no apparent predisposition to retinoblastoma. Almost two-thirds of the secondary tumors arising in patients with retinoblastoma are mesenchymal in origin. Over 60% of the mesenchymal tumors are osteosarcomas; the soft tissue sarcomas include fibrosarcoma, leiomyosarcoma, liposarcoma, and others. Friend et al. (1987) specifically demonstrated homozygous deletions of the RB1 locus in sporadic cases of leiomyosarcoma, malignant fibrous histiocytoma, and undifferentiated sarcoma in the absence of any history of retinoblastoma. Friend et al. (1988) reviewed the subject of tumor-suppressing genes in retinoblastoma and other disorders. Henson et al. (1994) found loss of heterozygosity for the RB1 protein in 16 of 54 informative high-grade astrocytomas but not in 12 low-grade gliomas. Deletion mapping with ranking markers revealed that the retinoblastoma locus was preferentially targeted by the deletions. SSCP analysis and direct DNA sequencing demonstrated mutations in the remaining retinoblastoma allele. This evidence suggested to the authors that whereas mutation of the p53 tumor suppressor gene (191170) is an early event in the formation of many astrocytomas, mutation of the retinoblastoma gene is associated with progression of the astrocytoma into high-grade astrocytoma or glioblastoma multiforme. Previous work had demonstrated frequent loss of 9p, 10, 13q, 17p, 19q, and 22q in astrocytomas. Mutations in the RB1 gene were described. Cance et al. (1990) found that leiomyosarcomas and other soft tissue sarcomas in which expression of the RB gene product was decreased were more aggressive than tumors in which this protein was expressed by nearly all cells. Moll et al. (2001) evaluated the influence of age at external beam irradiation (EBRT) on the occurrence of second primary tumors (SPTs) inside and outside the irradiation field in 263 patients with hereditary retinoblastoma. They calculated cumulative incidences of SPT in 3 subgroups: irradiation before 12 months of age (early EBRT), irradiation after 12 months of age (late EBRT), and no irradiation. They found that hereditary RB conferred an increased risk of the development of SPT, especially in patients treated with EBRT before 12 months of age. However, they concluded that the presence of similar numbers of SPTs inside and outside the irradiation field suggested that irradiation was not the cause. The authors concluded that their study did not show an age effect on radiation-related risk, but rather that early EBRT is probably a marker for other risk factors of SPT. Kivela et al. (2001) analyzed the association between retinoblastoma and sebaceous carcinoma (SC) of the eyelid to improve surveillance of RB survivors. They studied 11 children with hereditary RB who subsequently developed eyelid SC. Nine of the children developed SC within the field of radiation. All 9 had received a median of 46 Gy (range, 21-89) of EBRT at a median age of 16 months (range, 0.5-15 years of age). Their median age at SC diagnosis was 14 years (range, 8-30 years) and median interval from EBRT to SC diagnosis was 11 years (range, 5-26 years). The 2 children who had never received EBRT developed eyelid SC at ages 32 and 54 years. In this series, the cumulative probability of a 5-year survival of eyelid SC was 87%. The authors concluded that SC of the eyelid may occur in patients with hereditary RB regardless of primary treatment, especially within the EBRT field 5 to 15 years after radiotherapy. Brantley et al. (2002) examined expression of p53 and Rb tumor suppressor pathways in uveal melanomas following plaque radiotherapy. They found that plaque radiotherapy damaged DNA, inhibited cell division, and promoted cell death. They stated that these changes might be due, at least in part, to induction of p53, which activates genes involved both in cell cycle arrest and apoptosis. Their results also showed that plaque radiotherapy can cause alterations in the expression of Rb, but the authors noted that the significance of the latter finding would require further study. Gombos et al. (2007) identified 15 retinoblastoma patients with secondary acute myelogenous leukemia (sAML; see 601626), 13 of whom developed sAML in childhood. Mean latent period from RB to AML diagnosis was 9.8 years (median, 42 months). Nine cases were of the M2 or M5 French-American-British subtypes. Twelve patients (79%) had received chemotherapy with a topoisomerase II inhibitor, and 8 (43%) had received chemotherapy with an epipodophyllotoxin. Ten children died of their leukemia. Gombos et al. (2007) questioned whether chemotherapy was a risk factor for the development of sAML in this series of patients. Other Features Bonaiti-Pellie et al. (1975) found an increased frequency of malformations, especially cleft palate, in association with retinoblastoma and proposed that this argued for germinal mutation rather than somatic mutation. Gibbons et al. (1995) presented a patient in whom sporadic unilateral retinoblastoma occurred at an unusually early age (4 months) in the presence of Fanconi anemia (227650). In a second child, they found retinoblastoma in association with Bloom syndrome (210900), another chromosome breakage syndrome. Clinical Management Shields et al. (2000) analyzed patient management and prognosis after vitrectomy in eyes with unsuspected retinoblastoma. Retinoblastoma may present with atypical features such as vitreous hemorrhage or signs of vitreous inflammation, particularly in older children. Vitrectomy should be avoided in these cases until the possibility of underlying retinoblastoma has been excluded. The authors concluded that if vitrectomy has been performed in an eye with unsuspected retinoblastoma, enucleation combined with adjuvant chemotherapy, radiotherapy, or both, should be done without delay to prevent systemic tumor dissemination. Honavar et al. (2001) reviewed 45 consecutive patients who underwent an intraocular surgery after treatment for retinoblastoma: 34 (76%) underwent a single procedure (cataract surgery, scleral buckling procedure, or pars plana vitrectomy) and 11 (24%) underwent a combination of 2 or more procedures. Sixteen patients (36%) achieved final visual acuity better than 20/200 (legal blindness). Unfavorable outcomes included recurrence of retinoblastoma in 14 patients (31%), enucleation in 16 (36%), and systemic metastasis in 3 (7%). Five patients (20%) who underwent cataract surgery, 5 (63%) who underwent scleral buckling, and 9 (75%) who underwent pars plana vitrectomy had an unfavorable outcome. Median interval between completion of treatment for retinoblastoma and intraocular surgery was 26 months in patients with a favorable outcome versus 6 months in those with an unfavorable outcome. The authors concluded that cataract surgery was safe and effective in most cases. However, they cautioned that scleral buckling and pars plana vitrectomy might be associated with a much higher risk of recurrence of retinoblastoma, enucleation, or systemic metastasis. Honavar et al. (2002) reviewed their experience with 80 consecutive patients with unilateral sporadic retinoblastoma who had been treated by primary enucleation and had high-risk characteristics for metastasis on histopathology, e.g., anterior chamber seeding, iris infiltration, ciliary body infiltration, massive choroidal infiltration, invasion of optic nerve lamina cribrosa, retrolaminar optic nerve invasion, invasion of the optic nerve transection, scleral infiltration, or extrascleral extension. A single high-risk characteristic was present in 62.5%, while 37.5% had more than 2 high-risk characteristics. Postenucleation adjuvant therapy (chemotherapy with or without orbital external beam radiotherapy) was administered to 58%. Adjuvant therapy was not administered to 42% of patients. Metastasis occurred in 13% of patients at a median of 9 months (range 6-57 months). Only 4% (2/46) of patients who had received adjuvant therapy developed metastasis, versus 24% (8/34) of patients who had not received adjuvant therapy. This difference was statistically significant (P = .02). The authors reported no serious systemic complications of adjuvant therapy. Thus, they concluded that postenucleation adjuvant therapy was safe and effective in significantly reducing the occurrence of metastasis in patients with retinoblastoma manifesting high-risk histopathologic characteristics. In a retrospective study that included 100 enucleation specimens belonging to 96 patients with retinoblastoma, Abramson et al. (2003) analyzed the differences between the length of the optic nerve measured by the ophthalmologist in the operating room after enucleation and the length measured by the pathologist after fixation. They found a significant degree of shrinkage of the optic nerve after fixation prior to pathologic analysis. They cautioned that this must be taken into account when comparing different series and making recommendations for chemoprophylaxis based solely on histopathologic examination. Camassei et al. (2003) found that FAS (600212) activation increased with increased retinoblastoma aggressiveness and postulated that FAS inhibition could represent an alternative treatment strategy in advanced and resistant retinoblastomas. Poulaki et al. (2005) found that human retinoblastoma cell lines were resistant to death receptor (see DR5; 603612)-mediated apoptosis because of a deficiency of caspase-8 (CASP8; 601763) expression secondary to epigenetic gene silencing by overmethylation. Treatment with a demethylating agent restored CASP8 expression and sensitivity to apoptosis. Poulaki et al. (2005) suggested that a combination of demethylating agents with DR-activating modalities, such as TNF-related apoptosis-inducing ligand receptor (see 603163) monoclonal antibodies, might benefit patients with retinoblastoma. Siffroi-Fernandez et al. (2005) examined fibroblast growth factor (FGF) high and low affinity receptor (FGFR) expression, activation of FGFR1 (136350) by acidic FGF (FGF1; 131220), and proliferative effects on Y79 retinoblastoma cells. They found that Y79 retinoblastoma expresses protein and mRNA of all 4 FGFRs. FGFR1 was differentially phosphorylated by FGF1. Proliferation of Y79 cells induced by FGF1 was entirely mediated by FGFR1. FGF1-induced proliferation was dependent on the presence and sulfation of heparan sulfate proteoglycan (HSPG; 142460). Siffroi-Fernandez et al. (2005) concluded that their study demonstrated a role for the FGF1/FGFR1 pathway in retinoblastoma proliferation and might contribute to developing therapeutic strategies to limit retinoblastoma growth. De Jong et al. (2006) documented the growth, clinical course, and histopathology of retinoblastomas in the well-functioning fellow eye of a 27-year-old man whose left eye was enucleated at age 2 years for retinoblastomas. Despite irradiation, transscleral cryocoagulation, argon laser photocoagulation of tumors and their feeder vessels, and combination chemotherapy, the remaining eye required enucleation due to tumor recurrences and seeding, pseudohypopyon, and elevated intraocular pressure. The authors thought there was sufficient evidence indicating that this was not a recurrence of a spontaneously regressed retinoblastoma, and that the patient's rare mutation in the RB1 gene (614041.0026) could explain the atypical course. The case report also showed that the germinative lens epithelial layer in adults can still function despite high doses of ionizing radiation and chemotherapy. Inheritance Smith and Sorsby (1958) concluded that bilateral cases of retinoblastoma are most often familial. In their opinion, estimates of mutation rate of 2.3 x 10(-5) as given by Falls and Neel (1951) were too high. Many unilateral cases may be sporadic with a low risk (empirically, about 4%) to subsequent children or to offspring of the proband. Knudson (1971) proposed that a 2-mutation model best fits the data. In this view, a fraction of cases are nonhereditary and result from 2 somatic mutational events in one cell. The remainder are hereditary cases, occurring in persons susceptible by reason of having inherited one of the mutational events. (See review of Knudson (1986) on the 2-mutation model and other aspects of the genetics of human cancer.) Matsunaga (1982) suggested that the almost synchronous appearance of bilateral retinoblastoma argues against the 2-mutation model, which assumes that in the gene carriers the eyes acquire tumors independently. Age-specific incidence rates for 96 New Zealand patients with sporadic retinoblastoma peaked earlier for bilateral cases than for unilateral ones (Fitzgerald et al., 1983). The cumulative log survival until diagnosis for bilateral and unilateral patients followed linear and quadratic curves, respectively, thus supporting the 2-hit hypothesis. A germ cell mutation rate of 9.3 x 10(-6) to 10.9 x 10(-6) was estimated. Interestingly, retinoblastoma, which behaves as a dominant in pedigrees, results from a gene that is expressed only in the homozygote, i.e., is recessive. Since retinoblastoma results from the homozygous or hemizygous state of a gene at 13q14, it should perhaps be stated that the susceptibility is dominant. The total experience with retinoblastoma has been that 5 to 10% of cases have been inherited; 20 to 30% have been new germinal mutations; and 60 to 70% have been sporadic, i.e., somatic mutations. Dryja et al. (1989) and Zhu et al. (1989) found that in bilateral retinoblastoma there is a preferential retention of the paternal chromosome in the process of loss of heterozygosity (LOH). This may indicate that either (1) mutation of RB1 is more common during spermatogenesis than oogenesis as a result of differences between male and female meiosis, DNA methylation or environmental exposure; or (2) the paternal chromosome in the early embryo is more at risk for mutation, or deficient in DNA repair. Dryja et al. (1989) analyzed the parental origin of mutations at the retinoblastoma locus using RFLPs known to map at chromosomal band 13q14. Ten of 10 new germline mutations were derived from the father's chromosome 13, while 4 of 7 somatic mutations occurred in the maternal retinoblastoma allele. The authors suggested that new germline mutations at the retinoblastoma locus arise more frequently during spermatogenesis than during oogenesis, but that genomic imprinting does not play an important role in the development of somatic mutations leading to this malignancy. Matsunaga et al. (1990) found no parental age effect in 225 sporadic cases of bilateral retinoblastoma and in 10 sporadic cases of chromosome deletion or translocation involving 13q14 that was identified as of paternal origin. Parental exposure to ionizing radiation or chemical mutagens, the effect of which accumulates with age, does not seem to play a major role in the production of germinal mutations at the RB1 locus. Since analysis of month of birth of 753 children with sporadic unilateral retinoblastoma showed no significant deviation from controls or a cyclic trend, nonheritable retinoblastoma is not likely to be associated with viruses whose activity varies markedly with season. DerKinderen et al. (1990) found that fathers 50 years of age or older had a relative risk of 5.0 to have a child with sporadic hereditary retinoblastoma compared with fathers in the population in general and that mothers 35 years of age or older had a relative risk of 1.7 compared with mothers in the population in general. Sporadic retinoblastoma was defined as occurrence without a family history of the disease. These cases were further classified as sporadic hereditary retinoblastoma when the patient was bilaterally affected or when a patient with unilateral retinoblastoma without family history later had the birth of a child with retinoblastoma; or as sporadic nonhereditary retinoblastoma when there was no family history, only unilateral retinoblastoma, and no occurrence of a relative in whom retinoblastoma was subsequently diagnosed. In connection with retinoblastoma, there is no parent of origin effect in the inherited disorder to suggest imprinting; however, there is evidence of imprinting in relation to osteosarcoma (Hall, 1993). The gene is more often transmitted from the father in the case of RB-related osteosarcoma. New mutations in the retinoblastoma gene most often occur in the father. Munier et al. (1992) found evidence of segregation distortion in a study of 8 kindreds with hereditary retinoblastoma by concomitant ophthalmologic examination and determination of 7 intragenic RFLPs. There was preferential transmission of the mutant allele from fathers; there was no difference from a 1:1 segregation ratio among the children of female carriers. Epidemiologic studies indicated a preferential paternal transmission of mutant retinoblastoma alleles to offspring (Munier et al. (1992)), suggesting the occurrence of meiotic drive. To investigate this mechanism, Girardet et al. (2000) analyzed sperm samples from 6 individuals from 5 unrelated families affected with hereditary retinoblastoma. Single-sperm typing techniques were performed for each sample by study of 2 informative short tandem repeats located either in or close to the RB1 gene. The segregation probability of mutant RB1 alleles in sperm samples was assessed by use of the SPERMSEG program, which includes experimental parameters, recombination fractions between the markers, and segregation parameters. A total of 2,952 single sperm from the 6 donors were analyzed. They detected a significant segregation distortion in the data as a whole (P = 0.0099) and a significant heterogeneity in the segregation rate across donors (0.0092). Further analysis showed that this result could be explained by segregation distortion in favor of the normal allele in 1 donor only and that it does not provide evidence of the significant segregation distortion in the other donors. The segregation distortion favoring the mutant RB1 allele does not seem to occur during spermatogenesis, and, thus, meiotic drive may result either from various mechanisms, including a fertilization advantage or a better mobility in sperm bearing a mutant RB1 gene, or from the existence of a defectively imprinted gene located on the human X chromosome. Naumova and Sapienza (1994) presented epidemiologic and genetic analyses of sporadic and familial retinoblastoma suggesting the existence of an X-linked gene (308290) involved in the genesis of a significant fraction of new bilateral cases of the disease. From the finding of both sex-ratio distortion in favor of males and transmission-ratio distortion in favor of affecteds among the offspring of males with bilateral sporadic disease, they proposed the existence of a defective imprinting gene on the X chromosome. Sporadic cases of Wilms tumor and embryonal rhabdomyosarcoma exhibit preferential loss of maternal alleles at loci linked to the putative tumor suppressor genes on 11p; sporadic cases of osteosarcoma and bilateral retinoblastoma similarly show preferential loss of maternal alleles at loci linked to the tumor suppressor gene on 13q. These observations may be explained by preferential germline mutation of the father's tumor suppressor gene or by genome imprinting. Naumova et al. (1994) examined 74 cases of sporadic retinoblastoma for tumors in which at least 2 genetic events had occurred: loss of heterozygosity for 13q markers and formation of an isochromosome 6p. They found 16 cases containing both events. In 13 of 16 such tumors, the chromosome 13q that was lost and the chromosome 6p that was duplicated were derived from the same parent. Because the formation of an isochromosome 6p is thought to be a somatic event and perhaps related to tumor progression (Horsthemke et al., 1989), the germline mutation model does not predict a relationship between the 2 events. The genome imprinting model, on the other hand, assumes that the original cell that gave rise to the tumor bore a genome imprint. Because the imprinting process affects loci on many different chromosomes, genetic events involving 2 unlinked loci would be expected to be related with respect to parent of origin, if both loci are imprinted. Toguchida et al. (1989) examined 13 sporadic osteosarcomas and in 12 found evidence indicating that the initial mutation was in the paternal gene. The finding suggests the involvement of germinal imprinting in producing differential susceptibility of the 2 genes to mutation. There was a growing body of data indicating a difference in behavior of maternally and paternally derived autosomal genes. Germinal imprinting may be mediated by some epigenetic process such as de novo DNA methylation and be carried over to postzygotic stages. Sippel et al. (1998) evaluated 156 families with retinoblastoma in which the initial oncogenic mutation in the RB1 gene had been identified. In 15 of the families (approximately 10%) they were able to document mosaicism for the initial mutation in the retinoblastoma gene, either in the proband or in one of the proband's parents. Sippel et al. (1998) stated that the true incidence of mosaicism in this group was probably higher than 10%; in some additional families mosaicism was likely but could not be proven, because somatic or germline DNA from key family members was unavailable. In one mosaic father the mutation was detected in both sperm and leukocyte DNA; in a second, the mutation was detected only in sperm. The possibility of mosaicism should always be considered during genetic counseling of newly identified families with retinoblastoma and other disorders in which a high proportion of cases represent new mutations. Genetic tests of germline DNA can provide valuable information that is not available through analysis of somatic (leukocyte) DNA. Based on genomewide methylation analysis of a patient with multiple imprinting defects, Kanber et al. (2009) identified a differentially methylated CpG island in intron 2 of the RB1 gene. The CpG island is part of a 5-prime truncated, processed pseudogene derived from the KIAA0649 gene (614056) on chromosome 9 and corresponds to 2 small CpG islands in the open reading frame of the ancestral gene. It is methylated on the maternal chromosome 13 and acts as a weak promoter for an alternative RB1 transcript on the paternal chromosome 13. In 4 other KIAA0649 pseudogene copies, which are located on chromosome 22, the 2 CpG islands have deteriorated and the CpG dinucleotides are fully methylated. By analyzing allelic RB1 transcript levels in blood cells, as well as in hypermethylated and 5-aza-2-prime-deoxycytidine-treated lymphoblastoid cells, Kanber et al. (2009) found that differential methylation of the CpG island (CpG 85) skews RB1 gene expression in favor of the maternal allele. Thus, Kanber et al. (2009) concluded that RB1 is imprinted in the same direction as CDKN1C (600856), which operates upstream of RB1. The imprinting of 2 components of the same pathway indicates that there has been strong evolutionary selection for maternal inhibition of cell proliferation. ### Penetrance Macklin (1959) demonstrated irregularities in the inheritance, suggesting incomplete penetrance. In 10.5% of cases, affected persons were identified in collateral lines. Examples included (1) a bilateral case, his unilaterally affected brother and a bilaterally affected daughter of the latter person; (2) 6 bilaterally affected offspring of a woman who had 1 microphthalmic eye but refused examination; (3) several instances of 2 or more affected sibs with normal parents. Incomplete penetrance was reported by Connolly et al. (1983) and Onadim et al. (1992) among others. A striking difference in penetrance between 2 generations of the family described by Connolly et al. (1983) suggested the segregation of an additional epistatic, host-resistance gene. Bundey and Morten (1981) reported a rather similar pattern of intergenerational difference in penetrance. Scheffer et al. (1989) identified nonpenetrance of the RB gene by the use of linkage markers in family studies. Dryja et al. (1993) examined the molecular basis of incomplete penetrance in some retinoblastoma families. In 1 family, a germline deletion was shared by affected and unaffected obligate carriers. The deletion encompassed exon 4 of the RB gene and corresponded to a mutant protein without residues 127-166. In another pedigree, the phenomenon was only 'pseudo-low penetrance' because the appearance of incomplete penetrance was created by the fact that 2 distant relatives had independently derived mutations. Munier et al. (1993) reported 2 families with 'pseudo-low penetrance' resulting from familial aggregation of sporadic cases caused by independently derived mutations. Bia and Cowell (1995) noted that rare families show evidence of incomplete penetrance where individuals transmit the mutant gene without being affected themselves. Formal proof of incomplete penetrance requires identification of the predisposing mutation. They reported an extraordinary family in which different mutations were identified in first cousins with bilateral disease. One cousin carried a C-to-T transition in exon 8, which changed CGA (arg) at codon 123 to TGA (stop). This mutation was present also in his affected mother. The other cousin carried an 8-bp deletion in exon 20 that resulted in the generation of a downstream stop codon. This mutation was not present in his mother who was a half sister of the affected mother of his affected cousin. Thus, this was an example not of reduced penetrance but of independent constitutional germline mutations. Sakai et al. (1991) observed a germline mutation within the promoter region of RB in 2 different families showing incomplete penetrance. In a study of 5 RB families with low penetrance, Otterson et al. (1997) identified 3 separate germline RB mutations which showed different degrees of partial functional inactivation of the RB protein. Apparently, there are 2 categories of mutant low-penetrant RB alleles, those affecting the promoter region and those resulting in mutant proteins that retain partial activity. Familial retinoblastoma with incomplete penetrance is characterized by the absence of clinical disease in obligate carriers or the presence of children with unifocal tumors that are more characteristic of sporadic retinoblastoma. In an effort to quantitate these clinical observations, Lohmann et al. (1994) proposed a disease-eye ratio (DER) that scored for each family the ratio of the sum of the number of eyes with retinal tumors over the number of obligate carriers. Kindreds with classic familial retinoblastoma characteristically showed a DER score that approached 2.0, whereas families with incomplete penetrance had DER scores less than 1.5. Otterson et al. (1999) studied the RB-pocket-binding properties of 3 independent, mutant RB alleles that were present in the germline of 12 kindreds with the phenotype of incomplete penetrance of familial retinoblastoma. Each arose from alterations of single codons within the RB pocket domain, designated del480 (614041.0023), 661W (614041.0019), or 712R (614041.0024). The 3 mutants lacked pocket protein-binding activity in vitro but retained the wildtype ability to undergo cyclin-mediated phosphorylation in vivo. Each of the low-penetrant RB mutants exhibited marked enhancement of pocket protein binding when the cells were grown at reduced temperature. In contrast, in this temperature range no change in binding activity was seen with wildtype RB, a 706F mutant, or an adjacent, in vitro-generated point mutation (707W). Otterson et al. (1999) demonstrated that many families with incomplete penetrance of familial retinoblastoma carry unstable, mutant RB alleles with temperature-sensitive pocket protein-binding activity. Harbour (2001) stated that recent advances in understanding of the structure and function of the RB protein provided insights into the molecular basis of low-penetrance retinoblastoma. Low-penetrance retinoblastoma mutations either cause a reduction in the amount of normal RB that is produced (class 1 mutations) or result in a partially functional mutant RB (class 2 mutations). In a survey of germline RB1 gene mutations in Spanish retinoblastoma patients, Alonso et al. (2001) found splicing mutations associated with a low-penetrance phenotype. Most of the mutations affecting splice junctions corresponded to retinoblastoma cases of either sporadic or hereditary nature with delayed onset (32 months on average). In contrast, most of the nonsense and frameshift mutations were associated with an early age at diagnosis (8.7 months on average). In 2 unrelated families with incompletely penetrant retinoblastoma, Klutz et al. (2002) identified a splice-site mutation (IVS6+1G-T; 614041.0025) in the RB1 gene. Analysis of RNA from white blood cells showed that this mutation causes skipping of exon 6. Although this deletion results in a frameshift, most carriers of the mutation did not develop retinoblastoma. The relative abundance of the resultant nonsense mRNA varied between members of the same family and was either similar to or considerably lower than the transcript level of the normal allele. Moreover, variation of relative transcript levels was associated with both the sex of the parent that transmitted the mutant allele and phenotypic expression: all 8 carriers with similar abundance of nonsense and normal transcript had received the mutant allele from their mothers, and only 1 of them had developed retinoblastoma; by contrast, all 8 carriers with reduced abundance of the nonsense transcript had received the mutant allele from their fathers, and all but 2 of them had retinoblastoma. After treatment with cycloheximide, the relative abundance of transcripts from paternally inherited mutant alleles was partly restored, thus indicating that posttranscriptional mechanisms, rather than transcriptional silencing, were responsible for low levels of mutant mRNA. The data suggested that a specific RB1 mutation can be associated with differential penetrance, on the basis of the sex of the transmitting parent. Fitzek et al. (2002) observed an unexpected hypersensitivity in ionizing radiation in skin fibroblasts derived from unaffected parents of children with hereditary retinoblastoma. In at least 4 of these 5 families, there was no family history of retinoblastoma, indicating a new germline mutation. Fitzek et al. (2002) hypothesized that the increased parental cell sensitivity to radiation may reflect the presence of an as yet unrecognized genetic abnormality occurring in one or both parents of children with retinoblastoma. Chuang et al. (2006) used DNA microarray technology to determine whether differences in gene expression profiles occurred in the unaffected parents of patients with hereditary retinoblastoma compared to 'normal' individuals. Microarray analyses were validated by quantitative reverse transcription-PCR measurements. A distinct difference was observed in the patterns of gene expression between unaffected retinoblastoma parents and normal controls. The differences between the 2 groups were identified when as few as 9 genes were analyzed. Population Genetics Macklin (1960) stated that in the U.S. the frequency of retinoblastoma is about 1 in 23,000 live births. Jensen and Miller (1971) found that at ages 2 to 3 years a peak of mortality occurred which was 2.5 times greater in blacks than in whites. Whether this reflects a truly high frequency in blacks or some other factor such as higher mortality from delayed diagnosis is not clear. Pendergrass and Davis (1980) found an incidence of 3.58 cases among each million children under age 15 years. Over 90% were diagnosed before age 5 years. No difference was found between whites and blacks, but other non-whites had rates more than 4 times greater than those of whites. Bilateral disease occurred in 20%. No nonhereditary retinoblastomas (which represent 55-65% of all retinoblastoma cases) are bilateral. Bilateral and unilateral hereditary retinoblastoma represent, respectively, about 25-30% and 10-15% of all cases. Cytogenetics The earliest example of a cytogenetic change in a solid tumor was the description of partial deletion of a D group chromosome in retinoblastoma by Stallard (1962) and Lele et al. (1963). In 12 reported patients with a deletion of the long arm of a D chromosome, 7 had retinoblastoma, which in 3 instances was bilateral (Taylor, 1970; Gey, 1970). Cytogenetic evidence suggested that a locus for retinoblastoma is on the long arm of chromosome 13. In the patients of Orye et al. (1971) and a patient of Wilson et al. (1969), in which a 14q- karyotype was found, no clinical features of the type usually associated with 13q- were present. Orye et al. (1971) found deletion of a distal part of the long arm of one chromosome 13 in a case of bilateral retinoblastoma. The broadest of the three Giemsa bands normally present on the long arm was missing. Grace et al. (1971) described a patient with typical 13q- syndrome plus retinoblastoma (613884). The karyotype contained a ring D chromosome. Wilson et al. (1973) restudied their case of bilateral retinoblastoma with new banding techniques and concluded that it, like all the other deleted D-chromosome cases, was an instance of 13q-. Orye et al. (1974) suggested that deletion of 13q21 is mainly responsible for retinoblastoma. With the advent of banding techniques, the chromosome involved was identified as chromosome 13 and the critical segment common to all deletions as band 13q14 (Francke, 1976). Deletion of 13q22 was found by Riccardi et al. (1979), who reviewed published cases of retinoblastoma with abnormality of chromosome 13. They noted that, contrariwise, duplication of this segment has only mildly deleterious consequences. In 1 of 8 patients with retinoblastoma, Davison et al. (1979) found a reciprocal translocation of chromosomes 1 and 13. The breakpoint in chromosome 13 was at band q12, suggesting that the retinoblastoma locus is more proximal than thought from other data. Sparkes et al. (1979, 1980) found that retinoblastoma and esterase D (ESD; 133280) map to the same band, 13q14. They observed that quantitative and qualitative expression of esterase D in 5 persons with partial deletions or duplications of chromosome 13 supported localization of the gene to 13q14. The same band had been found deleted in cases of retinoblastoma. Rivera et al. (1981) concluded that the retinoblastoma and esterase D loci are in the proximal half of the 13q14 band. Benedict et al. (1983) studied a patient who had ESD activity 50% of normal but no deletion of 13q14 at the 550-band level. However, in 2 stem lines identified in a retinoblastoma from this patient, they found a missing chromosome 13 and no detectable ESD activity was found in the tumor. Therefore, in the tumor, the patient had total loss of genetic information at the location of the retinoblastoma gene. Thus, homozygosity appears to underlie this tumor. Knight et al. (1980) studied linkage of familial retinoblastoma with fluorescent markers of chromosome 13. Instances of discordant segregation were attributed to crossing-over. Nichols et al. (1980) studied a patient with a 13q;Xp translocation and retinoblastoma. The 13q14 band was translocated intact to the X chromosome rather than being the breakpoint of the translocation. Genetic inactivation of the derivative X chromosome shown by late labeling and other findings with resulting functional monosomy of the 13q14 band was considered likely. About 20 cases of abnormality involving the 13q14 band, as an aberration in all somatic cells, had been described by 1981 (Balaban-Malenbaum et al., 1981). Mosaicism for a 13q- cell line was found in 2 of 3 patients in a series of 42 that had abnormal karyotypes (Motegi, 1981). All 3 had bilateral sporadic retinoblastoma and the 2 mosaic cases had an apparently normal phenotype except for the eye tumors. Comparison of the structural changes in the tumor cells with those in fibroblasts of some patients supported Knudson's 2-hit hypothesis. Using 2 probes, Horsthemke et al. (1987) found deletions in nearly 20% of patients with bilateral or multifocal unilateral retinoblastoma. One probe also detected a RFLP useful as a genetic marker in some families. Three of 8 deletions did not include the esterase D locus and were undetectable by conventional cytogenetic analysis. Sequence analysis of the RB cDNA clones demonstrated a long open reading frame encoding a hypothetical protein with features suggestive of a DNA-binding function. Ejima et al. (1988) showed that cytogenetically visible germline mutations resulting in retinoblastoma are usually in the paternally derived gene. Such a bias would not be expected for sporadic (nonfamilial) tumors, where both mutations occur in somatic tissue, but there had been some indication of a bias toward initial somatic mutation in the paternally derived gene on chromosome 11 in sporadic Wilms tumor (Shroeder et al., 1987). Lemieux et al. (1989) used a method of minute band analysis to locate the RB locus in subband 13q14.11. The method involved high resolution G banding by BrdU using antibodies and gold. The banding was visualized by electron microscopy. Lemieux et al. (1989) suggested that the gain in resolution afforded by immunochemical banding, coupled with electron microscopy, would prove highly useful in detecting small chromosome anomalies in clinical syndromes and neoplasms. Greger et al. (1990) studied a family in which the father and 2 of his children had bilateral retinoblastoma. The father was found to be a mosaic for 2 different deletions, one of which showed a complex rearrangement. The 2 deletions shared 1 breakpoint but extended in opposite directions. Both retinoblastoma and Wilms tumor are rare childhood tumors associated with loss or inactivation of RB1, located on 13q14, and WT1 (607102), located on 11p13, respectively. Punnett et al. (2003) reported a unique family in which an insertional translocation of a chromosomal segment that included band 13q14 inserted into 11p13, causing childhood Wilms tumor in the father, and whose child developed bilateral retinoblastoma. Thus, the insertional translocation caused both tumors. The estimated risk for an offspring of this father to develop Wilms tumor was up to 50%, to develop retinoblastoma 25%, to have neither tumor 25%, and to have both tumors 0%. Mapping Sparkes et al. (1983) showed that the locus for the nondeletion form of retinoblastoma is closely linked to the ESD locus. Tight linkage to ESD was established by Connolly et al. (1983). Dryja et al. (1983) found quantitatively normal esterase D in all of 51 patients with retinoblastoma and no known chromosomal abnormality. Cowell et al. (1986) surveyed 200 retinoblastoma patients (75% bilateral and 25% familial) for dosage evidence of deletion of the esterase D locus. Nine patients with about half-normal levels were found; 5 had not been previously recognized as carriers of deletion. Duncan et al. (1987) found that a cDNA probe hybridized most strongly to 13q14.2 and 13q14.3. They restudied an individual in whom a deletion was said to have separated the closely linked ESD and RB1 loci, placing ESD proximal to RB1. Quantitative in situ hybridization studies of this deletion showed, however, that ESD was missing from the deleted chromosome 13 and duplicated on a normal homolog. This led them to conclude that the deletion in this individual cannot be used to determine the orientation or sublocalization of ESD and RB1 within the 13q14 region. Cowell et al. (1988) found a 50% level of esterase D activity and a small deletion in region 13q14 in a patient with retinoblastoma. The mother showed the same 50% of normal esterase D level and the same deletion, but had no retinal abnormality. Cowell et al. (1988) stated that this was the first instance of direct transmission of the deletion and also the first instance in which the deletion did not predispose to tumor formation. Higgins et al. (1989) used field inversion gel electrophoresis (FIGE) to construct a restriction map of approximately 1,000 kb of DNA surrounding the RB1 locus and to detect the translocation breakpoints in 3 retinoblastoma patients. The large size of the presumed RB1 gene, approximately 200 kb, and its multiple dispersed exons, complicate molecular screening for prenatal and presymptomatic diagnosis and for carrier detection. By FIGE, Higgins et al. (1989) could detect and map the translocation breakpoints of all 3 retinoblastoma patients within the putative RB1 gene, thus substantiating the authenticity of this candidate sequence and demonstrating the utility of FIGE in detecting chromosomal rearrangements affecting this locus. In the course of constructing a long-range restriction map around the RB gene by means of PFGE analysis, Blanquet et al. (1991) found evidence of possible genomic imprinting: the NruI restriction pattern differed according to the parental origin of the deletion or other rearrangement. Diagnosis ### Diagnosis and Counseling Ophthalmoscopic examination typically shows a white 'cat's eye' reflex and a retinal tumor in one or both eyes, usually by age 3 years. Sparkes et al. (1979, 1980) suggested that if linkage between retinoblastoma and esterase D were found, this would provide a means of genetic counseling and early diagnosis, including prenatal diagnosis. Turleau et al. (1983) added a fourth family to those with retinoblastoma due to deletion of the critical portion of 13q in the offspring of a parent with a balanced insertional translocation (Riccardi et al., 1979; Rivera et al., 1981; Strong et al., 1981). They pointed out that without karyotyping the recurrence risk after the birth of 1 case from normal parents might be thought to be virtually nil whereas in fact it is 25% if one of the normal parents is a carrier of an insertional translocation. The same risk, 25%, applies to occurrence of a trisomic offspring. Cavenee et al. (1985) showed that the chromosome 13 remaining in tumors from 2 hereditary retinoblastoma cases was derived from the affected parents. The ability to identify which chromosome of an affected parent carries the mutation predisposing to retinoblastoma would have obvious usefulness in genetic counseling. Cavenee et al. (1986) demonstrated the usefulness of multiple RFLP and isozymic markers flanking the RB1 locus in prenatal and postnatal prediction of susceptibility to retinoblastoma. Wiggs et al. (1988) used cloned fragments of a 'retinoblastoma gene' that detected RFLPs and tested the usefulness of these RFLPs in predicting cancer in 20 families with hereditary retinoblastoma. Predictions were possible in 19 of the 20 families; in 18 of the 19, the marker RFLPs showed a consistent association with the mutation predisposing to retinoblastoma. In the 19th kindred, there was a lack of cosegregation, which, however, may have been due to inaccuracy of the clinical diagnosis of the retinal lesion in the key member of the kindred. Greger et al. (1988) demonstrated the usefulness of linkage analysis with DNA markers in genetic counseling of families with hereditary retinoblastoma. Maat-Kievit et al. (1993) detected an enormous retinoblastoma at 21 weeks of gestation by means of ultrasound. Since about 75% of cases of retinoblastoma due to constitutional mutations represent new mutations, Janson and Nordenskjold (1994) recognized a need for methods to identify carriers of such germline mutations so that informed genetic counseling can be offered. Using pulsed field gel electrophoresis in a screening of 20 unrelated cases with bilateral retinoblastoma, 1 constitutional mutation was detected and found to be caused by a balanced translocation t(4;13), with the breakpoint within intron 17 of the retinoblastoma gene. Timely molecular diagnosis of RB1 mutations has many benefits: it enables earlier treatment, lower risk, and better health outcomes for patients with retinoblastoma; empowers families to make informed family-planning decisions; and costs less than conventional surveillance. However, complexity hinders its clinical implementation. Most RB1 mutations are unique and distributed throughout the RB1 gene, with no real hotspots. Richter et al. (2003) devised a sensitive and efficient strategy to identify RB1 mutations that combined quantitative multiplex PCR, double-exon sequencing, and promoter-targeted methylation-sensitive PCR. Optimization of test order by stochastic dynamic programming and the development of allele-specific PCR for 4 recurrent point mutations decreased the estimated turnaround time to less than 3 weeks and decreased direct costs by one-third. Using this multistep method, Richter et al. (2003) detected 89% of mutations (199 of 224) in bilaterally affected probands and both mutant alleles in 84% (112 of 134) of tumors from unilaterally affected probands. By revealing those family members who did not carry the mutation found in the related proband, molecular analysis enabled 97 at-risk children from 20 representative families to avoid 313 surveillance examinations under anesthetic and 852 clinic visits. The average savings in direct costs from clinical examinations avoided by children in these families substantially exceeded the cost of molecular testing. Moreover, health care savings would continue to accrue, as children in succeeding generations would avoid unnecessary repeated anesthetics and examinations. Rushlow et al. (2009) found that the RB1 gene mutation detection rate in 1,020 retinoblastoma families was increased by the use of highly sensitive allele-specific PCR (AS-PCR) to detect low-level mosaicism for 11 recurrent RB1 nonsense mutations. Mosaicism was evident in 23 (5.5%) of 421 bilaterally affected probands and in 22 (3.8%) of 572 unilaterally affected probands, as well as in 1 unaffected mother of a unilateral proband. Noting that half of the mosaic mutations were detectable only by AS-PCR, Rushlow et al. (2009) suggested that significant numbers of low-level mosaics with other classes of RB1 mutations might remain unidentified by current technologies. In addition, since only 1 (0.7%) of 142 unaffected parents showed somatic mosaicism for the proband's mutation, in contrast to an overall 4.5% somatic mosaicism rate for retinoblastoma patients, Rushlow et al. (2009) suggested that mosaicism for an RB1 mutation is highly likely to manifest as retinoblastoma. ### Screening Noorani et al. (1996) compared the direct health care costs of molecular and conventional screening of relatives of individuals affected with retinoblastoma. With variables set at the most likely values (baseline), the expected cost (in 1994 Canadian dollars) of conventional screening was $31,430 for a prototype family consisting of 7 at-risk relatives. The cost included 3 clinic examinations and 8 examinations under anesthetic over the first 3 years of life for each relative. Using baseline variables, the molecular strategy consisted of the screening of a prototype family of 1 proband and 7 at-risk relatives at a cost of $8,674, including identification of the RB1 mutation in the proband, subsequent testing of the relevant relatives for that mutation, and clinical follow-up similar to the conventional strategy for relatives with the mutation. Sensitivity analysis over the range of values for each variable revealed a significant saving of health care dollars by the molecular route, indicating the benefit of redirecting economic resources to molecular diagnosis in retinoblastoma. Zeschnigk et al. (1999) reported a PCR-based assay for the detection of methylation at the RB1 promoter. The assay gave results which were concordant with those achieved by Southern blot analysis in 40 samples. Tsai et al. (2004) reported the usefulness of protein truncation testing (PTT) for rapid detection and sequencing of germline mutations in the RB1 gene. Nineteen (70%) of 27 probands tested positive for germline mutations by PTT. In 1 kindred, the proband had negative PTT results but an additional affected relative had positive PTT results. Using a multitiered approach to genetic testing, 23 (85%) of the 27 kindreds had mutations identified, and those detected by PTT received a positive result in as few as 7 days. In control subjects, PTT produced no false-positive results. The authors concluded that when used as an initial screen, PTT can increase the yield of additional testing modalities, providing a timely and cost-effective approach for the diagnosis of heritable germline mutations in patients with retinoblastoma. Molecular Genetics Fung et al. (1987) used a cDNA probe to determine the lesion in retinoblastomas. In 16 of 40 retinoblastomas studied with a cDNA probe by Fung et al. (1987), a structural change in the RB gene was identifiable, including, in some cases, homozygous internal deletions with corresponding truncated transcripts. An osteosarcoma also had a homozygous internal deletion with a truncated transcript. Possible hotspots for deletion were identified within the RB genomic locus. Among those tumors with no identifiable structural change, there was either absence of an RB transcript or abnormal expression of the RB transcript. Bookstein et al. (1988) identified at least 20 exons in genomic clones of the RB gene and provisionally numbered them. With a unique sequence probe from intron 1, they detected heterozygous deletions in genomic DNA from 3 retinoblastoma cell lines and genomic rearrangements in fibroblasts from 2 hereditary retinoblastoma patients, indicating that intron 1 includes a frequent site for mutations conferring predisposition to retinoblastoma. Demonstration of a DNA deletion of exons 2-6 from 1 RB allele, as well as the demonstration of other deletions, explains the origin of shortened RB mRNA transcripts. The retinoblastoma candidate gene, 4.7R, does not show gross deletion or rearrangement in most retinoblastomas. Dunn et al. (1988) searched for more subtle mutations using the ribonuclease protection method for analysis of 4.7R mRNA from retinoblastomas. In the ribonuclease (RNase) protection assay, RNases A and T1 cleave single-stranded RNA at basepair mismatches in RNA:RNA or RNA:DNA hybrids. The test identifies only about 50% of single basepair mutations. Dunn et al. (1988) found that 5 of 11 RB tumors, which exhibited normal 4.7R DNA and normal-sized RNA transcripts, showed abnormal ribonuclease cleavage patterns. Three of the 5 mutations affected the same region of the mRNA, consistent with an effect on splicing involving an as yet unidentified 5-prime exon. Canning and Dryja (1989) found deletions in the retinoblastoma gene in 12 of 49 tumors from patients with retinoblastoma or osteosarcoma. Mapping of the deletion breakpoints revealed coincidence of no 2 breakpoints. Thus they could not support the conclusion of others regarding the existence of a 'hotspot' for deletion breakpoints in this gene. In 4 tumors, they sequenced 200 basepairs surrounding each deletion breakpoint. Three deletions had termini within pairs of short, direct repeats ranging in size from 4 to 7 basepairs. They interpreted this as indicating that 'slipped mispairing' may predominate in the generation of deletions at the RB locus. Short, direct repeats were incriminated in 15 of 20 deletions in the beta-globin locus. In other loci, Alu sequences at breakpoints are frequently found, e.g., in the LDL receptor gene (606945), the ADA gene (608958) and the beta-hexosaminidase gene (606869). Efstratiadis et al. (1980) argued that the repeats found at the breakpoints of deletions of the beta-globin locus are not long enough to mediate unequal crossing over via homologous recombination, thus requiring the alternative model, 'slipped mispairing' during DNA replication. Dunn et al. (1989) extended the characterization of mutations in RB1 using RNase protection of RB1 transcripts to locate probable mutations, followed by polymerase chain reaction (PCR) to amplify and sequence the mutant allele. Mutations were identified in 15 of 21 RB tumors; in 8 tumors, the precise error in nucleotide sequence was characterized. Each of 4 germline mutations involved a small deletion or duplication while 3 somatic mutations were point mutations leading to splice alterations and loss of an exon from the mature RB1 mRNA. By PCR techniques, Yandell et al. (1989) demonstrated single nucleotide changes in tumors from 7 patients with simplex retinoblastoma (with no family history of the disease). In 4 patients, the mutation involved only the tumor cells, and in 3 it involved normal somatic cells as well as tumor cells but was not found in either parent. Thus, these 3 represent new germinal mutations. All 3 were C-to-T transitions in the coding strand in the retinoblastoma gene. Two of the 3 occurred at CpG pairs. Since new germinal mutations of the retinoblastoma gene are more likely to occur on the paternal allele (Dryja et al., 1989), the overrepresentation of C-to-T transitions is probably the result of processes that occur during male gametogenesis. Direct analysis of disease-causing mutations are particularly applicable to diseases characterized by a high proportion of new mutations. This approach had been used successfully with Lesch-Nyhan syndrome (300322) and Duchenne muscular dystrophy (310200), which are associated with high frequencies of new point mutations and new deletions, respectively. Analysis of genomic DNA obviates the difficulty of having an RNA transcript or protein gene product for analysis and allows the detection of mutations that may occur at splice sites or other sequences that are excluded from the RNA transcript. Of the 10 mutations (7 retinoblastoma tumors plus 3 others), 5 occurred in the exon 21-24 region which represents only 15% of the coding sequence of the retinoblastoma gene. It has been found that aberrant proteins from which amino acids coded by these exons have been deleted lack binding activity for the adenovirus E1A dominant transforming protein. Blanquet et al. (1995) performed a mutation survey of the RB1 gene in 232 patients with hereditary or nonhereditary retinoblastoma. They systematically explored all 27 exons and flanking sequences, as well as the promoter. All types of point mutations were represented and found to be unequally distributed along the RB1 gene sequence. In the population studied, exons 3, 8, 18, and 19 were preferentially altered. Correlations between the phenotypic expression and molecular alterations were difficult to discern, at least for the missense and in-frame mutations. However, Blanquet et al. (1995) observed that some patients carrying mutations in exon 19 also developed nonocular tumors such as pineoblastoma, fibrosarcoma, or osteosarcoma. Germline mutations were detected in 36% of 25 familial cases, in 20.5% of bilateral sporadic or unilateral multifocal cases, and in 7.1% of unilateral sporadic cases. Because of the low level of detection of germline mutations in hereditary cases, they reasoned that other mechanisms of inactivation of RB1 must be involved. Lohmann et al. (1996) studied 119 patients with hereditary retinoblastoma for germline RB1 mutations. Southern blot hybridization and PCR fragment-length analysis revealed mutations in 48 patients. In the remaining 71 patients, they detected mutations in 51 (72%) by applying heteroduplex analysis, nonisotopic SSCP, and direct sequencing. Rare sequence variants were also found in 4 patients. No region of the RB1 gene was preferentially involved in single base substitutions. Recurrent transitions were observed at most of the 14 CGA codons within the RB1 gene. No mutation was observed in exons 25-27, although this region contains 2 CGA codons. This suggested to the authors that mutations within the 3-prime terminal region of the RB1 gene may not be oncogenic. For the entire series of 119 patients, mutations were identified in 99 (83%). The spectrum comprised 15% large deletions, 26% small length alterations, and 42% base substitutions. Lohmann et al. (1997) investigated the frequency and nature of constitutional RB1-gene mutations in patients with isolated unilateral retinoblastoma. A total of 45 mutations were detected in tumors from 36 patients. Thirty-nine of the mutations--including 34 small mutations, 2 large structural alterations, and hypermethylation in 3 tumors--were not detected in the corresponding peripheral blood DNA. In 6 (17%) of the 36 patients, a mutation was detected in constitutional DNA, and 1 of these mutations was known to be associated with reduced expressivity. The presence of a constitutional mutation was not associated with an early age at treatment. In 1 patient, somatic mosaicism was demonstrated by molecular analysis of DNA and RNA from peripheral blood. In 2 patients without a detectable mutation in peripheral blood, mosaicism was suggested because 1 of the patients showed multifocal tumors and the other later developed bilateral retinoblastoma. Hagstrom and Dryja (1999) investigated loss of heterozygosity in a set of matched retinoblastoma and leukocyte DNA samples from 158 patients informative for DNA polymorphisms. Loss of heterozygosity at the RB locus was observed in 101 cases, comprising 7 cases with a somatic deletion causing hemizygosity and 94 with homozygosity (isodisomy). Homozygosity was approximately equally frequent in tumors from male and female patients, among patients with a germline versus somatic initial mutation, and among patients in whom the initial mutation occurred on the maternal versus paternal allele. A set of 75 tumors exhibiting homozygosity was investigated with markers distributed in the interval 13cen-q14. Forty-one tumors developed homozygosity at all informative marker loci, suggesting that homozygosity occurred through chromosomal nondisjunction. The remaining cases exhibited mitotic recombination. There was no statistically significant bias in apparent nondisjunction versus mitotic recombination among male versus female patients or among patients with germline versus somatic initial mutations. Hagstrom and Dryja (1999) compared the positions of somatic recombination events in the analyzed interval with a previously reported meiotic recombination map. Although mitotic crossovers occurred throughout the assayed interval, they were more likely to occur proximally than a comparable number of meiotic crossovers. They observed 4 triple-crossover cases, suggesting negative interference for mitotic recombination, the opposite of what is usually observed for meiotic recombination. Bremner et al. (1997) studied a 4-kb deletion spanning exons 24 and 25 of the RB1 gene and associated with low penetrance, since only 39% of eyes at risk in this family developed retinoblastoma. This was said to have been the largest deletion observed in a low penetrance family. Unlike the usual RB mutations, which cause retinoblastoma in 95% of at-risk eyes and yield no detectable protein, the del24-25 allele transcribed a message splicing exon 23 to exon 26, resulting in a detectable protein that lacks 58 amino acids from the C-terminal domain, proving that this domain is essential for suppression of retinoblastoma. Two functions were partially impaired by del24-25, namely, nuclear localization and repression of E2F, consistent with the idea that low penetrance mutations generate 'weak alleles' by reducing but not eliminating essential activities. However, del24-25 ablated interaction of the RB protein with MDM2. Sampieri et al. (2006) identified mutations in the RB1 gene in 13 (37%) of 35 unrelated Italian patients with retinoblastoma. Mutations were identified in 6 of 9 familial cases and 7 of 26 sporadic cases. Eleven of the 13 mutations were novel. Gratias et al. (2007) analyzed 22 short tandem repeat loci on chromosome 16q in 58 patients with known RB1 mutations and detected loss of heterozygosity in 18 (31%) of 58 tumors, with a 5.7-Mb minimum deleted region in the telomeric part of 16q24 with a centromeric boundary at Mb 82.7 in exon 10 of the CDH13 gene (601364). There was no loss of expression of CDH13 or 2 other candidate suppressors at 16q24, CBFA2T3 (603870) and WFDC1 (605322), in retina compared to retinoblastoma tissue. Gratias et al. (2007) noted that almost all retinoblastomas with chromosome 16q24 loss showed diffuse intraocular seeding, suggesting that genetic alterations in the minimal deleted region are associated with impaired cell-to-cell adhesion. Zhang et al. (2012) showed that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss in retinoblastoma, Zhang et al. (2012) performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. Zhang et al. (2012) then evaluated the role of RB1 in genome stability and considered nongenetic mechanisms of cancer pathway deregulation. For example, the protooncogene SYK (600085) is upregulated in retinoblastoma and is required for tumor cell survival. Targeting SYK with a small molecule inhibitor induced retinoblastoma tumor cell death in vitro and in vivo. Thus, Zhang et al. (2012) concluded that retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss. Dommering et al. (2014) studied 529 patients with retinoblastoma from 433 unrelated families in the Dutch National Retinoblastoma Register. Mutations in RB1 were detected in 92% of bilateral and/or familial patients and in 10% of nonfamilial unilateral cases. Overall, germline mutations were detected in 187 (43%) of 433 RB families; the mutations were 37% nonsense, 21% splicing, 20% frameshift, 9% large indel, 5% missense, and 1% promoter, with 7% chromosomal deletions. Ten percent of patients were mosaic for the RB1 mutation. Six 3-generation families with incompletely penetrant RB1 mutations were identified. Dommering et al. (2014) noted that the frequency of type of RB1 mutation in this unbiased national cohort was the same as the mutation spectrum described worldwide. Genotype/Phenotype Correlations Lohmann et al. (1996) found no correlation between the location of frameshift or nonsense mutations and phenotypic features of retinoblastoma, including age at diagnosis, the number of tumor foci, and the manifestations of nonocular tumors. Taylor et al. (2007) studied 165 RB1 mutation carriers from 50 unrelated pedigrees with a family history of retinoblastoma. Twenty-five (50%) families had nonsense or frameshift mutations and showed high or complete disease penetrance. Two families with nonsense mutations in exon 1 showed slightly reduced penetrance, suggesting transcriptional modifiers or resistance to nonsense-mediated decay. Aberrant splicing mutations were identified in 13 (26%) families and associated with incomplete penetrance and variable expressivity. Eight (16%) families had large gene rearrangements associated with high penetrance. Promoter and missense mutations were associated with low penetrance. Six fully penetrant mutation carriers developed a secondary sarcoma at a median age of 15 years, regardless of mutation type. Retinomas were observed in patients with truncating mutations or large gene rearrangements. Pathogenesis Murphree and Benedict (1984) suggested that the RB1 gene is a model for a class of recessive human cancer genes that have a 'suppressor' or 'regulatory' function. The primary mechanism in the development of retinoblastoma is loss or inactivation of both alleles of this gene. This mechanism contrasts with that of putative human oncogenes which are thought to induce cancers following activation or alteration. The high incidence of second primary tumors among patients who inherit one retinoblastoma gene suggests that this cancer gene plays a key role in the etiology of several other primary malignancies. In some retinoblastomas, extra nonrandom copies of specific chromosomal regions occur, suggesting that an 'expressor' gene (possibly an oncogene) may be involved. On morphologic criteria, retinoblastoma had long been considered a malignancy of the photoreceptor cell lineage. Bogenmann et al. (1988) showed that this tumor grown in vitro expresses highly specific photoreceptor cell genes: transducin alpha subunit, which is specific to the cone cell, and transcripts for red or green cone cell photopigment. Bogenmann et al. (1988) found no marker genes specific to rod cells. Weichselbaum et al. (1988) presented evidence suggesting that in soft tissue sarcomas as well as in osteosarcomas, transcriptional inactivation or posttranscriptional downregulation of the RB gene may be important in etiology. They used hybridization with a cDNA probe for RB mRNA to analyze 3 soft tissue sarcomas and 4 osteosarcomas in patients without retinoblastoma. Most of the tumors studied did not express detectable levels of RB mRNA, whereas normal cells and epithelial tumor cells did. One osteosarcoma expressed a 2.4-kb transcript in addition to a normal 4.7-kb species. Kimchi et al. (1988) demonstrated that retinoblastoma cells lack receptors for TGF-beta. Whereas in control cells, in this case retinal cells from fetuses, treatment with TGF-beta inhibited cell division, treatment of retinoblastoma cells with the same substance had no effect on DNA synthesis, cell division, or cell morphology. Huang et al. (1988) demonstrated suppression of the neoplastic phenotype in cultured retinoblastoma or osteosarcoma cells by introduction of a cloned RB gene via retrovirus-mediated gene transfer. This is compelling evidence that the inactivation of the endogenous RB gene in these cells was a crucial step in tumorigenesis. Benedict et al. (1990) suggested that retinoblastoma may be unique in that functional loss of both RB alleles suffices for malignant development. In osteosarcoma, additional change of the p53 locus may be necessary, and in small-cell lung carcinoma, changes in both p53 and the short arm of chromosome 3 may be necessary. The results of many experiments indicate that the normal function of the RB gene product is a negative regulator of cellular proliferation which is achieved by sequestering a variety of nuclear proteins involved in cellular growth. DNA tumor virus oncoproteins transform cells, at least in part, by releasing these cellular proteins from inactive complex. Two of the cellular proteins that are bound, E2F (189971) and the MYC protein (NMYC; 164840), are transcription factors. Bandara et al. (1991) reported a naturally occurring loss-of-function RB allele encoding a protein that fails to complex with DRTF1 (189902). They also showed that cyclin A (CCNA; 123835) also complexes with DRTF1 and facilitates the efficient assembly of the RB protein into the complex. Goodrich et al. (1991) found that injection into cells of either full-length or a truncated form of the RB protein containing the T antigen-binding region inhibited progression from G1 into the S phase. Coinjection of anti-RB antibodies antagonized this effect. The results indicated that RB regulates cell proliferation by restricting cell cycle progression at a specific point in G1 and established a biologic assay for RB activity. Coinjection of RB with a T-antigen peptide or injection into cells expressing T antigen was accompanied by no inhibition of progression into S phase. This was interpreted as indicating that the transforming proteins of some DNA tumor viruses, including SV40 T antigen and adenovirus E1A, may promote cell growth, at least in part, by binding and inactivating RB. Sakai et al. (1991) studied the methylation pattern at the 5-prime end of the RB gene, including its promoter region and exon 1, in DNA purified from 56 primary retinoblastomas. The purpose was to investigate the possibility that hypermethylation of the promoter region might be responsible for loss of function of the gene giving rise to tumor. In 5 of the tumors, they found evidence for hypermethylation; all tumors were from unilateral, 'simplex' patients. No methylation abnormality was detected in DNA purified from the leukocytes of these patients. In 1 of the tumors, the hypermethylation was confined to 1 allele. No mutations to account for the allele-specific hypermethylation was found in a 1,306-bp sequence including the hypermethylated region. If hypermethylation indeed is the cause of the tumor, therapeutic agents that interfere with methylation of DNA might be effective. A significant proportion of disease-causing mutations in the RB1 gene result in the premature termination of protein synthesis, and most of these mutations occur as C-to-T transitions at CpG dinucleotides. Mancini et al. (1997) presented evidence confirming the view that such recurring CpG mutations are the result of the deamination of 5-methylcytosine within these CpGs. They used the sodium-bisulfite conversion method to detect cytosine methylation in representative exons of RB1. They analyzed DNA from a variety of tissues and specifically targeted CGA codons in RB1, where recurrent termination mutations had been reported. They found that DNA methylation within RB1 exons 8, 14, 25, and 27 appeared to be restricted to CpGs, including 6 CGA codons. Other codons containing methylated cytosines had not been reported to be mutated. Therefore, disease-causing mutations at CpGs in RB1 appear to be determined by several factors, including the constitutive presence of DNA methylation at cytosines within CpGs, the specific codon within which the methylated cytosine is located, and the particular region of the gene within which that codon resides. Gallie (1997) commented that the 'biology of the protein product of RB1 has ignited the field of cell cycle regulation, so that much more literature now refers to the retinoblastoma protein than to the disease.' The main point of her editorial, however, was to emphasize the need for a new kind of partnership between research, innovative entrepreneurial activities, and clinical management to get the most out of the investment that has been made in identifying human disease genes such as RB1. Nevins (2001) reviewed the role of the Rb/E2F pathway in cell proliferation, cell fate determination, and cancer. Van Aken et al. (2002) studied the cadherin-catenin complex in retinoblastoma and normal retina tissues. In both cases, they found that N-cadherin (114020) was associated with alpha- and beta-catenin (116805; 116806) but not with E- or P-cadherin. Moreover, retinoblastoma cells, in contrast with normal retina, expressed an N-cadherin/catenin complex that was irregularly distributed and weakly linked to the cytoskeleton. In retinoblastoma, this complex acted as an invasion promoter. Mohan et al. (2007) found an increase in N-cadherin and alpha-catenin expression and loss of E-cadherin and CD9 (143030) expression in invasive retinoblastoma and suggested that these antigens may contribute to RB tumor invasiveness. Tucker and Friedman (2002) reviewed the mechanisms through which hereditary tumors may arise and concluded that loss of both alleles of a particular tumor suppressor gene is a frequent, but not invariably necessary or sufficient, event. They presented 4 models, with possible examples, of how various tumors arise in patients with inherited tumor predisposition syndromes such as hereditary retinoblastoma, tuberous sclerosis complex (see 191100), or neurofibromatosis (see 162200). They noted that even tumors of 1 particular type may develop by more than 1 mechanism. The multistep model is similar to that proposed by Vogelstein and Kinzler (1993) for colorectal cancer. In the recruitment model, a second hit occurs at the disease locus, resulting in complete loss of function. These cells recruit other surrounding stromal cells that still retain 1 functional copy of the disease locus into the region, which promotes tumor progression. In the LOH model, all cells possess 1 mutation in the inherited disease-causing gene. One cell requires another mutation at an additional locus; this mutation could allow for tumor formation or a second somatic 'hit' at the disease locus may result in a tumor. In the haploinsufficiency model, cells having only 1 functional copy of the disease gene are more sensitive to proliferating stimuli, allowing a tumor to form. Xu et al. (2014) showed that postmitotic human cone precursors are uniquely sensitive to RB depletion. RB knockdown induced cone precursor proliferation in prospectively isolated populations and in intact retina. Proliferation followed the induction of E2F-regulated genes, and depended on factors having strong expression in maturing cone precursors and crucial roles in retinoblastoma cell proliferation, including MYCN (164840) and MDM2 (164785). Proliferation of RB-depleted cones and retinoblastoma cells also depended on the RB-related protein p107 (RBL1; 116957), SKP2 (601436), and a p27 (CDKN1B; 600778) downregulation associated with cone precursor maturation. Moreover, RB-depleted cone precursors formed tumors in orthotopic xenografts with histologic features and protein expression typical of human retinoblastoma. Xu et al. (2014) concluded that these findings provide a compelling molecular rationale for a cone precursor origin of retinoblastoma. Animal Model Windle et al. (1990) created transgenic mice by microinjecting fertilized ova with a chimeric gene containing the protein coding region of the SV40 T antigen (Tag) driven by the promoter of the luteinizing hormone beta-subunit gene. One of the male founders developed bilateral retinoblastomas at about age 5 months. The phenotype was heritable with complete penetrance in transgenic offspring in whom the tumors were first observed at about 2 months. Windle et al. (1990) demonstrated specific association between p105(Rb) and T antigen in mouse retinoblastoma tumor cells. Thus, evidence is provided for oncogenesis due to the ocular-specific expression of an Rb-binding oncoprotein that can functionally inactivate the Rb protein. Marino et al. (2000) generated a mouse model for medulloblastoma (155255) by Cre-LoxP-mediated inactivation of Rb and p53 tumor suppressor genes in the cerebellar external granular layer (EGL) cells. Recombination mediated by Gfap (137780) promoter-driven Cre was found both in astrocytes and in immature precursor cells of the EGL in the developing cerebellum. Gfap-Cre-mediated inactivation of Rb in a p53-null background produced mice that developed highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma. These tumors were identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the EGL cells during development. Marino et al. (2000) concluded that loss of function of Rb is essential for medulloblastoma development in the mouse and stated that their results strongly support the hypothesis that medulloblastomas arise from multipotent precursor cells located in the EGL. Lee et al. (1992) generated mice deficient for Rb by targeted disruption. The mice were nonviable and showed defects in neurogenesis and hematopoiesis (Lee et al., 1992; Jacks et al., 1992; Clarke et al., 1992). Inactivation of Rb in mice results in unscheduled cell proliferation, apoptosis, and widespread developmental defects, leading to embryonic death by day 14.5. Wu et al. (2003) showed that loss of Rb leads to excessive proliferation of trophoblast cells and a severe disruption of the normal labyrinth architecture in the placenta. This is accompanied by a decrease in vascularization and a reduction in placental transport function. Wu et al. (2003) used complementary techniques--tetraploid aggregation and conditional knockout strategies--to demonstrated that Rb-deficient embryos supplied with a wildtype placenta can be carried to term, but die soon after birth. Most of the neurologic and erythroid abnormalities thought to be responsible for the embryonic lethality of Rb-null animals were virtually absent in rescued Rb-null pups. Wu et al. (2003) concluded that these findings identified and defined a key function of RB in extraembryonic cell lineages that is required for embryonic development and viability, and provided a mechanism for the cell-autonomous versus non-cell-autonomous roles of RB in development. In a transgenic retinoblastoma mouse model (LH-beta-Tag mouse), Dawson et al. (2003) found that low doses of 1-alpha-hydroxyvitamin D2 (0.1-0.3 micrograms 5 times weekly for 5 weeks) inhibited retinoblastoma with no significant increase in mortality. To model sporadic cancers associated with inactivation of the RB tumor suppressor gene in humans, Sage et al. (2003) produced a conditional allele of the mouse Rb gene. Sage et al. (2003) demonstrated that acute loss of Rb in primary quiescent cells is sufficient for cell cycle entry and has phenotypic consequences different from germline loss of Rb function. This difference is explained in part by functional compensation by the Rb-related gene p107 (116957). Sage et al. (2003) also showed that acute loss of Rb in senescent cells leads to reversal of the cellular senescence program. Adipocyte precursor cells give rise to 2 major cell populations with different physiologic roles: white and brown adipocytes. Hansen et al. (2004) demonstrated that the retinoblastoma protein regulates white versus brown adipocyte differentiation. Functional inactivation of the retinoblastoma protein in wildtype mouse embryo fibroblasts and white preadipocytes by expression of simian virus-40 large T antigen resulted in the expression of the brown fat-specific uncoupling protein-1 (UCP1; 113730) in the adipose state. Rb-null mouse embryo fibroblasts and stem cells, but not the corresponding wildtype cells, differentiated into adipocytes with a gene expression pattern and mitochondria content resembling brown adipose tissue. From these and other observations, Hansen et al. (2004) proposed that the retinoblastoma protein acts as a molecular switch determining white versus brown adipogenesis, suggesting a previously uncharacterized function of this key cell cycle regulator in adipocyte lineage commitment and differentiation. By targeted disruption, Sage et al. (2006) deleted the Rb gene primarily in the inner ear. During early postnatal development, Rb -/- hair cells continued to divide and transduced mechanical stimuli. However, adult Rb -/- mice exhibited profound hearing loss due to progressive degeneration of the organ of Corti. Many Rb -/- vestibular hair cells survived and continued to divide in adult mice, and vestibular hair cells were functional. Day et al. (2002) developed Rb -/- prostate epithelial (PrE) cells from Rb -/- mouse embryos. Rb -/- PrE cells showed serum independence in culture and immortality in vivo. Cell cycle analysis revealed elevated S-phase DNA content accompanied by increased expression of cyclin E1 and proliferating cell nuclear antigen (PCNA; 176740). Rb -/- PrE cultures also exhibited a diminished ability to growth arrest under high-density culture conditions. MacPherson et al. (2003) generated mouse embryos with conditional Rb deletion in the central nervous system (CNS), peripheral nervous system (PNS), and lens, while maintaining normal erythropoiesis. In contrast to the massive CNS apoptosis in Rb-null embryos at embryonic day 13.5, conditional mutants did not have elevated apoptosis in the CNS, although there was significant apoptosis in the PNS and lens. Rb -/- cells in the CNS, PNS, and lens underwent inappropriate S-phase entry at embryonic day 13.5. By day 18.5, conditional mutants had increased brain size and weight and defects in skeletal muscle development. MacPherson et al. (2003) hypothesized that hypoxia is a necessary cofactor in the death of CNS neurons in the developing Rb mutant embryo. Haigis et al. (2006) found that Rb was expressed in all epithelial cells of mouse colon, whereas p107 was expressed predominantly in the lower half of the crypt, and p130 was expressed in the upper portion of the crypt and in the epithelium lining the lumen. Similarly, undifferentiated cells in the mouse small intestinal crypt expressed Rb and p107, whereas differentiated cells in the villi expressed Rb and p130. Conditional deletion of Rb or p130 increased p107 levels, and Rb/p130 double mutants had even higher levels of p107. Although mutating any of these 3 genes singly had little or no effect, loss of Rb and p107 or p130 together produced chronic hyperplasia and dysplasia of the small intestinal and colonic epithelium. In Rb/p130 double mutants, this hyperplasia was associated with defects in terminal differentiation of specific cell types and was dependent on the increased proliferation seen in the epithelium of mutant animals. In the transgenic retinoblastoma mouse model LH-beta-Tag, Jockovich et al. (2007) detected increased cell proliferation and angiogenesis in the retinal inner nuclear layer before morphologic neoplastic changes were evident. As tumor size increased, angiogenesis diminished concomitantly with the appearance of new vessels. Treatment with CA4P and anecortave acetate resulted in significant reductions in total vessel density. However, neither drug reduced the amount of alpha-smooth muscle actin-positive, mature vessels. Jockovich et al. (2007) concluded that these findings suggest a high potential value in targeting the process of angiogenesis in the treatment of children with retinoblastoma. Using optical coherence tomography (OCT) imaging in the T-antigen retinoblastoma (TAg-RB) mouse model, Wenzel et al. (2015) characterized TAg-positive cells as early as 2 weeks, corresponding to the earliest stages at which tumors are histologically evident, and well before thay are evident with funduscopy. Wenzel et al. (2015) concluded that OCT is a noninvasive imaging modality for tracking early TAg-RB tumor growth in vivo. History Fearon (1997) reviewed more than 20 hereditary cancer syndromes that had been defined and attributed to specific germline mutations in inherited cancer genes. All but 4 of these behaved as autosomal dominant disorders. Retinoblastoma was one of the first to be defined at the molecular level. INHERITANCE \- Autosomal dominant \- Somatic mutation HEAD & NECK Eyes \- Retinoblastoma (25% bilateral, 15% unilateral) \- Retinomas (translucent, grayish retinal mass protruding into the vitreous) \- Retinal calcification \- Retinal pigment epithelial migration and proliferation \- Leukocoria \- Vitreous hemorrhage (rare) \- Vitritis (rare) Mouth \- Cleft palate (rare) NEOPLASIA \- Osteogenic sarcoma \- Pinealoma (trilateral retinoblastoma) \- Leukemia \- Lymphoma \- Ewing sarcoma MISCELLANEOUS \- Incidence 1 in 15,000-28,000 births \- Approximately 40% of cases are inherited or new germline mutations \- Approximately 60% of cases are due to somatic mutations and are unilateral MOLECULAR BASIS \- Caused by mutation in the RB1 gene (RB1, 614041.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	RETINOBLASTOMA	c0035335	26,942	omim	https://www.omim.org/entry/180200	2019-09-22T16:35:12	{"doid": ["768"], "mesh": ["D012175"], "omim": ["180200"], "orphanet": ["790", "357034", "357027"], "synonyms": ["Alternative titles", "RB"], "genereviews": ["NBK1452"]}
Hereditary neuropathy with liability to pressure palsies is a disorder that affects peripheral nerves. These nerves connect the brain and spinal cord to muscles and sensory cells that detect touch, pain, and temperature. In people with this disorder, the peripheral nerves are unusually sensitive to pressure, such as the pressure that occurs when carrying heavy grocery bags, leaning on an elbow, or sitting without changing position, particularly with crossed legs. These activities would not normally cause sensation problems in people without the disorder. Hereditary neuropathy with liability to pressure palsies is characterized by recurrent episodes of numbness, tingling, and loss of muscle function (palsy) in the region associated with the affected nerve, usually an arm, hand, leg, or foot. An episode can last from several minutes to several months, but recovery is usually complete. Repeated incidents, however, can cause permanent muscle weakness or loss of sensation. This disorder is also associated with pain in the limbs, especially the hands. A pressure palsy episode results from pressure on a single nerve, and any peripheral nerve can be affected. Although episodes often recur, they can affect different nerves. The most common problem sites involve nerves in the wrists, elbows, and knees. The fingers, shoulders, hands, feet, and scalp can also be affected. Many people with this disorder experience carpal tunnel syndrome, which occurs when a nerve in the wrist (the median nerve) is involved. Carpal tunnel syndrome is characterized by numbness, tingling, and weakness in the hand and fingers. An episode in the hand may affect fine motor activities such as writing, opening jars, and fastening buttons. An episode of nerve compression in the knee can lead to a condition called foot drop, which makes walking, climbing stairs, or driving difficult or impossible. The symptoms of hereditary neuropathy with liability to pressure palsies usually begin during adolescence or early adulthood but may develop anytime from childhood to late adulthood. Symptoms vary in severity; many people never realize they have the disorder, while some people experience prolonged disability. Hereditary neuropathy with liability to pressure palsies does not affect life expectancy. ## Frequency Hereditary neuropathy with liability to pressure palsies is estimated to occur in 2 to 5 per 100,000 individuals. ## Causes Hereditary neuropathy with liability to pressure palsies is most commonly caused by the deletion of one copy of the PMP22 gene. This loss reduces the amount of PMP22 protein produced. Other PMP22 gene mutations that lead to a reduction of PMP22 protein can also cause the condition. The PMP22 protein is a component of myelin, a protective substance that covers nerves and promotes the efficient transmission of nerve impulses. Studies suggest that the PMP22 protein is particularly important in protecting nerves from physical pressure, helping them restore their structure after compression. Compression can interrupt nerve signaling, leading to the sensation commonly referred to as a limb "falling asleep." The ability of nerves to recover from normal, day-to-day pressure, for example when sitting for long periods, keeps the limbs from constantly losing sensation. The consequences of PMP22 gene mutations are not clearly understood. A shortage of PMP22 protein appears to make nerves less able to recover from compression, which impairs the transmission of nerve impulses, causing the signs and symptoms of hereditary neuropathy with liability to pressure palsies. ### Learn more about the gene associated with Hereditary neuropathy with liability to pressure palsies * PMP22 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hereditary neuropathy with liability to pressure palsies	c0393814	26,943	medlineplus	https://medlineplus.gov/genetics/condition/hereditary-neuropathy-with-liability-to-pressure-palsies/	2021-01-27T08:25:50	{"gard": ["5221"], "mesh": ["C536965"], "omim": ["162500"], "synonyms": []}
Giant-cell fibroblastoma SpecialtyOncology Giant-cell fibroblastoma is a rare type of soft-tissue tumor marked by painless nodules in the dermis (the inner layer of the two main layers of tissue that make up the skin) and subcutaneous (beneath the skin) tissue. These tumors may come back after surgery, but they do not spread to other parts of the body. They occur mostly in boys and are related to dermatofibrosarcoma protuberans.[1] ## References[edit] 1. ^ Cerio, R. (2012). Dermatopathology. Springer Science & Business Media. ISBN 9783642595523. Retrieved 13 November 2017. ## External links[edit] * Giant cell fibroblastoma entry in the public domain NCI Dictionary of Cancer Terms This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms". 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Giant-cell fibroblastoma	c3693482	26,944	wikipedia	https://en.wikipedia.org/wiki/Giant-cell_fibroblastoma	2021-01-18T18:58:39	{"mesh": ["D018223"], "umls": ["C3693482"], "wikidata": ["Q5558338"]}
Niemann–Pick disease, type C Niemann–Pick disease, type C is associated with NPC1 mutations SpecialtyEndocrinology, neurology Niemann–Pick type C (NPC) is a lysosomal storage disease associated with mutations in NPC1 and NPC2 genes. Niemann–Pick type C affects an estimated 1:150,000 people.[1] Approximately 50% of cases present before 10 years of age, but manifestations may first be recognized as late as the sixth decade. ## Contents * 1 Signs and symptoms * 2 Genetics * 2.1 "Type D" variant * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 5.1 Arimoclomol * 5.2 Hydroxypropyl-beta-cyclodextrin (HPbCD) * 5.3 Other treatments under investigation * 6 Prognosis * 7 Research directions * 8 References * 9 External links ## Signs and symptoms[edit] Niemann–Pick type C has a wide clinical spectrum. Affected individuals may have enlargement of the spleen (splenomegaly) and liver (hepatomegaly), or enlarged spleen or liver combined (hepatosplenomegaly), but this finding may be absent in later onset cases. Prolonged jaundice or elevated bilirubin can present at birth. In some cases, however, enlargement of the spleen or liver does not occur for months or years – or not at all. Enlargement of the spleen or liver frequently becomes less apparent with time, in contrast to the progression of other lysosomal storage diseases such as Niemann–Pick disease, Types A and B or Gaucher disease. Organ enlargement does not usually cause major complications.[citation needed] Progressive neurological disease is the hallmark of Niemann–Pick type C disease, and is responsible for disability and premature death in all cases beyond early childhood.[2] Classically, children with NPC may initially present with delays in reaching normal developmental milestones skills before manifesting cognitive decline (dementia). Neurological signs and symptoms include cerebellar ataxia (unsteady walking with uncoordinated limb movements), dysarthria (slurred speech), dysphagia (difficulty in swallowing), tremor, epilepsy (both partial and generalized), vertical supranuclear palsy (upgaze palsy, downgaze palsy, saccadic palsy or paralysis), sleep inversion, gelastic cataplexy (sudden loss of muscle tone or drop attacks), dystonia (abnormal movements or postures caused by contraction of agonist and antagonist muscles across joints), most commonly begins with inturning of one foot when walking (action dystonia) and may spread to become generalized, spasticity (velocity dependent increase in muscle tone), hypotonia, ptosis (drooping of the upper eyelid), microcephaly (abnormally small head), psychosis, progressive dementia, progressive hearing loss, bipolar disorder, major and psychotic depression that can include hallucinations, delusions, mutism, or stupor. In the terminal stages of Niemann–Pick type C disease, the patient is bedridden, with complete ophthalmoplegia, loss of volitional movement and severe dementia. ## Genetics[edit] Approximately 95% of Niemann–Pick type C cases are caused by genetic mutations in the NPC1 gene, referred to as type C1; 5% are caused by mutations in the NPC2 gene, referred to as type C2.[3] The clinical manifestations of types Niemann–Pick types C1 and C2 are similar because the respective genes are both involved in egress of lipids, particularly cholesterol, from late endosomes or lysosomes. The NPC1 gene is located on chromosome 18 (18q11-q12) and was described by researchers at the National Institutes of Health in July 1997.[4] * The NPC1 gene encodes a protein that is located in membranes inside the cell and is involved in the movement of cholesterol and lipids within cells.[5] A deficiency of this protein leads to the abnormal buildup of lipids and cholesterol within cell membranes. * The NPC2 gene encodes a protein that binds and transports cholesterol.[6][7] It has been shown to closely interact with NPC1.[8][9] ### "Type D" variant[edit] Type D Niemann–Pick has only been found in the French Canadian population of Yarmouth County, Nova Scotia, and is now known to be allelic with Niemann–Pick type C. Genealogical research indicates that Joseph Muise (c. 1679–1729) and Marie Amirault (1684 – c. 1735) are common ancestors to all people with Type D. This couple is the most likely origin for the type D variant.[10] ## Pathophysiology[edit] Niemann–Pick type C is biochemically, genetically and clinically distinct from Niemann–Pick Types A or and B. In Types A and B, there is complete or partial deficiency of the lysosomal enzyme called acid sphingomyelinase. In Niemann–Pick type C, the protein product of the major mutated gene NPC1 is not an enzyme but appears to function as a transporter in the endosomal-lysosomal system, which moves large water-insoluble molecules through the cell. The protein coded by the NPC2 gene more closely resembles an enzyme structurally but seems to act in cooperation with the NPC1 protein in transporting molecules in the cell. The disruption of this transport system results in the accumulation of cholesterol and glycolipids in lysosomes.[citation needed] Cholesterol and glycolipids have varied roles in the cell. Cholesterol is a major component of cell plasma membranes, which define the cell as a whole and its organelles. It is also the basic building block of steroid hormones, including neurosteroids. In Niemann–Pick type C, large amounts of free or unesterified cholesterol accumulate in lysosomes, and leads to relative deficiency of this molecule in multiple membranes and for steroid synthesis. The accumulation of glycosphingolipids in the nervous system has been linked to structural changes, namely ectopic dendritogenesis and meganeurite formation, and has been targeted therapeutically. Several theories have attempted to link the accumulation of cholesterol and glycolipids in the lysosomes with the malfunction of the NPC-1 protein. * Neufeld et al. hypothesized that the accumulation of mannose 6-phosphate receptors (MPRs) in the late endosome signals failure of retrograde trafficking of cholesterol via the trans Golgi network.[11] * Another theory suggests that the blockage of retrograde cholesterol breakdown in the late endosome is due to decreased membrane elasticity and thus the return vesicles of cholesterol to the trans Golgi Network cannot bud and form. * Iouannou, et al. have described similarities between the NPC1 protein and members of the resistance-nodulation-division (RND) family of prokaryotic permeases, suggesting a pumping function for NPC1.[12] * Recent 2008 evidence indicates that NPC-1 may play an important role in calcium regulation.[13] ## Diagnosis[edit] Niemann–Pick type C is diagnosed by assaying cultured fibroblasts for cholesterol esterfication and staining for unesterified cholesterol with filipin. The fibroblasts are grown from a small skin biopsy taken from a patient with suspected NPC. The diagnosis can be confirmed by identifying mutations in the NPC1 or NPC2 genes in 80–90% of cases. This specialized testing is available at Thomas Jefferson University Lysosomal Disease Testing Lab[14] and the Mayo Clinic.[15] ## Treatment[edit] There is no known cure for Niemann–Pick type C, nor is there any FDA-standard approved disease modifying treatment.[16] Supportive care is essential and substantially improves the quality of life of people affected by NPC. The therapeutic team may include specialists in neurology, pulmonology, gastroenterology, psychiatrist, orthopedics, nutrition, physical therapy and occupational therapy. Standard medications used to treat symptoms can be used in NPC patients. As patients develop difficulty with swallowing, food may need to be softened or thickened, and eventually, parents will need to consider placement of a gastrostomy tube (g-tube, feeding tube).[17] ### Arimoclomol[edit] In 2014, the European Medicines Agency (EMA) granted orphan drug designation to arimoclomol for the treatment of Niemann–Pick type C.[18] This was followed in 2015 by the U.S. Food and Drug Administration (FDA).[19] Dosing in a placebo-controlled phase II/III clinical trial to investigate treatment for Niemann–Pick type C (for patients with both type C1 and C2) using arimoclomol began in 2016.[20] Arimoclomol, which is orally administered, induces the heat shock response in cells and is well tolerated in humans.[21][22][23][24][excessive citations] ### Hydroxypropyl-beta-cyclodextrin (HPbCD)[edit] In April 2009, hydroxypropyl-beta-cyclodextrin (HPbCD) was approved under compassionate use by the U.S. Food and Drug Administration (FDA) to treat Addison and Cassidy Hempel,[25] identical twin girls suffering from Niemann–Pick type C disease. Medi-ports, similar to ports used to administer chemotherapy drugs, were surgically placed into the twins' chest walls and allow doctors to directly infuse HPbCD into their bloodstreams. Treatment with cyclodextrin has been shown to delay clinical disease onset, reduced intraneuronal storage and secondary markers of neurodegeneration, and significantly increased lifespan in both the Niemann–Pick type C mice[26] and feline[27] models. This is the second time in the United States that cyclodextrin alone has been administered in an attempt treat a fatal pediatric disease. In 1987, HPbCD was used in a medical case involving a boy suffering from severe hypervitaminosis A.[28] On May 17, 2010, the FDA granted Hydroxypropyl-beta-cyclodextrin orphan drug status and designated HPbCD cyclodextrin as a potential treatment for Niemann–Pick type C disease. On July 14, 2010, Dr. Caroline Hastings of UCSF Benioff Children's Hospital Oakland filed additional applications with the FDA requesting approval to deliver HPbCD directly into the central nervous systems of the twins in an attempt to help HPbCD cross the blood–brain barrier. The request was approved by the FDA on September 23, 2010, and bi-monthly intrathecal injections of HPbCD into the spine were administered starting in October 2010.[citation needed] On December 25, 2010, the FDA granted approval for HPbCD to be delivered via IV to an additional patient, Peyton Hadley, aged 13, under an IND through Rogue Regional Medical Center in Medford, Oregon. Soon after in March 2011, approval was sought for similar treatment of his sibling, Kayla, age 11, and infusions of HPbCD began shortly after. Both have since begun intrathecal treatments beginning in January 2012.[29] In April 2011, the National Institutes of Health (NIH), in collaboration with the Therapeutics for Rare and Neglected Diseases Program (TRND), announced they were developing a clinical trial utilizing cyclodextrin for Niemann–Pick type C patients. On September 20, 2011, the European Medicines Agency (EMA) granted HPbCD orphan drug status and designated the compound as a potential treatment for Niemann–Pick type C disease. On December 31, 2011, the FDA granted approval for IV HPbCD infusions for a fifth child in the United States, Chase DiGiovanni, under a compassionate use protocol. The child was 29 months old at the time of his first intravenous infusion, which was started in January 2012.[30] Due to unprecedented collaboration between individual physicians and parents of children afflicted with NPC, approximately 15 patients worldwide have received HPbCD cyclodextrin therapy under compassionate use treatment protocols. Treatment involves a combination of intravenous therapy (IV), intrathecal therapy (IT) and intracerebroventricular (ICV) cyclodextrin therapy. On January 23, 2013, a formal clinical trial to evaluate HPβCD cyclodextrin therapy as a treatment for Niemann–Pick disease, type C was announced by scientists from the NIH's National Center for Advancing Translational Sciences (NCATS) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). ### Other treatments under investigation[edit] One drug that has been tried is Miglustat.[31][32] Miglustat is a glucosylceramide synthase inhibitor, which inhibits the synthesis of glycosphingolipids in cells. It has been shown to delay the onset of disease in the NPC mouse, and published data from a multi-center clinical trial of Miglustat in the United States and England and from case reports suggests that it may ameliorate the course of human NPC. Several other treatment strategies are under investigation in cell culture and animal models of NPC. These include, cholesterol mobilization, neurosteroid (a special type of hormone that affects brain and other nerve cells) replacement using allopregnanolone,[3][33] rab overexpression to bypass the trafficking block (Pagano lab) and Curcumin as an anti-inflammatory and calcium modulatory agent.[13] The pregnane X receptor has been identified as a potential target.[34] Neural stem cells have also been investigated in an animal model, and clear evidence of life extension in the mouse model has been shown.[35] Low cholesterol diets are often used,[36] but there is no evidence of efficacy.[37] ## Prognosis[edit] The lifespan of patients with NPC is usually related to the age of onset. Children with antenatal or infantile onset usually succumb in the first few months or years of life, whereas adolescent and adult onset forms of Niemann–Pick type C have a more insidious onset and slower progression, and affected individuals may survive to the seventh decade. Adult cases of NPC are being recognized with increasing frequency. It is suspected that many patients affected by NPC are undiagnosed, owing to lack of awareness of the disease and the absence of readily available screening or diagnostic tests. For the same reasons the diagnosis is often delayed by many years.[citation needed] ## Research directions[edit] Loss of myelin in the central nervous system is considered to be a main pathogenic factor. Research uses animal models carrying the underlying mutation for Niemann–Pick disease, e.g. a mutation in the NPC1 gene Niemann–Pick type C disease. In this model the expression of Myelin gene Regulatory Factor (MRF) has been shown to be significantly decreased.[38] MRF is a transcription factor of critical importance in the development and maintenance of myelin sheaths.[39] A perturbation of oligodendrocyte maturation and the myelination process might therefore be an underlying mechanism of the neurological deficits.[38] Recent neuroimaging studies have shown patients with Niemann–Pick, type C to have a corpus callosum with microstructural abnormalities. Clear reductions in corpus callosum mean thickness and surface area have been shown when compared to age-matched controls.[40][41] Also, studies using diffusion tensor imaging have shown marked reductions in callosal fractional anisotropy, which suggests architectural abnormalities based on the directional flow of water.[41][42] These conclusions suggest that the corpus callosum plays an important role in the disease and should be explored for use as a biomarker of disease progression. Parents of children with NPC are being studied in an attempt to gain insight into the Ebola virus, which uses the protein encoded by NPC1 to enter cells. Researchers have found that mice with one normal copy of the NPC1 gene are more likely to survive Ebola infection than mice with normal two copies of the gene. Mice lacking any normal copy of NPC1 all survived. Studying cells from parents who are NPC disease carriers may allow for better understanding of how changes to the NPC1 gene affect Ebola risk.[43] Findings from Zhang et al[44] suggest that NPC is a late endocytic trafficking disease resulted, at least in part, from disruption of communication within late endocytic (LE) compartments and possibly between LE and other subcellular organelles. Crosstalk between the late endocytic compartment and other orgranelles such as mitochondria, endoplasmic reticulum, plasma membrane, as well as early endocytic compartments has become one of the most interesting frontiers in neurondegenerative disease research including Alzheimer's disease, Parkinson's disease, as well as lysosomal storage disorders.[45][46] ## References[edit] 1. ^ Chang TY, Reid PC, Sugii S, Ohgami N, Cruz JC, Chang CC (June 2005). "Niemann–Pick type C disease and intracellular cholesterol trafficking". The Journal of Biological Chemistry. 280 (22): 20917–20. doi:10.1074/jbc.R400040200. PMID 15831488. 2. ^ {{cite journal \|vauthors=Rimkunas VM, Graham MJ, Crooke RM, Liscum L\|title=TNF-{alpha} plays a role in hepatocyte apoptosis in Niemann–Pick type C liver disease\|journal=Journal of Lipid Research\|volume=50\|issue=2\|pages=327–33 \|date=February 2009\|pmid=18815434\|pmc=2636917\|doi=10.1194/jlr.M800415-JLR200}} 3. ^ a b Mellon SH, Gong W, Schonemann MD (March 2008). "Endogenous and synthetic neurosteroids in treatment of Niemann–Pick Type C disease". Brain Research Reviews. 57 (2): 410–420. doi:10.1016/j.brainresrev.2007.05.012. PMC 2323675. PMID 17629950. 4. ^ "NIH Scientists Identify Gene for Fatal Childhood Disorder, Niemann–Pick Type C". Newsroom. National Human Genome Research Institute. July 1997. 5. ^ Zhang JR, Coleman T, Langmade SJ, Scherrer DE, Lane L, Lanier MH, et al. (June 2008). "Niemann–Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking". The Journal of Clinical Investigation. 118 (6): 2281–2290. doi:10.1172/JCI32561. PMC 2381744. PMID 18483620. 6. ^ Bjurulf B, Spetalen S, Erichsen A, Vanier MT, Strøm EH, Strømme P (August 2008). "Niemann–Pick disease type C2 presenting as fatal pulmonary alveolar lipoproteinosis: morphological findings in lung and nervous tissue". Medical Science Monitor. 14 (8): CS71-5. PMID 18668002. 7. ^ Liou HL, Dixit SS, Xu S, Tint GS, Stock AM, Lobel P (December 2006). "NPC2, the protein deficient in Niemann–Pick C2 disease, consists of multiple glycoforms that bind a variety of sterols". The Journal of Biological Chemistry. 281 (48): 36710–36723. doi:10.1074/jbc.M608743200. PMID 17018531. 8. ^ Infante RE, Wang ML, Radhakrishnan A, Kwon HJ, Brown MS, Goldstein JL (October 2008). 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PMID 21596811. 41. ^ a b Walterfang M, Fahey M, Desmond P, Wood A, Seal ML, Steward C, et al. (July 2010). "White and gray matter alterations in adults with Niemann–Pick disease type C: a cross-sectional study". Neurology. 75 (1): 49–56. doi:10.1212/WNL.0b013e3181e6210e. PMID 20484681. S2CID 9062701. 42. ^ Trouard TP, Heidenreich RA, Seeger JF, Erickson RP (November 2005). "Diffusion tensor imaging in Niemann–Pick Type C disease". Pediatric Neurology. 33 (5): 325–330. doi:10.1016/j.pediatrneurol.2005.05.004. PMID 16243219. 43. ^ Marcus, Amy Dockser (2 November 2014). "Researchers Study Ebola Link to Gene in Rare Disease". Wall Street Journal. Retrieved 12 August 2016. 44. ^ Zhang M, Dwyer NK, Love DC, Cooney A, Comly M, Neufeld E, Pentchev PG, Blanchette-Mackie EJ, Hanover JA. Cessation of rapid late endosomal tubulovesicular trafficking in Niemann–Pick type C1 disease. Proceedings of the National Academy of Sciences. April 2001, 98 (8) 4466-4471; DOI: 10.1073/pnas.081070898 45. ^ Tate BA, Mathews PM, Targeting the Role of the Endosome in the Pathophysiology of Alzheimer's Disease: A Strategy for Treatment. Sci. Aging Knowl. Environ. 2006 (10), re2 (2006) 46. ^ Plotegher N, Duchen MR. Crosstalk between Lysosomes and Mitochondria in Parkinson’s Disease. Frontiers in Cell and Developmental Biology. 2017;5:110. doi:10.3389/fcell.2017.00110. ## External links[edit] * PubMed Classification D * ICD-10: E75.2 (ILDS E75.230) * ICD-9-CM: 272.7 * OMIM: 257220 601015 607623 607625 * MeSH: D052556 * DiseasesDB: 33390 External resources * eMedicine: derm/699 * GeneReviews: Niemann–Pick Disease Type C * v * t * e Lysosomal storage diseases: Inborn errors of lipid metabolism (Lipid storage disorders) Sphingolipidoses (to ceramide) From ganglioside (gangliosidoses) * Ganglioside: GM1 gangliosidoses * GM2 gangliosidoses (Sandhoff disease * Tay–Sachs disease * AB variant) From globoside * Globotriaosylceramide: Fabry's disease From sphingomyelin * Sphingomyelin: phospholipid: Niemann–Pick disease (SMPD1-associated * type C) * Glucocerebroside: Gaucher's disease From sulfatide (sulfatidoses * leukodystrophy) * Sulfatide: Metachromatic leukodystrophy * Multiple sulfatase deficiency * Galactocerebroside: Krabbe disease To sphingosine * Ceramide: Farber disease NCL * Infantile * Jansky–Bielschowsky disease * Batten disease Other * Cerebrotendineous xanthomatosis * Cholesteryl ester storage disease (Lysosomal acid lipase deficiency/Wolman disease) * Sea-blue histiocytosis * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive 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No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Niemann–Pick disease, type C	c0220756	26,945	wikipedia	https://en.wikipedia.org/wiki/Niemann%E2%80%93Pick_disease,_type_C	2021-01-18T18:38:46	{"mesh": ["D052556"], "umls": ["C0220756"], "icd-9": ["272.7"], "icd-10": ["E75.2"], "orphanet": ["646"], "wikidata": ["Q2067267"]}
A number sign (#) is used with this entry because immunodeficiency-19 (IMD19) is caused by homozygous mutation in the CD3D gene (186790) on chromosome 11q23. Description Immunodeficiency-19 (IMD19) is an autosomal recessive form of severe combined immunodeficiency (SCID) characterized by onset in early infancy of recurrent bacterial, viral, and fungal infections. Patients usually have chronic diarrhea, recurrent respiratory infections, and failure to thrive. Immunologic work-up shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype. The disorder is lethal in early childhood without bone marrow transplantation (summary by Yu et al., 2011). Clinical Features Dadi et al. (2003) reported 3 members of a kindred of Mennonite descent who had T-, B+, NK+ SCID. The proband was diagnosed immediately after birth because of 2 previous cases in the family. The proband subsequently underwent bone marrow transplantation and was alive and well, with full immune reconstitution, 3 years later. A male cousin of the proband was admitted at the age of 2 months with fever, tachypnea, and tachycardia and died of multiorgan failure. Adenovirus was identified in stool, urine, and bronchial secretions. Another male cousin of the proband was well and thriving until 2.5 months of age, when chronic diarrhea developed. He died at 3.5 months of age with respiratory distress and liver failure. Cytomegalovirus was identified in multiple tissues obtained at autopsy. That 2 of the 3 affected infants in this kindred died from viral infections before 4 months of age was a striking demonstration of the essential role of T cells in the defense against viruses, even weakly pathogenic adenoviruses and cytomegalovirus. The number of NK cells, as determined by staining for CD56 (116930), was normal in all patients. De Saint Basile et al. (2004) reported 3 children and 2 fetuses from 2 consanguineous families with IMD19. In 1 family, the first affected child presented with diarrhea and failure to thrive at 3 months of age. At age 5 months, she developed CMV hepatitis and died shortly afterward. The second child was diagnosed with T-,B+, NK+ SCID shortly after birth and received a bone marrow transplant, but died 6 months later. In the second family, the first affected child presented with candidiasis at 2 months of age. This was followed by diarrhea and pneumonitis. He received a bone marrow transplant, but later died. No T cells were detected by prenatal analysis of fetal blood samples from 2 subsequent pregnancies, and the pregnancies were terminated. Thymi from the 2 fetuses were smaller than normal and lacked normal corticomedullary differentiation. Thymocyte T-cell development was blocked at the CD3-positive/CD4 (186940)-positive/CD8 (see 186910)-negative/CD45RO (151460)-negative stage. No circulating CD3-positive T cells were found in any of the patients, and lymph nodes from the fetuses contained no CD3-positive T cells. These findings indicated that CD3D is necessary for early T-cell development. Yu et al. (2011) retrospectively studied a brother and sister with T-, B+, NK+ SCID who were homozygous for a truncating mutation in the CD3D gene (R68X; 186790.0001). The patients presented with typical clinical features, including failure to thrive, diarrhea, and recurrent and/or opportunistic infections, including fungal and CMV. Both had lymphopenia and absence of circulating CD3+ T cells, as well as decreased T-cell proliferative responses in vitro. Both underwent bone marrow transplantation; 1 sib died shortly thereafter, whereas the other was alive and well at age 16 years. Gil et al. (2011) reported 2 unrelated Ecuadorian male children from nonconsanguineous parents who presented at 13 and 5 months of age with IMD19 manifesting as SCID and low CD3 expression. Both patients were T-alpha/beta negative, T-gamma/delta positive, B positive, and NK positive. The patients received haploidentical CD34 (142230)-positive stem cell transplants at ages 23 and 8 months, respectively. The latter patient died, probably due to cytomegalovirus found in multiple organs at necropsy, but the former was well at age 4 years. Inheritance The transmission pattern of IMD19 in the family reported by Dadi et al. (2003) was consistent with autosomal recessive inheritance. Molecular Genetics In 3 affected patients from a Mennonite kindred with T-, B+, NK+ SCID, Dadi et al. (2003) identified a homozygous nonsense mutation in the CD3D gene (R68X; 186790.0001). In 2 patients with T-, B+, NK+ SCID, both from consanguineous families, de Saint Basile et al. (2004) identified homozygosity for different mutations in the CD3D gene. One patient had the previously reported R68X mutation, and the other had a C93X mutation (186970.0002). Gil et al. (2011) identified a homozygous splice-site mutation in the CD3D gene (IVS2+5G-A; 186790.0003) in the 2 unrelated Ecuadorian children they reported with IMD19. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Ears \- Otitis media, recurrent Mouth \- Thrush RESPIRATORY \- Respiratory infections, recurrent ABDOMEN Gastrointestinal \- Diarrhea \- Gastroenteritis IMMUNOLOGY \- Primary immunodeficiency \- Recurrent infections, bacterial, viral, and fungal \- Lymphopenia \- Lack of peripheral CD3+ T cells \- Decreased T-cell proliferative responses in vitro \- Normal B cells \- Normal NK cells MISCELLANEOUS \- Onset in infancy \- Death in infancy without bone marrow transplantation MOLECULAR BASIS \- Caused by mutation in the CD3 antigen, delta subunit gene (CD3D, 186790.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	IMMUNODEFICIENCY 19	c3810147	26,946	omim	https://www.omim.org/entry/615617	2019-09-22T15:51:26	{"omim": ["615617"], "orphanet": ["169160"], "synonyms": ["T-B+ SCID due to CD3delta/CD3epsilon/CD3zeta", "CD3-DELTA DEFICIENCY", "SCID, T CELL-NEGATIVE, B CELL-POSITIVE, NK CELL-POSITIVE", "Alternative titles", "SEVERE COMBINED IMMUNODEFICIENCY, T CELL-NEGATIVE, B CELL-POSITIVE, NK CELL-POSITIVE"]}
Deaf-blind American author, activist, and lecturer Helen Keller in 1904 Deafblindness is the condition of little or no useful hearing and little or no useful sight.[1][2] There are different degrees of vision loss and auditory loss within each individual, thus making the deafblind community unique with many types of deafblindness involved.[3] Because of this diversity, each deafblind individual's needs regarding lifestyle, communication, education, and work need to be addressed based on their degree of dual-modality deprivation in order to improve their ability to live independently. In 1994, it was estimated that roughly 35,000–40,000 United States residents are medically deafblind.[4] Helen Keller was a well-known example of a deafblind individual.[5] Furthermore, the deafblind community has its own culture, creating a community of deafblindness similar to the Deaf community and the blind community. Each community is made up of a group of individuals who have undergone similar experiences and have a homogeneous understanding of what it means to be deafblind, even with a large diversity of unique backgrounds.[6] Some deafblind individuals view their condition as a part of their identity.[7] ## Contents * 1 Epidemiology * 2 Communication * 3 Technology * 4 In popular culture * 5 See also * 6 References * 7 External links ## Epidemiology[edit] This article is in list format, but may read better as prose. You can help by converting this article, if appropriate. Editing help is available. (March 2018) The medical condition of deafblindness comes in different forms.[3] For some, this condition might occur congenitally from birth as a result of genetic defect, for others it happens suddenly due to a form of illness or accident that results in a modality deprivation of either vision or hearing, or both.[8] A person might be born deaf and become blind at a later stage in life, or vice versa. In any given case of deafblindness, there are many possible onsets and causes of this condition, some happen gradually, others happen unexpectedly and suddenly.[9] The diagnosis of deafblindness could be medically classified into specific types based on one’s symptoms and causes.[4] There are two overarching types of deafblindness: congenital and acquired.[9][10]:36–74 Congenital deafblindness: the condition of deafblindness from birth * Pregnancy complexities[10]:50–67 * Effects of alcohol/drugs * Fetal alcohol syndrome * A result of prematurity * Causes from illness/infection * Rubella * AIDS * Cytomegalovirus * Syphilis * Toxoplasmosis * Genetic conditions (evident from birth)[8][10]:37–49 * Anomalies/syndromes (there are numerous genetic defects that may contribute to one's medical condition of deafblindness, of which some of more well-known syndromes are listed) * CHARGE syndrome * Down syndrome * Marshall syndrome * Rubella syndrome * Stickler syndrome * Trisomy 13 Acquired deafblindnness: condition of deafblindness developmental later in life * Genetic conditions (evident at a later stage in life)[10]:37–49 * Usher syndrome * Alport syndrome * Age-related loss of modality (vision or auditory or both)[11] * Illness * Meningitis * Somatic injuries[10]:68- 74 * Brain damage/trauma * Stroke * Permanent physical damage (relating to vision or hearing) ## Communication[edit] Deafblind people communicate in many different ways as determined by the nature of their condition, the age of onset, and what resources are available to them. For example, someone who grew up deaf and experienced vision loss later in life is likely to use a sign language (in a visually modified or tactile form). Others who grew up blind and later became deaf are more likely to use a tactile mode of spoken/written language. Methods of communication include: * Use of residual hearing (speaking clearly, hearing aids, or cochlear implants) or sight (signing within a restricted visual field, writing with large print). * Tactile signing, sign language, or a manual alphabet such as the American Manual Alphabet or Deaf-blind Alphabet (also known as "two-hand manual") with tactile or visual modifications. * Interpreting services (such as sign language interpreters or communication aides). * Communication devices such as Tellatouch or its computerized versions known as the TeleBraille and Screen Braille Communicator. * Tadoma, a tactile modality. Multisensory methods have been used to help deafblind people enhance their communication skills. These can be taught to very young children with developmental delays (to help with pre-intentional communication), young people with learning difficulties, and older people, including those with dementia. One such process is Tacpac. Deafblind amateur radio operators generally communicate on 2-way radios using Morse code.[clarification needed] ## Technology[edit] Braille equipment includes a variety of multipurpose devices, which enhance access to distance communication. Some can be used as stand-alone devices connected via Wi-Fi, while others are paired with a mobile device to provide tactile access to e-mail, text messaging, and other modern communication resources. To receive Braille equipment, an eligible consumer must be proficient in Braille and must have access to the Internet or cellular service. The Telebraille does not have a computer communications modem but does have a TTY (TDD) modem. It was designed as a TTY for deaf-blind people and is also useful for face-to-face conversation. It has two components. The sighted component is a modified SuperCom TTY device. It has a qwerty keyboard and a single-line LED display. The display is regular size and is not particularly suited to people with low vision. The SuperCom TTY can be connected directly to the telephone line using a conventional telephone jack or the telephone receiver can be coupled to the SuperCom on a cradle on top of the device. Text flows past the display in a continuous stream, like tickertape. The SuperCom is connected to the Braille portion of the device by a cable that is about two feet long. The Braille display is about 15 characters in width, although there is a knockout to allow additional characters to be installed, at considerable additional cost. The Telebraille is able to communicate in ASCII mode but is not compatible with conventional computer modems. There is what looks like a RS-232 socket on the back of the Braille component, but the instructions for the Telebraille state that this jack is for "future use" and that no computer devices should be attached to it. A graphic Braille display can be used in sensing graphic data such as maps, images, and text data that require multiline display capabilities such spreadsheets and equations. Graphic Braille displays available in the market are DV-2 (from KGS[12]), Hyperbraille,[13] and TACTISPLAY Table/Walk (from Tactisplay Corp.[14]). For example, TACTISPLAY Table[15] can show 120100 resolution refreshable Braille graphics on one page.[16] ## In popular culture[edit] The 1959 play The Miracle Worker, and its film adaptation released in 1962, recounts Anne Sullivan's efforts to draw Helen Keller from her world of blindness and deafness.[17] The Who’s 1969 album Tommy tells one continuous life story about a deafblind boy named Tommy through songs. The 2005 Bollywood film Black featured Rani Mukerji as a deafblind character named Michelle McNally. The film Marie's Story (2014) relates the childhood and education of Marie Heurtin (1885-1921), a deafblind woman. Haben Girma, the first deafblind individual to graduate from Harvard Law School, released an autobiography entitled Haben: The Deafblind Woman Who Conquered Harvard Law in 2019.[18] ## See also[edit] Tadoma * Tangible symbol systems * Tommy (rock opera) * White cane (used by blind people to assist them in walking) ## References[edit] 1. ^ Keller, Helen (1938). Helen Keller's Journal, 1936-1937. Garden City, NY: Doubleday, Doran & Co. 2. ^ Kudlick, Catherine; Nielsen (2005). "Kim". Journal of American History. 4. 91 (Review of the Radical Lives of Helen Keller). 3. ^ a b Dammeyer, Jesper (November 2014). "Deafblindness: a review of the literature". Scandinavian Journal of Public Health. 42 (7): 554–562. doi:10.1177/1403494814544399. ISSN 1651-1905. PMID 25114064. 4. ^ a b Deaf-Blindness, NCDB: National Center on. "Overview on Deaf-Blindness". nationaldb.org. Retrieved 2018-03-27. 5. ^ "NCDB Selected Topics: Deaf-Blindness Overview". Nationaldb.org. Retrieved 2012-03-04. 6. ^ Deaf-Blindness, NCDB: National Center on. "Culture and Community". nationaldb.org. Retrieved 2018-03-27. 7. ^ "Identity – DeafBlind Connection – Minnesota State Academies". www.msa.state.mn.us. Retrieved 2018-03-27. 8. ^ a b "Conditions/Syndromes \| Deafblind Information". Deafblindness Support Services. Retrieved 2018-03-27. 9. ^ a b "Causes". nhs.uk. Retrieved 2018-03-27. 10. ^ a b c d e Heller, Kathryn; Kennedy, Cheryl. Etiologies and Characteristics of Deaf-Blindness (PDF). National Center on Deaf-Blindness. 11. ^ "HKNC: Common Causes of Combined Vision and Hearing Loss". www.helenkeller.org. Retrieved 2018-03-27. 12. ^ "Home of KGS Corporation". KGS Corporation. 13. ^ "Hyperbraille". Hyperbraille. 14. ^ "Home of Tactisplay Corp". Tactisplay Corp. 15. ^ "Full Page Braille Display being Launched by Tactisplay Corp". Tactisplay Corp. 16. ^ "This video shows operation of the device". Retrieved Sep 10, 2020. 17. ^ "The Miracle Worker (2000)". imdb.com. Retrieved 2017-12-23. 18. ^ Bobrow, Emily (2 August 2019). "Haben Girma Is a Trailblazer for the Deaf and Blind". The Wall Street Journal. Retrieved 7 November 2020. ## External links[edit] * Media related to Deafblindness at Wikimedia Commons * The National Center On Deaf-Blindness Official informational website on deafblindness in United States. * The Helen Keller National Center for Deaf-Blind Youths and Adults Helen Keller Services website catering for the deaf-blind and blind communities. * World Federation of the Deaf-blind Website for worldwide information concerning deafblindness. * Able Australia Informational website on deafblindness in Australia. * "Haben Girma Homepage" About Haben Girma, the first deafblind Harvard Law School graduate. * 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Deafblindness	c1955603	26,947	wikipedia	https://en.wikipedia.org/wiki/Deafblindness	2021-01-18T19:10:15	{"mesh": ["D054062"], "wikidata": ["Q843356"]}
Naxos disease Other namesDiffuse non-epidermolytic palmoplantar keratoderma with woolly hair and cardiomyopathy Cutaneous phenotype of Naxos disease: woolly hair (A), palmar (B) and plantar (C) keratoses. Naxos disease (also known as "Diffuse non-epidermolytic palmoplantar keratoderma with woolly hair and cardiomyopathy,"[1] "Diffuse palmoplantar keratoderma with woolly hair and arrhythmogenic right ventricular cardiomyopathy firstly described in Naxos island by Dr Nikos Protonotarios,"[1] and "Naxos disease"[1]) is a cutaneous condition characterized by a palmoplantar keratoderma.[1] The prevalence of the syndrome is up to 1 in every 1000 people in the Greek islands.[2] It has been associated with mutations in the genes encoding the proteins desmoplakin, plakoglobin, desmocollin-2, and SRC-interacting protein (SIP).[3][4] A variation of Naxos syndrome is known as Carvajal syndrome.[2] ## See also[edit] * Olmsted syndrome * List of cutaneous conditions * List of conditions caused by problems with junctional proteins ## References[edit] 1. ^ a b c d Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ a b Protonotarios, Nikos; Tsatsopoulou, Adalena (2006). "Naxos disease: Cardiocutaneous syndrome due to cell adhesion defect". Orphanet Journal of Rare Diseases. 1 (1): 4. doi:10.1186/1750-1172-1-4. PMC 1435994. PMID 16722579. 3. ^ McKoy G, Protonotarios N, Crosby A, et al. (June 2000). "Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease)". Lancet. 355 (9221): 2119–24. doi:10.1016/S0140-6736(00)02379-5. PMID 10902626. S2CID 39821701. 4. ^ "Keratoderma with woolly hair". Genetics Home Reference. April 17, 2018. Retrieved April 17, 2018. ## External links[edit] Classification D * OMIM: 601214 * MeSH: C538346 * v * t * e Cytoskeletal defects Microfilaments Myofilament Actin * Hypertrophic cardiomyopathy 11 * Dilated cardiomyopathy 1AA * DFNA20 * Nemaline myopathy 3 Myosin * Elejalde syndrome * Hypertrophic cardiomyopathy 1, 8, 10 * Usher syndrome 1B * Freeman–Sheldon syndrome * DFN A3, 4, 11, 17, 22; B2, 30, 37, 48 * May–Hegglin anomaly Troponin * Hypertrophic cardiomyopathy 7, 2 * Nemaline myopathy 4, 5 Tropomyosin * Hypertrophic cardiomyopathy 3 * Nemaline myopathy 1 Titin * Hypertrophic cardiomyopathy 9 Other * Fibrillin * Marfan syndrome * Weill–Marchesani syndrome * Filamin * FG syndrome 2 * Boomerang dysplasia * Larsen syndrome * Terminal osseous dysplasia with pigmentary defects IF 1/2 * Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1 * Striate palmoplantar keratoderma 3 * Epidermolytic hyperkeratosis * IHCM * KRT2E (Ichthyosis bullosa of Siemens) * KRT3 (Meesmann juvenile epithelial corneal dystrophy) * KRT4 (White sponge nevus) * KRT5 (Epidermolysis bullosa simplex) * KRT8 (Familial cirrhosis) * KRT10 (Epidermolytic hyperkeratosis) * KRT12 (Meesmann juvenile epithelial corneal dystrophy) * KRT13 (White sponge nevus) * KRT14 (Epidermolysis bullosa simplex) * KRT17 (Steatocystoma multiplex) * KRT18 (Familial cirrhosis) * KRT81/KRT83/KRT86 (Monilethrix) * Naegeli–Franceschetti–Jadassohn syndrome * Reticular pigmented anomaly of the flexures 3 * Desmin: Desmin-related myofibrillar myopathy * Dilated cardiomyopathy 1I * GFAP: Alexander disease * Peripherin: Amyotrophic lateral sclerosis 4 * Neurofilament: Parkinson's disease * Charcot–Marie–Tooth disease 1F, 2E * Amyotrophic lateral sclerosis 5 * Laminopathy: LMNA * Mandibuloacral dysplasia * Dunnigan Familial partial lipodystrophy * Emery–Dreifuss muscular dystrophy 2 * Limb-girdle muscular dystrophy 1B * Charcot–Marie–Tooth disease 2B1 * LMNB * Barraquer–Simons syndrome * LEMD3 * Buschke–Ollendorff syndrome * Osteopoikilosis * LBR * Pelger–Huet anomaly * Hydrops-ectopic calcification-moth-eaten skeletal dysplasia Microtubules Kinesin * Charcot–Marie–Tooth disease 2A * Hereditary spastic paraplegia 10 Dynein * Primary ciliary dyskinesia * Short rib-polydactyly syndrome 3 * Asphyxiating thoracic dysplasia 3 Other * Tauopathy * Cavernous venous malformation Membrane * Spectrin: Spinocerebellar ataxia 5 * Hereditary spherocytosis 2, 3 * Hereditary elliptocytosis 2, 3 Ankyrin: Long QT syndrome 4 * Hereditary spherocytosis 1 Catenin * APC * Gardner's syndrome * Familial adenomatous polyposis * plakoglobin (Naxos syndrome) * GAN (Giant axonal neuropathy) Other * desmoplakin: Striate palmoplantar keratoderma 2 * Carvajal syndrome * Arrhythmogenic right ventricular dysplasia 8 * plectin: Epidermolysis bullosa simplex with muscular dystrophy * Epidermolysis bullosa simplex of Ogna * plakophilin: Skin fragility syndrome * Arrhythmogenic right ventricular dysplasia 9 * centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II) Related topics: Cytoskeletal proteins This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Naxos syndrome	c1832600	26,948	wikipedia	https://en.wikipedia.org/wiki/Naxos_syndrome	2021-01-18T19:01:20	{"gard": ["9795"], "mesh": ["C538346"], "umls": ["C1832600"], "orphanet": ["34217"], "wikidata": ["Q1332565"]}
Idiopathic pulmonary hemosiderosis is a rare disease characterized by repeated episodes of bleeding into the lungs, which can cause anemia and lung disease. The body is able to remove most of the blood from the lungs, but a large amount of iron is left behind. Over time, this iron can cause permanent damage to the lungs (fibrosis). Symptoms can resemble pneumonia and include coughing, coughing up blood (hemoptysis), difficulty breathing, and wheezing. The cause of idiopathic pulmonary hemosiderosis is unknown. Diagnosis is based on ruling out other kinds of pulmonary hemosiderosis, and tests may include imaging, laboratory tests, and a lung biopsy. Treatment often includes corticosteroids or other immunosuppressive medications. The prognosis may vary depending on the amount of pulmonary bleeding and age of diagnosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Idiopathic pulmonary hemosiderosis	c0020807	26,949	gard	https://rarediseases.info.nih.gov/diseases/6763/idiopathic-pulmonary-hemosiderosis	2021-01-18T17:59:49	{"mesh": ["C536281"], "omim": ["178550"], "umls": ["C0020807"], "orphanet": ["99931"], "synonyms": ["Hemosiderosis, pulmonary, with deficiency of gamma-a globulin", "Alveolar hypoventilation syndrome", "Pulmonary hemosiderosis"]}
Trilogy of Fallot SpecialtyMedical genetics The Trilogy of Fallot is a rare congenital heart disease consisting of the following defects: pulmonary valve stenosis, right ventricular hypertrophy and atrial septal defect. This disease is 1.6-1.8% of all congenital heart defects.[citation needed] ## Contents * 1 Mechanism * 1.1 The Three Malformations * 2 Diagnosis * 3 Treatment * 4 History * 5 References * 6 External links ## Mechanism[edit] Trilogy of Fallot is a combination of three congenital heart defects: pulmonary stenosis, right ventricular hypertrophy, and an atrial septal defect. The first two of these are also found in the more common tetralogy of Fallot. However, the tetralogy has a ventricular septal defect instead of an atrial one, and it also involves Pulmonary Valve Stenosis Right Ventricular Hypertrophy Right Ventricular Hypertrophy an overriding aorta. Atrial Septal Defect ### The Three Malformations[edit] Condition Description Pulmonary Stenosis A malformation near or on the pulmonary valve (the valve between the right ventricle and the pulmonary artery) that causes the opening of the valve to be narrowed, affecting blood flow. This narrowing can occur when one or more of the cusps is too thick or is otherwise defective, preventing the valve from opening fully and properly. [1] Right Ventricular Hypertrophy The right ventricle is more muscular than normal, causing a characteristic boot-shaped appearance as seen by chest X-ray. This enlargement is generally a secondary condition, resulting from increased pressure. Pulmonary valve defects resulting in tricuspid regurgitation, a common effect of pulmonary stenosis, can cause this increase in muscle mass.[2] Atrial Septal Defect An atrial septal defect is a hole in the septum that divides the right and left atria (the upper two chambers) of the heart. In the heart of a developing fetus, there are several holes between the atria, however these are expected to close before birth. This congenital condition arises if one of these holes remains. [3] Depending on the severity of the defect, it may need to be repaired surgically, as a significant defect can cause further damage to the heart and lungs.[4] ## Diagnosis[edit] This section is empty. You can help by adding to it. (September 2017) Clinically trilogy of Fallot can have cardiomegaly, less symptomatic when compared to ToF, JVP increased, a wave is more elevated, delayed P2, apex beat will be of LV type. S4+, ejection click+, On doing Cath, RV angiogram, when RV is flicked, to create a RV ectopic, there is post ectopic potentiation of the murmur, unlike ToF ## Treatment[edit] Thoracotomy is used to surgically correct this pathology.[5] ## History[edit] It is named in honor of its discoverer: Etienne Fallot.[6] ## References[edit] 1. ^ "Pulmonary valve stenosis - Symptoms and causes". Mayo Clinic. Retrieved 2020-04-14. 2. ^ Bhattacharya, Priyanka T.; Sharma, Sandeep (2020), "Right Ventricular Hypertrophy", StatPearls, StatPearls Publishing, PMID 29763051, retrieved 2020-04-14 3. ^ CDC (2019-11-19). "Congenital Heart Defects - Facts about Atrial Septal Defects \| CDC". Centers for Disease Control and Prevention. Retrieved 2020-04-14. 4. ^ "Atrial septal defect (ASD) - Symptoms and causes". Mayo Clinic. Retrieved 2020-04-14. 5. ^ Wang YQ, Chen RK, Ye WW, et al. (1999). "Open-heart surgery in 48 patients via a small right anterolateral thoracotomy". Tex Heart Inst J. 26 (2): 124–8. PMC 325616. PMID 10397435. 6. ^ synd/2283 at Who Named It? ## External links[edit] Classification D * ICD-10: Q21.3 ICD9 = 746.09, 746.8 (CDC/BPA 746.84) * MeSH: D014286 * v * t * e Congenital heart defects Heart septal defect Aortopulmonary septal defect * Double outlet right ventricle * Taussig–Bing syndrome * Transposition of the great vessels * dextro * levo * Persistent truncus arteriosus * Aortopulmonary window Atrial septal defect * Sinus venosus atrial septal defect * Lutembacher's syndrome Ventricular septal defect * Tetralogy of Fallot Atrioventricular septal defect * Ostium primum Consequences * Cardiac shunt * Cyanotic heart disease * Eisenmenger syndrome Valvular heart disease Right * pulmonary valves * stenosis * insufficiency * absence * tricuspid valves * stenosis * atresia * Ebstein's anomaly Left * aortic valves * stenosis * insufficiency * bicuspid * mitral valves * stenosis * regurgitation Other * Underdeveloped heart chambers * right * left * Uhl anomaly * Dextrocardia * Levocardia * Cor triatriatum * Crisscross heart * Brugada syndrome * Coronary artery anomaly * Anomalous aortic origin of a coronary artery * Ventricular inversion This article about a congenital malformation is a stub. You can help Wikipedia by expanding it. * v * t * e This article about a medical condition affecting the circulatory system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Trilogy of Fallot	c0041022	26,950	wikipedia	https://en.wikipedia.org/wiki/Trilogy_of_Fallot	2021-01-18T18:46:56	{"mesh": ["D014286"], "icd-9": ["746.8", "746.09"], "wikidata": ["Q1394671"]}
Opioid addiction is a long-lasting (chronic) disease that can cause major health, social, and economic problems. Opioids are a class of drugs that act in the nervous system to produce feelings of pleasure and pain relief. Some opioids are legally prescribed by healthcare providers to manage severe and chronic pain. Commonly prescribed opioids include oxycodone, fentanyl, buprenorphine, methadone, oxymorphone, hydrocodone, codeine, and morphine. Some other opioids, such as heroin, are illegal drugs of abuse. Opioid addiction is characterized by a powerful, compulsive urge to use opioid drugs, even when they are no longer required medically. Opioids have a high potential for causing addiction in some people, even when the medications are prescribed appropriately and taken as directed. Many prescription opioids are misused or diverted to others. Individuals who become addicted may prioritize getting and using these drugs over other activities in their lives, often negatively impacting their professional and personal relationships. It is unknown why some people are more likely to become addicted than others. Opioids change the chemistry of the brain and lead to drug tolerance, which means that over time the dose needs to be increased to achieve the same effect. Taking opioids over a long period of time produces dependence, such that when people stop taking the drug, they have physical and psychological symptoms of withdrawal (such as muscle cramping, diarrhea, and anxiety). Dependence is not the same thing as addiction; although everyone who takes opioids for an extended period will become dependent, only a small percentage also experience the compulsive, continuing need for the drug that characterizes addiction. Opioid addiction can cause life-threatening health problems, including the risk of overdose. Overdose occurs when high doses of opioids cause breathing to slow or stop, leading to unconsciousness and death if the overdose is not treated immediately. Both legal and illegal opioids carry a risk of overdose if a person takes too much of the drug, or if opioids are combined with other drugs (particularly tranquilizers called benzodiazepines). ## Frequency Misuse of prescription opioids and heroin affects more than 2 million Americans and an estimated 15 million people worldwide each year. The prevalence of opioid misuse and addiction is rapidly increasing. In 2016, more than 20,000 deaths in the United States were caused by an overdose of prescription opioids, and another 13,000 deaths resulted from heroin overdose. Drug overdoses are now the leading cause of death in U.S. adults under age 50, and opioids account for more than half of all drug overdose deaths. ## Causes The causes of opioid addiction are complex. This condition results from a combination of genetic, environmental, and lifestyle factors, some of which have not been identified. Many of the genes that are thought to play a role in opioid addiction are involved in the endogenous opioid system, which is the body's internal system for regulating pain, reward, and addictive behaviors. It consists of opioid substances produced naturally within the body (called endogenous opioids) and their receptors, into which opioids fit like keys into locks. Opioids introduced from outside the body (called exogenous opioids), including opioid medications and heroin, also exert their effects by acting on these receptors. Variations in the genes that provide instructions for making opioid receptors have been studied extensively as genetic risk factors for opioid addiction. Researchers suspect that differences in the receptors' structure and function influence how the body responds to opioids. Opioid receptors are found in the nervous system, where they are embedded in the outer membrane of nerve cells (neurons). When endogenous or exogenous opioids attach (bind) to the receptors, the interaction triggers a series of chemical changes within and between neurons that leads to feelings of pleasure and pain relief. The mu (μ) opioid receptor, which is produced from the OPRM1 gene, is the primary receptor for most opioid drugs. Common variations in the OPRM1 gene appear to influence how the body responds to opioids, including the amount of an opioid medication needed to achieve pain relief. At least in some populations, these variations have also been associated with the risk of opioid addiction. Variations in genes involved in other aspects of nervous system function have also been studied as risk factors for opioid addiction. Some of these genes play roles in various neurotransmitter pathways, in which chemicals called neurotransmitters and their receptors relay signals from one neuron to another. Other genes provide instructions for proteins that help control the growth, survival, and specialization (differentiation) of neurons. Although variations in several of these genes have been associated with opioid addiction, it is unclear how these genetic changes influence the way in which the nervous system responds to opioids. Opioid addiction is a complex disorder, and nongenetic factors also play a critical role. Factors that have been shown to increase the risk of opioid addiction include a history of substance abuse; depression or other psychiatric disorders; childhood abuse or neglect; and certain personality traits, including impulsivity and sensation-seeking. Living in poverty and in a rural area, associating with others who abuse opioids or other substances, and having easy access to prescription or illegal opioids also contribute to a person's risk of opioid addiction. It is likely that a combination of health, social, economic, and lifestyle factors interact with genetic factors to determine an individual's risk. ### Learn more about the genes associated with Opioid addiction * BDNF * COMT * GRIN2A * OPRM1 Additional Information from NCBI Gene: * ABCB1 * AVPR1A * CSNK1E * CYP2B6 * DRD2 * DRD3 * DRD4 * FKBP5 * GABRG1 * GAD1 * GAL * HTR1B * OPRD1 * OPRK1 * OPRL1 * PDYN * PNOC ## Inheritance Pattern Opioid addiction does not have a clear pattern of inheritance, although many affected individuals have a family history of addiction to opioids or other substances. People who have family members with addiction appear to have a higher risk of addiction themselves. This increased risk is likely due in part to shared genetic factors, but it may also be related to environment, lifestyle, and other nongenetic influences that are shared by members of a family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Opioid addiction	c1864733	26,951	medlineplus	https://medlineplus.gov/genetics/condition/opioid-addiction/	2021-01-27T08:24:57	{"omim": ["610064"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that focal or diffuse nonepidermolytic palmoplantar keratoderma (PPKNEFD) is caused by heterozygous mutation in the KRT6C gene (612315) on chromosome 12q13. Clinical Features Wilson et al. (2010) described 3 families with focal palmoplantar keratoderma (PPKF). The first family (family 1) involved a father and son with PPKF who both exhibited plantar blistering; neither showed nail changes. In family 2 there were 6 affected individuals over 4 generations who showed minor nail changes, particularly nail hypertrophy of the fifth toe only, but no other ectodermal features. Family 3 consisted of 9 affected individuals over 4 generations; the proband experienced blistering in the summer months and had subtle leukokeratosis along the buccal bite line as well as occasional nail splinter hemorrhages. Although all affected individuals had relatively mild, site-restricted keratoderma and very minor or absent nail changes, they all experienced a significant amount of pain or discomfort, requiring secondary medical care. Bowden (2010) noted close similarities between the phenotype in these patients and that of patients with hereditary painful callosities (114140). Akasaka et al. (2011) reported a Japanese family in which a 26-year-old man had diffuse hyperkeratosis of the soles of the feet that had developed at around 5 years of age, as well as small hyperkeratotic plaques on his hands that were believed to be related to mechanical stress due to his occupation as an ironworker. His son exhibited focal hyperkeratotic plaques of the feet with blister formation that developed at age 4 years, but did not show any hand lesions. The proband's 36-year-old sister also had focal hyperkeratotic plaques of the plantar surface, present since childhood, some of which were associated with clavus formation and were painful on walking. Her hands were uninvolved. All 3 affected individuals had hyperhidrosis of the soles, but nails were normal. The proband and his sister stated that their father also developed many calluses on the soles of his feet. Biopsy of the proband's soles showed nonepidermolytic orthohyperkeratosis and acanthosis of the epidermis. A clinical diagnosis of nonepidermolytic focal and diffuse PPK was made. Kubo et al. (2013) studied a 4-generation Japanese family segregating autosomal dominant focal plantar keratoderma. The proband was a 26-year-old man who developed thickened skin on the soles of his feet at 10 years of age. He had focal hyperkeratotic plaques, some of which caused severe pain while walking. His palms were not affected, the nails of his hands and feet appeared normal, and no oral leukokeratosis was observed. Histologic examination of affected plantar skin showed severe hyperkeratosis and some heterogeneity in the eosin staining of the keratinocyte cytoplasm. His 8-year-old daughter had slight focal hyperkeratosis on her soles, which was first noted at 5 years of age and had recently become painful. Her palms and the nails of her hands and feet were not affected. The proband's sister, mother, maternal aunt and uncle, and maternal grandmother were also affected but declined examination. Mapping In two 4-generation families segregating autosomal dominant focal palmoplantar keratoderma, Wilson et al. (2010) analyzed microsatellite markers and excluded the type I keratin locus on chromosome 17; however, markers within the type II keratin locus on chromosome 12 were consistent with linkage. Molecular Genetics In two 4-generation families with focal palmoplantar keratoderma mapping to chromosome 12q13 as well as a father and son with PPKF, Wilson et al. (2010) excluded mutations in the KRT6A (148041) and KRT6B (148042) genes, and identified heterozygous mutations in the KRT6C gene (612315) in all 3 families: the father and son (family 1) and affected members of family 2 had an in-frame 3-bp deletion (612315.0001), whereas affected members of family 3 had an in-frame 27-bp deletion (612315.0002). Both mutations segregated fully with disease in each family; however, the 3-bp deletion was also present in 3 of 335 population controls. Wilson et al. (2010) suggested that KRT6C mutations might be a common genetic predisposing factor for plantar callus formation, which may be relatively mild and not always come to clinical attention. In 3 affected members of a Japanese family with focal or diffuse keratoderma in a primarily plantar distribution, who were negative for mutation in the KRT6A, KRT6B, KRT16 (148067), or KRT17 (148069) genes, Akasaka et al. (2011) identified a heterozygous missense mutation in the KRT6C gene (E472K; 612315.0003). In a father and daughter with focal plantar keratoderma, Kubo et al. (2013) sequenced the candidate gene KRT6C and identified heterozygosity for the E472K mutation, which was not present in an unaffected son. Transfection studies in HaCaT cells showed collapse of the keratin filament network in a dose-dependent manner, suggesting that the mutation has a dominant-negative effect on keratin filament network formation. INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Mild leukokeratosis of buccal bite line (in some patients) SKIN, NAILS, & HAIR Skin \- Palmoplantar keratoderma, focal \- Palmoplantar keratoderma, diffuse (in some patients) \- Plantar blistering \- Hyperhidrosis of plantar surface (in some patients) \- Clavus formation (rare) Skin Histology \- Nonepidermolytic orthohyperkeratosis \- Acanthosis Nails \- Hypertrophic nail changes, mild (in some patients) \- Splinter hemorrhages of nails (in some patients) MISCELLANEOUS \- Some patients have only plantar surface involvement MOLECULAR BASIS \- Caused by mutation in the keratin-6C gene (KRT6C, 612315.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PALMOPLANTAR KERATODERMA, NONEPIDERMOLYTIC, FOCAL OR DIFFUSE	c3810394	26,952	omim	https://www.omim.org/entry/615735	2019-09-22T15:51:05	{"doid": ["0050428"], "omim": ["615735"], "orphanet": ["402003"], "synonyms": [], "genereviews": ["NBK1280"]}
Alcohol withdrawal syndrome Ethanol SpecialtyAddiction Medicine, Critical Care Medicine, Psychiatry SymptomsAnxiety, shakiness, sweating, vomiting, fast heart rate, mild fever[1] ComplicationsHallucinations, delirium tremens, seizures[1] Usual onsetSix hours following the last drink[2] DurationUp to a week[2] CausesReduction or cessation of alcohol intake after a period of excessive use[1] Diagnostic methodClinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar)[3] TreatmentBenzodiazepines, thiamine[2] Frequency~50% of people with alcoholism upon reducing use[3] Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use.[1] Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever.[1] More severe symptoms may include seizures, seeing or hearing things that others do not, and delirium tremens (DTs).[1] Symptoms typically begin around six hours following the last drink, are worst at 24 to 72 hours, and improve by seven days.[2][3] Alcohol withdrawal may occur in those who are alcohol dependent.[1] This may occur following a planned or unplanned decrease in alcohol intake.[1] The underlying mechanism involves a decreased responsiveness of GABA receptors in the brain.[3] The withdrawal process is typically followed using the Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar).[3] The typical treatment of alcohol withdrawal is with benzodiazepines such as chlordiazepoxide or diazepam.[2] Often the amounts given are based on a person's symptoms.[2] Thiamine is recommended routinely.[2] Electrolyte problems and low blood sugar should also be treated.[2] Early treatment improves outcomes.[2] In the Western world about 15% of people have problems with alcoholism at some point in time.[3] About half of people with alcoholism will develop withdrawal symptoms upon reducing their use, with four percent developing severe symptoms.[3] Among those with severe symptoms up to 15% die.[2] Symptoms of alcohol withdrawal have been described at least as early as 400 BC by Hippocrates.[4][5] It is not believed to have become a widespread problem until the 1700s.[5] ## Contents * 1 Signs and symptoms * 1.1 Progression * 1.2 Protracted withdrawal * 2 Pathophysiology * 2.1 Kindling * 3 Diagnosis * 4 Treatment * 4.1 Benzodiazepines * 4.2 Vitamins * 4.3 Anticonvulsants * 4.4 Prevention of further drinking * 4.5 Other * 5 Prognosis * 5.1 Substances impairing recovery * 6 References * 7 External links ## Signs and symptoms[edit] Signs and symptoms of alcohol withdrawal occur primarily in the central nervous system. The severity of withdrawal can vary from mild symptoms such as sleep disturbances and anxiety to severe and life-threatening symptoms such as alcoholic hallucinosis, delirium tremens, and autonomic instability. Withdrawal usually begins 6 to 24 hours after the last drink.[6] It can last for up to one week.[7] To be classified as alcohol withdrawal syndrome, patients must exhibit at least two of the following symptoms: increased hand tremor, insomnia, nausea or vomiting, transient hallucinations (auditory, visual or tactile), psychomotor agitation, anxiety, tonic–clonic seizures, and autonomic instability.[8] The severity of symptoms is dictated by a number of factors, the most important of which are degree of alcohol intake, length of time the individual has been using alcohol, and previous history of alcohol withdrawal.[8] Symptoms are also grouped together and classified: * Alcohol hallucinosis: patients have transient visual, auditory, or tactile hallucinations, but are otherwise clear.[8] * Withdrawal seizures: seizures occur within 48 hours of alcohol cessations and occur either as a single generalized tonic-clonic seizure or as a brief episode of multiple seizures.[9] * Delirium tremens: hyperadrenergic state, disorientation, tremors, diaphoresis, impaired attention/consciousness, and visual and auditory hallucinations.[8] This usually occurs 24 to 72 hours after alcohol cessation. Delirium tremens is the most severe form of withdrawal and occurs in 5 to 20% of patients experiencing detoxification and 1/3 of patients experiencing withdrawal seizures.[9] ### Progression[edit] Typically the severity of the symptoms experienced depends on the amount and duration of prior alcohol consumption as well as the number and severity of previous withdrawals. Even the most severe of these symptoms can occur as soon as 2 hours after cessation; this rapid onset alongside the syndrome's unpredictability necessitates either pre-planned hospitalization, treatment coordinated with a doctor, or at the very least rapid access to medical care; a supporting system of friends or family should also be introduced prior to addressing detoxification. In many cases, however, symptoms follow a reasonably predictable time frame as exampled below: Six to 12 hours after the ingestion of the last drink, withdrawal symptoms such as shaking, headache, sweating, anxiety, nausea, or vomiting occur.[10] Other comparable symptoms may also occur in this period. Twelve to 24 hours after cessation, the condition may progress to such major symptoms as confusion, hallucinations[10] (with awareness of reality), tremor, agitation, and similar ailments. At 24 to 48 hours following the last ethanol ingestion, the possibility of seizures should be anticipated.[10] Meanwhile, none of the earlier withdrawal symptoms will have abated. Seizures carry the risk of death for the alcoholic. Although the patient's condition usually begins to improve after 48 hours, withdrawal symptoms sometimes continue to increase in severity and advance to delirium tremens, which is characterized by hallucinations that are indistinguishable from reality, severe confusion, seizures, high blood pressure, and fever that can persist anywhere from 4 to 12 days.[10] ### Protracted withdrawal[edit] See also: Protracted withdrawal syndrome A protracted alcohol withdrawal syndrome occurs in many alcoholics when withdrawal symptoms continue beyond the acute withdrawal stage but usually at a subacute level of intensity and gradually decreasing with severity over time. This syndrome is sometimes referred to as the post-acute-withdrawal syndrome. Some withdrawal symptoms can linger for at least a year after discontinuation of alcohol. Symptoms can include a craving for alcohol, inability to feel pleasure from normally pleasurable things (known as anhedonia), clouding of sensorium, disorientation, nausea and vomiting or headache.[11] Insomnia is a common protracted withdrawal symptom that persists after the acute withdrawal phase of alcohol. Insomnia has also been found to influence relapse rate. Studies have found that magnesium or trazodone can help treat the persisting withdrawal symptom of insomnia in recovering alcoholics. Insomnia can be difficult to treat in alcoholics because many of the traditional sleep aids (e.g., benzodiazepine receptor agonists and barbiturate receptor agonists) work via a GABAA receptor mechanism and are cross-tolerant with alcohol. However, trazodone is not cross-tolerant with alcohol.[12][13][14] The acute phase of the alcohol withdrawal syndrome can occasionally be protracted. Protracted delirium tremens has been reported in the medical literature as a possible but unusual feature of alcohol withdrawal.[15] ## Pathophysiology[edit] Chronic use of alcohol leads to changes in brain chemistry especially in the GABAergic system. Various adaptations occur such as changes in gene expression and down regulation of GABAA receptors. During acute alcohol withdrawal, changes also occur such as upregulation of alpha4 containing GABAA receptors and downregulation of alpha1 and alpha3 containing GABAA receptors. Neurochemical changes occurring during alcohol withdrawal can be minimized with drugs which are used for acute detoxification. With abstinence from alcohol and cross-tolerant drugs these changes in neurochemistry gradually return towards normal.[16][17] Adaptations to the NMDA system also occur as a result of repeated alcohol intoxication and are involved in the hyper-excitability of the central nervous system during the alcohol withdrawal syndrome. Homocysteine levels, which are elevated during chronic drinking, increase even further during the withdrawal state, and may result in excitotoxicity.[18] Alterations in ECG (in particular an increase in QT interval) and EEG abnormalities (including abnormal quantified EEG) may occur during early withdrawal.[18] Dysfunction of the hypothalamic–pituitary–adrenal axis and increased release of corticotropin-releasing hormone occur during both acute as well as protracted abstinence from alcohol and contribute to both acute and protracted withdrawal symptoms. Anhedonia/dysphoria symptoms, which can persist as part of a protracted withdrawal, may be due to dopamine underactivity.[19] ### Kindling[edit] See also: Kindling (sedative–hypnotic withdrawal) Kindling is a phenomenon where repeated alcohol detoxifications leads to an increased severity of the withdrawal syndrome. For example, binge drinkers may initially experience no withdrawal symptoms, but with each period of alcohol use followed by cessation, their withdrawal symptoms intensify in severity and may eventually result in full-blown delirium tremens with convulsive seizures. Alcoholics who experience seizures during detoxification are more likely to have had previous episodes of alcohol detoxification than patients who did not have seizures during withdrawal. In addition, patients with previous withdrawal syndromes are more likely to have more medically complicated alcohol withdrawal symptoms. Kindling can cause complications and may increase the risk of relapse, alcohol-related brain damage and cognitive deficits. Chronic alcohol misuse and kindling via multiple alcohol withdrawals may lead to permanent alterations in the GABAA receptors.[20] The mechanism behind kindling is sensitization of some neuronal systems and desensitization of other neuronal systems which leads to increasingly gross neurochemical imbalances. This in turn leads to more profound withdrawal symptoms including anxiety, convulsions and neurotoxicity.[21] Binge drinking is associated with increased impulsivity, impairments in spatial working memory and impaired emotional learning. These adverse effects are believed to be due to the neurotoxic effects of repeated withdrawal from alcohol on aberrant neuronal plasticity and cortical damage. Repeated periods of acute intoxication followed by acute detoxification has profound effects on the brain and is associated with an increased risk of seizures as well as cognitive deficits. The effects on the brain are similar to those seen in alcoholics who have been detoxified repeatedly but not as severe as in alcoholics who have no history of prior detox. Thus the acute withdrawal syndrome appears to be the most important factor in causing damage or impairment to brain function. The brain regions most sensitive to harm from binge drinking are the amygdala and prefrontal cortex.[22] People in adolescence who experience repeated withdrawals from binge drinking show impairments of long-term nonverbal memory. Alcoholics who have had two or more alcohol withdrawals show more frontal lobe cognitive dysfunction than alcoholics who have experienced one or no prior withdrawals. Kindling of neurons is the proposed cause of withdrawal-related cognitive damage. Kindling from repeated withdrawals leads to accumulating neuroadaptational changes. Kindling may also be the reason for cognitive damage seen in binge drinkers.[23] ## Diagnosis[edit] Many hospitals use the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol in order to assess the level of withdrawal present and therefore the amount of medication needed.[8] When overuse of alcohol is suspected but drinking history is unclear, testing for elevated values of carbohydrate-deficient transferrin or gammaglutamyl transferase can help make the diagnosis of alcohol overuse and dependence more clear. The CIWA has also been shortened (now called the CIWA-Ar), while retaining its validity and reliability, to help assess patients more efficiently due to the life-threatening nature of alcohol withdrawal.[24] Other conditions that may present similarly include benzodiazepine withdrawal syndrome (a condition also mainly caused by GABAA receptor adaptation). ## Treatment[edit] Benzodiazepines are effective for the management of symptoms as well as the prevention of seizures.[25] Certain vitamins are also an important part of the management of alcohol withdrawal syndrome. In those with severe symptoms inpatient care is often required.[6] In those with lesser symptoms treatment at home may be possible with daily visits with a health care provider.[6] ### Benzodiazepines[edit] Benzodiazepines are the most commonly used medication for the treatment of alcohol withdrawal and are generally safe and effective in suppressing symptoms of alcohol withdrawal.[26] This class of medication is generally effective in symptoms control, but need to be used carefully. Although benzodiazepines have a long history of successfully treating and preventing withdrawal, there is no consensus on the ideal one to use. The most commonly used agents are long-acting benzodiazepines, such as chlordiazepoxide and diazepam. These are believed to be superior to other benzodiazepines for treatment of delirium and allow for longer periods between doses. However, benzodiazepines with intermediate half-lives like lorazepam may be safer in people with liver problems.[7] The primary debate between use of long-acting benzodiazepines and short-acting is that of ease of use. Longer-acting drugs, such as diazepam, can be administered less frequently. However, evidence does exist that "symptom-triggered regimens" such as those used when treating with lorazepam, are as safe and effective, but have decreased treatment duration and medication quantity used.[7] Although benzodiazepines are very effective at treating alcohol withdrawal, they should be carefully used. Benzodiazepines should only be used for brief periods in alcoholics who are not already dependent on them, as they share cross tolerance with alcohol. There is a risk of replacing an alcohol addiction with benzodiazepine dependence or adding another addiction. Furthermore, disrupted GABA benzodiazepine receptor function is part of alcohol dependence and chronic benzodiazepines may prevent full recovery from alcohol induced mental effects.[27][28] The combination of benzodiazepines and alcohol can amplify the adverse psychological effects of each other causing enhanced depressive effects on mood and increase suicidal actions and are generally contraindicated except for alcohol withdrawal.[29] ### Vitamins[edit] Alcoholics are often deficient in various nutrients, which can cause severe complications during alcohol withdrawal, such as the development of Wernicke syndrome. To help to prevent Wernicke syndrome, alcoholics should be administered a multivitamin preparation with sufficient quantities of thiamine and folic acid. During alcohol withdrawal, the prophylactic administration of thiamine, folic acid, and pyridoxine intravenously is recommended before starting any carbohydrate-containing fluids or food. These vitamins are often combined into a banana bag for intravenous administration.[30] ### Anticonvulsants[edit] Very limited evidence indicates that topiramate or pregabalin may be useful in the treatment of alcohol withdrawal syndrome.[31] Limited evidence supports the use of gabapentin or carbamazepine for the treatment of mild or moderate alcohol withdrawal as the sole treatment or as combination therapy with other medications; however, gabapentin does not appear to be effective for treatment of severe alcohol withdrawal and is therefore not recommended for use in this setting.[31][32] A 2010 Cochrane review similarly reported that the evidence to support the role of anticonvulsants over benzodiazepines in the treatment of alcohol withdrawal is not supported.[33] Paraldehyde combined with chloral hydrate showed superiority over chlordiazepoxide with regard to life-threatening side effects and carbamazepine may have advantages for certain symptoms.[33] Long term anticonvulsant medications are not usually recommended in those who have had prior seizures due to withdrawal.[34] ### Prevention of further drinking[edit] There are three medications used to help prevent a return to drinking: naltrexone, acamprosate, and disulfiram. They are used after withdrawal has occurred.[35] ### Other[edit] Clonidine may be used in combination with benzodiazepines to help some of the symptoms.[8] There is insufficient evidence to support the use of baclofen for alcohol withdrawal syndrome.[36] Antipsychotics, such as haloperidol, are sometimes used in addition to benzodiazepines to control agitation or psychosis.[8] Antipsychotics may potentially worsen alcohol withdrawal as they lower the seizure threshold. Clozapine, olanzapine, or low-potency phenothiazines (such as chlorpromazine) are particularly risky; if used, extreme caution is required.[37] While intravenous ethanol could theoretically be used, evidence to support this use, at least in those who are very sick, is insufficient.[38] ## Prognosis[edit] Failure to manage the alcohol withdrawal syndrome appropriately can lead to permanent brain damage or death.[39] It has been proposed that brain damage due to alcohol withdrawal may be prevented by the administration of NMDA antagonists, calcium antagonists, and glucocorticoid antagonists.[40] ### Substances impairing recovery[edit] Continued use of benzodiazepines may impair recovery from psychomotor and cognitive impairments from alcohol.[41] Cigarette smoking may slow down or interfere with recovery of brain pathways in recovering alcoholics.[42] ## References[edit] 1. ^ a b c d e f g h National Clinical Guideline Centre (2010). "2 Acute Alcohol Withdrawal". Alcohol Use Disorders: Diagnosis and Clinical Management of Alcohol-Related Physical Complications (No. 100 ed.). London: Royal College of Physicians (UK). Archived from the original on 31 January 2014. Retrieved 21 October 2016. 2. ^ a b c d e f g h i j Simpson, SA; Wilson, MP; Nordstrom, K (September 2016). "Psychiatric Emergencies for Clinicians: Emergency Department Management of Alcohol Withdrawal". The Journal of Emergency Medicine. 51 (3): 269–73. doi:10.1016/j.jemermed.2016.03.027. PMID 27319379. 3. ^ a b c d e f g Schuckit, MA (27 November 2014). "Recognition and management of withdrawal delirium (delirium tremens)". The New England Journal of Medicine. 371 (22): 2109–13. doi:10.1056/NEJMra1407298. PMID 25427113. 4. ^ Martin, Scott C. (2014). The SAGE Encyclopedia of Alcohol: Social, Cultural, and Historical Perspectives. SAGE Publications. p. Alcohol Withdrawal Scale. ISBN 9781483374383. Archived from the original on 2016-10-22. 5. ^ a b Kissin, Benjamin; Begleiter, Henri (2013). The Biology of Alcoholism: Volume 3: Clinical Pathology. Springer Science & Business Media. p. 192. ISBN 9781468429374. Archived from the original on 2016-10-22. 6. ^ a b c Muncie HL, Jr; Yasinian, Y; Oge', L (Nov 1, 2013). "Outpatient management of alcohol withdrawal syndrome". American Family Physician. 88 (9): 589–95. PMID 24364635. 7. ^ a b c McKeon, A; Frye, MA; Delanty, N (August 2008). "The alcohol withdrawal syndrome". Journal of Neurology, Neurosurgery, and Psychiatry. 79 (8): 854–62. doi:10.1136/jnnp.2007.128322. PMID 17986499. S2CID 2139796. 8. ^ a b c d e f g Bayard M, McIntyre J, Hill KR, Woodside J (March 2004). "Alcohol withdrawal syndrome". Am Fam Physician. 69 (6): 1443–50. PMID 15053409. Archived from the original on 2008-10-16. 9. ^ a b Manasco, A; Chang, S; Larriviere, J; Hamm, LL; Glass, M (November 2012). "Alcohol withdrawal". 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"Kindling in Alcohol Withdrawal" (PDF). Alcohol Health & Research World. 22 (1). Archived (PDF) from the original on 2010-12-15. 22. ^ Stephens, DN.; Duka, T. (Oct 2008). "Cognitive and emotional consequences of binge drinking: role of amygdala and prefrontal cortex". Philos Trans R Soc Lond B Biol Sci. 363 (1507): 3169–79. doi:10.1098/rstb.2008.0097. PMC 2607328. PMID 18640918. 23. ^ Courtney, KE; Polich, J (Jan 2009). "Binge Drinking in Young Adults: Data, Definitions, and Determinants". Psychol Bull. 135 (1): 142–56. doi:10.1037/a0014414. PMC 2748736. PMID 19210057. 24. ^ Sullivan, JT; Sykora, K; Schneiderman, J; Naranjo, CA; Sellers, EM (1989). "Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar)". Br J Addict. 84 (11): 1353–7. CiteSeerX 10.1.1.489.341. doi:10.1111/j.1360-0443.1989.tb00737.x. PMID 2597811. 25. ^ Amato L, Minozzi S, Vecchi S, Davoli M (2010). Amato L (ed.). "Benzodiazepines for alcohol withdrawal". Cochrane Database Syst Rev. 3 (3): CD005063. doi:10.1002/14651858.CD005063.pub3. PMID 20238336. 26. ^ Bird, RD; Makela, EH (January 1994). "Alcohol withdrawal: what is the benzodiazepine of choice?". The Annals of Pharmacotherapy. 28 (1): 67–71. doi:10.1177/106002809402800114. PMID 8123967. S2CID 24312761. 27. ^ Toki S, Saito T, Nabeshima A, Hatta S, Watanabe M, Takahata N (February 1996). "Changes in GABAA receptor function and cross-tolerance to ethanol in diazepam-dependent rats". Alcohol. Clin. Exp. Res. 20 (1 Suppl): 40A–44A. doi:10.1111/j.1530-0277.1996.tb01726.x. PMID 8659687. 28. ^ Rassnick S, Krechman J, Koob GF (April 1993). "Chronic ethanol produces a decreased sensitivity to the response-disruptive effects of GABA receptor complex antagonists". Pharmacol. Biochem. Behav. 44 (4): 943–50. doi:10.1016/0091-3057(93)90029-S. PMID 8385785. S2CID 5909253. 29. ^ Ziegler PP (August 2007). "Alcohol use and anxiety". 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Cochrane Database Syst Rev. 3 (3): CD005064. doi:10.1002/14651858.CD005064.pub3. PMID 20238337. Archived from the original (PDF) on 2013-01-05. Retrieved 2010-04-22. 34. ^ "American Epilepsy Society Choosing Wisely". www.choosingwisely.org. Retrieved 30 August 2018. 35. ^ "Acamprosate: A New Medication for Alcohol Use Disorders" (PDF). 2005. Archived from the original (PDF) on 6 September 2015. Retrieved 8 January 2016. 36. ^ Liu, J; Wang, LN (April 2015). "Baclofen for alcohol withdrawal". Cochrane Database of Systematic Reviews. 4 (4): CD008502. doi:10.1002/14651858.CD008502.pub4. PMID 25836263. 37. ^ Ebadi, Manuchair (23 October 2007). "Alphabetical presentation of drugs". Desk Reference for Clinical Pharmacology (2nd ed.). USA: CRC Press. p. 512. ISBN 978-1-4200-4743-1. 38. ^ Hodges, B; Mazur, JE (November 2004). "Intravenous ethanol for the treatment of alcohol withdrawal syndrome in critically ill patients". Pharmacotherapy. 24 (11): 1578–85. doi:10.1592/phco.24.16.1578.50945. PMID 15537562. 39. ^ Hanwella R, de Silva V (June 2009). "Treatment of alcohol dependence". Ceylon Med J. 54 (2): 63–5. doi:10.4038/cmj.v54i2.877. PMID 19670554. 40. ^ Hunt, WA. (November–December 1993). "Are binge drinkers more at risk of developing brain damage?". Alcohol. 10 (6): 559–61. doi:10.1016/0741-8329(93)90083-Z. PMID 8123218. 41. ^ Gitlow, Stuart (1 October 2006). Substance Use Disorders: A Practical Guide (2nd ed.). USA: Lippincott Williams and Wilkins. pp. 95–96. ISBN 978-0-7817-6998-3. 42. ^ Durazzo TC; Meyerhoff DJ (2007). "Neurobiological and neurocognitive effects of chronic cigarette smoking and alcoholism". Front. Biosci. 12 (8–12): 4079–100. doi:10.2741/2373. PMID 17485360. Archived from the original on 2011-05-25. ## External links[edit] Classification D * ICD-10: F10.23, F10.23(0-9) * ICD-9-CM: 291.81 * DiseasesDB: 3543 External resources * MedlinePlus: 000764 * CIWA-Ar for Alcohol Withdrawal * Alcohol Detox Guidelines Example * v * t * e Psychoactive substance-related disorder General * SID * Substance intoxication / Drug overdose * Substance-induced psychosis * Withdrawal: * Craving * Neonatal withdrawal * Post-acute-withdrawal syndrome (PAWS) * SUD * Substance abuse / Substance-related disorders * Physical dependence / Psychological dependence / Substance dependence Combined substance use * SUD * Polysubstance dependence * SID * Combined drug intoxication (CDI) Alcohol SID Cardiovascular diseases * Alcoholic cardiomyopathy * Alcohol flush reaction (AFR) Gastrointestinal diseases * Alcoholic liver disease (ALD): * Alcoholic hepatitis * Auto-brewery syndrome (ABS) Endocrine diseases * Alcoholic ketoacidosis (AKA) Nervous system diseases * 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[Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Alcohol withdrawal syndrome	c0236663	26,953	wikipedia	https://en.wikipedia.org/wiki/Alcohol_withdrawal_syndrome	2021-01-18T18:49:54	{"icd-9": ["291.81"], "icd-10": ["F10.3"], "wikidata": ["Q2914873"]}
A number sign (#) is used with this entry because X-linked dominant hypophosphatemic rickets is caused by mutation in the phosphate-regulating endopeptidase gene (PHEX; 300550) on chromosome Xp22. For a general phenotypic description and a discussion of genetic heterogeneity of hypophosphatemic rickets, see 193100. Description X-linked dominant hypophosphatemic rickets, although variable in its expressivity, is characterized by rickets with bone deformities, short stature, dental anomalies, and at the biologic level, hypophosphatemia with low renal phosphate reabsorption, normal serum calcium level with hypocalciuria, normal or low serum level of vitamin D (1,25(OH)2D3, or calcitriol), normal serum level of PTH, and increased activity of serum alkaline phosphatases (summary by Gaucher et al., 2009). Clinical Features Winters et al. (1958) observed hypophosphatemia in a large North Carolina family of English-Scottish extraction. The degree of depression of serum phosphate was the same in males and females, although the severity of bone disease was much less severe in females. There were no instances of male-to-male transmission of either bone disease or hypophosphatemia, and all daughters of hypophosphatemic males were themselves hypophosphatemic, suggesting X-linked dominant inheritance. Affected persons, both males and females, showed a reduction in renal phosphate reabsorption per glomerular filtration rate (TmP/GFR) to about 50% of normal. In a study of patients with hypophosphatemia, Stickler (1969) concluded that hypophosphatemia was already present in the neonatal period, that alkaline phosphatase was elevated at 1 month of age, and that early treatment with high doses of vitamin D did not prevent growth failure. Patients with the X-linked disorder do not show muscle weakness, tetany, or hypocalcemia. Adults, especially males, with XLH may develop progressive ankylosis of the spine and major joints, simulating ankylosing spondylitis (106300). Highman et al. (1970) reported compression of the spinal cord or 'spinal stenosis,' and noted that treatment with vitamin D may be responsible. Moser and Fessel (1974) commented on the misdiagnosis of ankylosing spondylitis in adults. Adams and Davies (1986) described 4 XLH patients with spinal cord compression; 3 had successful treatment with decompressive laminectomy. At surgery, new bone formation in the ligamentum flavum and thickening of laminae were found to be responsible for the canal stenosis and cord compression. Computed tomography was useful in evaluating the site and extent of intraspinal new bone formation. Polisson et al. (1985) studied the calcification and ossification of entheses (tendons, ligaments, and joint capsules) in 26 patients from 11 kindreds with XLH. They found entheses involvement in 69% of patients, with the most commonly affected sites being the hand and sacroiliac joints. Histologic examination of 1 case showed intratendinous lamellar bone without inflammatory cells. Polisson et al. (1985) concluded that calcification of entheses is an integral part of XLH, which can be differentiated from degenerative disorders and seronegative spondyloarthropathies. Hardy et al. (1989) analyzed the skeletal radiographic features in 38 'essentially untreated' adults with XLH. Osteoarthritis was common in the ankles, wrists, knees, feet, and sacroiliac joints. All of the older patients had enthesopathy, often accompanied by extra ossicles. Curvatures of the lower-extremity long bones were common in all age groups. Other findings included flaring of the iliac wings, trapezoidal distal femoral condyles, shortening of the talar neck, and flattening of the talar dome. The findings were more severe in men. Shields et al. (1990) used the index they call PRATIO (ratio of pulp area to tooth area) to study patients with X-linked hypophosphatemia. They found high values in affected males and intermediate values in heterozygous females, suggesting primary expression of the causative gene in the teeth, as well as in the kidney. Patients with XLH have normal or low serum levels of 1,25-dihydroxyvitamin D3 (also known as calcitriol, the active form of vitamin D), despite having hypophosphatemia, which is a known stimulus of 25-hydroxyvitamin D-1-alpha-hydroxylase activity (CYP27B1; 609506). Administration of parathyroid hormone (PTH; 168450) results in blunted stimulation of serum calcitriol levels in both humans and the murine model of XLH, the 'Hyp' mouse. However, Econs et al. (1992) found that calcitriol concentrations increased in XLH patients in response to calcitonin (114130), as had been observed in the mouse. The findings indicated that patients with XLH have an incomplete defect in the regulation of 25-hydroxyvitamin D-1-alpha-hydroxylase activity: no response to PTH, but normal response to calcitonin. Deafness has been rarely reported in humans with X-linked hypophosphatemia (Davies et al., 1984; O'Malley et al., 1985). However, Fishman et al. (2004) concluded that hearing impairment is not a feature of XLH in childhood. They found that 15 of 15 children under the age of 18 years showed no deficits attributable to XLH; 1 had hearing loss due to other causes. Three of 10 parents with XLH did show sensorineural hearing loss, suggesting that hearing loss in adults is due to XLH, particularly in cases with severe bone involvement. Clinical Management Glorieux et al. (1972) found growth restoration in patients with XLH when inorganic phosphate and vitamin D2 were administered, consistent with the theory that the defect was primarily due to loss of phosphate at the level of the renal tubule. They also showed a direct correlation between the level of serum inorganic phosphate and whole blood oxygen pressure at 50% oxygen saturation, and speculated that low Pi may inhibit synthesis of 2,3-diphosphoglycerate in red cells with resulting inhibition of release of oxygen to tissues. Glorieux et al. (1972) suggested that this might be the mechanism of growth retardation. On the basis of a follow-up study, McNair and Stickler (1969) questioned whether vitamin D therapy had any beneficial effect on growth in familial hypophosphatemic rickets. Stickler and Morgenstern (1989) analyzed heights and symptoms of 52 patients, aged at least 18 years, with hypophosphatemic rickets. They found no evidence that any form of treatment had any effect on adult height, symptoms, or alkaline phosphatase levels. There was a negative relation between adult height and the number of osteotomies undergone. Stickler and Morgenstern (1989) concluded that complications of treatment with vitamin D, such as renal failure, which appeared secondary to vitamin D intoxication in 3 patients in their twenties, outweighed any possible benefits. Both vitamin D and phosphate supplementation are necessary for the treatment of X-linked hypophosphatemia, whereas calcitriol alone and phosphate alone appear to suffice in the autosomal dominant (193100) and autosomal recessive (241520) disorders, respectively. Harrell et al. (1985) found that complete healing of the bone lesions in X-linked hypophosphatemic patients could be induced with supraphysiologic doses of calcitriol, 1,25(OH)2-vitamin D, in combination with oral phosphorus. Although calcitriol dose reduction was necessary once healing was achieved, bone was maintained normally for up to a year on lower doses of 1,25(OH)-vitamin D and continued phosphorus supplementation. However, therapy only partially corrected skeletal lesions and was often complicated by hyperparathyroidism. Because of the disputed value of phosphate and vitamin D therapy and the recognized complication of nephrocalcinosis, Verge et al. (1991), in Sydney, Australia, studied therapy in 9 boys and 15 girls and compared the results with those reported in 1971 in 16 untreated Australian patients. The 19 patients treated for at least 2 years before the onset of puberty had a mean height standard-deviation score of -1.08, as compared with -2.05 in the untreated historical controls. Nineteen of the 24 patients had nephrocalcinosis detected on renal ultrasonography. The grade of nephrocalcinosis was significantly correlated with the mean phosphate dose, but not with the dose of vitamin D or the duration of therapy. However, all patients had normal serum creatinine concentrations. Glorieux (1991) suggested that the reason Verge et al. (1991) failed to find a correlation with the dose of vitamin D was due to their use of a narrow range of dosages in their patients. Glorieux (1991) commented that combined treatment had brought about a dramatic decrease in the need for corrective osteotomies in this disorder and that the question of whether treatment should be continued after growth has ceased remained an open question. He also referred to the informative patient described by Harrison et al. (1966): a girl with dwarfism and X-linked hypophosphatemic rickets had severe vitamin D intoxication at the age of 3 years, which permanently reduced her glomerular filtration rate by 50%. As a consequence of the renal dysfunction, her serum phosphate concentration thereafter became normal and her growth rate accelerated so that her height reached the 50th percentile by the time she became an adult. Petersen et al. (1992) reviewed the growth patterns of 20 children with XLH. Their findings suggested that calcitriol has a direct effect on the renal tubule to improve reclamation of inorganic phosphate in this disorder. Heterozygous girls appeared to respond to therapy better than did hemizygous boys, an observation that provided evidence for a gene dosage effect in the expression of this disorder. Firth et al. (1985) reported 2 patients with hypophosphatemic rickets in whom long-term (over 10 years) therapy with phosphate and vitamin D resulted in hypercalcemic hyperparathyroidism with surgically proven adenomatous hyperplasia, consistent with tertiary hyperparathyroidism. Rivkees et al. (1992) reported the development of tertiary hyperparathyroidism in 3 girls with hypophosphatemic rickets treated with high doses of phosphate and vitamin D. Even in the presence of very high parathyroid hormone, oral phosphate lowered serum calcium and stimulated further PTH secretion. Surgical resection in all 3 cases showed profound multiglandular parathyroid hyperplasia. Carpenter et al. (1994) demonstrated exaggerated nocturnal rises in PTH in patients with XLH. They suggested that hyperparathyroidism in untreated XLH is a secondary event that compensates for impaired skeletal calcium mobilization. Hyperparathyroidism may contribute to the pathogenesis of nephrocalcinosis and precede the development of tertiary hyperparathyroidism. Although 2 of their patients with previous elevations of PTH showed normalization after medication adjustments, continued therapy appeared to aggravate the hyperparathyroidism. Tertiary hyperparathyroidism is thus a complication of treatment that exacerbates the primary disease process of renal tubular phosphate wasting, often prompting an increase in supplementary phosphate, which further stimulates the parathyroid gland. Savio et al. (2004) reported 6 unrelated patients with XLH who developed tertiary hyperparathyroidism after long-term therapy with phosphate and vitamin D. After parathyroidectomy, the patients developed severe hypocalcemia necessitating intravenous calcium infusion. Long-term, all patients achieved normocalcemia. In a placebo-controlled trial of 24,25(OH)2D3 supplementation in 15 HYP patients, Carpenter et al. (1996) found that supplementation with 24,25(OH)2D3 normalized PTH values in 9 subjects (peak PTH was 46.5 +/- 6.6 pmol/L at entry, 42.3 +/- 5.9 pmol/L after placebo, and 23.3 +/- 5.4 pmol/L after 24,25(OH)2D3). Nephrogenous cAMP decreased at night, coincident with the decrease in PTH, and serum phosphorus was slightly greater with 24,25(OH)2D3 treatment. Radiographic features of rickets improved during 24,25(OH)2D3 supplementation in children, and osteoid surface decreased in bone biopsies of adults. Despite oral phosphate and 1,25-dihydroxyvitamin D3 treatment, many patients with X-linked hypophosphatemic rickets have suboptimal growth and bone healing. In a study of 19 well-controlled HYP patients, Makitie et al. (2003) found that the 8 patients who had treatment before age 1.0 years had higher median height z-scores than the 11 patients with treatment onset after age 1.0 years. Scores were higher in the early treatment group at treatment onset (-0.4 SD vs -1.7 SD), at the end of the first treatment year (-0.7 SD vs -1.8 SD), throughout childhood, and until predicted adult height. The degree of hypophosphatemia was similar in both groups, but serum alkaline phosphatase remained higher in the second group throughout childhood. Radiographic signs of rickets were more marked in the second group, but even patients with early treatment developed significant skeletal changes of rickets. The authors concluded that treatment commenced in early infancy results in improved outcome in patients with XLH, but does not completely normalize skeletal development. Nehgme et al. (1997) evaluated cardiovascular status in 13 XLH patients. While their serum calcium and creatinine clearances were normal, they all had mild to moderate nephrocalcinosis. Left ventricular hypertrophy was diagnosed by electrocardiogram in 3 and by ultrasonography in 7. Although baseline blood pressures (BP) were normal, the patients showed an abnormal increase in diastolic BP at all levels of workload; their peak/(mean +/- SD) exercise diastolic BP was 91 +/- 12 versus 72 +/- 6 mm Hg in controls (p less than 0.0001). The authors suggested that patients with XLH should be monitored closely for the development of hypertension and left ventricular hypertrophy. Seikaly et al. (1997) studied the effects of recombinant growth hormone (GH; 139250) therapy on height, mineral metabolism, parathyroid function, serum 1,25-(OH)2 vitamin D, osteocalcin, growth hormone, urinary calcium, phosphate, nephrocalcinosis, renal function, and bone density in 5 children with XLH. The growth velocity standard deviation score was -1.90 +/- 0.40 during 12 months of placebo administration and 4.04 +/- 1.50 during 12 months of recombinant GH therapy. An increase in serum phosphate from 0.88 +/- 0.07 to 1.17 +/- 0.14 mmol/L, and in the tubular maximum for phosphate reabsorption from 2.12 +/- 0.15 to 3.41 +/- 0.25 mg/dL, was observed after 3 months of recombinant GH therapy. However, both serum phosphate and tubular maximum for phosphate reabsorption were unchanged from baseline after 6, 9, and 12 months of recombinant GH therapy. Seikaly et al. (1997) concluded that patients with XLH have an improvement in linear growth and a transient increase in serum phosphate attributable to a transient decrease in urinary phosphate excretion when treated with recombinant GH. Liu et al. (2011) measured the serum levels of FGF23 (605380) and indices of mineral metabolism over 24 hours in 7 untreated patients with X-linked hypophosphatemia and in 6 controls after a single subcutaneous injection of 200 IU of salmon calcitonin. The patients had a significant drop in serum FGF23 level from baseline 4 hours after injection, and levels remained below baseline for 16 hours. The controls showed no significant change in FGF23 levels. Liu et al. (2011) suggested that their study raised the possibility that calcitonin is a therapeutic option for patients with X-linked hypophosphatemia. Carpenter et al. (2018) performed an open-label, phase 2 clinical trial randomly assigning 52 children between 5 and 12 years of age with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab, a monoclonal antibody that targets FGF23, either every 2 weeks or every 4 weeks. The primary endpoint was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score. In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Treatment with burosumab improved the severity of rickets, linear growth, renal tubular phosphate reabsorption, and serum phosphorus levels. Physical ability improved and pain decreased. Nearly all the adverse events were mild or moderate in severity. Carpenter et al. (2018) concluded that burosumab at a dose of approximately 1.0 mg/kg administered every 2 weeks is an appropriate regimen for improving renal tubular phosphate reabsorption and clinical outcomes in children with X-linked hypophosphatemia. Pathogenesis By an oral phosphate tolerance test, Condon et al. (1970) demonstrated defective intestinal absorption of phosphate in familial hypophosphatemia. Short et al. (1973) demonstrated a defect in transport of inorganic phosphate by intestinal mucosa in familial hypophosphatemia. Earp et al. (1970) and Cohanim et al. (1972) found that treatment with 25-hydroxycholecalciferol was ineffective in patients with familial hypophosphatemic rickets, suggesting that the basic defect was not in the conversion of vitamin D to the active form. Glorieux and Scriver (1972) postulated a defect in the parathyroid hormone-sensitive component of phosphate transport in kidney cells. Since calcium promotes phosphate reabsorption, the authors suggested that any beneficial effect of vitamin D therapy was secondary to the effects on calcium metabolism. Short et al. (1974) proposed that the renal tubule in XLH is hyperresponsive to the phosphaturic effect of parathyroid hormone. Quarles and Drezner (2001) reviewed the pathophysiology of X-linked hypophosphatemia. Mapping From a study of the comparative mapping of the human and mouse X chromosomes and the location of mouse Hpdr (also symbolized Hyp), Buckle et al. (1985) predicted that the human HPDR locus may be either between GLA (300644) and HPRT (308000) or in the distal part of Xp. Studying 11 XLH families with RFLP markers, Read et al. (1986) mapped the XLH locus distal to DXS41, which had been located at Xp22.31-p21.3 by in situ hybridization (peak lod score of 4.82 at 10% recombination). Machler et al. (1986) found closer linkage with DXS41 (peak lod of 5.084 at theta = 0.00); there was no recombination in 17 meiotic events. Both groups concluded that the location on distal Xp is consistent with the scheme that relates the mouse and human X chromosomes by 2 inverted insertions (Buckle et al., 1985). Thakker et al. (1987) established that the HPDR1 locus lies distal to DXS41 and proximal to DXS43, located 11 cM and 14 cM, respectively, from the 2 markers. Econs et al. (1990) demonstrated linkage of the XLH gene to a polymorphic probe derived from the glycine receptor alpha-2 gene (GLRA2; 305990). Econs et al. (1991) identified closely situated flanking markers in region Xp22.2-p22.1. In 14 of 15 families with X-linked hypophosphatemia inherited through 2 or more generations, Rowe et al. (1992) found close linkage to 3 DNA markers. The 1 exception was a family with a large number of recombinants, 4 of which were double recombinants. Rowe et al. (1992) suggested that the disease in this family (family A) mapped elsewhere on the X chromosome or on an autosome. This family had been described by Read et al. (1986) and by Thakker et al. (1987, 1990), and was later found to have autosomal dominant disease (193100) caused by mutation in the FGF23 gene (ADHR Consortium, 2000). Molecular Genetics In 3 unrelated patients with X-linked hypophosphatemia, the HYP Consortium (1995) identified 3 different mutations in the PHEX gene (300550.0001-300550.0003). Holm et al. (1997) identified mutations in the PHEX gene in 9 of 22 unrelated patients: 3 nonsense mutations, a 1-bp deletion leading to a frameshift, a donor-splice site mutation, and missense mutations in 4 patients (see, e.g., 300550.0004-300550.0006). In affected members of a kindred originally reported by Frymoyer and Hodgkin (1977) as having a distinct disorder they designated as 'adult-onset vitamin D-resistant hypophosphatemic osteomalacia' (AVDRR), Econs et al. (1998) identified a missense mutation in the PHEX gene (L555P; 300550.0007). Econs et al. (1998) concluded that there is only one form of X-linked dominant phosphate wasting. Sabbagh et al. (2000) stated that 131 HYP-causing mutations in the PHEX gene had been reported. They announced the creation of an online PHEX mutation database for the collection and distribution of information on PHEX mutations. Cho et al. (2005) identified mutations in the PHEX gene in 8 of 17 unrelated Korean patients with hypophosphatemic rickets; the 9 patients without mutations were all female. No genotype-phenotype correlations were identified among the children with PHEX mutations. Treatment with vitamin D and phosphate was frequently complicated by hypercalciuria, hypercalcemia, nephrocalcinosis, or hyperparathyroidism. Makras et al. (2008) described 3 members of a family in which a splice site mutation in the PHEX gene resulted in hypophosphatemic rickets with muscle dysfunction and normal growth (300550.0011). Animal Model For a description of the 'Hyp' mouse, a model for XLH, see 300550. History Levine et al. (2009) reviewed the elucidation of the genetic cause of X-linked hypophosphatemic rickets and examined in detail the clinical and laboratory features of the original patient, 'W.M.,' described by Albright et al. (1937). INHERITANCE \- X-linked dominant GROWTH Height \- Short stature Other \- Growth retardation HEAD & NECK Head \- Frontal bossing Ears \- Hearing loss has been reported in some adults with severe disease Teeth \- Hypomineralization of enamel \- Defect in dentin maturation \- Enlarged pulp chambers \- Recurrent dental abscesses GENITOURINARY Kidneys \- Renal phosphate wasting \- Decreased tubular maximum for phosphate reabsorption per glomerular filtration rate (TmP/GFR) SKELETAL \- Rickets in children \- Osteomalacia in adults \- Osteoarthritis, more common in adults \- Joint pain \- Bone pain \- Calcification of entheses (tendons, ligaments, joint capsules), more common in adults Skull \- Increased anteroposterior skull length Spine \- Spinal cord compression \- Spinal stenosis Pelvis \- Flaring of the iliac wings Limbs \- Bowing of the legs \- Lower limb deformities \- Frayed, irregular metaphyses \- Curvatures of the femur, tibia, fibula \- Trapezoidal distal femoral condyles \- Pseudofractures in adults Feet \- Shortening of the talar neck \- Flattening of the talar dome LABORATORY ABNORMALITIES \- Hypophosphatemia \- Increased serum alkaline phosphatase \- Normal to mildly increased serum parathyroid hormone (PTH) \- Normal serum calcium \- Inappropriately normal to low-normal serum 1,25-dihydroxyvitamin D3 \- Abnormal response of 25-hydroxyvitamin D-1-alpha-hydroxylase activity ( 609506 ) to hypophosphatemia MISCELLANEOUS \- Onset by 1 year of age \- Highly variable phenotype \- In general, men have more severe disease than women \- See also autosomal dominant hypophosphatemic rickets ( 193100 ) MOLECULAR BASIS \- Caused by mutation in the phosphate regulating endopeptidase homolog, X-linked, gene (PHEX, 300550.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HYPOPHOSPHATEMIC RICKETS, X-LINKED DOMINANT	c0733682	26,954	omim	https://www.omim.org/entry/307800	2019-09-22T16:18:10	{"doid": ["0050445"], "mesh": ["D053098"], "omim": ["307800"], "orphanet": ["89936"], "synonyms": ["Alternative titles", "HYPOPHOSPHATEMIA, X-LINKED", "HYP", "VITAMIN D-RESISTANT RICKETS, X-LINKED", "HYPOPHOSPHATEMIC VITAMIN D-RESISTANT RICKETS"], "genereviews": ["NBK83985"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2017) Humeral avulsion of the glenohumeral ligament (HAGL) is defined as an avulsion (tearing away) of the inferior glenohumeral ligament from the anatomic neck of the humerus.[1] In other words, it occurs when we have disruption of the ligaments that join the humerus to the glenoid. HAGL tends to occur in 7.5-9.3% of cases of anterior shoulder instability.[2] Making it an uncommon cause of anterior shoulder instability. Avulsion of this ligamentous complex may occur in three sites: glenoid insertion (40%), the midsubstance (35%) and the humeral insertion (25%).[3] Bony humeral avulsion of the glenohumeral ligament (BHAGL) refers when we have HAGL with bony fracture.[3] ## Contents * 1 Signs and Symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Signs and Symptoms[edit] Signs and symptoms of a dislocation or rotator cuff tear such as: * Significant pain, which can sometimes be felt past the shoulder, along the arm. * Inability to move the arm from its current position, particularly in positions with the arm reaching away from the body and with the top of the arm twisted toward the back. * Numbness of the arm. * Visibly displaced shoulder. Some dislocations result in the shoulder appearing unusually square. * No bone in the side of the shoulder showing shoulder has become dislocated. ## Causes[edit] Most commonly due to anterior shoulder dislocation caused by hyperabduction and external rotation of the arm. Usually in young men who play contact sports (E.g. rugby, football, volleyball, basketball, etc.).[4] Frequent anterior (frontward) subluxation also poses a great risk factor. ## Diagnosis[edit] The inferior glenohumeral ligament attaches to the glenoid labrum(cartilage which surrounds the "shoulder socket") at one end, and at the other end attaches to the anatomic neck of the humerus(the section of the humerus which is directly below the head of the humerus which rotates within the "shoulder socket").[5] In between these two attachment points the ligament droops down to give the appearance of a U, wherein(on the right side of the body), the left end of the U is its attachment to the humerus, and the right end is its attachment to the glenoid labrum. Excessive stress on the inferior glenohumeral ligament, often due to physical trauma, can cause the end attached to the humerus to detach and fall down, transforming the U-shaped appearance of the ligament into a J-shaped appearance called the "J" Sign. On the left side of the body—where it is the right side of the ligament which is attached to humerus— the U becomes a reverse "J" Sign.[4] Imaging (MRI) is the best modality for diagnosis where the presence of the "J" sign on an MRI indicates that this detachment has occurred. Clinical differential diagnosis of anterior shoulder instability include: * Bankart lesions * Anterior labroligamentous periosteal sleeve avulsions * glenolabral articular disruption (GLAD) lesions * HAGL ## Treatment[edit] Treatment is surgical reconstruction via arthroscopy. ## References[edit] 1. ^ A. Khanna, MRI for Orthopaedic Surgeons, Thieme 2009 2. ^ MRI of HAGL Lesions: Four Arthroscopically Confirmed Cases of False-Positive Diagnosis J. Stuart Melvin1, John D. MacKenzie, Elliott Nacke, Brian J. Sennett1 and Lawrence Wells.2008, 3. ^ a b Gaillard, Frank. "Humeral avulsion of the glenohumeral ligament". radiopaedia. Retrieved 30 November 2011. 4. ^ a b Christian L. Carlson, MD, MS The “J” Sign 5. ^ Gray, Henry. "Humeral Articulation or Shoulder-joint". Anatomy of the Human Body. Retrieved 30 November 2011. ## External links[edit] * Radiopaedia homepage * Images at Radiology(rsna.org):“J” sign, Arthroscopic image. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Humeral avulsion of the glenohumeral ligament	None	26,955	wikipedia	https://en.wikipedia.org/wiki/Humeral_avulsion_of_the_glenohumeral_ligament	2021-01-18T19:06:30	{"umls": ["CL458493"], "wikidata": ["Q17145662"]}
Hemarthrosis Other namesHaemarthrosis Lipohemarthrosis (blood and fat in the joint space) seen in a person with a subtle tibial plateau fracture. The arrow indicates a fluid level between the upper fat component and the lower blood component. SpecialtyOrthopedics Hemarthrosis is a bleeding into joint spaces. It is a common feature of hemophilia. ## Contents * 1 Causes * 2 Diagnosis * 3 Treatment * 4 Complications * 5 References * 6 External links ## Causes[edit] It usually follows injury but occurs mainly in patients with a predisposition to hemorrhage such as those being treated with warfarin (or other anticoagulants) and patients with hemophilia. It can be associated with knee joint arthroplasty.[1] It has also been reported as a part of hemorrhagic syndrome in the Crimean-Congo Hemorrhagic Fever, suggesting a viral cause to the bleeding in a joint space.[2][3] ## Diagnosis[edit] Synovial fluid examination[4][5] Type WBC per mm3 % neutrophils Viscosity Appearance Normal <200 0 High Transparent Osteoarthritis <5000 <25 High Clear yellow Trauma <10,000 <50 Variable Bloody Inflammatory 2,000-50,000 50-80 Low Cloudy yellow Septic arthritis >50,000 >75 Low Cloudy yellow Gonorrhea ~10,000 60 Low Cloudy yellow Tuberculosis ~20,000 70 Low Cloudy yellow Inflammatory = gout, rheumatoid arthritis, rheumatic fever Hemarthrosis is diagnosed through the methods listed below: A physical examination is the first step, the joints of the patient are moved and bent to study the functioning.[6] Synovial Fluid analysis is another method to diagnose Hemarthrosis. It involves a small needle being inserted into the joint to draw the fluid.[7] Reddish-colored hue of the sample is an indication of the blood being present. Imaging tests are normally done. The tests also include MRI, Ultrasound and X-ray test, which give better information about the joint inflammation.[8] ## Treatment[edit] In hemophilia it may occur spontaneously, and recurrent hemarthroses are a major cause of disability in that patient group due to hemophilic arthropathy, requiring synovectomy, joint replacement[9] and increased medical therapy to prevent further bleeding episodes. Reducing hemarthroses events using intravenous administration of blood clotting factor concentrate on a regular basis starting in early childhood, reduces joint deterioration and increases the person's quality of life compared to "on demand" treatment (treating after a bleed).[10] The minimal effective dose and best dosage frequency have not been established.[10] It is not clear, due to lack of sufficient data, if preventative therapy with clotting factor concentrate is also effective at reducing joint deterioration if treatment is started after joint damage has occurred.[10] ## Complications[edit] Up to a quarter of all severe ligament or capsular knee injuries leading to a hemarthrosis are associated with cartilage damage that can lead to progressive degenerative arthritis.[11] * X-ray of Hemarthrosis * X-ray of Hemarthrosis ## References[edit] 1. ^ Ohdera T, Tokunaga M, Hiroshima S, Yoshimoto E, Matsuda S (2004). "Recurrent hemarthrosis after knee joint arthroplasty: etiology and treatment". J Arthroplasty. 19 (2): 157–61. doi:10.1016/j.arth.2003.09.009. PMID 14973857. 2. ^ Ahmeti, Salih; Ajazaj-Berisha, Lindita; Halili, Bahrije; Shala, Anita (Apr 2014). "Acute arthritis in Crimean-Congo hemorrhagic fever". Journal of Global Infectious Diseases. 6 (2): 79–81. doi:10.4103/0974-777X.132052. PMC 4049045. PMID 24926169. 3. ^ Heyman, Paul; Cochez, Christel; Hofhuis, Agnetha; van der Giessen, Joke; Sprong, Hein; Porter, Sarah Rebecca; Losson, Bertrand; Saegerman, Claude; Donoso-Mantke, Oliver; Niedrig, Matthias; Papa, Anna (2010). "A Clear and Present Danger: Tick-borne Diseases in Europe". Expert Rev Anti Infect Ther. 8 (1): 33–50. doi:10.1586/eri.09.118. PMID 20014900. 4. ^ Flynn, John A.; Choi, Michael J.; Wooster, L. Dwight (2013). Oxford American Handbook of Clinical Medicine. OUP USA. p. 400. ISBN 978-0-19-991494-4. 5. ^ Seidman, Aaron J.; Limaiem, Faten (2019), "Synovial Fluid Analysis", StatPearls, StatPearls Publishing, PMID 30725799, retrieved 2019-12-19 6. ^ "Hemarthrosis". Healthline. Retrieved 2017-11-21. 7. ^ "Hemarthrosis - What You Need to Know". Drugs.com. Retrieved 2017-11-21. 8. ^ Baker, C. L. (June 1992). "Acute hemarthrosis of the knee". Journal of the Medical Association of Georgia. 81 (6): 301–305. ISSN 0025-7028. PMID 1607844. 9. ^ Dunn AL (Sep 2005). "Management and prevention of recurrent hemarthrosis in patients with hemophilia". Current Opinion in Hematology. 12 (5): 390–4. doi:10.1097/01.moh.0000169285.66841.c8. PMID 16093785. 10. ^ a b c Iorio, Alfonso; Marchesini, Emanuela; Marcucci, Maura; Stobart, Kent; Chan, Anthony Kc (2011-09-07). "Clotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A or B" (PDF). The Cochrane Database of Systematic Reviews (9): CD003429. doi:10.1002/14651858.CD003429.pub4. hdl:2434/231551. ISSN 1469-493X. PMID 21901684. 11. ^ Goldberg A, Stansby G "Surgical Talk" 2nd edition ## External links[edit] Classification D * ICD-10: M25.0 * ICD-9-CM: 719.1 * MeSH: D006395 * DiseasesDB: 29653 * v * t * e Diseases of joints General * Arthritis * Monoarthritis * Oligoarthritis * Polyarthritis Symptoms * Joint pain * Joint stiffness Inflammatory Infectious * Septic arthritis * Tuberculosis arthritis Crystal * Chondrocalcinosis * CPPD (Psudogout) * Gout Seronegative * Reactive arthritis * Psoriatic arthritis * Ankylosing spondylitis Other * Juvenile idiopathic arthritis * Rheumatoid arthritis * Felty's syndrome * Palindromic rheumatism * Adult-onset Still's disease Noninflammatory * Hemarthrosis * Osteoarthritis * Heberden's node * Bouchard's nodes * Osteophyte * v * t * e Disorders of bleeding and clotting Coagulation · coagulopathy · Bleeding diathesis Clotting By cause * Clotting factors * Antithrombin III deficiency * Protein C deficiency * Activated protein C resistance * Protein S deficiency * Factor V Leiden * Prothrombin G20210A * Platelets * Sticky platelet syndrome * Thrombocytosis * Essential thrombocythemia * DIC * Purpura fulminans * Antiphospholipid syndrome Clots * Thrombophilia * Thrombus * Thrombosis * Virchow's triad * Trousseau sign of malignancy By site * Deep vein thrombosis * Bancroft's sign * Homans sign * Lisker's sign * Louvel's sign * Lowenberg's sign * Peabody's sign * Pratt's sign * Rose's sign * Pulmonary embolism * Renal vein thrombosis Bleeding By cause Thrombocytopenia * Thrombocytopenic purpura: ITP * Evans syndrome * TM * TTP * Upshaw–Schulman syndrome * Heparin-induced thrombocytopenia * May–Hegglin anomaly Platelet function * adhesion * Bernard–Soulier syndrome * aggregation * Glanzmann's thrombasthenia * platelet storage pool deficiency * Hermansky–Pudlak syndrome * Gray platelet syndrome Clotting factor * Hemophilia * A/VIII * B/IX * C/XI * von Willebrand disease * Hypoprothrombinemia/II * Factor VII deficiency * Factor X deficiency * Factor XII deficiency * Factor XIII deficiency * Dysfibrinogenemia * Congenital afibrinogenemia Signs and symptoms * Bleeding * Bruise * Hematoma * Petechia * Purpura * Nonthrombocytopenic purpura By site * head * Epistaxis * Hemoptysis * Intracranial hemorrhage * Hyphema * Subconjunctival hemorrhage * torso * Hemothorax * Hemopericardium * Pulmonary hematoma * abdomen * Gastrointestinal bleeding * Hemobilia * Hemoperitoneum * Hematocele * Hematosalpinx * joint * Hemarthrosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hemarthrosis	c0018924	26,956	wikipedia	https://en.wikipedia.org/wiki/Hemarthrosis	2021-01-18T19:01:45	{"mesh": ["D006395"], "umls": ["C0018924"], "wikidata": ["Q1642040"]}
Low-grade fibromyxoid sarcoma Micrograph of a low-grade fibromyxoid sarcoma. H&E stain. SpecialtyPathology Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of low grade sarcoma first described by Harry Evans in 1987. It is characterized by a long and indolent clinical course and the possibility of local recurrence or distant metastases in a subset of patients. Unlike many other types of cancer, low grade fibromyxoid sarcoma can metastasize after many years, sometimes decades after the initial presentation of the tumor.[1] ## References[edit] 1. ^ Evans, Harry L (2011). "Low-Grade Fibromyxoid Sarcoma: A Clinicopathologic Study of 33 Cases With Long-Term Follow-Up". The American Journal of Surgical Pathology. 35 (10): 1450–1462. doi:10.1097/PAS.0b013e31822b3687. PMID 21921785. ## External links[edit] Classification D [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Low-grade fibromyxoid sarcoma	c1275282	26,957	wikipedia	https://en.wikipedia.org/wiki/Low-grade_fibromyxoid_sarcoma	2021-01-18T18:45:33	{"umls": ["C1275282"], "wikidata": ["Q6692756"]}
## Clinical Features Leshinsky-Silver et al. (2003) reported a 2-month-old male who was referred to clinic for evaluation of cholestatic jaundice, pancreatic insufficiency, and hypertyrosinemia. He was the first offspring of 2 healthy, highly consanguineous Azerbaijani Jews. Family history was remarkable for 3 infant deaths: 2 severely retarded paternal aunts and a maternal aunt who died of alleged sepsis. Pregnancy was normal until 35 weeks' gestation, when it was terminated because of oligohydramnion. Birth weight and head circumference were age-appropriate and delivery was uneventful. On the fifth day of life the patient became apathetic and mottled and refused eating. Metabolic evaluation revealed hyperammonemia, which was treated with sodium benzoate and sodium phenylacetate, and severe respiratory alkalosis with lacticacidosis. Tyrosine was 1,934 nmol/ml, alanine 607 nmol/ml, citrulline 76 nmol/ml, phenylalanine 424 nmol/ml, and lysine 426 nmol/ml. Urinary orotic acid and succinylacetone were normal. On the sixth day of life spontaneous recovery occurred. He developed mild hyperbilirubinemia and an elevated serum alpha-fetoprotein of 7,000 ng/ml (normal 0-15 ng/ml). On reevaluation at 2 months of age, he had cholestatic jaundice and pancreatic insufficiency, with increased blood ammonia, increased lactic acid, and elevated tyrosine. The serum alpha-fetoprotein was severely increased at 141,000 ng/ml. There was no indication of renal tubular acidosis, but urinary aminolevulinic acid and porphobilinogen were high. Comprehensive evaluation was unrevealing, and diagnostic liver biopsy showed prominent bridging, septal fibrosis, and widening of portal spaces, with prominent mixed inflammatory infiltrate, associated with interface hepatitis. Bile duct proliferation with numerous bile plugs was identified. The hepatic lobules showed prominent cholestatic changes. Electron microscopy revealed hepatocytes with a large number of mitochondria, which were altered in shape and size. Some mitochondria were very large. Complex I + III and complex II + III were markedly reduced, while complex II, IV, and citrate synthase (CS) were within the normal limits. The ratio of I + III/CS, I + III/IV, II + III/CS, and II + III/IV were significantly reduced, especially the last. The activity of complexes II + III was restored by the addition of CoQ1. Following the liver biopsy, CoQ treatment was instituted along with an antioxidant cocktail and therapy for pancreatic insufficiency. Liver tests showed improvement, but by the age of 9 months microcephaly, developmental delay, and sensorineural deafness were evident. A brain MRI revealed bilateral hypodensities of the basal ganglia, characteristic of Leigh disease (256000). Leshinsky-Silver et al. (2003) suggested that their patient suffered from a CoQ biosynthesis defect, which would be consistent with the transient tyrosinemia. The patient did not have neonatal liver insufficiency due to mitochondrial depletion or deletion (e.g., 557000), as he had a completely normal complex IV activity. Leshinsky-Silver et al. (2003) suggested that this case represented a neonatal autosomal recessive disorder of CoQ biosynthesis with involvement of the gastrointestinal (liver and pancreas) and central nervous systems. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CoQ-RESPONSIVE OXPHOS DEFICIENCY	c1842463	26,958	omim	https://www.omim.org/entry/608158	2019-09-22T16:08:13	{"mesh": ["C535470"], "omim": ["608158"]}
A rare neurologic disease characterized by a specific pattern of white matter abnormalities on brain imaging (magnetic resonance imaging, MRI), as well as mild ataxia, headaches, mild visual impairment, learning difficulties and cases of male infertility. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Leukoencephalopathy with mild cerebellar ataxia and white matter edema	c3810242	26,959	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363540	2021-01-23T17:57:53	{"omim": ["615651"], "icd-10": ["E75.2"]}
For a phenotypic description and a discussion of genetic heterogeneity of lung cancer, see 211980. Inheritance Although cigarette smoking and some occupational exposures greatly increase the risk of lung cancer, familial factors also clearly play a major role. Tokuhata and Lilienfeld (1963) provided epidemiologic evidence for familial aggregation of lung cancer after accounting for personal smoking, which suggested the possible interaction of genes, shared environment, and common lifestyle factors in the etiology of lung cancer. Fraumeni et al. (1975) reported an increased risk of lung cancer mortality in sibs of probands with lung cancer, and a positive family history was identified as a risk factor for lung cancer in a number of case-control studies. Mapping Bailey-Wilson et al. (2004) conducted a genomewide linkage analysis of 52 extended pedigrees ascertained through probands with lung cancer who had several first-degree relatives with the same disease. Multipoint linkage analysis, under a simple autosomal dominant model, of all 52 families with 3 or more individuals affected by lung, throat, or laryngeal cancer, yielded a maximum heterogeneity lod score (hlod) of 2.79 at 155 cM on chromosome 6q. A subset of 38 pedigrees with 4 or more affected individuals yielded a multipoint hlod of 3.47 at 155 cM. Analysis of a further subset of 23 multigenerational pedigrees with 5 or more affected individuals yielded a multipoint hlod score of 4.26 at the same position. The results localized a major susceptibility locus influencing lung cancer risk to 6q23-q25. To explore the effect of smoking on risk for lung cancer among carriers of the susceptibility haplotype, Bailey-Wilson et al. (2004) obtained the most likely haplotypes from 21 of the 23 multigenerational pedigrees; then all individuals were scored as either carriers (223, of which 87 were affected, and 90.4% of the affected individuals smoked) or noncarriers (344, of which 19 were affected, and 83% of affected individuals smoked). Further analyses showed a mild effect of increasing smoking on risk for lung cancer among carriers, whereas, among noncarriers, there was a significant effect of smoking on risk for lung cancer. When smoking was treated as a categorical yes/no variable, Bailey-Wilson et al. (2004) found that smoking increased risk for both carriers and noncarriers. These sets of observations suggested that smoking at any level increased risk in carriers of inherited susceptibility from a locus on chromosome 6q, whereas increased smoking increased risk for noncarriers. Molecular Genetics Veeriah et al. (2010) provided evidence that PARK2 (602544) on chromosome 6q25-q27 can act as a tumor suppressor gene in lung cancer. Among 242 human cancers, different somatic point mutations in the PARK2 gene were found in 4 lung cancers and some other cancers. These somatic mutations in occurred in the same domains as germline Parkinson disease 2 (600116) mutations, including the ubiquitin-like domain (UBL), the RING finger domain, and the in-between RING fingers domain (IBR). In vitro functional studies in tumor cell lines showed that tumor growth was greater in cells with mutant PARK2, that wildtype PARK2 decreased tumor growth in vivo, and that mutant PARK2 caused decreased PARK2 function which could promote tumor cell growth. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	LUNG CANCER SUSCEPTIBILITY 1	c1837089	26,960	omim	https://www.omim.org/entry/608935	2019-09-22T16:06:54	{"omim": ["608935"]}
Familial focal epilepsy with variable foci is a rare genetic epilepsy disorder characterized by autosomal dominant lesional and nonlesional focal epilepsy with variable penetrance. Focal seizures emanate from different cortical locations (temporal, frontal, centroparietal, parietal, parietaloccipital, occipital) in different family members, but for each individual a single focus remains constant throughout lifetime. Seizure type (tonic, tonic-clonic or hyperkinetic) and severity varies among family members and tends to decrease (but do not disappear) during adulthood. Many patients have an aura and show automatisms during diurnal seizures whereas others have nocturnal seizures. Most individuals are of normal intelligence but patients with intellectual disability, autistic spectrum disorder and obsessive-compulsive disorder have been described. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Familial focal epilepsy with variable foci	c1858477	26,961	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98820	2021-01-23T18:55:19	{"mesh": ["C565785"], "omim": ["604364", "617116", "617118"], "synonyms": ["FFEVF", "Familial partial epilepsy with variable foci"]}
## Clinical Features Chudley et al. (1999) reported a family in which 3 males spanning 2 generations had a syndromic form of moderate mental retardation with seizures and dysmorphic facial features. Common dysmorphic features included prominent glabella, prognathism, synophrys, and hirsutism; hypertelorism and large ears were each noted in 2 patients. The 2 older patients, who were in their forties, showed slowly progressive unsteady gait and progressive weakness, and 1 of them was found to have cerebellar atrophy and electrophysiologic evidence of a peripheral neuropathy. All had low serum immunoglobulins and 2 had specific absence of plasma and secretory IgA, although only 1 patient had recurrent infections. Mapping Using microsatellite markers on the X chromosome to evaluate a family with X-linked syndromic mental retardation, Chudley et al. (1999) found linkage to a region on chromosome Xq21.33-q23 between DXS1170 and DXS8067 (maximum 2-point lod score of 2.23 at DXS1120). Haplotype analysis delineated a region either 16 or 20 Mb in size. INHERITANCE \- X-linked recessive HEAD & NECK Face \- Prominent glabella \- Prognathism Ears \- Prominent ears Eyes \- Synophrys \- Hypertelorism SKELETAL Spine \- Kyphosis \- Scoliosis Hands \- Single palmar creases SKIN, NAILS, & HAIR Hair \- Hirsutism NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mental retardation, moderate \- Poor speech \- Seizures \- Unsteady gait \- Ataxia \- Cerebellar atrophy, mild (1 patient) Peripheral Nervous System \- Peripheral neuropathy (1 patient) IMMUNOLOGY \- Decreased IgG \- Decreased IgA, plasma and secretory \- Decreased IgM MISCELLANEOUS \- One family with 3 affected males has been reported (as of October 2011) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MENTAL RETARDATION, X-LINKED, SYNDROMIC, CHUDLEY-SCHWARTZ TYPE	c3275471	26,962	omim	https://www.omim.org/entry/300861	2019-09-22T16:19:21	{"omim": ["300861"], "synonyms": ["Alternative titles", "MENTAL RETARDATION, X-LINKED, WITH SEIZURES, HYPOGAMMAGLOBULINEMIA, AND GAIT DISTURBANCE"]}
In medicine, an endogenous infection is a disease arising from an infectious agent already present in the body but previously asymptomatic.[1][2][3] ## References[edit] 1. ^ Hendrik K.F.van Saene; C.P. Stoutenbeek; Peter Lawin; I.McA. Ledingham (6 December 2012). Infection Control in Intensive Care Units by Selective Decontamination: The Use of Oral Non-Absorbable and Parenteral Agents. Springer Science & Business Media. pp. 143–4. ISBN 978-3-642-83752-4. 2. ^ H.K.F. van Saene; G. Sganga; L. Silvestri (6 December 2012). Infection in the Critically Ill: an Ongoing Challenge. Springer Science & Business Media. p. 64. ISBN 978-88-470-2242-3. 3. ^ Laura Ester Ziady; Nico Small (December 2005). Prevent and Control Infection: Application Made Easy. Juta and Company Ltd. pp. 13–15. ISBN 978-0-7021-6790-4. This infectious disease article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Endogenous infection	c4289590	26,963	wikipedia	https://en.wikipedia.org/wiki/Endogenous_infection	2021-01-18T19:00:36	{"umls": ["CL508739"], "wikidata": ["Q5712478"]}
5-alpha reductase deficiency is a condition that affects male sexual development before birth and during puberty. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes). Their bodies, however, do not produce enough of a hormone called dihydrotestosterone (DHT). DHT has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth. Many people with 5-alpha reductase deficiency are born with external genitalia that appear female. In other cases, the external genitalia do not look clearly male or clearly female (sometimes called ambiguous genitalia). Still other affected infants have genitalia that appear predominantly male, often with an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias). During puberty, an increase in the levels of male sex hormones leads to the development of some secondary sex characteristics, such as increased muscle mass, deepening of the voice, development of pubic hair, and a growth spurt. The penis and scrotum (the sac of skin that holds the testes) grow larger. Unlike many men, people with 5-alpha reductase deficiency do not develop much facial or body hair. Most affected individuals are unable to have biological children without assisted reproduction. Children with 5-alpha reductase deficiency are often raised as girls. Some of these individuals adopt a male gender role in adolescence or early adulthood, while others adopt a female gender role. ## Frequency 5-alpha reductase deficiency is a rare condition; the exact incidence is unknown. Large families with affected members have been found in several countries, including the Dominican Republic, Papua New Guinea, Turkey, and Egypt. ## Causes Mutations in the SRD5A2 gene cause 5-alpha reductase deficiency. The SRD5A2 gene provides instructions for making an enzyme called steroid 5-alpha reductase 2. This enzyme is involved in processing androgens, which are hormones that direct male sexual development. Specifically, the enzyme is responsible for a chemical reaction that converts the hormone testosterone to DHT. DHT is essential for the normal development of male sex characteristics before birth, particularly the formation of the external genitalia. Mutations in the SRD5A2 gene prevent steroid 5-alpha reductase 2 from effectively converting testosterone to DHT in the developing reproductive tissues. These hormonal factors underlie the changes in sexual development seen in infants with 5-alpha reductase deficiency. During puberty, the testes produce more testosterone. Researchers believe that people with 5-alpha reductase deficiency develop secondary male sex characteristics in response to higher levels of this hormone. Some affected people also retain a small amount of 5-alpha reductase 2 activity, which may produce DHT and contribute to the development of secondary sex characteristics during puberty. ### Learn more about the gene associated with 5-alpha reductase deficiency * SRD5A2 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the SRD5A2 gene in each cell have a mutation. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they do not show signs and symptoms of the condition. Although people who are genetically female (with two X chromosomes in each cell) may inherit mutations in both copies of the SRD5A2 gene, their sexual development is not affected. The development of female sex characteristics does not require DHT, so a lack of steroid 5-alpha reductase 2 activity does not cause physical changes in these individuals. Only people who have mutations in both copies of the SRD5A2 gene and are genetically male (with one X and one Y chromosome in each cell) have the characteristic signs of 5-alpha reductase deficiency. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	5-alpha reductase deficiency	c0268297	26,964	medlineplus	https://medlineplus.gov/genetics/condition/5-alpha-reductase-deficiency/	2021-01-27T08:25:16	{"gard": ["5680"], "mesh": ["C535830"], "omim": ["264600"], "synonyms": []}
49,XXXYY syndrome is a rare gonosome anomaly syndrome characterized by a eunuchoid habitus with gynecoid fat distribution and shape, normal to tall stature, moderate to severe intellectual disability, distinctive facial features (e.g. prominent forehead, epicanthic folds, broad nasal bridge, prognathism), gynecomastia, hypogonadism, cryptorchidism, small penis and behavioral abnormalities (incl. solitary, passive disposition but prone to aggressive outbursts, autistic). Skeletal malformations, such as delayed bone age, fifth finger clinodactyly, elbow malformations and slow molar development, 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	49,XXXYY syndrome	None	26,965	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261534	2021-01-23T19:08:07	{"gard": ["10922"], "icd-10": ["Q98.8"]}
Dust Mite Allergy Other namesHouse dust allergy SpecialtyEmergency medicine SymptomsSymptoms CausesMite droppings TreatmentCutting down mite numbers A scanning electron micrograph of a female dust mite. Dust mite allergy, also known as house dust allergy, is a sensitization and allergic reaction to the droppings of house dust mites. The allergy is common[1][2] and can trigger allergic reactions such as asthma, eczema or itching. It is the manifestation of a parasitosis. The mite's gut contains potent digestive enzymes (notably Peptidase 1) that persist in their feces and are major inducers of allergic reactions such as wheezing. The mite's exoskeleton can also contribute to allergic reactions. Unlike scabies mites or skin follicle mites, house dust mites do not burrow under the skin and are not parasitic.[3] The symptoms can be avoided or alleviated by a number of measures. In general, cutting down mite numbers may reduce these reactions while others say efforts to remove these mites from the environment have not been found to be effective.[4] Immunotherapy may be useful in those affected.[4] Subcutaneous injections have better evidence than under the tongue dosing.[5] Topical steroids as nasal spray or inhalation may be used.[6] House dust mites (Dermatophagoides pteronyssinus) aggregate. Severe dust mite infestation in the home has been linked to atopic dermatitis and epidermal barrier damage has been documented.[7] ## Symptoms[edit] Dust mite allergy symptoms include: * Cough * Facial pressure and pain * Itchy, red or watery eyes * Itchy nose, roof of mouth or throat * Nasal congestion * Postnasal drip * Runny nose, sneezing * Swollen, blue-colored skin under your eyes If the dust mite allergy contributes to asthma: * Audible whistling or wheezing sound when exhaling * Bouts of coughing or wheezing that are worsened by a respiratory virus such as a cold or the flu * Chest tightness or pain * Difficulty breathing * Trouble sleeping caused by shortness of breath, coughing or wheezing[8][4][9] ## References[edit] 1. ^ Alderman, Lesley (2011-03-04). "Who Should Worry About Dust Mites (and Who Shouldn't)". The New York Times. ISSN 0362-4331. Retrieved 2020-07-23. 2. ^ "Dust Mite Allergy" (PDF). NHS. 3. ^ Ogg, Barb. "Managing House Dust Mites" (PDF). Extension, Institute of Agriculture and Natural Resources, University of Nebraska–Lincoln. Retrieved 24 January 2019. 4. ^ a b c Biagtan, M; Viswanathan, R; Bush, RK (December 2014). "Immunotherapy for house dust mite sensitivity: where are the knowledge gaps?". Current Allergy and Asthma Reports. 14 (12): 482. doi:10.1007/s11882-014-0482-0. PMC 5034865. PMID 25354663. 5. ^ Eifan, AO; Calderon, MA; Durham, SR (November 2013). "Allergen immunotherapy for house dust mite: clinical efficacy and immunological mechanisms in allergic rhinitis and asthma". Expert Opinion on Biological Therapy. 13 (11): 1543–56. doi:10.1517/14712598.2013.844226. PMID 24099116. 6. ^ Carrard, A; Pichler, C (April 2012). "[House dust mite allergy]". Therapeutische Umschau. 69 (4): 249–52. doi:10.1024/0040-5930/a000281. PMID 22477664. 7. ^ Cork, Michael J; Robinson, Darren A; Vasilopoulos, Yiannis; Ferguson, Adam; Moustafa, Manar; MacGowan, Alice; Duff, Gordon W; Ward, Simon J; Tazi-Ahnini, Rachid (2006). "New perspectives on epidermal barrier dysfunction in atopic dermatitis: Gene–environment interactions". Journal of Allergy and Clinical Immunology. 118 (1): 3–21, quiz 22–3. doi:10.1016/j.jaci.2006.04.042. PMID 16815133. 8. ^ "Dust mite allergy - Symptoms and causes". Mayo Clinic. Retrieved 2020-07-23. 9. ^ Lee, Young Ji; Han, Soo Jung; Lee, Hun; Kim, Jin Sun; Seo, Kyoung Yul (2016). "Development of Allergic Conjunctivitis Induced by House Dust Mite Extract FromDermatophagoides pteronyssinus". Investigative Ophthalmology & Visual Science. 57 (4): 1773–81. doi:10.1167/iovs.15-17340. ISSN 1552-5783. PMID 27074380. ## Further reading[edit] * List of mites associated with cutaneous reactions * List of allergens * House dust mite * Allergy * Asthma and Allergy Friendly * v * t * e Allergic conditions Respiratory system * Allergic rhinitis (hay fever) * Asthma * Hypersensitivity pneumonitis * Eosinophilic pneumonia * Eosinophilic granulomatosis with polyangiitis * Allergic bronchopulmonary aspergillosis * Farmer's lung * Laboratory animal allergy Skin * Angioedema * Urticaria * Atopic dermatitis * Allergic contact dermatitis * Hypersensitivity vasculitis Blood and immune system * Serum sickness Circulatory system * Anaphylaxis Digestive system * Coeliac disease * Eosinophilic gastroenteritis * Eosinophilic esophagitis * Food allergy * Egg allergy * Milk intolerance Nervous system * Eosinophilic meningitis Genitourinary system * Acute interstitial nephritis Other conditions * Drug allergy * Allergic conjunctivitis * Latex allergy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Dust mite allergy	c0339808	26,966	wikipedia	https://en.wikipedia.org/wiki/Dust_mite_allergy	2021-01-18T18:39:15	{"umls": ["C0339808"], "icd-10": ["T78.4"], "wikidata": ["Q1286499"]}
Limited systemic sclerosis (also known as sine scleroderma) is a type of systemic scleroderma that is characterized by Raynaud's phenomenon and the buildup of scar tissue (fibrosis) on one or more internal organs but not the skin. While the exact cause of limited systemic sclerosis is unknown, it is believed to originate from an autoimmune reaction which leads to the overproduction of collagen (a tough protein which normally strengthens and supports connective tissues throughout the body). When fibrosis affects internal organs, it can lead to impairment or failure of the affected organs. The most commonly affected organs are the esophagus, heart, lungs, and kidneys. Internal organ involvement may be signaled by heartburn, difficulty swallowing (dysphagia), high blood pressure (hypertension), kidney problems, shortness of breath, diarrhea, or impairment of the muscle contractions that move food through the digestive tract (intestinal pseudo-obstruction). While there is no treatment that controls or stops the underlying problem (the overproduction of collagen), many of the symptoms of limited systemic sclerosis can be managed. Many people require a team of specialists to address their symptoms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Limited systemic sclerosis	c1290138	26,967	gard	https://rarediseases.info.nih.gov/diseases/9749/limited-systemic-sclerosis	2021-01-18T17:59:22	{"umls": ["C1290138"], "orphanet": ["220407"], "synonyms": ["Systemic sclerosis sine scleroderma", "Progressive systemic sclerosis sine scleroderma", "Scleroderma, sine"]}
Erythropoietic protoporphyria (EPP) is an inherited disorder of the heme metabolic pathway characterized by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. ## Epidemiology EPP has been reported worldwide, with prevalence ranging between 1/75,000 and 1/200,000. ## Clinical description EPP usually manifests in early infancy upon the first exposure to sun. EPP is characterized by cutaneous manifestations of acute painful photosensitivity with erythema and edema, sometimes with petechiae, together with stinging and burning sensations without blistering, upon exposure to sunlight or artificial light (400-700 nm). These episodes have a variable severity depending on the exposure duration and may result in chronic permanent lesions on exposed skin. As protoporphyrin is a lipophilic molecule that is excreted by the liver, EPP patients are at risk of cholelithiasis with obstructive episodes, and chronic liver disease that might evolve to acute liver failure. ## Etiology In most patients, EPP results from a partial deficiency of the last enzyme of the heme biosynthetic pathway, ferrochelatase (encoded by the (FECH gene; 18q21.2-q21.3). EPP appears to be inherited as an autosomal dominant disease, the clinical expression of which is modulated by the presence of the hypomorphic FECH IVS3-48C allele trans, but recessive inheritance with two mutated FECH alleles has also been described. In about 2% of patients, overt disease was recently shown to be caused by gain-of-function mutations in the erythroid-specific aminolevulinic acid synthase 2 (ALAS2; Xp11.21) gene and named X-linked dominant protoporphyria. ## Diagnostic methods Diagnosis is established by finding increased levels of protoporphyrin in plasma and red blood cells, and detection of a plasma fluorescence peak at 634 nm. Investigations for hepatic involvement, ferrochelatase activity level, genetic analysis (FECH mutations, presence of the hypomorphic FECH IVS3-48C allele trans and ALAS2 mutations) and family studies are advisable. ## Differential diagnosis Differential diagnosis includes phototoxic drug reactions, hydroa vacciniforme, solar urticaria, contact dermatitis, angioedema and, in some cases, other types of porphyria (see these terms). ## Management and treatment Management includes avoidance of exposure to light and protection against visible light using sunscreen with a high UVA index and a high critical wavelength (>370 nm), reduction of protoporphyrin levels (either through reduction of erythropoiesis by transfusion or administration of the bile sequestering agent cholestyramine) and prevention of progression of possible liver disease to liver failure. As the major risk in EPP patients is liver disease, a regular follow-up of hepatic involvement is essential. Sequential hepatic and bone marrow transplantation should be considered as a suitable treatment for the most severe cases of EPP with hepatic involvement. ## Prognosis EPP is a lifelong disorder for which the prognosis depends on the evolution of the hepatic disease. However, photosensitivity may have a significant impact on quality of life of EPP patients. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Autosomal erythropoietic protoporphyria	c0162568	26,968	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79278	2021-01-23T18:40:51	{"gard": ["4527"], "mesh": ["D046351"], "omim": ["177000"], "umls": ["C0162568"], "icd-10": ["E80.0"], "synonyms": ["EPP"]}
Grundbacher (1972) suggested that genes on the X chromosome determine the quantity of immunoglobulin M, because the concentration in serum is one-third higher in females than in males and intrafamilial correlations are higher between sons and mothers than between sons and fathers. Even higher IgM was observed in XXX females (Rhodes et al., 1969) and XO females had levels like normal males. Adinolfi et al. (1978) extended the observations in man and mouse. Washburn et al. (1965) concluded that bacterial infections are a more significant problem in males than in females. Escobar et al. (1979) measured serum concentrations of immunoglobulins G, A and M in 93 pairs of monozygotic twins, their spouses and their offspring. The hypothesis that the human X chromosome carries genes that control the level of IgM was tested with three different approaches. The results indicate that environmental factors are primarily responsible for the observed variation in the levels of IgG and IgA, whereas variance of IgM was mostly the result of X-linked gene effects. IgM deficiency as an X-linked trait leading to predisposition to meningococcal meningitis was suggested by Hobbs et al. (1967) and Hobbs (1986). Misc \- IgM deficiency predisposition to meningococcal meningitis Immunology \- Immunoglobulin M quantity Inheritance \- X-linked ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	IMMUNOGLOBULIN M, LEVEL OF	c1839966	26,969	omim	https://www.omim.org/entry/308250	2019-09-22T16:18:09	{"omim": ["308250"]}
Primary juvenile glaucoma A child with right eye buphthalmos, developed due to congenital glaucoma. SpecialtyOphthalmology TreatmentGoniotomy, trabeculotomy[1] Primary juvenile glaucoma is glaucoma that develops due to ocular hypertension and is evident either at birth or within the first few years of life.[2] It is caused due to abnormalities in the anterior chamber angle development that obstruct aqueous outflow in the absence of systemic anomalies or other ocular malformation.[3] ## Contents * 1 Presentation * 1.1 Systemic associations * 2 Genetics * 3 Diagnosis * 3.1 Differential diagnosis * 4 Treatment * 5 Epidemiology * 6 See also * 7 References * 8 Further reading * 9 External links ## Presentation[edit] The typical infant who has congenital glaucoma usually is initially referred to an ophthalmologist because of apparent corneal edema. The commonly described triad of epiphora (excessive tearing), blepharospasm and photophobia may be missed until the corneal edema becomes apparent.[3] ### Systemic associations[edit] Two of the more commonly encountered disorders that may be associated with congenital glaucoma are Aniridia and Sturge-Weber syndrome.[citation needed] ## Genetics[edit] JOAG is an autosomal dominant condition. The primary cause is the myocilin protein dysfunction. Myocilin gene mutations are identified in approximately 10% of patients affected by juvenile glaucoma. ## Diagnosis[edit] The diagnosis is clinical. The intraocular pressure (IOP) can be measured in the office in a conscious swaddled infant using a Tonopen or hand-held Goldmann tonometer. Usually, the IOP in normal infants is in the range of 11-14 mmHg.[3] Buphthalmos and Haab's striae can often be seen in case of congenital glaucoma.[citation needed] ### Differential diagnosis[edit] Corneal cloudiness may have myriad of causes. Corneal opacity that results from hereditary dystrophies is usually symmetric. Corneal enlargement may result from megalocornea, a condition in which the diameter of the cornea is larger than usual and the eye is otherwise normal.[citation needed] ## Treatment[edit] The preferred treatment of congenital glaucoma is surgical, not medical. The initial procedures of choice are goniotomy or trabeculotomy if the cornea is clear, and trabeculectomy ab externo if the cornea is hazy. The success rates are similar for both procedures in patients with clear corneas. Trabeculectomy and shunt procedures should be reserved for those cases in which goniotomy or trabeculotomy has failed. Cyclophotocoagulation is necessary in some intractable cases but should be avoided whenever possible because of its potential adverse effects on the lens and the retina.[4] ## Epidemiology[edit] In the United States, the incidence of primary congenital glaucoma is about one in 10,000 live births. Worldwide, the incidence ranges from a low of 1:22,000 in Northern Ireland to a high of 1:2,500 in Saudi Arabia and 1:1,250 in Romania. In about two-thirds of cases, it is bilateral. The distribution between males and females varies with geography. In North America and Europe, it is more common in boys, whereas in Japan it is more common in girls.[5] Congenital glaucoma * Incidence: one in every 10000-15000 live births. * Bilateral in up to 80% of cases. * Most cases are sporadic (90%). However, in the remaining 10% there appears to be a strong familial component. ## See also[edit] * Axenfeld syndrome * Peters-plus syndrome * Weill–Marchesani syndrome ## References[edit] 1. ^ "The glaucomas". Parsons' diseases of the eye (22nd ed.). New Delhi, India: Elsevier. 15 July 2015. ISBN 978-81-312-3818-9. 2. ^ Wiggs, JL; Damji, KF; Haines, JL; Pericak-Vance, MA; Allingham, RR (Jan 1996). "The distinction between juvenile and adult-onset primary open-angle glaucoma". American Journal of Human Genetics. 58 (1): 243–4. PMC 1914955. PMID 8554064. 3. ^ a b c Yanoff, Myron; Duker, Jay S. (2009). Ophthalmology (3rd ed.). Mosby Elsevier. ISBN 9780323043328. 4. ^ Basic and clinical science course (2011–2012). Glaucoma. American Academy of Ophthalmology. ISBN 978-1615251179. 5. ^ Diagnosis and Treatment of Primary Congenital Glaucoma Archived 2014-10-19 at the Wayback Machine ## Further reading[edit] * Lively GD, Alward, WL, Fingert JH. Juvenile open-angle glaucoma: 22-year-old Caucasian female referred in 1990 for evaluation of elevated intraocular pressure (IOP). EyeRounds.org. September 17, 2008. ## External links[edit] * 231300 * 137750; MYOC * 137750; CYP1B1 * Juvenile Glaucoma at eMedicine on eMedicine * Glaucoma for Children on AAPOS. * Congenital Primary Glaucoma on patient.info * GeneReview/NCBI/NIH/UW entry on Primary Congenital Glaucoma * Glaucoma entry on PGCFA * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis * v * t * e Congenital malformations and deformations of eyes Adnexa Eyelid * Ptosis * Ectropion * Entropion * Distichia * Blepharophimosis * Ablepharon * Marcus Gunn phenomenon Lacrimal apparatus * Congenital lacrimal duct obstruction Globe Entire eye * Anophthalmia (Cystic eyeball, Cryptophthalmos) * Microphthalmia Lens * Ectopia lentis * Aphakia Iris * Aniridia Anterior segment * Axenfeld–Rieger syndrome Cornea * Keratoglobus * Megalocornea Other * Buphthalmos * Coloboma (Coloboma of optic nerve) * Hydrophthalmos * Norrie disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Primary juvenile glaucoma	c1533041	26,970	wikipedia	https://en.wikipedia.org/wiki/Primary_juvenile_glaucoma	2021-01-18T19:11:00	{"gard": ["2485"], "umls": ["C1533041"], "icd-9": ["365.4"], "icd-10": ["Q15.0"], "orphanet": ["98976"], "wikidata": ["Q3108582"]}
This article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. Please help to improve this article by introducing more precise citations. (February 2020) (Learn how and when to remove this template message) Ringbone is exostosis (bone growth) in the pastern or coffin joint of a horse. In severe cases, the growth can encircle the bones, giving ringbone its name. It has been suggested by some authors that such a colloquial term, whilst commonly used, might be misleading and that it would be better to refer to this condition as osteoarthritis of the inter-phalangeal joints in ungulates (Rogers and Waldron, 1995: 34-35). Ringbone can be classified by its location, with "high ringbone" occurring on the lower part of the large pastern bone or the upper part of the small pastern bone. "Low ringbone" occurs on the lower part of the small pastern bone or the upper part of the coffin bone. High ringbone is easier seen than low ringbone, as low ringbone occurs in the hoof of the horse. However, low ringbone may be seen if it becomes serious, as it creates a bony bump on the coronet of the horse. ## Contents * 1 Causes * 2 Signs * 3 Treatment * 4 Prognosis * 5 Sources ## Causes[edit] * Excessive tension on the tendons, ligaments, and joint capsules of the pastern area can strain the periosteum. The body compensates by growing bone at the stresspoint. Strain on the extensor tendon, the superficial digital flexor tendon branches, the collateral ligaments, and the distal sesamoidean ligaments are all common factors. If these tissues are stretched or torn, and the joint is instabilized by the injury, new bone is produced to help to stabilize the joint. * Osteoarthritis (the endstage of degenerative joint disease) of the pastern or coffin joint is a very common cause of articular ringbone. Bone is then produced to try to immobilize the joint and to relieve the chronic inflammation of the joint capsule. This process may take years, and lameness will continue until the joint is completely immobilized. * Trauma to the periosteum can cause bone growth on the pastern bone. However, this is usually not progressive unless nearby soft tissue was also harmed and thus the joint instability was affected. * Poor shoeing and conformation, such as long, sloping pasterns, upright pasterns, long-toes with low heels, pigeon toes, splay foot, or unbalanced feet may predispose the horse to ringbone, as they create uneven stress on the pastern and coffin joint, unequal tension on the soft tissues, or worsen the concussion that is absorbed by the pastern area. ## Signs[edit] Ringbone usually occurs in the front legs but can also be in the hind legs, and is usually worse in one leg than the other. Ringbone is most often found in mature horses, especially those in intensive training. High ringbone: The horse will have a bony growth around the pastern area, and the pastern will have less mobility. The horse will show pain when the pastern joint is moved or rotated. Early cases will have a lameness score of 1-2 out of 5, with little or no bony swelling seen, although possibly felt when compared to the opposite pastern. Lameness will worsen to a grade 2-3 on a scale of 5 as the ringbone worsens. Low ringbone: The horse will have moderate lameness (grade 2-3), even in early cases, because of the closeness of the ringbone to the other structures in the hoof. When severe or very advanced, the bony growth will be able to be seen on the coronet. ## Treatment[edit] Ringbone is degenerative (unless it is caused by direct trauma). Treatment works to slow down the progress of the bony changes and alleviate the horse's pain, rather than working to cure it. Shoeing: The farrier should balance the hoof and apply a shoe that supports the heels and allows for an easy breakover. NSAIDs: or non-steroidal anti-inflammatory drugs help to alleviate the pain and reduce inflammation within and around the joints. Often NSAIDs make the horse comfortable enough to continue ridden work, which is good for the horse's overall health. Joint injections: The pastern joint can be injected directly, typically with a form of corticosteroid and hyaluronic acid. Extracorporeal shockwave therapy: A high intensity specialized percussion device can help to remodel new bone tissue and decrease pain. Arthrodesis: the fusion of the two bones of the pastern joints eliminates the instability of the joint, and thus the inflammation. This procedure may then eliminate the horse's lameness as well. However, surgical alteration of the joint can promote the growth of bone in the area, which is cosmetically displeasing. Arthrodesis of the coffin joint is usually not performed due to the location of the joint (within the hoof) and because the coffin joint needs some mobility for the horse to move correctly (unlike the pastern joint, which is very still). Interleukin-1 receptor antagonist protein (IRAP) blocks IL-1 from binding to tissues and inhibits the damaging consequences of IL-1. Microcurrent technology: Tissue, including muscle, tendons, ligaments, skin and bone, is formed from a large mass of similar cells that perform specific functions. These cells use tiny sequences of electric current, measured in millionths of an amp, to organise, monitor and regulate a stable state within the body. When there is injury, damage or disease to a tissue, there is disruption to the normal electrical current within the cells and things fail to work properly. By introducing the correct sequences the body's natural electric circuitry is replicated and kick starts and accelerates normal functioning. ## Prognosis[edit] If the ringbone is close to a joint, the prognosis for the horse's continued athletic use is not as good as if the ringbone is not near a joint. Ringbone that is progressing rapidly has a poorer prognosis as well. Horses that are not performing strenuous work, such as jumping or working at speed, will probably be usable for years to come. However, horses competing in intense sports may not be able to continue at their previous level, as their pastern joints are constantly stressed. ## Sources[edit] King, Christine, BVSc, MACVSc, and Mansmann, Richard, VDM, PhD. 1997. "Equine Lameness." Equine Research, Inc. Pages 694-699. Rogers, J and Waldron, T. 1995. "A Field Guide to Joint Disease in Archaeology". Chichester: John Wiley & Sons. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Ringbone	c0264075	26,971	wikipedia	https://en.wikipedia.org/wiki/Ringbone	2021-01-18T18:48:56	{"wikidata": ["Q931365"]}
A number sign (#) is used with this entry because of evidence that resistance to diastolic hypertension can result from variation in the gene encoding beta member 1 of subfamily M of the large conductance calcium-activated potassium channels (KCNMB1; 603951) on chromosome 5q35. Description Hypertension is a significant risk factor for cardiac and renal disease, arteriosclerosis, retinopathy, and stroke. Systolic hypertension reflects an increase in the force of cardiac contraction, whereas diastolic hypertension reflects an increase in peripheral vascular resistance. Normalization of blood pressure is associated with reductions in morbidity and mortality related to end-organ damage. Molecular Genetics By direct sequencing of the exons encoding the KCNMB1 gene in 11 severely hypertensive and 12 strictly normotensive individuals, Fernandez-Fernandez et al. (2004) identified a 352G-A transition in the third exon (603951.0001), corresponding to a glu65-to-lys (E65K) substitution. They screened a population sample of 3,876 randomly selected participants for this mutation and found genotype frequencies of 78.4% for EE homozygotes, 20% for EK heterozygotes, and 1.6% for KK homozygotes. The frequency of the E65K mutation (KK + KE) decreased with increasing diastolic blood pressure (DBP) values, from 21.6% in the normotensive group to 3.2% in the severely hypertensive group (p = 0.008). The age- and sex-adjusted ORs for K carriers with diastolic blood pressures greater than or equal to 105 mm Hg and 110 mm Hg were 0.39 (95% CI, 0.17-0.93, p = 0.034) and 0.12 (95% CI, 0.02-0.90, p = 0.039), respectively. The magnitude and direction of the associations were consistent with a protective effect of the K allele against the severity of diastolic hypertension and with a progressively deleterious effect of the EE genotype. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Vascular \- Resistance to moderate and severe diastolic hypertension MOLECULAR BASIS \- Resistance conferred by mutation in the potassium large conductance calcium-activated channel, subfamily M, beta member 1 gene (KCNMB1, 603951.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HYPERTENSION, DIASTOLIC, RESISTANCE TO	c1837739	26,972	omim	https://www.omim.org/entry/608622	2019-09-22T16:07:33	{"mesh": ["C563897"], "omim": ["608622"]}
A number sign (#) is used with this entry because of evidence that polycystic liver disease-4 with or without kidney cysts (PCLD4) is caused by heterozygous mutation in the LRP5 gene (603506) on chromosome 11q13. Description PCLD4 is an autosomal dominant disease characterized by adult-onset of liver cysts arising from the bile duct epithelium. Some patients may develop a few kidney cysts, but these are often incidental and do not result in renal failure (summary by Cnossen et al., 2014). For a discussion of genetic heterogeneity of polycystic liver disease, see PCLD1 (174050). Clinical Features Cnossen et al. (2014) reported a large multigenerational Dutch family in which at least 16 individuals spanning 3 generations had polycystic liver disease. The severity of the disease varied within the family. Many patients also had a few kidney cysts, although none had clinically significant renal disease. Another smaller Dutch family, a smaller Moroccan family, and a Dutch patient with sporadic disease were also reported. Clinical details were sparse. Inheritance The transmission pattern of PCLD4 in the families reported by Cnossen et al. (2014) was consistent with autosomal dominant inheritance. There was some evidence of age-related incomplete penetrance. Molecular Genetics In affected individuals from 4 unrelated families with PCLD4, Cnossen et al. (2014) identified 4 different heterozygous missense mutations in the LRP5 gene (603506.0035-603506.0038). Two mutations affected the extracellular domain, and 2 affected the intracellular domain. The mutation in the first family was found by whole-exome sequencing and confirmed by Sanger sequencing; the 3 other mutations were found by direct sequencing of the LRP5 gene in a cohort of 150 probands with cystic liver disease. The mutations segregated with the disorder in the families. In vitro functional expression studies of 2 of the variants showed that they resulted in decreased WNT (see, e.g., 164820) signaling activation in response to Wnt3a (606359) compared to wildtype, as well as altered expression of some target genes in this pathway. None of the patients carrying mutations had evidence of clinical features of other LRP5-related disorders, including bone density or ocular abnormalities. ### Associations Pending Confirmation Based on the putative overlap between polycystic liver disease and polycystic kidney disease (PKD), Cnossen et al. (2016) screened the LRP5 gene in 79 probands with PKD. Four different missense variants (W560C, R1036Q, R1135C, and Q1156H) were identified in 4 probands. However, in 2 families (families A and D), there was not clean segregation of the LRP5 variant with the disorder, and individuals also carried variants in the PKD1 gene (601313). The R1036Q variant identified in a patient with sporadic disease (family B) had a high frequency (1/245) in public databases. The R1135C variant in family C also had a relatively high frequency (1/1,300) among European Americans in the Exome Sequencing Project database and was found in the proband's unaffected mother and older sister. In vitro functional expression assays using a luciferase marker demonstrated that 3 of the variants (W560C, R1036Q, and Q1156H) resulted in impaired activation of Wnt3a-induced canonical WNT signaling compared to wildtype. Two variants (W560C and R1036Q) resulted in an increase in AXIN2 (604025) expression. The findings suggested that LRP5 variants may also contribute to kidney cysts by altering Wnt signaling. INHERITANCE \- Autosomal dominant ABDOMEN Liver \- Liver cysts, small and large GENITOURINARY Kidneys \- Kidney cysts (in some patients) MISCELLANEOUS \- Variable phenotype \- Cysts are usually detected in adulthood \- Patients do not develop severe renal disease \- Liver disease can be mild or severe \- Incomplete penetrance MOLECULAR BASIS \- Caused by mutation in the low density lipoprotein receptor-related protein 5 gene (LRP5, 603506.0035 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	POLYCYSTIC LIVER DISEASE 4 WITH OR WITHOUT KIDNEY CYSTS	c4693479	26,973	omim	https://www.omim.org/entry/617875	2019-09-22T15:44:38	{"omim": ["617875"]}
Osmophobia SpecialtyPsychology Osmophobia or olfactophobia refers to a fear, aversion, or psychological hypersensitivity to odors. The phobia generally occurs in chronic migraine sufferers who may have odor triggered migraines.[citation needed] Such migraines are most frequently triggered by foul odors, but the hypersensitivity may extend to all odors. One study found as many as 25% of migraine sufferers had some degree of osmophobia. The condition may also be present in individuals in substance withdrawal, specifically opioid withdrawal syndrome, where it is usually associated with nausea and/or vomiting. The term osmophobia comes from the Greek ὀσμή - osmē, meaning "smell, odour"[1] and φόβος - phobos, "fear".[2] Olfactophobia comes from the Latin olfacto, "to smell at".[3] ## See also[edit] * List of phobias * Olfactory Reference Syndrome ## References[edit] 1. ^ ὀσμή, Henry George Liddell, Robert Scott, A Greek-English Lexicon, on Perseus 2. ^ φόβος, Henry George Liddell, Robert Scott, A Greek-English Lexicon, on Perseus 3. ^ olfacto, Charlton T. Lewis, Charles Short, A Latin Dictionary, on Perseus ## External links[edit] * Kelman L (November 2004). "The place of osmophobia and taste abnormalities in migraine classification: a tertiary care study of 1237 patients". Cephalalgia. 24 (11): 940–6. doi:10.1111/j.1468-2982.2004.00766.x. PMID 15482356.[dead link] * Kelman L (2004). "Osmophobia and taste abnormality in migraineurs: a tertiary care study". Headache. 44 (10): 1019–23. doi:10.1111/j.1526-4610.2004.04197.x. PMID 15546266. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Osmophobia	c1261977	26,974	wikipedia	https://en.wikipedia.org/wiki/Osmophobia	2021-01-18T19:04:28	{"wikidata": ["Q1772026"]}
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Diseases of the foot" – news · newspapers · books · scholar · JSTOR (November 2014) Flatfoot in a 55 year old woman with ankle and knee arthritis Vascular ischemia of the toes with the characteristic cyanosis Chilblains, also called perniosis Bunion and hammer toe Foot disease in a Ziguinchor hospital, Senegal, 1973 Athlete's foot, a fungal infection Diseases of the foot generally are not limited, that is they are related to or manifest elsewhere in the body[citation needed]. However, the foot is often the first place some of these diseases or a sign or symptom of others appear.[1] This is because of the foot's distance from the central circulation, the heart and its constant exposure to pressures from the ground and the weight of the body[citation needed]. The foot may look simple but is a complex structure with 26 bones, 33 joints, numerous muscles, nerves and different ligament types. Any part of the foot can be affected. Some foot disorders may present with just a mild ache, but other foot disorders can be very serious and limit ability to walk or bear weight. Most minor cases of foot pain respond to home care treatments except when severe pain is present as it is a disabling condition and usually needs some type of medical attention. If foot pain is not treated in time, it can lead to long term disability and continuing damage to the foot.[2] ## Contents * 1 Causes * 2 Diagnosis * 3 Skin and nails * 4 Arthritic foot conditions * 5 Pain relief * 6 Vascular disorders * 7 See also * 8 References ## Causes[edit] The most common cause of foot pain is wearing ill fitting shoes. Women often wear tight shoes that are narrow and constrictive, and thus are most prone to foot problems. Tight shoes often cause overcrowding of toes and result in a variety of structural defects. The next most common cause of foot disease is overuse or traumatic injuries.[3] ## Diagnosis[edit] Besides a physical examination, an x-ray MRI or an ultrasound study may be obtained to assess the soft tissues and blood vessels. Standardized questionnaires and scoring systems, like the American Orthopaedic Foot & Ankle Society (AOFAS) foot and ankle questionnaires, can help elicit the history and physical exam necessary to make and accurate diagnosis of foot and ankle conditions.[4] ## Skin and nails[edit] Further information: Nail diseases Often there is a distinction made between conditions of the dorsal skin and plantar skin. Common examples include callus thickened skin, fungal infections of the skin (athlete's foot) or nails (onychomycosis), viral infection of verrucae, and ingrowing toenails that may cause bacterial nail infections (paronychia). Corns and calluses are chunky tough layers of skin that develop on the foot to protect underlying skin from pressure and friction. Corns and calluses are very common and do not look pleasant. Corns and calluses generally need treatment only if they cause problems. For most people, the best treatment of corns and calluses is to eliminate the source of friction or pressure.[5] Ingrown toe nail is a disorder where the nail starts to grow into the soft fleshy area of the toe. It causes intense redness, pain and swelling. Ingrown toe nails often affect the big toe. The best treatment for ingrown toe nails is to get the nail partially or completely removed.[6] ## Arthritic foot conditions[edit] Arthritic foot conditions often present differently from arthritis other areas of the body. Achilles tendinitis results from stress on calf muscles and Achilles tendon. This strong tendon often gets inflamed while playing sports like basketball. The tendon gets irritated and does cause moderate pain . When treated promptly, the tendinitis is relieved. Sometimes, the Achilles tendon can rupture if it is overstretched. When the Achilles tendon ruptures, one may feel a sudden pop followed by sharp pain. Rupture of the Achilles tendon makes it impossible to walk. Bunion is an abnormal bony mass that forms on the big toe and points outwards. This deformity is unsightly and painful. When the big toe enlarges at the base, it can force the other toes to crowd against each other. Over time, the big toe pushes outwards and alters the normal outline of the foot. Bunions occur for many reasons but the most common is not wearing proper shoes, arthritis and different inherited structural defects. Flat feet (Pes planus foot) essentially means that the arch inside the foot is flat. This very common painless disorder may occur at birth or after pregnancy. Flat feet generally do not cause problems but may sometimes cause the foot to rotate inwards (pronation). There are orthotic shoe insoles (foot orthotics) that help correct flat feet. Surgery does not correct flat feet and should be avoided.[citation needed] Hammer toes are unsightly and reveal a toe that is curled due to a bend in the middle joint of the toe. A hammer toe occur chiefly because the shoe is too tight at the front or the heels are too high. In such situations, the toe is strained against the front of the shoe and results in an abnormal twist.[7] Relieving pain, pressure, changing shoe wear or wearing a type of shoe insert is adequate for most people. Gout often presents with pain and tenderness at the base of the big toe. Generally women are more prone to gout after menopause. An acute attack of gout is intensely painful and walking on the foot is impossible. Gout is essentially a disorder caused by precipitation of uric acid crystals in the joint. Plantar fasciitis is a very common cause of heel pain. The thick fibrous bands at the bottom of the heel get inflamed and cause excruciating pain. The pain occurs the moment you step out of bed. After a few hours, the pain does subside but can return after prolonged periods of standing. Plantar fasciitis is most common in runners, obese individuals, women who are pregnant and those who wear shoes with inadequate heel support. The treatment of this agonizing disorder involves pain control, steroid injections, proper foot wear and rest. ## Pain relief[edit] In some cases, foot diseases and painful conditions can be treated. Synovium hydrates the cartilage in the heel and can bring pain relief quickly. Synovium gel looks as well as strongly smells like urine, straying some consumers away. However this only occurs after expiration. Blood thinners can also work however are deemed as bad relievers by medical practitioners due to the fact that they can contribute to headaches and in some cases increase foot pain afterwards. ## Vascular disorders[edit] Atherosclerotic restriction to the arterial supply in peripheral artery occlusive disease may result in painful arterial ulcers of the ankle and foot, or give rise of gangrene of the toes and foot. Immobility of a person may result in prolonged pressure applied to the heels causing pressure sores. Impaired venous drainage from the foot in varicose veins may sequentially result in brown haemosiderin discolouration to the ankle and foot, varicose stasis dermatitis and finally venous ulcers. Other disorders of the foot include osteoarthritis of the joints, peripheral neuropathy and plantar warts.[8] ## See also[edit] * List of disorders of foot and ankle Wikimedia Commons has media related to Diseases and disorders of the human feet. ## References[edit] 1. ^ [1] Top of Foot Pain: Causes and Treatments. Retrieved on 2017-01-01 2. ^ Foot Injuries and Disorders Medline Plus. Retrieved on 2010-01-20 3. ^ Orthopedic Surgery Mayo Clinic. Retrieved on 2010-01-20 4. ^ "AOFAS ankle-hindfoot score description and calculator – orthotoolkit". Retrieved January 10, 2018. 5. ^ Foot & Ankle Fractures, Sprains and Dislocations Archived March 12, 2010, at the Wayback Machine New York Online Access To Health. Retrieved on 2010-01-20 6. ^ Ingrown Toenails Podiatry Network. Retrieved on 2010-01-20 7. ^ Foot Disease Archived 2009-12-13 at the Wayback Machine Hammertoe Information. Retrieved on 2010-01-20 8. ^ Foot Pain Retrieved on 2010-01-20 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Diseases of the foot	c0016510	26,975	wikipedia	https://en.wikipedia.org/wiki/Diseases_of_the_foot	2021-01-18T18:57:12	{"mesh": ["D005534"], "umls": ["C0016510"], "wikidata": ["Q5282137"]}
## Clinical Features Bamforth et al. (1989) described congenital shortness of the costocoracoid ligament in many members of a Canadian family. Affected persons had fixation of the scapula to the first rib, resulting in cosmetic deformity with rounding of the shoulders and loss of the anterior clavicular contour as the main concern of the affected persons. Movements requiring rotation or retraction of the scapula were limited, but this did not interfere with normal activities. One affected member of the family was turned down for active military service during World War II because he was unable to carry a backpack. Surgical treatment, which revealed a short costocoracoid ligament and sometimes ossification, consisted of excision of the ligament and resulted in some cosmetic correction. The abnormality results in a pectoral girdle which is reminiscent of that seen in monotremes such as the duck-billed platypus and spiny anteater. These animals have powerful front legs for digging and require pectoral stability rather than mobility. Skel \- Congenitally short costocoracoid ligament \- Scapula fixed to first rib \- Round shoulders \- Loss of anterior clavicular contour \- Limited scapular motion Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	COSTOCORACOID LIGAMENT, CONGENITALLY SHORT	c1852523	26,976	omim	https://www.omim.org/entry/122580	2019-09-22T16:42:49	{"mesh": ["C536448"], "omim": ["122580"], "orphanet": ["2391"]}
Systemic polyarteritis nodosa (PAN; see this term) is a chronic systemic necrotizingvasculitis of adults and childrenaffecting small- and medium-sized vessels and characterized by formation of microaneurysms leading to serious generalized disease and multi-organ involvement. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Systemic polyarteritis nodosa	c0031036	26,977	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=439762	2021-01-23T16:52:51	{"mesh": ["D010488"], "umls": ["C0031036"], "icd-10": ["M30.0"], "synonyms": ["Systemic PAN", "Systemic periarteritis nodosa"]}
Warfarin resistance is a condition that is characterized by a high tolerance for a "blood-thinning" medication called warfarin. Warfarin is an anticoagulant that is often prescribed to people who are at an increased risk for blood clots. Some people with a warfarin resistance do not respond to the drug at all, while others can achieve the benefits of warfarin treatment at a high dose. In either case, affected people will still be at an elevated risk for blood clots when given the standard dose of warfarin. The metabolism of warfarin and the drug's effects in the body are complex traits that are determined by several genes as well as environmental and lifestyle factors such as gender, age, weight, diet, and other medications. One specific genetic polymorphism in the VKORC1 gene accounts for approximately 20% of variation in the response to warfarin and can be passed on to future generations in an autosomal dominant 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Warfarin resistance	c0750384	26,978	gard	https://rarediseases.info.nih.gov/diseases/12721/warfarin-resistance	2021-01-18T17:57:09	{"mesh": ["C563039"], "omim": ["122700"], "synonyms": []}
Haemophilus meningitis SpecialtyNeurology Haemophilus meningitis is a form of bacterial meningitis caused by the Haemophilus influenzae bacteria. It is usually (but not always) associated with Haemophilus influenzae type b.[1] Meningitis involves the inflammation of the protective membranes that cover the brain and spinal cord. Haemophilus meningitis is characterized by symptoms including fever, nausea, sensitivity to light, headaches, stiff neck, anorexia, and seizures.[2][3] Haemophilus meningitis can be deadly, but antibiotics are effective in treating the infection, especially when cases are caught early enough that the inflammation has not done a great deal of damage.[2] Before the introduction of the Hib vaccine in 1985,[4] Haemophilus meningitis was the leading cause of bacterial meningitis in children under the age of five. However, since the creation of the Hib vaccine, only two in every 100,000 children contract this type of meningitis.[2] Five to ten percent of cases can be fatal,[5] although the average mortality rate in developing nations is seventeen percent,[3] mostly due to lack of access to vaccination as well as lack of access to medical care needed to combat the meningitis. ## Contents * 1 Symptoms * 2 Risk factors * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Prognosis * 7 References * 8 External links ## Symptoms[edit] Possible symptoms of Haemophilus meningitis include:[2][3] * Nausea or vomiting * Fever * Headache * Sensitivity to light * Seizures * Anorexia * change in mental status, such as irritability * stiff neck ## Risk factors[edit] While the Haemophilus influenzae bacteria are unable to survive in any environment outside of the human body, humans can carry the bacteria within their bodies without developing any symptoms of the disease. It spreads through the air when an individual carrying the bacteria coughs or sneezes.[4] The risk of developing Haemophilus meningitis is most directly related to an individual's vaccination history, as well as the vaccination history of the general public. Herd immunity, or the protection that unvaccinated individuals experience when the majority of others in their proximity are vaccinated, does help in the reduction of meningitis cases, but it does not guarantee protection from the disease.[3] Contact with other individuals with the disease also vastly increases the risk of infection. A child in the presence of family members sick with Haemophilus meningitis or carrying the bacteria is 585 times more likely to catch Haemophilus meningitis.[6] Additionally, siblings of individuals with the Haemophilus influenzae meningitis receive reduced benefits from certain types of immunization.[7] Similarly, children under two years of age have a greater risk of contracting the disease when attending day care, especially in their first month of attendance, due to the maintained contact with other children who might be asymptomatic carriers of the Hib bacteria.[3] ## Diagnosis[edit] This section is empty. You can help by adding to it. (February 2019) ## Prevention[edit] Before the widespread use of the Hib vaccine, Haemophilus meningitis accounted for 40%-60% of all meningitis cases in children under the age of fifteen, and 90% of all meningitis cases in children under the age of five.[3] Vaccination can reduce incidence.[8] Vaccination has reduced the occurrences of Haemophilus meningitis by 87-90% in countries with widespread access to the Hib vaccine.[3] Rates are still high in areas with limited levels of vaccination.[9] Less-developed countries as well as countries with medical infrastructure that has been damaged in any way, such as from warfare, do not have such widespread access to the vaccine and thus experience higher rates of meningitis cases. Multiple conjugate Hib vaccines are available for use, though, and are extremely effective when given to infants.[5] Additionally, the vaccine has only the side effects of reddened skin and swelling at the location of the injection.[5] ## Treatment[edit] Because it is a bacterial disease, the primary method of treatment for Haemophilus meningitis is anti-bacterial therapy. Common antibiotics include ceftriaxone[2][3] or cefotaxime, both of which can combat the infection and thus reduce inflammation in the meninges, or the membranes that protect the brain and spinal cord. Anti-inflammatories such as corticosteroids, or steroids produced by the body to reduce inflammation, can also be used to fight the meningeal inflammation in an attempt to reduce risk of mortality and reduce the possibility of brain damage. ## Prognosis[edit] Survivors of Haemophilus meningitis may experience permanent damage caused by inflammation around the brain, mostly involving neurological disorders. Long-term complications include brain damage, hearing loss, and mental disability.[5] Other possible long-term effects are reduced IQ, cerebral palsy, and the development of seizures.[10] Children that survive the disease are more often held back in school, and are more likely to require special education services.[10] Negative long-term effects are more likely in subjects whose treatments were delayed, as well as in subjects who were given antibiotics to which the bacteria was resistant.[3] Ten percent of survivors develop epilepsy, while close to twenty percent of survivors develop hearing loss ranging from mild loss to deafness. About 45% of survivors experience no negative long-term effects.[3] ## References[edit] 1. ^ Al-Tawfiq JA (2007). "Haemophilus influenzae type e meningitis and bacteremia in a healthy adult". Intern. Med. 46 (4): 195–8. doi:10.2169/internalmedicine.46.1807. PMID 17301516. 2. ^ a b c d e "Meningitis - H. influenzae". MedlinePlus. U.S. National Library of Medicine. Retrieved 23 October 2014. 3. ^ a b c d e f g h i j Haran Chandrasekar, Pranatharthi; Cavaliere, Robert; Stanley Rust Jr, Robert; Swaminathan, Subramanian. "Haemophilus Meningitis". Medscape. Retrieved 28 October 2014. 4. ^ a b "Haemophilus influenzae type b (Hib)". The History of Vaccines. The College of Physicians of Philadelphia. Retrieved 12 November 2014. 5. ^ a b c d "Haemophilus influenzae type b (Hib)". World Health Organization. World Health Organization. Retrieved 30 October 2014. 6. ^ Ward JI, Fraser DW, Baraff LJ, Plikaytis BD (July 1979). "Haemophilus influenzae meningitis. A national study of secondary spread in household contacts". N. Engl. J. Med. 301 (3): 122–6. doi:10.1056/NEJM197907193010302. PMID 313003. 7. ^ Granoff DM, Squires JE, Munson RS, Suarez B (August 1983). "Siblings of patients with Haemophilus meningitis have impaired anticapsular antibody responses to Haemophilus vaccine". J. Pediatr. 103 (2): 185–91. doi:10.1016/s0022-3476(83)80342-4. PMID 6603504. 8. ^ Miranzi Sde S, de Moraes SA, de Freitas IC (July 2007). "Impact of the Haemophilus influenzae type b vaccination program on HIB meningitis in Brazil". Cad Saude Publica. 23 (7): 1689–95. doi:10.1590/s0102-311x2007000700021. PMID 17572819. 9. ^ Minz S, Balraj V, Lalitha MK, Murali N, Cherian T, Manoharan G, Kadirvan S, Joseph A, Steinhoff MC (July 2008). "Incidence of Haemophilus influenzae type b meningitis in India". Indian J. Med. Res. 128 (1): 57–64. PMID 18820360. 10. ^ a b D'Angio CT, Froehlke RG, Plank GA, Meehan DJ, Aguilar CM, Lande MB, Hugar L (September 1995). "Long-term outcome of Haemophilus influenzae meningitis in Navajo Indian children". Arch Pediatr Adolesc Med. 149 (9): 1001–8. doi:10.1001/archpedi.1995.02170220067009. PMID 7655584. ## External links[edit] Classification D * ICD-10: G00.0 * ICD-9-CM: 320.0 * MeSH: D008583 * 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 * v * t * e Meningitis and other diseases of meninges Meningitis * Arachnoiditis * Bacterial * Tuberculous * Haemophilus * Pneumococcal * Viral * Herpesviral * Fungal * Cryptococcal * Aseptic * Drug-induced Other * Meningoencephalitis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Haemophilus meningitis	c0025292	26,979	wikipedia	https://en.wikipedia.org/wiki/Haemophilus_meningitis	2021-01-18T18:28:03	{"mesh": ["D008583"], "icd-10": ["G00.0"], "wikidata": ["Q17119372"]}
Neuromyelitis optica (NMO) and NMO spectrum disorders are inflammatory demyelinating diseases of the central nervous system characterized mainly by attacks of uni- or bilateral optic neuritis (ON) and acute myelitis. ## Epidemiology NMO has a worldwide distribution and estimated prevalence of 1-2/100,000. ## Clinical description Patients present with acute, often severe, attacks of blindness and paraparesis or quadriparesis, accompanied by sensory and sphincter impairments. Most patients have relapsing attacks (separated by months or years with partial recovery), with usually sequential index episodes of ON and myelitis. A relapsing course is more frequent in women, and nearly 90% of patients are female (typically late middle-aged). More rarely, the disease course is monophasic, with nearly simultaneous index episodes of ON and myelitis. This form may occur in younger individuals with no sex predilection. Rarely, patients experience other neurological manifestations, including intractable vomiting and nausea due to inflammation in the medulla, endocrine and sleep disorders due to involvement of the hypothalamus, and attacks of cerebral edema that may cause confusion or coma. Patients with NMO frequently have other systemic autoimmune disorders, such as systemic lupus erythematosus (SLE), Sjögren's syndrome or myasthenia gravis (see these terms). ## Etiology Etiology is unknown but NMO is believed to be an autoimmune disease associated with autoantibodies to aquaporin-4. ## Diagnostic methods Diagnosis is primarily clinical, but MRI evidence of long spinal cord lesions extending over three or more vertebral segments during an acute attack of myelitis is helpful in differentiating this disorder from multiple sclerosis (MS), as are normal brain MRI findings in the early stages of NMO. When aquaporin-4 antibodies are detected, their specificity allows diagnosis of NMO in circumstances when the clinical diagnosis is less straightforward, such as in patients with a first event of transverse myelitis or in patients with atypical brain lesions (such patients are said to have NMO spectrum disorders). Asian opticospinal MS (OSMS) is a relapsing form of MS described in Japan that selectively targets the optic nerve and spinal cord. The presence of a long spinal cord lesion during acute attacks of myelitis is not required for diagnosis of Asian OSMS. many patients with this diagnosis have NMO and aquaporin-4 autoantibodies, but some are ultimately recognized as having prototypic MS. ## Differential diagnosis Differential diagnoses include MS; idiopathic, viral, paraneoplastic and connective tissue disease (e.g. SLE)-associated myelitis; ischemic and connective tissue associated optic neuropathies (see these terms). ## Management and treatment Acute attacks are treated with high dose intravenous corticosteroids and if this fails, with plasma exchange. Long-term maintenance treatments are immunosuppressive drugs (azathioprine or mycophenolate mofetil), combined with corticosteroids in some patients, or rituximab therapy. ## Prognosis The prognosis is variable: patients may recover completely from individual attacks, but residual neurological deficits are common and sometimes severe. Unrecognized or untreated, up to 30% of patients may die in the first 5 years of their illness of an attack of severe myelitis leading to respiratory failure. A high proportion of patients will become legally blind in one or both eyes and/or have substantial residual paraparesis. The impact of early treatment with an effective long term agent is unknown, but current evidence suggests that the attack rate may be reduced by over 50% with effective immunosuppressive 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Neuromyelitis optica spectrum disorder	c0027873	26,980	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=71211	2021-01-23T18:41:56	{"gard": ["6267"], "mesh": ["D009471"], "umls": ["C0027873"], "icd-10": ["G36.0"], "synonyms": ["Devic disease", "NMOSD"]}
Ollier disease is a disorder characterized by multiple enchondromas, which are noncancerous (benign) growths of cartilage that develop within the bones. These growths most commonly occur in the limb bones, especially in the bones of the hands and feet; however, they may also occur in the skull, ribs, and bones of the spine (vertebrae). Enchondromas may result in severe bone deformities, shortening of the limbs, and fractures. The signs and symptoms of Ollier disease may be detectable at birth, although they generally do not become apparent until around the age of 5. Enchondromas develop near the ends of bones, where normal growth occurs, and they frequently stop forming after affected individuals stop growing in early adulthood. As a result of the bone deformities associated with Ollier disease, people with this disorder generally have short stature and underdeveloped muscles. Although the enchondromas associated with Ollier disease start out as benign, they may become cancerous (malignant). In particular, affected individuals may develop bone cancers called chondrosarcomas, especially in the skull. People with Ollier disease also have an increased risk of other cancers, such as ovarian cancer or liver cancer. People with Ollier disease usually have a normal lifespan, and intelligence is unaffected. The extent of their physical impairment depends on their individual skeletal deformities, but in most cases they have no major limitations in their activities. A related disorder called Maffucci syndrome also involves multiple enchondromas but is distinguished by the presence of red or purplish growths in the skin consisting of tangles of abnormal blood vessels (hemangiomas). ## Frequency Ollier disease is estimated to occur in 1 in 100,000 people. ## Causes In most people with Ollier disease, the disorder is caused by mutations in the IDH1 or IDH2 gene. These genes provide instructions for making enzymes called isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2, respectively. These enzymes convert a compound called isocitrate to another compound called 2-ketoglutarate. This reaction also produces a molecule called NADPH, which is necessary for many cellular processes. IDH1 or IDH2 gene mutations cause the enzyme produced from the respective gene to take on a new, abnormal function. Although these mutations have been found in some cells of enchondromas in people with Ollier disease, the relationship between the mutations and the signs and symptoms of the disorder is not well understood. Mutations in other genes may also account for some cases of Ollier disease. ### Learn more about the genes associated with Ollier disease * IDH1 * IDH2 ## Inheritance Pattern Ollier disease is not inherited. The mutations that cause this disorder are somatic, which means they occur during a person's lifetime. A somatic mutation occurs in a single cell. As that cell continues to grow and divide, the cells derived from it also have the same mutation. In Ollier disease, the mutation is thought to occur in a cell during early development before birth; cells that arise from that abnormal cell have the mutation, while the body's other cells do not. This situation is called mosaicism. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Ollier disease	c0014084	26,981	medlineplus	https://medlineplus.gov/genetics/condition/ollier-disease/	2021-01-27T08:25:51	{"gard": ["7251"], "mesh": ["D004687"], "omim": ["166000"], "synonyms": []}
Epidural abscess SpecialtyNeurology An epidural abscess refers to a collection of pus and infectious material located in the epidural space superficial to the dura mater which surrounds the central nervous system. Due to its location adjacent to brain or spinal cord, epidural abscesses have the potential to cause weakness, pain, and paralysis. ## Contents * 1 Types * 1.1 Spinal Epidural Abscess * 1.2 Cranial epidural abscess * 2 References ## Types[edit] ### Spinal Epidural Abscess[edit] Spinal epidural abscess (SEA) is a collection of pus or inflammatory granulation between the dura mater and the vertebral column.[1] Currently the annual incidence rate of SEAs is estimated to be 2.5-3 per 10,000 hospital admissions. Incidence of SEA is on the rise, due to factors such as an aging population, increase in use of invasive spinal instrumentation, growing number of patients with risk factors such as diabetes and intravenous drug use.[1] SEAs are more common in posterior than anterior areas,[2] and the most common location is the thoracolumbar area, where epidural space is larger and contains more fat tissue.[3] SEAs are more common in males, and can occur in all ages, although highest prevalence is during the fifth and seventh decades of life.[1] ### Cranial epidural abscess[edit] A cranial epidural abscess involves pus and granulation tissue accumulation in between the dura mater and cranial bone. These typically arise (along with osteomyelitis of a cranial bone) from infections of the ear or paranasal sinuses. They rarely can be caused by distant infection or an infected cerebral venous sinus thrombosis. Staphylococcus aureus is the most common pathogen. Symptoms include pain at the forehead or ear, pus draining from the ear or sinuses, tenderness overlying the infectious site, fever, neck stiffness, and in rare cases focal seizures. Treatment requires a combination of antibiotics and surgical removal of infected bone.[4] ## References[edit] 1. ^ a b c Sendi, P.; Bregenzer, T.; Zimmerli, W. (3 November 2007). "Spinal epidural abscess in clinical practice" (PDF). QJM. 101 (1): 1–12. doi:10.1093/qjmed/hcm100. PMID 17982180. 2. ^ Darouiche, RO (Nov 9, 2006). "Spinal epidural abscess". The New England Journal of Medicine. 355 (19): 2012–20. doi:10.1056/NEJMra055111. PMID 17093252. 3. ^ Akalan, N; Ozgen, T (2000). "Infection as a cause of spinal cord compression: a review of 36 spinal epidural abscess cases". Acta Neurochirurgica. 142 (1): 17–23. doi:10.1007/s007010050002. PMID 10664371. S2CID 23610039. 4. ^ Ropper, Allan H.; Samuels, Martin A. (2009). Adams and Victor's Principles of Neurology (Ninth ed.). New York: McGraw Hill. ISBN 9780071499927. Classification D * MeSH: D020802 External resources * MedlinePlus: 001416 article/232570 at eMedicine * v * t * e Focal lesions of the spinal cord General * Myelopathy * Myelitis * Spinal cord compression By location * Brown-Séquard syndrome * Posterior cord syndrome * Anterior cord syndrome * Central cord syndrome * Cauda equina syndrome Other * Polio * Demyelinating disease * Transverse myelitis * Tropical spastic paraparesis * Epidural abscess * Syringomyelia * Syringobulbia * Morvan's syndrome * Sensory ataxia * Tabes dorsalis * Abadie's sign * Subacute combined degeneration of spinal cord * Vascular myelopathy * Anterior spinal artery syndrome * Foix–Alajouanine syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Epidural abscess	c0270629	26,982	wikipedia	https://en.wikipedia.org/wiki/Epidural_abscess	2021-01-18T18:34:38	{"mesh": ["D020802"], "umls": ["C0270629"], "wikidata": ["Q18353735"]}
Asbestos warning label. Figure A shows the location of the lungs, airways, pleura, and diaphragm in the body. Figure B shows lungs with asbestos-related diseases, including pleural plaque, lung cancer, asbestosis, plaque on the diaphragm, and mesothelioma. Left-sided mesothelioma (seen on the right of the picture): chest CT All types of asbestos fibers are known to cause serious health hazards in humans.[1][2][3] The most common diseases associated with chronic exposure to asbestos are asbestosis and mesothelioma.[4] Amosite and crocidolite are considered the most hazardous asbestos fiber types;[5] however, chrysotile asbestos has also produced tumors in animals and is a recognized cause of asbestosis and malignant mesothelioma in humans,[6] and mesothelioma has been observed in people who were occupationally exposed to chrysotile, family members of the occupationally exposed, and residents who lived close to asbestos factories and mines.[7] During the 1980s and again in the 1990s it was suggested at times that the process of making asbestos cement could "neutralize" the asbestos, either via chemical processes or by causing cement to attach to the fibers and changing their physical size; subsequent studies showed that this was untrue, and that decades-old asbestos cement, when broken, releases asbestos fibers identical to those found in nature, with no detectable alteration.[8] ## Contents * 1 Risks * 1.1 Asbestos-related diseases * 2 Safety and exposure prevention * 2.1 Common building materials containing asbestos * 2.2 Identification and assessment * 2.3 Environmental asbestos * 3 Biological interactions * 3.1 Mechanisms of carcinogenicity * 3.2 Chemistry * 3.3 Smoking and asbestos * 4 History of health concerns and regulation * 4.1 Until 1900 * 4.2 1900s–1910s * 4.3 1920s–1930s * 4.4 1940s * 4.5 1950s * 4.6 1960s–1980s * 4.7 Modern regulation * 4.7.1 United States * 4.7.2 Canada * 4.7.3 United Kingdom * 4.7.4 New Zealand * 4.7.5 Australia * 4.7.6 Brazil * 4.7.7 Japan * 4.7.8 South Korea * 4.7.9 Singapore * 4.7.10 Turkey * 4.8 Delayed recognition * 5 Litigation * 6 Criticisms of asbestos regulation * 7 References * 8 External links ## Risks[edit] Exposure to asbestos in the form of fibers is always considered dangerous. Working with, or exposure to, material that is friable, or materials or works that could cause release of loose asbestos fibers, is considered high risk. However, in general, people who become ill from inhaling asbestos have been regularly exposed in a job where they worked directly with the material. According to the National Cancer Institute, "A history of asbestos exposure at work is reported in about 70 percent to 80 percent of all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos."[9] A paper published in 1998, in the American Journal of Respiratory and Critical Care Medicine, concurs, and comments that asbestosis has been reported primarily in asbestos workers, and appears to require long-term exposure, high concentration for the development of the clinical disease. There is also a long latency period (the time taken between harmful contact and emergence of the actual resulting illness) of about 12 to 20 years,[10] and potentially up to 40 years. The most common diseases associated with chronic exposure to asbestos are asbestosis and mesothelioma.[11] According to OSHA,[12] "there is no 'safe' level of asbestos exposure for any type of asbestos fiber.[13][14] Asbestos exposures as short in duration as a few days have caused mesothelioma in humans. Every occupational exposure to asbestos can cause injury or disease; every occupational exposure to asbestos contributes to the risk of getting an asbestos related disease."[12][15][16] ### Asbestos-related diseases[edit] Main article: Asbestos-related diseases Diseases commonly associated with asbestos include: * Asbestosis: Progressive fibrosis of the lungs of varying severity, progressing to bilateral fibrosis, honeycombing of the lungs on radiological view with symptoms including rales and wheezing. Individuals who have been exposed to asbestos via home, environment, or work should notify their doctors about exposure history. * Asbestos warts: caused when the sharp fibers lodge in the skin and are overgrown causing benign callus-like growths. * Pleural plaques: discrete fibrous or partially calcified thickened area which can be seen on X-rays of individuals exposed to asbestos. Although pleural plaques are themselves asymptomatic, in some patients this develops into pleural thickening. * Diffuse pleural thickening: similar to above and can sometimes be associated with asbestosis. Usually no symptoms shown but if exposure is extensive, it can cause lung impairment. * Pneumothorax: Some reports have also linked the condition of pneumothorax to asbestos related diseases. * Malignant mesothelioma: an aggressive and incurable tumour arising from mesothelial cells of the pleura (the lining of the thoracic cavity). ## Safety and exposure prevention[edit] Asbestos exposure becomes an issue if asbestos containing materials become airborne, such as due to deterioration or damage. Building occupants may be exposed to asbestos, but those most at risk are persons who purposely disturb materials, such as maintenance or construction workers. Housekeeping or custodial employees may be at an increased risk as they may potentially clean up damaged or deteriorated asbestos containing materials without knowing that the material contains asbestos. Asbestos abatement or remediation workers and emergency personnel such as firefighters may also become exposed.[17] Asbestos-related diseases have been diagnosed in asbestos workers' family members, and in residents who live close to asbestos mines or processing plants.[18] ### Common building materials containing asbestos[edit] Currently in the United States, several thousand products manufactured and/or imported today still contain asbestos.[citation needed] In many parts of the industrialized world, particularly the European Union, asbestos was phased out of building products beginning in the 1970s with most of the remainder phased out by the 1980s. Even with an asbestos ban in place, however, asbestos may be found in many buildings that were built and/or renovated from the late 1800s through the present day. Residential building materials containing asbestos include a variety of products, such as: stipple used in textured walls and ceilings; drywall joint filler compound; asbestos contaminated vermiculite, vinyl floor tile; vinyl sheet flooring; window putty; mastic; cement board; asbestos cement pipes and flues; furnace tape; and stucco. Asbestos is widely used in roofing materials, mainly corrugated asbestos cement roof sheets and asbestos shingles sometimes called transite. Other sources of asbestos-containing materials include fireproofing and acoustic materials.[19] ### Identification and assessment[edit] A fiber cannot be identified or ruled out as asbestos, either using the naked eye or by simply looking at a fiber under a regular microscope. The most common methods of identifying asbestos fibers are by using polarized light microscopy (PLM) or transmission electron microscopy (TEM). PLM is less expensive, but TEM is more precise and can be used at lower concentrations of asbestos. If asbestos abatement is performed, completion of the abatement is verified using visual confirmation and may also involve air sampling. Air samples are typically analyzed using phase contrast microscopy (PCM). PCM involves counting fibers on a filter using a microscope. Airborne occupational exposure limits for asbestos are based on using the PCM method. The American Conference of Governmental Industrial Hygienists has a recommended Threshold Limit Value (TLV) for asbestos of 0.1 fibers/mL over an 8-hour shift. OSHA in the United States and occupational health and safety regulatory jurisdictions in Canada use 0.1 fibers/mL over an 8-hour shift as their exposure limits.[20] ### Environmental asbestos[edit] Asbestos can be found naturally in the air outdoors and in some drinkable water, including water from natural sources.[21] Even nonoccupationally exposed members of the human population have tens to hundreds of thousands of asbestos fibers per gram of dry lung tissue, equivalent to millions of fibers in each lung.[22] Asbestos from natural geologic deposits is known as "naturally occurring asbestos" (NOA). Health risks associated with exposure to NOA are not yet fully understood, and current US federal regulations do not address exposure from NOA. Many populated areas are in proximity to shallow, natural deposits which occur in 50 of 58 California counties and in 19 other US states. In one study, data was collected from 3,000 mesothelioma patients in California and 890 men with prostate cancer, a malignancy not known to be related to asbestos. The study found a correlation between the incidence of mesotheliomas and the distance a patient lived from known deposits of rock likely to include asbestos; the correlation was not present when the incidence of prostate cancer was compared with the same distances. The risk of mesothelioma declined by 6% for every 10 km (6.2 mi) that an individual had lived away from a likely asbestos source.[23] Portions of El Dorado County, California are known to contain natural amphibole asbestos formations at the surface.[23][24] The USGS studied amphiboles in rock and soil in the area in response to an EPA sampling study and subsequent criticism of the EPA study. The EPA study was refuted by its own peer reviewers and never completed or published. The study found that many amphibole particles in the area meet the counting rule criteria used by the EPA for chemical and morphological limits, but do not meet morphological requirements for commercial-grade-asbestos. The executive summary pointed out that even particles that do not meet requirements for commercial-grade-asbestos may be a health threat and suggested a collaborative research effort to assess health risks associated with "Naturally Occurring Asbestos." However, the main criticism pointed at EPA was that their testing was conducted in small isolated areas of El Dorado where there were no amphibole asbestos deposits, thus the language regarding amphibole, nonfibrous "particles". Actual surface amphibole deposits in residential areas were ignored for testing purposes. Because of this, no final findings were published by ATSDR.[25] A great deal of Fairfax County, Virginia was also found to be underlaid with tremolite. The county monitored air quality at construction sites, controlled soil taken from affected areas, and required freshly developed sites to lay 6 inches (150 mm) of clean, stable material over the ground.[23] Globally, samples collected from Antarctic ice indicate chrysotile asbestos has been a ubiquitous contaminant of the environment for at least 10,000 years. Snow samples in Japan have shown ambient background levels are one to two orders of magnitude higher in urban than in rural areas. Higher concentrations of airborne asbestos fibers are reported in urban areas where there is more ACM (asbestos containing materials) and mechanisms of release (vehicles braking and weathering of asbestos cement materials); concentrations in the range of 1–20 ng/m3 have been reported. Fibers longer than 5μm are rarely found in rural areas. Ambient concentrations using TEM analysis have been based on mass measurements.[26] ## Biological interactions[edit] ### Mechanisms of carcinogenicity[edit] Stanton and Layard hypothesized in 1977–78 that toxicity of fibrous materials is not initiated by chemical effects;[27] that is, any trigger-effects of asbestos must presumably be physical, such as mechanical damage which might disrupt normal cell activity—especially mitosis. There is experimental evidence that very slim fibers (<60 nm, <0.06 μm in breadth) tangle destructively with chromosomes (being of comparable size).[28][29] This is likely to cause the sort of mitosis disruption expected in cancer. ### Chemistry[edit] Asbestos fibers (SEM micrograph) Individual asbestos fibers are invisible to the unaided human eye because their size is about 3–20 μm wide and can be as slim as 0.01 μm. Fibers ultimately form because when these minerals originally cooled and crystallized, they formed by the polymeric molecules lining up parallel with each other and forming oriented crystal lattices. These crystals thus have three cleavage planes, and in this case, there are two cleavage planes which are much weaker than the third. When sufficient force is applied, they tend to break along their weakest directions, resulting in a linear fragmentation pattern and hence a fibrous form. This fracture process can keep occurring and one larger asbestos fiber can ultimately become the source of hundreds of much thinner and smaller fibers. When fibers or asbestos structures from asbestos containing materials (ACM) become airborne, the process is called primary release. Primary release mechanisms include abrasion, impaction, fallout, air erosion, vibration, and fire damage. Secondary release occurs when settled asbestos fibers and structures are resuspended as a result of human activities. In unoccupied buildings or during unoccupied periods, fiber release typically occurs by fallout or is induced by vibration or air erosion.[26] Friability of a product containing asbestos means that it is so soft and weak in structure that it can be broken with simple finger crushing pressure. Friable materials are of the most initial concern because of their ease of damage. The forces or conditions of usage that come into intimate contact with most non-friable materials containing asbestos are substantially higher than finger pressure. ### Smoking and asbestos[edit] Smoking has a supra-additive effect in increasing the risk of lung cancer in those exposed to asbestos.[30] Studies have shown an increased risk of lung cancer among smokers who are exposed to asbestos compared to nonsmokers.[31] ## History of health concerns and regulation[edit] For additional chronological citations, see also, List of asbestos disease medical articles ### Until 1900[edit] Early concern in the modern era on the health effects of asbestos exposure can be found in several sources. Among the earliest were reports in Britain. The annual reports of the Chief Inspector of Factories in 1898 included a report from Lucy Deane which stated that asbestos had "easily demonstrated" health risks.[32][33] At about the same time, what was probably the first study of mortality among asbestos workers was reported in France.[34] While the study describes the cause of death as chalicosis, a generalized pneumoconiosis, the circumstances of the employment of the fifty workers whose death prompted the study suggest that the root cause was asbestos or mixed asbestos-cotton dust exposure. ### 1900s–1910s[edit] Micrograph demonstrating asbestosis of the lung (ferruginous bodies). H&E stain. Awareness of asbestos-related diseases can be found in the early 1900s, when London doctor H. Montague Murray conducted a post mortem exam on a young asbestos factory worker who died in 1899. Dr. Murray gave testimony on this death in connection with an industrial disease compensation hearing. The post-mortem confirmed the presence of asbestos in the lung tissue, prompting Dr. Murray to express as an expert opinion his belief that the inhalation of asbestos dust had at least contributed to, if not actually caused, the death of the worker.[35] The record in the United States was similar. Early observations were largely anecdotal in nature and did not definitively link the occupation with the disease, followed by more compelling and larger studies that strengthened the association. One such study, published in 1918, noted: All of these processes unquestionably involve a considerable dust hazard, but the hygienic aspects of the industry have not been reported upon. It may be said, in conclusion, that in the practice of American and Canadian life insurance companies, asbestos workers are generally declined on account of the assumed health-injurious conditions of the industry.[36] ### 1920s–1930s[edit] Widespread recognition of the occupational risks of asbestos in Britain was reported in 1924 by a Dr. Cooke, a pathologist, who introduced a case description of a 33-year-old female asbestos worker, Nellie Kershaw, with the following: "Medical men in areas where asbestos is manufactured have long suspected the dust to be the cause of chronic bronchitis and fibrosis ..."[37] Dr. Cooke then went on to report on a case in 1927 involving a 33-year-old male worker who was the only survivor out of ten workers in an asbestos carding room. In the report he named the disease "asbestosis".[38] Dr. Cooke's second case report was followed, in the late 1920s, by a large public health investigation (now known as the Merewether report after one of its two authors) that examined some 360 asbestos-textile workers (reported to be about 15% of the total comparable employment in Britain at the time) and found that about a quarter of them suffered from pulmonary fibrosis.[39] This investigation resulted in improved regulation of the manufacturing of asbestos-containing products in the early 1930s. Regulations included industrial hygiene standards, medical examinations, and inclusion of the asbestos industry into the British Workers' Compensation Act.[40] The first known U.S. workers' compensation claim for asbestos disease was in 1927. In 1930, the first reported autopsy of an asbestosis sufferer was conducted in the United States and later presented by a doctor at the Mayo Clinic, although in this case the exposure involved mining activities somewhere in South America.[41] In 1930, the major asbestos company Johns-Manville produced a report, for internal company use only, about medical reports of asbestos worker fatalities.[42] In 1932, a letter from U.S. Bureau of Mines to asbestos manufacturer Eagle-Picher stated, in relevant part, "It is now known that asbestos dust is one of the most dangerous dusts to which man is exposed."[43] In 1933, Metropolitan Life Insurance Co. doctors found that 29% of workers in a Johns-Manville plant had asbestosis.[42] Likewise, in 1933, Johns-Manville officials settled lawsuits by 11 employees with asbestosis on the condition that the employees' lawyer agree to never again "directly or indirectly participate in the bringing of new actions against the Corporation."[43] In 1934, officials of two large asbestos companies, Johns-Manville and Raybestos-Manhattan, edited an article about the diseases of asbestos workers written by a Metropolitan Life Insurance Company doctor. The changes downplayed the danger of asbestos dust.[43] In 1935, officials of Johns-Manville and Raybestos-Manhattan instructed the editor of Asbestos magazine to publish nothing about asbestosis.[43] In 1936, a group of asbestos companies agreed to sponsor research on the health effects of asbestos dust, but required that the companies maintain complete control over the disclosure of the results.[42] ### 1940s[edit] In 1942, an internal Owens-Corning corporate memo referred to "medical literature on asbestosis ... scores of publications in which the lung and skin hazards of asbestos are discussed."[42] Testimony given in a federal court in 1984 by Charles H. Roemer, formerly an employee of Unarco, described a meeting in the early 1940s between Unarco officials, J-M President Lewis H. Brown and J-M attorney Vandiver Brown. Roemer stated, "I'll never forget, I turned to Mr. Brown, one of the Browns made this crack (that Unarco managers were a bunch of fools for notifying employees who had asbestosis), and I said, 'Mr. Brown, do you mean to tell me you would let them work until they dropped dead?' He said, 'Yes. We save a lot of money that way.'"[44] In 1944, a Metropolitan Life Insurance Company report found 42 cases of asbestosis among 195 asbestos miners.[42] ### 1950s[edit] In 1951, asbestos companies removed all references to cancer before allowing publication of research they sponsored.[45] In 1952, Dr. Kenneth Smith, Johns-Manville medical director, recommended (unsuccessfully) that warning labels be attached to products containing asbestos. Later, Smith testified: "It was a business decision as far as I could understand ... the corporation is in business to provide jobs for people and make money for stockholders and they had to take into consideration the effects of everything they did and if the application of a caution label identifying a product as hazardous would cut into sales, there would be serious financial implications."[46] In 1953, National Gypsum's safety director wrote to the Indiana Division of Industrial Hygiene, recommending that acoustic plaster mixers wear respirators "because of the asbestos used in the product." Another company official noted that the letter was "full of dynamite" and urged that it be retrieved before reaching its destination. A memo in the files noted that the company "succeeded in stopping" the letter, which "will be modified."[47] ### 1960s–1980s[edit] Through the 1970s, asbestos was used to fireproof roofing and flooring, for heat insulation, and for a variety of other purposes. The material was used in fire-check partitioning and doors on North Sea Oil Production Platforms and Rigs. During the mid-to late 1980s, public health concern focused on potential asbestos fiber exposures of building occupants and workers in buildings containing asbestos containing building materials (ACBM) and their risks of developing lung cancer or mesothelioma. As a consequence, the Health Effects Institute (Cambridge, MA) convened a panel to evaluate the lifetime cancer risk of general building occupants as well as service workers.[48] ### Modern regulation[edit] Main article: Asbestos and the law #### United States[edit] Researcher using a fiber length classifier to produce length-selected fibers of asbestos for toxological studies. The United States remains one of the few developed countries to not completely ban asbestos.[49] While it is banned its use for certain items, it is legal for use in products such as clothing, pipeline wraps, vinyl floor tiles, millboards, cement pipes, disk brake pads, gaskets and roof coatings.[50] In 1989 the EPA issued the Asbestos Ban and Phase Out Rule but in 1991, asbestos industry supporters challenged and overturned the ban in a landmark lawsuit: Corrosion Proof Fittings v. the Environmental Protection Agency. Although the case resulted in several small victories for asbestos regulation, the EPA ultimately did not put an end to asbestos use. This ruling leaves many consumer products that can still legally contain trace amounts of asbestos. For a clarification of products which legally contain asbestos, read the EPA's clarification statement.[51] In 2010, Washington State banned asbestos in automotive brakes starting in 2014.[52] The Occupational Safety and Health Administration (OSHA), has set limits of 100,000 fibers with lengths greater than or equal to 5 μm per cubic meter of workplace air for eight-hour shifts and 40-hour work weeks.[53] #### Canada[edit] In Canada, asbestos is not presently banned,[54] though its use has declined since the mid-1970s and early 1980s. Products containing asbestos are regulated by the Asbestos Products Regulation (SOR 2007/260).[55] On December 16, 2016, parliament stated that as of 2018, all use of asbestos will be totally banned. #### United Kingdom[edit] In the United Kingdom, blue and brown asbestos materials were banned outright in 1985 while the import, sale and second hand reuse of white asbestos was outlawed in 1999. The 2012 Control of Asbestos Regulations state that owners of non-domestic buildings (e.g., factories and offices) have a "duty to manage" asbestos on the premises by making themselves aware of its presence and ensuring the material does not deteriorate, removing it if necessary. Employers, e.g. construction companies, whose operatives may come into contact with asbestos must also provide annual asbestos training to their workers.[56] #### New Zealand[edit] In 1984, the import of raw amphibole (blue and brown) asbestos into New Zealand was banned. In 2002 the import of chrysotile (white) asbestos was also banned.[57] In 2015 the government announced that the importation of asbestos would be completely banned with very limited exceptions (expected to be applied to replacement parts for older machines) that would be reviewed on a case-by-case basis.[58] North-west of Nelson, in the Upper Takaka Valley is New Zealand's only commercially harvested asbestos mine. A low-grade Chrysotile was mined here from 1908 to 1917 but only 100 tons was washed and taken out by packhorse. A new power scheme enabled work to renew and between 1940 and 1949, 40 tons a month was mined by the Hume Company. This continued to 1964, when, due to the short length of its fibre, the limited commercial viability forced mining to cease.[59][60] #### Australia[edit] Asbestos Products Ltd exporting asbestos The use of crocidolite (blue) asbestos was banned in 1967, while the use of amosite (brown) asbestos continued in the construction industry until the mid-1980s. It was finally banned from building products in 1989, though it remained in gaskets and brake linings until 31 December 2003, and cannot be imported, used or recycled.[61][62] Asbestos continues to be a problem. Two out of three homes in Australia built between World War II and the early 1980s still contain asbestos.[63] The union that represents workers tasked with modifying electrical meter boxes at residences stated that workers should refuse to do this work until the boxes have been inspected for asbestos,[64] and the head of the Australian Council of Trade Unions (ACTU) has called on the government to protect its citizens by ridding the country of asbestos by 2030.[65] Handlers of asbestos materials must have a B-Class license for bonded asbestos and an A-Class license for friable asbestos. The town of Wittenoom, in Western Australia was built around a blue asbestos mine. The entire town continues to be contaminated, and has been disincorporated, allowing local authorities to remove references to Wittenoom from maps and roadsigns. #### Brazil[edit] Despite the mining and use of asbestos reaching the country's Supreme Court, Brazil is the world's third-largest producer and exporter of chrysotile asbestos.[66] São Paulo State law 12.684/07 prohibits the use of any product which utilizes asbestos but many buildings are still constructed of products containing asbestos. As a result, it is estimated that up to 15,000 Brazilians die each year of exposure to asbestos.[67] #### Japan[edit] Revelations that hundreds of workers had died in Japan over the previous few decades from diseases related to asbestos sparked a scandal in mid-2005.[68] Tokyo had, in 1971, ordered companies handling asbestos to install ventilators and check health on a regular basis; however, the Japanese government did not ban crocidolite and amosite until 1995, and a near complete ban with a few exceptions on asbestos was implemented in 2006, with the remaining exceptions being removed in March 2012 for a full-fledged ban.[69] #### South Korea[edit] In May 1997, the manufacture and use of crocidolite and amosite, commonly known as blue and brown asbestos, were fully banned in South Korea.[70] In January 2009, a full-fledged ban on all types of asbestos occurred when the government banned the manufacture, import, sale, storage, transport or use of asbestos or any substance containing more than 0.1% of asbestos.[71] In 2011, South Korea became the world's sixth country to enact an asbestos harm aid act, which entitles any Korean citizen to free lifetime medical care as well as monthly income from the government if he or she is diagnosed with an asbestos-related disease.[72] #### Singapore[edit] Use of all types of asbestos has been banned in Singapore since 1989. Currently, only removal of asbestos-containing materials is allowed in Singapore and the Ministry of Manpower must be notified before work commences. #### Turkey[edit] A complete ban on asbestos in Turkey went into effect in 2011.[73] Finland The manufacture and import of asbestos containing building materials was banned from 1993 onwards, while the selling and use of such materials was banned from 1994.[74] ### Delayed recognition[edit] Soviet made asbestos, after 1983. No EHS information. In a 1998 paper, medical historian Peter Bartrip examines why awareness and legislation appear to have lagged unduly, compared to evidence of the risks of asbestos.[75] The paper concludes by agreeing with a previous paper ('Asbestos: a chronology of its origins and health effects', British Journal of Independent Medicine, 1990) and the 1930 report of Edward Mereweather (a factory medical inspector involved in the legislative investigations of the time), that despite theories suggesting a coverup and historical evidence that could be cobbled together after the fact, it is more likely that the issue was one of hindsight. According to Bartrip, Mereweather's 1930 report identified six relevant issues:[75]:p.422 1. Significant commercial exploitation of asbestos was still relatively new. 2. The industry was small and employed comparatively few workers, particularly in dusty processes. 3. The disease developed slowly and unobtrusively. 4. The disease was easily confused with tuberculosis. 5. Affected workers left the industry and therefore fell out of sight of Factory Inspectors. (Gee, below, states that studies "focused on factories, rather than users") 6. Medical research had concentrated on dusts containing free silica. There had been earlier discussion, notably a few brief comments by Factory Inspectors Adelaide Anderson and Edgar Collis during 1898–1911, described by Bartrip as minor reports of no great substance in otherwise very large reports about factory workers.[75]:p.423–424 As a result, he concludes that between 1898 and the late 1920s, all that can be said is that, "the dangers of the material were slowly beginning to be appreciated".[75]:p.423–424 As of 1927, the Senior Medical Inspector had reported that the effect of asbestos dust inhalation "was as yet imperfectly understood".[75]:p.422–423 A second paper, by Gee & Greenberg, noted additional factors:[76] 1. The discovery of carcinogenicity of smoking at approximately the same time as the 1950s asbestos studies, had made it far harder to prove a proposed causative link for asbestos. 2. Anecdotal evidence and hearsay noted by local doctors and inspectors, was not pursued or taken seriously. 3. "Negative" cancer studies were used, which are poor at detecting statistically significant pathology rates unless they include follow-up for around 30 years. 4. A "latency lacuna" exists and contributes to complacency (also reported by Knox 1965) – as the consequences of exposure take decades to arise, by the time they occur it is possible to argue convincingly that "standards have improved" and that therefore the risk is eliminated; however this in turn is not confirmed for another 30 years by which time the same argument can be raised again. Compared to short-term needs, a "speculative" risk not yet confirmed may carry less weight, until long after the time when action could be taken. 5. Long term surveys and sanction regimes failed to match short term pressures within politics, nor those within industry; in the case of asbestos they were inadequate. 6. Fallacious arguments were used, such as the observation that many asbestos workers remained healthy into old age as evidence of lack of risk or lack of harm. As even the most harmful occupation can have numerous apparent healthy survivors this is an example of "absence of evidence" being interpreted as "evidence of absence". 7. As late as 1967, even The Lancet was capable of writing that "it would be ludicrous to outlaw this valuable and often irreplaceable material in all circumstances (as) asbestos can save more lives than it can possibly endanger". ## Litigation[edit] The examples and perspective in this section may not represent a worldwide view of the subject. You may improve this section, discuss the issue on the talk page, or create a new section, as appropriate. (February 2010) (Learn how and when to remove this template message) Main article: Asbestos and the law Litigation related to asbestos is regarded as one of the largest litigation cases in legal history in terms of duration, claim size, and scope. Factors responsible for this include: 1. Asbestos use was extremely widespread: It was used across many sectors, countries, industries and uses. It was also widespread in society itself, being used not in limited "niche" areas but within many everyday products, in housing, fire protection, and even decorative material such as Artex, as well as numerous other ways. Over 50% of homes in some countries contained asbestos even after its ban there.[77] So it was somewhat ubiquitous; 2. Knowledge or suspicion of health issues existed for a long time: The health issues related to asbestos were known, suspected, or reported, for decades, with modern medical coverage dating back to the 19th century. 3. Impact was severe, and included factors that tend to lead to high claims: serious and fatal disease; also apart from death the costs include long term care and disability, care costs, lifetime loss of income, and other high value compensations. 4. Relatively easy to be at risk: asbestos-related diseases are caused by inhaling tiny airborne fibers, therefore any activity related to asbestos that led to loose dust or fibers could potentially cause disease (Secondary asbestosis). As a result, illness occurred not only in the widespread primary industries using asbestos, such as the asbestos mining and processing businesses, but also across industries that might handle their products (construction and demolition, repairs, fire safety), persons who disturbed asbestos products in their homes or workplaces, and even those who laundered clothing used by asbestos workers.[78] 5. Illnesses arise long after exposure: asbestos related diseases can arise decades after actual exposure. 6. Asbestos industry alleged misconduct: alleged concealing, distorting, and suppressing of risk related information, by asbestos related businesses. As of 1999[update], trends indicate that the worldwide rate at which people are diagnosed with asbestos-related diseases will likely increase through the next decade.[79][80] Analysts have estimated that the total cost of asbestos litigation in the USA alone is over $250 billion.[81] In the United Kingdom, more people died in 2011 from asbestos-related causes (4721) than in all types of traffic and transport accidents combined, and new reported cases were estimated at 2126.[82] In the United States, asbestos litigation is the longest, most expensive mass tort in U.S. history, involving more than 8,400 defendants and 730,000 claimants as of 2002 according to the RAND Corporation,[83] and at least one defendant reported claim counts in excess of $800,000 in 2006.[84] The federal legal system in the United States has dealt with numerous counts of asbestos-related suits, which often included multiple plaintiffs with similar symptoms. In 1999 there were 200,000 related cases pending in the federal court system of the United States.[85] Further, it is estimated that within the next 40 years, the number of cases may increase to 700,000. These numbers help explain how there are thousands of current pending cases. Litigation of asbestos materials has been slow. Companies sometimes counter saying that health issues do not currently appear in their worker or workers, or sometimes are settled out of court.[86] The volume of the asbestos liability has concerned manufacturers and insurers and reinsurers.[87] The amounts and method of allocating compensation have been the source of many court cases, and government attempts at resolution of existing and future cases. In 1999 the United States considered but did not enact the Fairness in Asbestos Compensation Act.[88] Between 1981 and the present, many asbestos companies have filed for bankruptcy.[89] While companies filed for bankruptcy, this limited payouts to those who were actually affected by the material. Christopher Edley, Jr. commented what the 1999 act ultimately would have done if passed would be to "limit punitive damages that seek retribution for the decisions of long-dead executives for conduct that took place decades ago."[88] Litigation exists outside the United States in England, Scotland, Ireland, the Netherlands, France, Italy, and Japan among other nations (though the amounts awarded in these countries are not as large as in the US). See the companion article for further information. In Australia a significant and controversial case was brought against the industrial building materials company James Hardie, which had mined and sold asbestos related products for many years. ## Criticisms of asbestos regulation[edit] Criticisms of regulation include the discredited suggestion by Dixy Lee Ray that the Space Shuttle Challenger disintegrated because the maker of O-ring putty was pressured by the EPA into ceasing production of asbestos-laden putty.[90][91] However, the putty used in Challenger's final flight contained asbestos, and failures in the putty were not responsible for the failure of the O-ring that led to loss of the shuttle.[91][92] Asbestos was also used in the first forty floors of the World Trade Center north tower causing an airborne contamination among lower Manhattan after the towers collapsed in the September 11 attacks, causing Steven Milloy of the libertarian Cato Institute to suggest that the World Trade Center towers could still be standing or at least would have stood longer had a 1971 ban not stopped the completion of the asbestos coating above the 64th floor.[93][94] This was not considered in the National Institute of Standards and Technology's report on the towers' collapse, on the basis that all fireproofing materials, regardless of their construction, are required to obtain a fire-resistance rating prior to installation, and all fiber-based lightweight commercial spray fireproofing materials are vulnerable to the dispersive effects of high speed/high energy impacts, as these are outside the fire testing upon which all ratings are based. Therefore, asbestos would have made little or no difference in preventing the towers' collapse, if used as fireproofing, and upon collapse any asbestos, however used, would still have been largely dispersed into the air within the massive dust cloud.[95][96][97] ## References[edit] 1. ^ Asbestos: elimination of asbestos-related diseases. World Health Organization. July 2014 2. ^ Straif, K; Benbrahim-Tallaa, L; Baan, R; Grosse, Y; Secretan, B; El Ghissassi, F; Bouvard, V; Guha, N; Freeman, C; Galichet, L; Cogliano, V; WHO International Agency for Research on Cancer Monograph Working Group (2009). "A review of human carcinogens—Part C: Metals, arsenic, dusts, and fibres" (PDF). The Lancet. Oncology. 10 (5): 453–4. doi:10.1016/S1470-2045(09)70134-2. PMID 19418618. 3. ^ Collegium Razmzzini 2010 Statement on Asbestos. collegiumramazzini.org 4. ^ ATSDR – Asbestos – Health Effects. (1 April 2008). ATSDR Home. 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Retrieved 12 January 2010. 92. ^ Oberg, James (25 January 2011) 7 myths about the Challenger shuttle disaster. NBC News 93. ^ Milloy, Steven (18 January 2007) The Junkman's Answer to Terrorism: Use More Asbestos Archived 2013-05-13 at the Wayback Machine. prwatch.org. 2001 94. ^ Milloy, Steven (18 January 2007) Asbestos Fireproofing Might Have Prevented World Trade Center Collapse. Fox News Channel. 95. ^ Asbestos and the WTC collapse. info-pollution.com 96. ^ Wright, R. N. (2003) "Center for Fire Research in the 70s", pp. 9–19 in Building and Fire Research at NBS/NIST, 1975–2000. NIST 97. ^ Eagar, Thomas W.; Musso, Christopher (2001). "Why Did the World Trade Center Collapse? Science, Engineering, and Speculation". JOM. 53 (12): 8–11. Bibcode:2001JOM....53l...8E. doi:10.1007/s11837-001-0003-1. ## External links[edit] Wikimedia Commons has media related to Health impact of asbestos. * About Your House – General Series – Asbestos * British Government Health and Safety Executive (HSE) essential guides * Hazards magazine's comprehensive asbestos resource pages * The Miracle Mineral Fiber – Asbestos * Asbestos: Magic mineral or deadly dust?, CBC Digital Archives * About Asbestos (2006), European Agency for Safety and Health at Work (OSHA) * A USGS map of "Naturally Occurring Asbestos" in Eastern America * Occupational exposure to asbestos and man-made vitreous fibres and risk of lung cancer: a multicenter case-control study in Europe, Rafael Carel et al. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Health impact of asbestos	None	26,983	wikipedia	https://en.wikipedia.org/wiki/Health_impact_of_asbestos	2021-01-18T18:56:43	{"wikidata": ["Q30314121"]}
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: "Numerophobia" – news · newspapers · books · scholar · JSTOR (April 2016) (Learn how and when to remove this template message) Numerophobia Other namesMath anxiety SpecialtyPsychiatry Numerophobia, arithmophobia or mathematics anxiety is an anxiety disorder,[1][2][page needed] where the condition is fear of dealing with numbers or mathematics. Sometimes numerophobia refers to fear of particular numbers.[3][4] ## Fears of specific numbers[edit] * Tetraphobia – Fear of 4 * Triskaidekaphobia – Fear of 13 * Heptadecaphobia \- Fear of 17 * 23 enigma – Fear of 23 * Hexakosioihekkaidekaphobia \- Fear of 666 ## References[edit] 1. ^ "How to Find Out in Psychology: A Guide to the Literature and Methods of Research", p 119 2. ^ Numerophobia Psychological, disorder (February 2004). Understanding Psychology by Feldman. ISBN 9780070586987. 3. ^ Kerr, Alistair W.; Hall, Howard K.; Kozub, Stephen A. (2002-03-08). Doing Statistics With SPSS. SAGE. p. 3. ISBN 978-1-4462-3071-8. 4. ^ Doctor, Ronald Manual; Kahn, Ada P.; Adamec, Christine A. (2010-05-12). The Encyclopedia of Phobias, Fears, and Anxieties, Third Edition. Infobase Publishing. p. 361. ISBN 978-1-4381-2098-0. * v * t * e Superstition Main topics * Amulet * Evil eye * Luck * Omen * Talismans * Myth and ritual Lists * List of superstitions * List of lucky symbols * List of bad luck signs * Sailors' superstitions * Theatrical superstitions Africa * Buda * Gris-gris * Sampy * Sleeping child Americas * Ascalapha odorata * Carranca * Cooties * Curupira * Djucu * Fortune cookie * Groundhog Day * I'noGo tied * Oscar love curse * Susto * White lighter myth * Witch window Asia * Superstition in India * Superstition in Pakistan * Japanese superstitions * Bhoot (ghost) * Chhaupadi * Churel * Ghosts in Bengali culture * Jackal's horn * Kuai Kuai culture * Muhurta * Navaratna * Nazar battu * Pichal Peri * Puppy pregnancy syndrome * Akabeko * Kanai Anzen * Maneki-neko * Okiagari-koboshi * Omamori * Fan death * Agimat * Arbularyo * Barang * Kulam * Lihi * Pagtatawas * Pasma * Usog * Kuman Thong * Palad khik * Takrut * Nang Kwak * White elephant * Curse of 39 * Jin Chan * Numbers in Chinese culture * Superstitions of Malaysian Chinese Europe * August curse * Barbary macaques in Gibraltar * Bayern-luck * Blarney Stone * Cimaruta * Cornicello * The Goodman's Croft * Himmelsbrief * Icelandic magical staves * In bocca al lupo * Kitchen witch * Klabautermann * Mooncalf * Nazar * Need-fire * Painted pebbles * Powder of sympathy * Rabbit rabbit rabbit * Ravens of the Tower of London * Russian traditions and superstitions * Spilling water for luck * The Scottish Play * Troll cross * Tycho Brahe days * Witch post * Wolfssegen General * 11:11 * 4 (Four-leaf clover, Tetraphobia) * 7 (Seventh son of a seventh son) * 8 * 9 * 13 (Friday the 13th, The Thirteen Club, Thirteenth floor, Triskaidekaphobia) * 108 * 111 * 666 (Number of the Beast) * Ace of spades * Auspicious wedding dates * Baseball superstition * Beginner's luck * Black cat * Bread and butter * Break a leg * Chain letter * Cramp-ring * Curse * Davy Jones' Locker * Dead man's hand * End-of-the-day betting effect * Fear of frogs * Fear of ghosts * First-foot * Flying Dutchman * Four Eleven Forty Four * Gambler's conceit * Good luck charm * Human sacrifice * Jinx * Knocking on wood * Law of contagion * Literomancy * Lock of hair * Maternal impression * Miasma theory * Nelson * Numismatic charm * Penny * Rabbit's foot * Rainmaking * Ship sponsor * Shoes on a table * Sign of the horns * Something old * Spilling salt * Statue rubbing * Three on a match * Threshold * Toi toi toi * 27 Club * Wishing well * Witch ball * Witching hour Related * Apotropaic magic * Astrology and science * Coincidence * Debunker * Divination * Folk religion * Fortune-telling * Magic and religion * Magical thinking * Numerology * Perceptions of religious imagery in natural phenomena * Post hoc ergo propter hoc * Traditional medicine * Urban legend * Jew * Muslim This article about a mental disorder is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Numerophobia	None	26,984	wikipedia	https://en.wikipedia.org/wiki/Numerophobia	2021-01-18T18:38:40	{"wikidata": ["Q5439400"]}
A rare otorhinolaryngological malformation characterized by a dermoid cyst along the nasal dorsum or glabella, lined by keratinized squamous epithelium and containing intraluminal keratin and mature adnexal structures, such as hair follicles, sebaceous and sweat glands. The majority of nasal dermoid cysts are superficial, rarely they extend intracranially. The cysts are typically benign but are susceptible to recurrent infections that may progress to osteomyelitis, meningitis or an intracranial abscess. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Nasal dermoid cyst	c1833473	26,985	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141103	2021-01-23T18:29:49	{"mesh": ["C563455"], "omim": ["600679"], "umls": ["C1833473"], "icd-10": ["Q18.8"], "synonyms": ["Nasal dermoid sinus cyst"]}
A multiple congenital malformation syndrome characterized by typical facial dysmorphism, myopia and other ocular findings, hearing loss, agenesis of the corpus callosum, low-molecular-weight proteinuria, and variable intellectual disability. Congenital diaphragmatic hernia (CDH) and/or omphalocele are common. ## Epidemiology The prevalence and incidence of Donnai-Barrow syndrome (DBS) are difficult to estimate. Fewer than 50 individuals from about 20 families have been reported. DBS affects all ethnicities; it is more commonly diagnosed in the offspring of consanguineous unions. Males and females are affected equally. ## Clinical description Almost all patients have the following features: agenesis/hypogenesis of the corpus callosum, enlarged anterior fontanelle, marked sensorineural hearing loss and hypertelorism. Characteristic facial features include: down-slanting palpebral fissures, short nose with flat nasal bridge, tall broad forehead, widow's peak in the anterior hairline, and sometimes prominent globes. About 40% of patients have CDH and/or omphalocele. Developmental delay and variable intellectual deficit are frequent. High myopia (> 6 diopters), a distinctive optic nerve head dysgenesis, and an increased risk of retinal detachment may lead to progressive loss of vision. Iris coloboma, Focal segmental glomerulosclerosis and proximal tubule dysfunction (rarely progressing to renal insufficiency) are reported occasionally. ## Etiology DBS is an autosomal recessive disorder caused by loss of function variants in the LRP2 low-density lipoprotein receptor-related protein 2 gene (2q31.1) encoding the protein megalin, expressed on multiple absorptive epithelia, notably in the brain, kidney, and eye. Megalin plays an important role in endocytosis of numerous ligands and in various signaling pathways. ## Diagnostic methods Diagnosis is suggested by a combination of clinical and neuroimaging features along with a typical pattern of low-molecular-weight proteinuria, increased urinary levels of retinol-binding protein (RBP) and RBP/creatinine ratio. The diagnosis is confirmed by molecular genetic testing. ## Differential diagnosis DBS has a characteristic constellation of clinical features limiting differential diagnoses. However, some overlapping signs are found in tetrasomy 12p, Fryns, Chudley-McCullough, Acrocallosal, and Craniofrontonasal syndromes. The renal phenotype partly resembles Dent disease and Lowe syndrome. The ocular phenotype may be suggestive of Stickler syndrome. ## Antenatal diagnosis Detection of hypertelorism, agenesis of the corpus callosum, and either CDH or omphalocele by prenatal imaging should raise suspicion of DBS. Prenatal diagnosis for at-risk pregnancies is possible and requires prior identification of the disease-causing mutation in the family. ## Genetic counseling DBS is an autosomal recessive disorder. Genetic counseling should be provided to parents of affected children and to their relatives. Parents of an affected child are obligate carriers for the disease-causing allele. The sole exception reported to date is a patient with DBS due to uniparental disomy (UPD). ## Management and treatment Regular screening of vision, hearing, and renal function should be established. Corrective lenses, preventive treatment for retinal detachment, and hearing aids and/or cochlear implants may be required. CDH and/or omphalocele, when present, necessitate surgical intervention. Specific adapted education for vision, hearing and intellectual disabilities should be provided as is needed for affected children. ## Prognosis Affected individuals can achieve useful vision and hearing with correction. Overall health status in patients is generally good in childhood and adolescence. End-stage kidney failure is a rare and life-threatening complication. Pre- or peri-natal presentation with diaphragmatic and abdominal wall defects requires surgical intervention and is associated with elevated morbidity and mortality. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Donnai-Barrow syndrome	c1857277	26,986	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2143	2021-01-23T19:06:49	{"gard": ["1899"], "mesh": ["C536390"], "omim": ["222448"], "umls": ["C1857277"], "icd-10": ["Q87.8"], "synonyms": ["DBS/FOAR syndrome", "Diaphragmatic hernia-exomphalos-hypertelorism syndrome", "Diaphragmatic hernia-hypertelorism-myopia-deafness syndrome", "Diaphragmatic hernia-hypertelorism-myopia-hearing loss syndrome", "FOAR syndrome", "Facio-oculo-acoustico-renal syndrome", "Holmes-Schepens syndrome", "Syndrome of ocular and facial anomalies, telecanthus and deafness", "Syndrome of ocular and facial anomalies, telecanthus and hearing loss"]}
Trisomy 17 mosaicism is a chromosomal abnormality in which there are three copies of chromosome 17 in some cells of the body, rather than the usual two copies. Trisomy 17 mosaicism is one of the rarest trisomies in humans. It is often incorrectly called trisomy 17 (also referred to as full trisomy 17), which is when three copies of chromosome 17 are present in all cells of the body. Full trisomy 17 has never been reported in a living individual in the medical literature. Few cases of trisomy 17 mosaicism have been described, most having been detected during pregnancy through a test called amniocentesis. Only a few individuals have had a confirmed diagnosis of trisomy 17 mosaicism after birth. Because the proportion and location of cells with trisomy 17 differs from case to case, the presence and severity of signs and symptoms may vary significantly from person to person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Trisomy 17 mosaicism	c1096168	26,987	gard	https://rarediseases.info.nih.gov/diseases/5317/trisomy-17-mosaicism	2021-01-18T17:57:17	{"mesh": ["C538044"], "umls": ["C1096168"], "orphanet": ["1711"], "synonyms": ["Chromosome 17 duplication", "Trisomy 17", "Chromosome 17 trisomy", "Chromosome 17, trisomy", "Chromosome 17, trisomy mosaicism"]}
## Summary ### Clinical characteristics. GRIN2B-related neurodevelopmental disorder is characterized by mild to profound developmental delay / intellectual disability (DD/ID) in all affected individuals. Muscle tone abnormalities (spasticity and/or hypotonia, occasionally associated with feeding difficulties), as well as epilepsy and autism spectrum disorder (ASD) / behavioral issues, are common. Other infantile- or childhood-onset findings include microcephaly; dystonic, dyskinetic, or choreiform movement disorder; and/or cortical visual impairment. Brain MRI reveals a malformation of cortical development in a minority of affected individuals. To date, fewer than 100 individuals with GRIN2B-related neurodevelopmental disorder have been reported. ### Diagnosis/testing. The diagnosis of a GRIN2B-related neurodevelopmental disorder is established in a proband by identification of either a heterozygous pathogenic variant or exon or whole-gene deletion of GRIN2B on molecular genetic testing. ### Management. Treatment of manifestations: DD/ID, muscle tone abnormalities (spasticity, hypotonia, and feeding difficulties), epilepsy, ASD/behavioral issues, movement disorders, and/or cortical visual impairment are treated as per standard practice. Surveillance: Of clinical manifestations as clinically indicated. ### Genetic counseling. GRIN2B-related neurodevelopmental disorder is inherited in an autosomal dominant manner. All probands reported to date with a GRIN2B-related neurodevelopmental disorder whose parents have undergone molecular genetic testing have the disorder as a result of a de novo GRIN2B pathogenic variant or deletion. Risk to future pregnancies is presumed to be low as the proband most likely has a de novo GRIN2B pathogenic variant or deletion; however, given the theoretic possibility of parental germline mosaicism, recurrence risk to sibs is estimated at 1%, and thus prenatal testing for pregnancies at risk and preimplantation genetic testing may be considered. ## Diagnosis Formal diagnostic criteria for GRIN2B-related neurodevelopmental disorder have not been established. ### Suggestive Findings GRIN2B-related neurodevelopmental disorder should be considered in individuals with the following clinical and/or brain MRI findings. Clinical findings * Mild-to-profound developmental delay (DD) or intellectual disability (ID) AND * Any of the following features presenting in infancy or childhood: * Epilepsy * Autism spectrum disorder / behavioral issues * Microcephaly * Muscle tone abnormalities such as hypotonia (occasionally associated with feeding difficulties) and spasticity * Dystonic, dyskinetic, or choreiform movement disorder * Cortical visual impairment Brain MRI findings. MRI reveals a malformation of cortical development (MCD) consisting of diffuse cortical dysplasia including polymicrogyria (see Polymicrogyria Overview), hypoplastic corpus callosum, enlarged/dysplastic basal ganglia, and hippocampal dysplasia. The MCD can also resemble the tubulinopathies spectrum (see Tubulinopathies Overview). ### Establishing the Diagnosis The diagnosis of a GRIN2B-related neurodevelopmental disorder is established in a proband by identification of either a heterozygous pathogenic variant or exon or whole-gene deletion of GRIN2B on molecular genetic testing (see Table 1). (Note that larger contiguous-gene deletions including but not limited to GRIN2B are not discussed in this GeneReview.) Molecular genetic testing approaches can include use of a multigene panel, chromosomal microarray analysis, and/or more comprehensive genomic testing. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotypes of many disorders with intellectual disability overlap, most children with GRIN2B-related neurodevelopmental disorder are diagnosed by genomic testing. Note: Single-gene testing (sequence analysis of GRIN2B, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended. * An intellectual disability multigene panel that includes GRIN2B and other genes of interest (see Differential Diagnosis) typically provides the best opportunity to identify the genetic cause of the condition at the most reasonable cost while limiting identification of pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For GRIN2B-related disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including GRIN2B) that cannot be detected by sequence analysis. * Comprehensive genomic testing does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is most commonly used; genome sequencing is also possible. 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 GRIN2B-Related Neurodevelopmental Disorder View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method GRIN2BSequence analysis 382/86 4 Gene-targeted deletion/duplication analysis 5 or chromosomal microarray (CMA) 64/86 4 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. For references, see Molecular Genetics, Pathogenic variants. Note: Three additional individuals with contiguous gene deletions (not included in these calculations) have been reported: two with chromosome translocations and one with a chromosome inversion disrupting GRIN2B [Endele et al 2010, Talkowski et al 2012]. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including GRIN2B) that cannot be detected by sequence analysis. The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the 12p13.1 region (which includes GRIN2B). CMA designs in current clinical use target the 12p13.1 region. ## Clinical Characteristics ### Clinical Description GRIN2B-related neurodevelopmental disorder is characterized in all affected individuals by mild to profound developmental delay / intellectual disability (DD/ID). Epilepsy (seen in 51%) and autism spectrum disorder (ASD) and autistic-like behaviors (26%) are common. Other infantile- or childhood-onset findings include microcephaly; muscle tone abnormalities (hypotonia, spasticity); dystonic, dyskinetic, or choreiform movement disorder; and/or cortical visual impairment. To date, fewer than 100 individuals with GRIN2B-related neurodevelopmental disorder have been reported in cohorts of individuals with DD/ID/ASD, early-onset epilepsy, and malformations of cortical development (MCD). Unless otherwise noted, the information in this section is based on extended data of Platzer et al [2017]. Detailed clinical assessment was available for 61 patients, with specification of ID in 54. Brain MRI was performed in 47 patients. #### DD/ID The degree of DD/ID can be severe or profound (61%, 33/54), moderate (24%, 13/54), or mild (15%, 8/54) using standard assessments of psychomotor development or IQ testing. Signs of developmental regression have been noted in four children (7%, 4/61), one of whom had transient regression of language skills at age six years with improvement beginning at age eight years and another who had recurrent periods of global regression starting at age three years. No detailed information is available for the other two children. #### Muscle Tone Abnormalities Hypotonia has been reported in more than half the patients (56%, 34/61). Five (15% of those with muscular hypotonia) required tube feeding. All five of these individuals had severe ID. Spasticity was seen in 14 (23%) of 61 patients, all with severe ID. #### Epilepsy Epilepsy is present in 31 (51%) of 61 of individuals and characterized by the following. Features * Onset is from birth to age nine years. * Seizure frequency ranges from multiple episodes per day to a few seizures per year. * Seizures are refractory to antiepileptic drugs in approximately half of individuals treated. Seizure types * Seizures may be generalized (58%, 18/31) and/or focal (48%, 15/31) and/or epileptic spasms (35%, 11/31) with some patients displaying multiple seizure types over time. * EEG patterns comprise generalized, focal, and multifocal epileptiform activity and/or hypsarrhythmia. Syndromes. Most children with epileptic spasms also show hypsarrhythmia or hypsarrhythmia-like EEG patterns and fulfill diagnostic criteria for West syndrome. #### ASD Autistic features were seen in 16 (26%) of 61 individuals. In addition, in one study of the behavioral phenotype of five individuals with GRIN2B-related neurodevelopmental disorder without ASD, the authors observed hyperactivity, impulsivity, distractibility, stereotypies, short attention span, sleeping problems, and social behavior that is friendly but lacking boundaries [Freunscht et al 2013]. #### Other Microcephaly occurred in 11 (18%) of 61 individuals; all 11 had severe ID. Three of these also had an MCD. Movement disorders (10%, 6/61) included involuntary dystonic, dyskinetic, and/or choreiform movements. Cortical visual impairment (CVI) (8%, 5/61) has been reported in four patients: three also had an MCD, and the fourth, who had a normal brain MRI, was identified in a cohort of individuals with ID and CVI [Bosch et al 2016]. Note: A report of an individual with approximately 50% mosaicism for a GRIN2B pathogenic missense variant in blood (no other tissues were tested) did not provide sufficient clinical information to allow comparison of the phenotype with individuals with a heterozygous germline pathogenic variant [Stosser et al 2018]. #### Brain Imaging A malformation of cortical development (MCD) has been seen in six (13%) of 47 patients; the diffuse cortical dysplasia was consistent with that of polymicrogyria (see Polymicrogyria Overview). Cortical findings included a mixture of large and small gyri separated by shallow sulci (Figure 1). The gray-white border appeared smooth. #### Figure 1. MRI of patients with malformation of cortical development A-D: patient 1; E-H: patient 2; I-L: patient 3; M-P: patient 4; Q-T: patient 5; U-X: patient 6; AA-DD: normal control Other findings included the following: * Hypoplastic corpus callosum of varying degrees * Enlarged and mildly dysplastic basal ganglia * Hippocampal dysplasia with thick leaves and open hilus * Enlarged tecta * Absent septum pellucidum The malformation of cortical development is also consistent with that of tubulinopathies (see Tubulinopathies Overview). The identified individuals with MCD display a very similar degree of severity, and there are no reports of affected individuals with less pronounced malformations of cortical development. Generalized cerebral volume loss indicating cerebral atrophy was seen in four other patients (9%, 4/47). ### Genotype-Phenotype Correlations Variant class and intellectual outcome show a significant correlation: heterozygotes for a GRIN2B pathogenic variant resulting in a null allele (e.g., nonsense or frameshift variants, deletion involving whole exons or the entire gene, translocation and inversion disrupting GRIN2B) tended to display mild or moderate ID, while heterozygotes for pathogenic missense variants displayed severe ID (Fisher's exact test, p=0.0079 ) [Platzer et al 2017]. Missense variants in GRIN2B that cause a malformation of cortical development are located in transmembrane domain M3, in the ligand-binding domain S2, and in the linker between S2 and the transmembrane domain M4, a finding consistent with GRIN1 variants causing an MCD [Fry et al 2018] (see GRIN1-Related Neurodevelopmental Disorder). ### Penetrance Penetrance of GRIN2B-related neurodevelopmental disorder is thought to be 100%. ### Prevalence The prevalence of GRIN2B-related neurodevelopmental disorder in the general population is unknown. To date, fewer than 100 individuals have been reported. The prevalence of GRIN2B-related neurodevelopmental disorder among individuals with neurodevelopmental disorders and/or childhood-onset epilepsy is around 0.2% [Platzer et al 2017]. ## Differential Diagnosis Phenotypic features associated with heterozygous GRIN2B pathogenic variants are not sufficient to diagnose GRIN2B-related neurodevelopmental disorder. All genes known to be associated with ID, early-onset epileptic encephalopathy, and malformations of cortical development (especially diffuse polymicrogyria and tubulinopathies) should be included in the differential diagnosis of GRIN2B-related neurodevelopmental disorder (see Table 2) as individuals with GRIN2B-related neurodevelopment disorder can present with a combination of clinically unspecific phenotypes such as DD/ID/ASD and/or epilepsy. The underlying genetic causes of these phenotypes comprise a very heterogeneous group of disorders, as is the case with tubulinopathies, polymicrogyria, and their differential diagnoses. ### Table 2. Genes to Consider in the Differential Diagnosis of GRIN2B-Related Neurodevelopmental Disorder View in own window PhenotypeGenes 1GeneReview/OMIM Intellectual disability>180Autosomal dominant: OMIM PS156200 Autosomal recessive: OMIM PS249500 Nonsyndromic, X-linked: OMIM PS309530 Syndromic, X-linked: OMIM PS309510 Early-onset epileptic encephalopathy>50OMIM PS308350 Polymicrogyria~50Polymicrogyria Overview TubulinopathiesTUBA1A TUBA8 TUBB TUBG1 TUBB2A TUBB2B TUBB3Tubulinopathies Overview 1\. See linked GeneReview or OMIM phenotypic series entry for further information. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with GRIN2B-related neurodevelopmental disorder, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to diagnosis) are recommended. ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with GRIN2B-Related Neurodevelopmental Disorder View in own window System/ConcernEvaluationComment OcularOphthalmologicAssess for cortical visual impairment. Gastrointestinal/ FeedingFeeding, nutrition status, weight gainDetermine if tube feeding is required. MusculoskeletalClinical evaluation for tone abnormalitiesAssess for muscular hypotonia &/or spasticity. NeurologicNeurologicIncl clinical evaluation for movement disorders, EEG, brain MRI Psychiatric/ BehavioralNeuropsychiatricFor individuals age >12 mos: screening for behavior concerns incl sleep disturbances, ADHD, anxiety, &/or traits suggestive of ASD Miscellaneous/ OtherDevelopmental assessmentIncl motor, speech/language, general cognitive, vocational skills Consultation w/clinical geneticist &/or genetic counselor ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder ### Treatment of Manifestations ### Table 4. Treatment of Manifestations in Individuals with GRIN2B-Related Neurodevelopmental Disorder View in own window Manifestation/ConcernTreatmentConsiderations/Other Abnormal vision &/or strabismusStandard treatment(s) as recommended by experienced ophthalmologist SeizuresStandard treatment w/AEDs by experienced neurologist 1Many different AEDs may be effective; no one AED has been demonstrated effective specifically for this disorder. Hypotonia, spasticity, & movement disorderStandard treatment(s) as recommended by experienced neurologist AED = antiepileptic drug 1\. Education of parents regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for parents or caregivers of children diagnosed with epilepsy, see Epilepsy & My Child Toolkit. #### 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 United States, 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. #### 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. #### 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 (e.g., medication used to treat ADHD) when necessary. Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist. ### Surveillance ### Table 5. Recommended Surveillance for Individuals with GRIN2B-Related Neurodevelopmental Disorder View in own window System/ConcernEvaluationFrequency OcularOphthalmologicAs clinically indicated GastrointestinalFeeding, nutrition status, weight gain MusculoskeletalMonitor gross & fine motor development in those w/tone abnormalities. NeurologicMonitor treatment effectiveness in those w/seizures, movement disorders, &/or spasticity. PsychiatricBehavioral assessment for anxiety, attention, & aggressive or self-injurious behavior Miscellaneous/ OtherMonitor developmental progress & educational needs. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation In vitro studies on oocytes of Xenopus laevis suggest a beneficial treatment response of pathogenic missense GRIN2B gain-of-function variants to blockers of the N-methyl D-aspartate receptor (e.g., memantine, radiprodil) [Lemke et al 2014, Mullier et al 2017, Platzer et al 2017]. However, a significant clinical benefit from treatment with such compounds has not yet been demonstrated [Platzer 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. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	GRIN2B-Related Neurodevelopmental Disorder	None	26,988	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK501979/	2021-01-18T21:23:47	{"synonyms": ["GRIN2B Encephalopathy"]}
Sexual paraphilia involving feces This article is about the paraphilia. For dung-feeding fungi, see Coprophilous fungi. For the form of Tourette syndrome, see coprolalia. Coprophilia (from Greek κόπρος, kópros—"excrement" and φιλία, philía—"liking, fondness"), also called scatophilia or scat (Greek: σκατά, skatá—"feces"),[1] is the paraphilia involving sexual arousal and pleasure from feces.[2][3] In the Diagnostic and Statistical Manual of Mental Disorders (DSM), published by the American Psychiatric Association, it is classified under 302.89—Paraphilia NOS (Not Otherwise Specified) and has no diagnostic criteria other than a general statement about paraphilias that says "the diagnosis is made if the behavior, sexual urges, or fantasies cause clinically significant distress or impairment in social, occupational, or other important areas of functioning". Furthermore, the DSM-IV-TR notes, "Fantasies, behaviors, or objects are paraphilic only when they lead to clinically significant distress or impairment (e.g. are obligatory, result in sexual dysfunction, require participation of nonconsenting individuals, lead to legal complications, interfere with social relationships)". Although there may be no connection between coprophilia and sadomasochism (SM), the limited data on the former comes from studies of the latter. A study of 164 males in Finland from two SM clubs found that 18.2% had engaged in coprophilia; 3% as a sadist, 6.1% as a masochist, and 9.1% as both.[4] In the study pool 18% of heterosexuals and 17% of homosexuals had tried coprophilia, showing no statistically significant difference between heterosexuals and homosexuals. In a separate article analyzing 12 men who engaged in bestiality, an additional analysis of an 11-man subgroup revealed that six had engaged in coprophilic behavior, compared with only one in the matched control group consisting of 12 SM-oriented males who did not engage in bestiality.[5] ## Cleveland steamer The Cleveland steamer is a colloquial term for a form of coprophilia, where someone defecates on their partner's chest. The term received news attention through its use in a U.S. Congress staff hoax email and being addressed by the United States Federal Communications Commission.[6] ## See also * 2 Girls 1 Cup * Anilingus * Ass to mouth—removing the penis from the passive partner's anus followed by its immediate insertion into the mouth * Coprophagia—the consumption of feces * Dirty Sanchez—an urban legend which involves smearing feces under the nose of the partner in the form of a moustache * Flatulence fetishism * Hot Karl (slang) * Sadomasochism * Scatology * Urolagnia (also known as urophilia)—a paraphilia involving sexual pleasure from urine ## References 1. ^ Holmes, Ronald M. Sex Crimes: Patterns and Behavior. Thousand Oaks: Sage Publications. p. 244. ISBN 0-7619-2417-5. OCLC 47893709. 2. ^ Corsini, Raymond J. (2002). The Dictionary of Psychology. Philadelphia: Brunner-Routledge. p. 224. ISBN 1-58391-328-9. OCLC 48932974. 3. ^ Flora, Rudy (2001). How to Work with Sex Offenders: A Handbook for Criminal Justice, Human Service, and Mental Health Professionals. New York: Haworth Clinical Practice Press. p. 91. ISBN 0-7890-1499-8. OCLC 45668958. 4. ^ N. Kenneth Sandnabba; Pekka Santtila; Niklas Nordling (August 1999). "Sexual Behavior and Social Adaptation Among Sadomasochistically-Oriented Males". Journal of Sex Research. 36: 273–282. doi:10.1080/00224499909551997. 5. ^ Sandnabba N. K.; Santtila P.; Nordling N.; Beetz A. M.; Alison L. (November 2002). "Characteristics of a Sample of Sadomasochistically-oriented Males with Recent Experience of Sexual Contact with Animals". Deviant Behavior. 23 (6). doi:10.1080/01639620290086503. 6. ^ State Of Shock \| Shock Jocks \| Pop Culture News \| News + Notes \| Entertainment Weekly \| 1 ## Further reading * Fritscher, Jack (1978). "Review of END PRODUCT: THE FIRST TABOO by Dan Sabbath and Mandel Hall, Preface by Abby Rockefeller. URIZEN BOOKS, N.Y., 1977. 287 pp" (PDF). Drummer. No. 22. Retrieved December 28, 2018. * Xavier CM (June 1955). "Coprophilia; a clinical study". Br J Med Psychol. 28 (2–3): 188–90. doi:10.1111/j.2044-8341.1955.tb00893.x. PMID 14389628. ## External links * The dictionary definition of coprophilia at Wiktionary * Media related to Coprophilia at Wikimedia Commons * 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Coprophilia	c0270500	26,989	wikipedia	https://en.wikipedia.org/wiki/Coprophilia	2021-01-18T18:31:18	{"icd-10": ["F65.8"], "wikidata": ["Q464215"]}
Human granulocytic anaplasmosis Other namesHuman granulocytic ehrlichiosis (HGE)[1][2] Anaplasma phagocytophilum cultured in human SpecialtyInfectious disease Human granulocytic anaplasmosis (HGA) is a tick-borne, infectious disease caused by Anaplasma phagocytophilum, an obligate intracellular bacterium that is typically transmitted to humans by ticks of the Ixodes ricinus species complex, including Ixodes scapularis and Ixodes pacificus in North America. These ticks also transmit Lyme disease and other tick-borne diseases.[3] The bacteria infect white blood cells called neutrophils, causing changes in gene expression that prolong the life of these otherwise short-lived cells.[4] ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Major surface proteins * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 History * 7 Epidemiology * 8 Terminology * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] Signs and symptoms may include:[citation needed] * fever * severe headache * muscle aches (myalgia) * chills and shaking, similar to the symptoms of influenza * nausea * vomiting * loss of appetite * unintentional weight loss * abdominal pain * cough * diarrhea, * aching joints * sensitivity to light * weakness * fatigue * change in mental status (extreme confusion, memory loss, inability to comprehend environment- interaction, reading, etc.) * temporary loss of basic motor skills Symptoms may be minor, as evidenced by surveillance studies in high-risk areas. Gastrointestinal tract symptoms occur in less than half of patients and a skin rash is seen in less than 10% of patients.[5] It is also characterized by a low number of platelets, a low number of white blood cells, and elevated serum transaminase levels in the majority of infected patients.[5] Even though people of any age can get HGA, it is usually more severe in the aging or immune-compromised. Some severe complications may include respiratory failure, kidney failure, and secondary infections.[citation needed] ## Cause[edit] A. phagocytophilum is transmitted to humans by Ixodes ticks. These ticks are found in the US, Europe, and Asia. In the US, I. scapularis is the tick vector in the East and Midwest states, and I. pacificus in the Pacific Northwest.[6] In Europe, the I. ricinus is the main tick vector, and I. persulcatus is the currently known tick vector in Asia.[7] The major mammalian reservoir for A. phagocytophilum in the eastern United States is the white-footed mouse, Peromyscus leucopus. Although white-tailed deer and other small mammals harbor A. phagocytophilum, evidence suggests that they are not a reservoir for the strains that cause HGA.[8][9] A tick that has a blood meal from an infected reservoir becomes infected themselves. If an infected tick then latches onto a human the disease is then transmitted to the human host and A. phagocytophilum symptoms can arise.[10] Anaplasma phagocytophilum shares its tick vector with other human pathogens, and about 10% of patients with HGA show serologic evidence of coinfection with Lyme disease, babesiosis, or tick-borne meningoencephalitis.[11] While it is rare, it is possible for HGA to be transmitted human-to-human via a blood transfusion, in which case it is called Transfusion-Transmitted Anaplasmosis (TTA).[12] ### Major surface proteins[edit] Many MSPs are found in Anaplasma and those which interact with Anaplasma can mainly be found in A. marginale and A. phagocytophilum.[13] There are many different phenotypic traits that are associated with MSPs, because each MSP can only infect certain animals in certain conditions.[13] A. phagocytophilum infects the most vast array of living things, including humans, and all around the world.[13] A. marginale evolved to be more specific in infecting animals, such as deer and cattle in the subtropics and tropics.[13] The main difference between these two MSPs is that the host cell for A. phagocytophilum is the granulocyte, while the host cell for A. marginale is erythrocytes.[13] It is likely that these MSPs coevolved, because they had previously interacted via tick-pathogen interaction.[13] Anaplasma MSPs can not only cooperate with vertebrates, but also invertebrates, which make these phenotypes evolve faster than others, because they have a lot of selective forces acting on them.[13] ## Diagnosis[edit] Clinically, HGA is essentially indistinguishable from human monocytic ehrlichiosis, the infection caused by Ehrlichia chaffeensis, and other tick-borne illnesses such as Lyme disease may be suspected.[14] As Ehrlichia serologies can be negative in the acute period, PCR is very useful for diagnosis.[15] ## Prevention[edit] Currently, there is no vaccine against human granulocytic anaplasmosis, so antibiotics are the only form of treatment.[7] The best way to prevent HGA is to prevent getting tick bites.[16] ## Treatment[edit] Doxycycline is the treatment of choice. If anaplasmosis is suspected, treatment should not be delayed while waiting for a definitive laboratory confirmation, as prompt doxycycline therapy has been shown to improve outcomes.[14] Presentation during early pregnancy can complicate treatment. Doxycycline compromises dental enamel during development.[17] Although rifampin is indicated for post-delivery pediatric and some doxycycline-allergic patients, it is teratogenic. Rifampin is contraindicated during conception and pregnancy.[18] If the disease is not treated quickly, sometimes before the diagnosis, the person has a high chance of mortality.[7] Most people make a complete recovery, though some people are intensively cared for after treatment.[7] A reason for a person needing intensive care is if the person goes too long without seeing a doctor or being diagnosed.[7] The majority of people, though, make a complete recovery with no residual damage.[7] ## History[edit] The first outbreak of Human Granulocytic Anaplasmosis (HGA) in the United States was in a patient in early 1990 in Wisconsin. He was kept in the hospital in Minnesota for testing, but died without a diagnosis.[7] Over the next couple of years, many people within the same area of Wisconsin and Minnesota had come down with the same symptoms.[7] It was discovered in 1994 that it was Human Granulocytic Ehrlichiosis (HGE), later to be known as HGA.[10] ## Epidemiology[edit] From the first reported case in 1994 until 2010, HGA's rates of incidence have exponentially increased.[19] This is likely because HGA is found where there are ticks that carry and transmit Lyme disease, also known as Borrelia burgdorferi, and babesiosis, which is found in the northeastern and midwestern United States, which has seemingly increased in the past couple of decades.[19] Before 2000, there were less than 300 cases reported per year. In 2000, there were only 350 reported cases.[19] From 2009-2010, HGA experienced a 52% increase in the number of cases reported.[19] ## Terminology[edit] Although the infectious agent is known to be from the Anaplasma genus, the term "human granulocytic ehrlichiosis" (HGE) is often used, reflecting the prior classification of the organism. E. phagocytophilum and E. equi were reclassified as Anaplasma phagocytophilum.[citation needed] ## See also[edit] * Ehrlichiosis ## References[edit] 1. ^ Malik A, Jameel M, Ali S, Mir S (2005). "Human granulocytic anaplasmosis affecting the myocardium". J Gen Intern Med. 20 (10): C8–10. doi:10.1111/j.1525-1497.2005.00218.x. PMC 1490240. PMID 16191146. 2. ^ "Human Anaplasmosis Basics - Minnesota Dept. of Health". Archived from the original on 2018-03-14. Retrieved 2009-04-13. 3. ^ Holden, K.; Boothby, J. T.; Anand, S.; Massung, R. F. (2003). "Browse BioOne Complete". Journal of Medical Entomology. 40 (4): 534–9. doi:10.1603/0022-2585-40.4.534. ISSN 0022-2585. PMID 14680123. 4. ^ Lee HC, Kioi M, Han J, Puri RK, Goodman JL (September 2008). "Anaplasma phagocytophilum-induced gene expression in both human neutrophils and HL-60 cells". Genomics. 92 (3): 144–51. doi:10.1016/j.ygeno.2008.05.005. PMID 18603403. 5. ^ a b Murray, Patrick R.; Rosenthal, Ken S.; Pfaller, Michael A. Medical Microbiology, Fifth Edition. United States: Elsevier Mosby, 2005 6. ^ Dumler JS, Madigan JE, Pusterla N, Bakken JS (July 2007). "Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment". Clinical Infectious Diseases. 45 (Suppl 1): S45–51. doi:10.1086/518146. PMID 17582569. 7. ^ a b c d e f g h Bakken, Johan S.; Dumler, J. Stephen (2006-10-01). "Clinical Diagnosis and Treatment of Human Granulocytotropic Anaplasmosis". Annals of the New York Academy of Sciences. 1078 (1): 236–247. Bibcode:2006NYASA1078..236B. doi:10.1196/annals.1374.042. ISSN 1749-6632. PMID 17114714. 8. ^ "Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever, Ehrlichioses, and Anaplasmosis --- United States A Practical Guide for Physicians and Other Health-Care and Public Health Professionals". www.cdc.gov. Retrieved 2015-10-21. 9. ^ Massung RF, Courtney JW, Hiratzka SL, Pitzer VE, Smith G, Dryden RL (October 2005). "Anaplasma phagocytophilum in white-tailed deer". Emerging Infectious Diseases. 11 (10): 1604–6. doi:10.3201/eid1110.041329. PMC 3366735. PMID 16318705. 10. ^ a b Dumler, J. Stephen; Choi, Kyoung-Seong; Garcia-Garcia, Jose Carlos; Barat, Nicole S.; Scorpio, Diana G.; Garyu, Justin W.; Grab, Dennis J.; Bakken, Johan S. (2005). "Human Granulocytic Anaplasmosis and Anaplasma phagocytophilum". Emerging Infectious Diseases. 11 (12): 1828–1834. doi:10.3201/eid1112.050898. PMC 3367650. PMID 16485466. 11. ^ Dumler JS, Choi KS, Garcia-Garcia JC, et al. (December 2005). "Human granulocytic anaplasmosis and Anaplasma phagocytophilum". Emerging Infectious Diseases. 11 (12): 1828–34. doi:10.3201/eid1112.050898. PMC 3367650. PMID 16485466. 12. ^ Goel, Ruchika; Westblade, Lars F.; Kessler, Debra A.; Sfeir, Maroun; Slavinski, Sally; Backenson, Bryon; et al. (August 2018). "Death from transfusion-transmitted anaplasmosis". Emerging Infectious Diseases. 24 (8): 1548–1550. doi:10.3201/eid2408.172048. PMC 6056119. PMID 30016241. 13. ^ a b c d e f g de la Fuente, José; Kocan, Katherine M.; Blouin, Edmour F.; Zivkovic, Zorica; Naranjo, Victoria; Almazán, Consuelo; Esteves, Eliane; Jongejan, Frans; Daffre, Sirlei (2010-02-10). "Functional genomics and evolution of tick–Anaplasma interactions and vaccine development". Veterinary Parasitology. Ticks and Tick-borne Pathogens. 167 (2–4): 175–186. doi:10.1016/j.vetpar.2009.09.019. hdl:10261/144221. PMID 19819630. 14. ^ a b Hamburg BJ, Storch GA, Micek ST, Kollef MH (March 2008). "The importance of early treatment with doxycycline in human ehrlichiosis". Medicine. 87 (2): 53–60. doi:10.1097/MD.0b013e318168da1d. PMID 18344803. S2CID 2632346. 15. ^ Prince LK, Shah AA, Martinez LJ, Moran KA (August 2007). "Ehrlichiosis: making the diagnosis in the acute setting". Southern Medical Journal. 100 (8): 825–8. doi:10.1097/smj.0b013e31804aa1ad. PMID 17713310. 16. ^ Wormser, Gary P.; Dattwyler, Raymond J.; Shapiro, Eugene D.; Halperin, John J.; Steere, Allen C.; Klempner, Mark S.; Krause, Peter J.; Bakken, Johan S.; Strle, Franc (2006-11-01). "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases. 43 (9): 1089–1134. doi:10.1086/508667. ISSN 1058-4838. PMID 17029130. 17. ^ Muffly T, McCormick TC, Cook C, Wall J (2008). "Human granulocytic ehrlichiosis complicating early pregnancy". Infect Dis Obstet Gynecol. 2008: 1–3. doi:10.1155/2008/359172. PMC 2396214. PMID 18509484. 18. ^ Krause PJ, Corrow CL, Bakken JS (September 2003). "Successful treatment of human granulocytic ehrlichiosis in children using rifampin". Pediatrics. 112 (3 Pt 1): e252–3. doi:10.1542/peds.112.3.e252. PMID 12949322. 19. ^ a b c d "Statistics \| Anaplasmosis \| CDC". www.cdc.gov. Retrieved 2015-11-08. ## External links[edit] * CDC Emerging Infectious Diseases for more information about HGE Classification D * ICD-10: A79.8 * ICD-9-CM: 083.8 * MeSH: D016873 * DiseasesDB: 31663 External resources * MedlinePlus: 001381 * eMedicine: med/3391 ped/655 emerg/159 * 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 * 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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 * v * t * e Tick-borne diseases and infestations Diseases Bacterial infections Rickettsiales * Anaplasmosis * Boutonneuse fever * Ehrlichiosis (Human granulocytic, Human monocytotropic, Human E. ewingii infection) * Scrub typhus * Spotted fever rickettsiosis * Pacific Coast tick fever * American tick bite fever * rickettsialpox * Rocky Mountain spotted fever) Spirochaete * Baggio–Yoshinari syndrome * Lyme disease * Relapsing fever borreliosis Thiotrichales * Tularemia Viral infections * Bhanja virus * Bourbon virus * Colorado tick fever * Crimean–Congo hemorrhagic fever * Heartland bandavirus * Kemerovo tickborne viral fever * Kyasanur Forest disease * Omsk hemorrhagic fever * Powassan encephalitis * Severe fever with thrombocytopenia syndrome * Tete orthobunyavirus * Tick-borne encephalitis Protozoan infections * Babesiosis Other diseases * Tick paralysis * Alpha-gal allergy * Southern tick-associated rash illness Infestations * Tick infestation Species and bites Amblyomma * Amblyomma americanum * Amblyomma cajennense * Amblyomma triguttatum Dermacentor * Dermacentor andersoni * Dermacentor variabilis Ixodes * Ixodes cornuatus * Ixodes holocyclus * Ixodes pacificus * Ixodes ricinus * Ixodes scapularis Ornithodoros * Ornithodoros gurneyi * Ornithodoros hermsi * Ornithodoros moubata Other * Rhipicephalus sanguineus [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Human granulocytic anaplasmosis	c4476477	26,990	wikipedia	https://en.wikipedia.org/wiki/Human_granulocytic_anaplasmosis	2021-01-18T19:10:23	{"gard": ["71"], "mesh": ["D000712"], "icd-9": ["083.8"], "icd-10": ["A79.8"], "wikidata": ["Q992139"]}
Sneddon syndrome Other namesEhrmann-Sneddon syndrome, Livedo racemosa-cerebrovascular accident syndrome, Livedo reticularis-cerebrovascular accident syndrome[1] This condition is inherited in an autosomal recessive manner[2] SpecialtyRheumatology Sneddon's syndrome[1] is a form of arteriopathy characterized by several symptoms, including: * Severe, transient neurological symptoms or stroke * Livedo reticularis, or livedo racemosa ## Contents * 1 Signs and symptoms * 2 Pathogenesis * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 History * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] Sneddon's syndrome generally manifests with stroke or severe, transient neurological symptoms, and a skin rash (livedo reticularis). Livedo reticularis appears as a bluish-purple, netlike mottling of the skin. Sneddon's syndrome may instead present with livedo racemosa, which involves larger, less organized patches of bluish-purple mottling of the skin. Both are generally found first in the extremities, both worsen in cold and either may occur without Sneddon's Syndrome or any other systemic disease.[citation needed] Sneddon's Syndrome can be characterized by: transient amnesia, transient aphasia, palsy, headaches, hypertension, transient ischemic attacks (TIA), stroke,[3] coronary disease and dementia.[4] The skin manifestations may precede the neurologic symptoms by years.[3] ## Pathogenesis[edit] Sneddon's syndrome is a progressive, noninflammatory arteriopathy leading to the characteristic skin condition and to cerebrovascular problems, including stroke, transient ischemic attack (TIA), severe but transient neurological symptoms thought to be caused by cerebral vasospasm, coronary disease and early-onset dementia. Progressive compromise of arterial linings in Sneddon's produces clotting, for which high-dose warfarin is most commonly prescribed, and can also cause the development of systemic arterial plaque when cholesterol levels are normal.[citation needed] ## Diagnosis[edit] There are no diagnostic tests on which all Sneddon's patients will have abnormal results, although brain MRI and skin biopsy are often abnormal. The diagnosis is based on a detailed history and physical examination. About 40-60% of patients with the syndrome test positive for antiphospholipid antibodies. ## Treatment[edit] Sneddon's patients are generally treated with warfarin, maintaining a high INR of 3-4.[1] Because most will experience significant relief of symptoms after several months of consistent INR in this range, treatment with warfarin is often used as a diagnostic tool. ## Epidemiology[edit] Sneddon's syndrome is a rare condition that is usually misdiagnosed.[3] It occurs in families and may be inherited in an autosomal dominant fashion. Sneddon's Syndrome most often becomes apparent in women in their thirties, though cases do occur in men and in children. Generally, Livedo precedes cerebrovascular involvement by roughly ten years, and many years of cerebrovascular involvement precede the development of dementia, when it occurs.[citation needed] ## History[edit] It is named for Ian Bruce Sneddon.[5][6] In 1965, Dr. Sneddon first reported 6 patients with a distinct skin rash and cerebrovascular accidents (strokes).Sneddon's Syndrome was formerly understood to be a type of autoimmune disease called antiphospholipid syndrome, although it has been reclassified as a noninflammatory cerebrovascular disease. It should be considered in patients diagnosed with vasculitis when standard treatments fail. ## See also[edit] * Livedoid vasculopathy * List of cutaneous conditions ## References[edit] 1. ^ a b c Berlit, Peter. "Sneddon's Syndrome". Orphanet. 2. ^ "OMIM Entry - # 182410 - SNEDDON SYNDROME". omim.org. Retrieved 11 August 2017. 3. ^ a b c Johnson, Klaus Wolff, Richard Allen (2009). Fitzpatrick's color atlas and synopsis of clinical dermatology (6th ed.). New York: McGraw-Hill Medical. p. Section 14. ISBN 978-0071599757. 4. ^ Adams; et al. Principles of Neurology, 6th Edition. p. 861. 5. ^ synd/1732 at Who Named It? 6. ^ Sneddon IB (April 1965). "Cerebrovascular lesions and livedo reticularis". British Journal of Dermatology. 77 (4): 180–185. doi:10.1111/j.1365-2133.1965.tb14628.x. PMID 14278790. ## Further reading[edit] * Schellong S, Weissenborn K, Niedermeyer J, Wollenhaupt J, Sosada M, Ehrenheim C, Lubach D (1997). "Classification of Sneddon's syndrome". Vasa. 26 (3): 215–21. PMID 9286155. ## External links[edit] Classification D * ICD-10: M30.8 (ILDS M30.820) * OMIM: 182410 * MeSH: D018860 * DiseasesDB: 12257 * v * t * e Cerebrovascular diseases including stroke Ischaemic stroke Brain * Anterior cerebral artery syndrome * Middle cerebral artery syndrome * Posterior cerebral artery syndrome * Amaurosis fugax * Moyamoya disease * Dejerine–Roussy syndrome * Watershed stroke * Lacunar stroke Brain stem * Brainstem stroke syndrome * Medulla * Medial medullary syndrome * Lateral medullary syndrome * Pons * Medial pontine syndrome / Foville's * Lateral pontine syndrome / Millard-Gubler * Midbrain * Weber's syndrome * Benedikt syndrome * Claude's syndrome Cerebellum * Cerebellar stroke syndrome Extracranial arteries * Carotid artery stenosis * precerebral * Anterior spinal artery syndrome * Vertebrobasilar insufficiency * Subclavian steal syndrome Classification * Brain ischemia * Cerebral infarction * Classification * Transient ischemic attack * Total anterior circulation infarct * Partial anterior circulation infarct Other * CADASIL * Binswanger's disease * Transient global amnesia Haemorrhagic stroke Extra-axial * Epidural * Subdural * Subarachnoid Cerebral/Intra-axial * Intraventricular Brainstem * Duret haemorrhages General * Intracranial hemorrhage Aneurysm * Intracranial aneurysm * Charcot–Bouchard aneurysm Other * Cerebral vasculitis * Cerebral venous sinus thrombosis * v * t * e Systemic vasculitis Large vessel * Takayasu's arteritis * Giant cell arteritis Medium vessel * Polyarteritis nodosa * Kawasaki disease * Thromboangiitis obliterans Small vessel Pauci-immune * c-ANCA * Granulomatosis with polyangiitis * p-ANCA * Eosinophilic granulomatosis with polyangiitis * Microscopic polyangiitis Type III hypersensitivity * Cutaneous small-vessel vasculitis * IgA vasculitis Ungrouped * Acute hemorrhagic edema of infancy * Cryoglobulinemic vasculitis * Bullous small vessel vasculitis * Cutaneous small-vessel vasculitis Other * Goodpasture syndrome * Sneddon's syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Sneddon's syndrome	c0282492	26,991	wikipedia	https://en.wikipedia.org/wiki/Sneddon%27s_syndrome	2021-01-18T18:53:13	{"gard": ["7664"], "mesh": ["D018860"], "umls": ["C0282492"], "icd-10": ["M30.8"], "orphanet": ["820"], "wikidata": ["Q684840"]}
A number sign (#) is used with this entry because of evidence that Sneddon syndrome (SNDNS) is caused by compound heterozygous mutation in the CECR1 gene (ADA2; 607575) on chromosome 22q11. One such family has been reported. Mutation in the ADA2 gene can also cause vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome (VAIHS; 615688), which shows earlier onset. Description Sneddon syndrome is a noninflammatory arteriopathy characterized by onset of livedo reticularis in the second decade and onset of cerebrovascular disease in early adulthood (summary by Bras et al., 2014). Livedo reticularis occurs also with polyarteritis nodosa, systemic lupus erythematosus, and central thrombocythemia, any one of which may be accompanied by cerebrovascular accidents (Bruyn et al., 1987). Clinical Features Sneddon (1965) described 6 patients (5 females, 1 male), varying in age from 20 to 48 years, who had association of livedo reticularis with cerebrovascular accident. Rebollo et al. (1983) reported 8 patients and concluded that the disorder was inherited as an autosomal dominant in 3 of them. Multiple occlusions and medium-sized arteries were demonstrated by cerebral and hand arteriograms. Digital artery biopsies showed intimal hyperplasia in 7 cases and recanalized thrombosis in 1. Rebollo et al. (1983) concluded that the Sneddon syndrome is a genetic progressive arteriopathy, occlusive and noninflammatory, involving medium-sized vessels. Scott and Boyle (1986) reported 2 sibs with the disorder. The 24-year-old proposita had generalized livedo reticularis and progressive intellectual decline. Brain imaging showed multifocal areas of cerebral infarction, occlusive disease of major vessels, and arteriovenous malformation, and moya-moya type anastomoses. Berciano (1988) pointed out that the phenotype may be restricted to an unperceived livedo reticularis and that detailed investigation of relatives had rarely been done or commented on in published reports; hence, the role of genetic factors in this disorder may have escaped attention. Zelger et al. (1993) provided long-term follow-up of 21 patients. They specifically commented that family history was negative in all of them; in the case of 9 of the 21 patients, first- and second-degree relatives had risk factors such as precocious vascular disorders (peripheral occlusive vascular disease, myocardial infarction, or ischemic strokes before age 60 years), but in these patients disease course and intensity were no different from those in the remaining patients. Zelger et al. (1993) considered the disorder to be vasculitic in nature. Kalashnikova et al. (1991) investigated the relationship of Sneddon syndrome to the antiphospholipid syndrome (107320), which in turn is related to systemic lupus erythematosus and other autoimmune disorders that tend to aggregate in families, but provided no genetic information. Pettee et al. (1994) presented the clinical, hematologic, and radiographic findings in 2 brothers with Sneddon syndrome associated with antiphospholipid antibodies. One brother had anticardiolipin antibody and the other had lupus anticoagulant, which was detected only upon repeated blood testing. Pettee et al. (1994) suggested that in familial cases of antiphospholipid antibody syndrome, inherited predisposition is involved in disease pathogenesis. Hilton and Footitt (2003) described the neuropathologic findings in an isolated case of Sneddon syndrome in a 64-year-old man who died of myocardial infarction. Several months before death, the man had suffered several strokes, and physical exam showed 'florid' livedo reticularis affecting his trunk, arms, and legs. He was also found to have a lupus anticoagulant. Histologic examination showed multiple small, predominantly cortical, infarcts, with focal hyperplasia and fibrotic occlusion of arterial vessels in the superficial white matter, cortex, and leptomeninges. Occasional arterial thrombi were seen. The authors concluded that Sneddon syndrome is caused by a noninflammatory arteriopathy affecting superficial cerebral vessels. Mascarenhas et al. (2003) reported 3 Portuguese brothers with Sneddon syndrome. Two presented with ischemic strokes at 28 and 42 years of age, and the third with hemorrhagic strokes at ages 23 and 34 years. A 32-year-old sister was examined, but had no evidence of cerebrovascular events. All patients had normal cerebral angiography. All patients also had persistent violaceous livedo reticularis, primarily on the lower limbs and trunk, that began in the teenage years. Skin biopsy of the reticular pattern showed partial endothelial detachment in dermohypodermic blood vessels in only 1 patient. The 3 brothers had atrophic scars on the lower limbs from seasonal ulceration. A maternal aunt and uncle reportedly had livedo reticularis or livedoid vasculitis. This family had previously been reported by Santo et al. (2002). Legierse et al. (2008) reported 3 unrelated patients with a clinical diagnosis of Sneddon syndrome. All presented in their twenties with focal neurologic signs resulting from intracerebral ischemic attacks. Neurologic symptoms included hemianopsia, headache, hemiplegia, facial paralysis, and dysarthria. All developed livedo racemosa within a few years after onset of neurologic signs and symptoms. Two patients developed hypertension associated with renal dysfunction thought to result from thickened renal vessels. Skin biopsy of 2 patients showed the classic findings of Sneddon syndrome, with small arteries showing intimal proliferation, thickened walls, and occasional occlusion. Immunostaining was positive for smooth muscle cells in the vessels. Skin biopsy in the third patient showed only a few slightly dilated small vessels, but otherwise was normal. Legierse et al. (2008) noted the difficulty of defining the diagnostic criteria of Sneddon syndrome and stated that although there is no gold standard for the diagnosis of this disorder, skin biopsy should be performed. Molecular Genetics In 3 Portuguese sibs with Sneddon syndrome, previously reported by Mascarenhas et al. (2003), Bras et al. (2014) identified compound heterozygous missense mutations in the CECR1 gene (T119A, 607575.0010 and G142S, 607575.0011). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants were not performed. Population Genetics Sneddon syndrome has an incidence of about 4 per million per year. It is more common in women and usually presents in young adulthood (Legierse et al., 2008). Nomenclature Bruyn et al. (1987) stated that in the European literature the term 'livedo reticularis' is used for the cutaneous vascular phenomenon that disappears after the skin is warmed, whereas 'livedo racemosa' is used for the findings that persist after warming. On the other hand, in the American literature, reticulated skin coloration that disappears after warming in infants and young adults is referred to as 'cutis marmorata,' reserving the term 'livedo reticularis' for the permanent change. It should be noted, however, that Sneddon, a British dermatologist, used the term 'livedo reticularis.' INHERITANCE \- Autosomal recessive CARDIOVASCULAR Vascular \- Cerebrovascular ischemic attacks \- Cerebrovascular hemorrhagic attacks \- Hypertension SKIN, NAILS, & HAIR Skin \- Livedo racemosa (usually on trunk and/or lower extremities) \- Erythematous, irregular netlike pattern of vessels Skin Histology \- Intimal proliferation of small arteries \- Occlusion of small arteries NEUROLOGIC Central Nervous System \- Cerebrovascular ischemic attacks, transient (proceed secondary neurologic findings) \- Headaches \- Visual changes \- Hemiplegia \- Dysarthria \- Facial palsy \- Seizures \- Tremor \- Cognitive decline LABORATORY ABNORMALITIES \- Associated with serum anti-phospholipid antibodies in about 50% of patients MISCELLANEOUS \- Incidence of 4 per million per year \- Secondary features include arterial hypertension and renal involvement \- Women are more often affected \- Onset in young adulthood \- Progressive disorder \- One family with confirmed CECR1 mutation has been reported (last curated August 2014) MOLECULAR BASIS \- Caused by mutation in the cat eye syndrome chromosome region, candidate 1 gene (CECR1, 607575.0010 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SNEDDON SYNDROME	c0282492	26,992	omim	https://www.omim.org/entry/182410	2019-09-22T16:34:44	{"doid": ["13096"], "mesh": ["D018860"], "omim": ["182410"], "orphanet": ["820"], "synonyms": ["Alternative titles", "LIVEDO RETICULARIS AND CEREBROVASCULAR ACCIDENTS"]}
Ocular condition of early onset in which one or either eye turns inward Infantile esotropia SpecialtyOphthalmology Infantile esotropia is an ocular condition of early onset in which one or either eye turns inward. It is a specific sub-type of esotropia and has been a subject of much debate amongst ophthalmologists with regard to its naming, diagnostic features, and treatment. ## Contents * 1 Presentation * 1.1 Cross-fixation * 2 Cause * 3 Diagnosis * 3.1 Differential Diagnosis * 4 Treatment * 4.1 Initially * 4.2 Surgery * 5 References * 6 External links ## Presentation[edit] Historically the term 'congenital strabismus' was used to describe constant esotropias with onset between birth and six months of age. However, this term was felt to be an inadequate classification as it covered a variety of esotropias with different causes, features and prognoses. In 1988, American ophthalmologist Gunter K. Von Noorden discussed what he described as 'Essential Infantile Esotropia'.[1] He described the condition as: > "early acquired, not... congenital ..., although congenital factors may favor its development between the ages of 3 and 6 months" and identified this squint sub-type as having the following features: 1. Onset between birth and six months of age. 2. Large size (greater than 30 dioptres) 3. Stable size 4. Not associated with abnormalities of the central nervous system. 5. Often associated with defective abduction (outward movement) and excessive adduction (inward movement) of the eyes. 6. Also associated with oblique muscle dysfunction and Dissociated Vertical Deviation. 7. Initial alternation of the squint present with crossed fixation, i.e. the affected individual uses the left eye to look right and the right eye to look left. 8. Limited potential for binocular vision. The same condition had also previously been described by other ophthalmologists, notably Cianca (1962) who named it Cianca's Syndrome and noted the presence of manifest latent nystagmus, and Lang (1968) who called it Congenital Esotropia Syndrome and noted the presence of abnormal head postures. In both cases, however, the essential characteristics were the same, but with emphasis placed on different elements of the condition. Helveston [2] (1993) further clarified and expanded upon von Noorden's work, and incorporated the work of both Lang and Cianca into his summary of the characteristics of the condition: 1. Esotropia between 10 and 90 dioptres in size 2. Either alternation or fixation preference may be present (if the latter then amblyopia may result). 3. Neurologically normal. 4. Hyperopic correction does not eliminate or significantly reduce the squint size. 5. Frequent nystagmus (latent or manifest latent). 6. The patient may or may not have any or all of the following associated conditions: Oblique muscle dysfunction, vertical incomitance, dissociated vertical deviation, asymmetric optokinetic nystagmus, torticollis. 7. Presence will be 'confirmed' by six months. 8. Best treatment results in subnormal binocular vision. The expressions congenital esotropia, infantile esoptropia, idiopathic infantile esotropia and essential infantile esotropia are often used interchangeably. ### Cross-fixation[edit] Cross-fixation congenital esotropia, also called Cianci's syndrome is a particular type of large-angle infantile esotropia associated with tight medius rectus muscles. With the tight muscles, which hinder adduction, there is a constant inward eye turn. The patient cross-fixates, that is, to fixate objects on the left, the patient looks across the nose with the right eye, and vice versa. The patient tends to adopt a head turn, turning the head to the right to better see objects in the left visual field and turning the head to the left to see those in the right visual field. Binasal occlusion can be used to discourage cross-fixation.[3] However, the management of cross-fixation congenital esotropia usually involves surgery.[4] ## Cause[edit] This remains undetermined at the present time. A recent study by Major et al.[5] reports that: > Prematurity, family history or secondary ocular history, perinatal or gestational complications, systemic disorders, use of supplemental oxygen as a neonate, use of systemic medications, and male sex were found to be significant risk factors for infantile esotropia. Further recent evidence indicates that a cause for infantile strabismus may lie with the input that is provided to the visual cortex.[6] In particular, neonates who suffer injuries that, directly or indirectly, perturb binocular inputs into the primary visual cortex (V1) have a far higher risk of developing strabismus than other infants.[7] ## Diagnosis[edit] ### Differential Diagnosis[edit] Clinically Infantile esotropia must be distinguished from: 1. VIth Cranial nerve or abducens palsy 2. Nystagmus Blockage Syndrome 3. Esotropia arising secondary to central nervous system abnormalities (in cerebral palsy for example) 4. Primary Constant esotropia 5. Duane's Syndrome ## Treatment[edit] According to a Cochrane review of 2012, controversies remain regarding type of surgery, non-surgical intervention and age of intervention.[8] The aims of treatment are as follows: * The elimination of any amblyopia * A cosmetically acceptable ocular alignment * Long-term stability of eye position * Binocular cooperation ### Initially[edit] It is essential that a child with strabismus is presented to the ophthalmologist as early as possible for diagnosis and treatment in order to allow best possible monocular and binocular vision to develop. Initially, the patient will have a full eye examination to identify any associated pathology, and any glasses required to optimise acuity will be prescribed – although infantile esotropia is not typically associated with refractive error. Studies have found that approximately 15% of infantile esotropia patients have accommodative esotropia. For these patients, antiaccommodative therapy (with spectacles) is indicated before any surgery as antiaccommodative therapy fully corrects their esotropia in many cases and significantly decreases their deviation angle in others.[9][10] Amblyopia will be treated via occlusion treatment (using patching or atropine drops) of the non-squinting eye with the aim of achieving full alternation of fixation. Management thereafter will be surgical. As alternative to surgery, also botulinum toxin therapy has been used in children with infantile esotropia.[11][12][13] Furthermore, as accompaniment to ophthalmologic treatment, craniosacral therapy may be performed in order to relieve tension[14][15] (see also: Management of strabismus). ### Surgery[edit] Controversy has arisen regarding the selection and planning of surgical procedures, the timing of surgery and about what constitutes a favourable outcome. 1\. Selection and planning Some ophthalmologists, notably Ing [16] and Helveston,[17] favour a prescribed approach often involving multiple surgical episodes whereas others prefer to aim for full alignment of the eyes in one procedure and let the number of muscles operated upon during this procedure be determined by the size of the squint. 2\. Timing and outcome This debate relates to the technical anatomical difficulties of operating on the very young versus the possibility of an increased potential for binocularity associated with early surgery. Infants are often operated upon at the age of six to nine months of age[18] and in some cases even earlier at three or four months of age.[19] Some emphasize the importance of intervening early such as to keep the duration of the patient's abnormal visual experience to a minimum.[20] Advocates of early surgery believe that those who have their surgery before the age of one are more likely to be able to use both eyes together post-operatively. A Dutch study (ELISSS)[21] compared early with late surgery in a prospective, controlled, non-randomized, multicenter trial and reported that: > Children operated early had better gross stereopsis at age six as compared to children operated late. They had been operated more frequently, however, and a substantial number of children in both [originally-recruited] groups had not been operated at all. Other studies also report better results with early surgery, notably Birch and Stager[22] and Murray et al.[23] but do not comment on the number of operations undertaken. A recent study on 38 children concluded that surgery for infantile esotropia is most likely to result in measureable stereopsis if patient age at alignment is not more than 16 months.[24] Another study found that for children with infantile esotropia early surgery decreases the risk of dissociated vertical deviation developing after surgery.[25] Aside the strabismus itself, there are other aspects or conditions that appear to improve after surgery or botulinum toxin eye alignment. Study outcomes have indicated that after surgery the child catches up in development of fine-motor skills (such as grasping a toy and handling a bottle) and of large-muscle skills (such as sitting, standing, and walking) in case a developmental delay was present before.[26] Evidence also indicates that as of the age of six, strabismic children become less accepted by their peers, leaving them potentially exposed to social exclusion starting at this age unless their eye positioning is corrected by this time[27] (see also: Psychosocial effects of strabismus). ## References[edit] 1. ^ von Noorden G.k.; A Reassessment of Infantile esotropia. XLIV Edward jackson Memorial lecture; American Journal of Ophthalmology, 1988; 105:1-10 2. ^ Helveston EM (1993). "19th annual Frank Costenbader Lecture--the origins of congenital esotropia". Journal of Pediatric Ophthalmology and Strabismus. 30 (4): 215–32. PMID 8410573. 3. ^ Marc B. Taub; Mary Bartuccio; Dominick Maino (26 September 2012). Visual Diagnosis and Care of the Patient with Special Needs. Lippincott Williams & Wilkins. p. 303. ISBN 978-1-4511-7834-0. 4. ^ Kenneth W. Wright; Yi Ning J. Strube (19 November 2014). Color Atlas Of Strabismus Surgery: Strategies and Techniques. Springer. pp. 16–17. ISBN 978-1-4939-1480-7. 5. ^ Major, Archima; Maples, W.C.; Toomey, Shannon; DeRosier, Wesley; Gahn, David (2007). "Variables associated with the incidence of infantile esotropia". Optometry - Journal of the American Optometric Association. 78 (10): 534–541. doi:10.1016/j.optm.2006.11.017. ISSN 1529-1839. PMID 17904494. 6. ^ Lawrence Tychsen (2012). "The Cause of Infantile Strabismus Lies Upstairs in the Cerebral Cortex, Not Downstairs in the Brainstem". Archives of Ophthalmology. 130 (8). pp. 1060–1061. doi:10.1001/archophthalmol.2012.1481. 7. ^ Tychsen L (2007). "Causing and curing infantile esotropia in primates: the role of decorrelated binocular input (an American Ophthalmological Society thesis)". Transactions of the American Ophthalmological Society. 105: 564–93. PMC 2258131. PMID 18427630. 8. ^ Elliott, S; Shafiq, A (29 July 2013). "Interventions for infantile esotropia". The Cochrane Database of Systematic Reviews. 7 (7): CD004917. doi:10.1002/14651858.CD004917.pub3. PMC 7388175. PMID 23897277. 9. ^ S.A. Havertape; C.R. Whitfill; O.A. Cruz (1999). "Early-onset accommodative esotropia". Journal of Pediatric Ophthalmology and Strabismus. 36 (2): 69–73. PMID 10204132. 10. ^ F. Koç; H. Ozal; E. Firat (August 2003). "Is it possible to differentiate early-onset accommodative esotropia from early-onset essential esotropia?". Eye (Lond). 17 (6): 707–710. doi:10.1038/sj.eye.6700483. PMID 12928681. 11. ^ Thouvenin D, Lesage-Beaudon C, Arné JL (January 2008). "(translated from French) Botulinum injection in infantile strabismus. Results and incidence on secondary surgery in a long-term survey of 74 cases treated before 36 months of age". J Fr Ophtalmol. 31 (1): 42–50. doi:10.1016/S0181-5512(08)70329-2. PMID 18401298. Retrieved January 3, 2019. 12. ^ de Alba Campomanes AG, Binenbaum G, Campomanes Eguiarte G (April 2010). "Comparison of botulinum toxin with surgery as primary treatment for infantile esotropia". J Aapos. 14 (2): 111–116. doi:10.1016/j.jaapos.2009.12.162. PMID 20451851. 13. ^ Gursoy, Huseyin; Basmak, Hikmet; Sahin, Afsun; Yildirim, Nilgun; Aydin, Yasemin; Colak, Ertugrul (2012). "Long-term follow-up of bilateral botulinum toxin injections versus bilateral recessions of the medial rectus muscles for treatment of infantile esotropia". Journal of American Association for Pediatric Ophthalmology and Strabismus. 16 (3): 269–273. doi:10.1016/j.jaapos.2012.01.010. ISSN 1091-8531. PMID 22681945. 14. ^ Clinical Application of Neuromuscular Techniques: Practical Case Study Exercises. Elsevier Health Sciences. 2005. p. 48. ISBN 978-0-443-10000-0. 15. ^ Leon Chaitow (2005). Cranial Manipulation: Theory and Practice : Osseous and Soft Tissue Approaches. Elsevier Health Sciences. p. 9. ISBN 978-0-443-07449-3. 16. ^ Ing, M.R. (February 1983). "Early Surgical Alignment for Congenital Esotropia". Ophthalmology. 90 (2): 132–135. doi:10.1016/s0161-6420(83)34586-3. PMC 1312199. PMID 6856250. 17. ^ Helveston, E.M.; Ellis, F.D.; Patterson, J.H.; Weber, J. (May 1978). "Augmented Recession of the Medial Recti". Ophthalmology. 85 (5): 507–511. doi:10.1016/s0161-6420(78)35647-5. PMID 673330. 18. ^ Esotropia (Crossed Eyes), Pediatric Ophthalmic Consultants 19. ^ Experts discuss infantile esotropia, airbag injuries and timing of surgery, Ocular Surgery News U.S. Edition, June 1, 2002 (downloaded 3 October 2013) 20. ^ Birch EE, Wang J (2009). "Stereoacuity outcomes after treatment of infantile and accommodative esotropia". Optometry and Vision Science (Review). 86 (6): 647–52. doi:10.1097/OPX.0b013e3181a6168d. PMC 2769257. PMID 19390468. 21. ^ Simonsz HJ; Kolling GH; Unnebrink K. (December 2005). "Final report of the early vs. late infantile strabismus surgery study (ELISSS), a controlled, prospective, multicenter study". Strabismus. 4 (13). pp. 169–199. PMID 16361188. 22. ^ Birch EE, Stager DR Sr.Long-term motor and sensory outcomes after early surgery for infantile esotropia. J AAPOS. 2006 Oct;10(5):409-13 23. ^ Murray AD, Orpen J, Calcutt C. Changes in the functional binocular status of older children and adults with previously untreated infantile esotropia following late surgical realignment. J AAPOS. 2007 Apr;11(2):125-30. Epub 2007 Feb 15 24. ^ Eren Çerman; Muhsin Eraslan; Mehdi S. Öğüt (2014). "The relationship of age when motor alignment is achieved and the subsequent development of stereopsis in infantile esotropia". Journal of American Association for Pediatric Ophthalmology and Strabismus. 18 (3). pp. 222–225. doi:10.1016/j.jaapos.2013.12.017. 25. ^ Arslan U, Atilla H, Erkam N (June 2010). "Dissociated vertical deviation and its relationship with time and type of surgery in infantile esotropia". The British Journal of Ophthalmology. 94 (6): 740–2. doi:10.1136/bjo.2008.157016. PMID 20508049. 26. ^ Babies' Development 'Catches Up' After Surgery To Fix Crossed Eyes, sciencedaily.com, 21 April 2008 (downloaded 4 October 2013) 27. ^ Six-Year-Olds With Squint Less Likely to Be Invited to Birthday Parties, Study Suggests, sciencedaily.com, 19 August 2010 (downloaded 4 October 2013) ## External links[edit] Classification D External resources * eMedicine: article/1198876 * Infantile esotropia, Medscape, updated 30 May 2012 * v * t * e Congenital malformations and deformations of eyes Adnexa Eyelid * Ptosis * Ectropion * Entropion * Distichia * Blepharophimosis * Ablepharon * Marcus Gunn phenomenon Lacrimal apparatus * Congenital lacrimal duct obstruction Globe Entire eye * Anophthalmia (Cystic eyeball, Cryptophthalmos) * Microphthalmia Lens * Ectopia lentis * Aphakia Iris * Aniridia Anterior segment * Axenfeld–Rieger syndrome Cornea * Keratoglobus * Megalocornea Other * Buphthalmos * Coloboma (Coloboma of optic nerve) * Hydrophthalmos * Norrie disease * v * t * e 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abduction * Parental responsibility * Parenting plan * Paternity * Paternity fraud [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Infantile esotropia	c0339619	26,993	wikipedia	https://en.wikipedia.org/wiki/Infantile_esotropia	2021-01-18T18:28:14	{"umls": ["C0339619"], "wikidata": ["Q3733047"]}
Uremic frost on forehead and scalp Uremic frost is a colloquial description for crystallized urea deposits that can be found on the skin of those affected by chronic kidney disease.[1] In states of prolonged kidney failure and subsequent uremia, the high level of urea in the bloodstream leads to high levels of urea secreted by eccrine sweat glands as a component of sweat. As water evaporates off of the skin, it results in crystallization of the remaining urea. This condition is more common in severe, untreated uremia and is associated with serum BUN levels >200\. It is becoming rare in people with chronic kidney disease managed on long-term hemodialysis, with estimated prevalence between 0.8 and 3%.[2][3][4] ## References[edit] 1. ^ Dennis, Mark; Bowen, William Talbot; Cho, Lucy (2012). "Uraemic frost". Mechanisms of Clinical Signs. Elsevier. p. 556. ISBN 978-0729540759; pbk 2. ^ Lynde, Carrie; Kraft, John. "Skin manifestations of kidney disease". Parkhurst Exchange. Retrieved 2 October 2014. 3. ^ Falodun O, Ogunbiyi A, Salako B, George AK (March 2011). "Skin changes in patients with chronic renal failure". Saudi J Kidney Dis Transpl. 22 (2): 268–72. PMID 21422624. 4. ^ Udayakumar P, Balasubramanian S, Ramalingam KS, Lakshmi C, Srinivas CR, Mathew AC (2006). "Cutaneous manifestations in patients with chronic renal failure on hemodialysis". Indian J Dermatol Venereol Leprol. 72 (2): 119–25. doi:10.4103/0378-6323.25636. PMID 16707817. This article about an endocrine, nutritional, or metabolic disease is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Uremic frost	c0333569	26,994	wikipedia	https://en.wikipedia.org/wiki/Uremic_frost	2021-01-18T18:29:50	{"umls": ["C0333569"], "wikidata": ["Q18395101"]}
X-linked intellectual disability, Hedera type is a rare X-linked intellectual disability syndrome characterized by an onset in infancy of delayed motor and speech milestones, generalized tonic-clonic seizures and drop attacks, and mild to moderate intellectual disability. Additional, less common manifestations include scoliosis, ataxia (resulting in progressive gait disturbance), and bilateral pes planovalgus. Physical appearance is normal with no dysmorphic features reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	X-linked intellectual disability, Hedera type	c1845543	26,995	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93952	2021-01-23T17:06:24	{"mesh": ["C564516"], "omim": ["300423"], "synonyms": ["MRXSH"]}
X-linked intellectual disability, Armfield type is characterised by intellectual deficiency, short stature, seizures, and small hands and feet. It has been described in six males from three generations of one family. Three of them also had cataracts/glaucoma and two of them had cleft palate. The locus has been mapped to the terminal 8 Mb of Xq28. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	X-linked intellectual disability, Armfield type	c1846057	26,996	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85276	2021-01-23T17:18:23	{"mesh": ["C564551"], "omim": ["300261"], "umls": ["C1846057"], "icd-10": ["Q87.8"], "synonyms": ["Armfield syndrome"]}
Phonological dyslexia is a reading disability that is a form of alexia (acquired dyslexia),[1] resulting from brain injury, stroke, or progressive illness and that affects previously acquired reading abilities. The major distinguishing symptom of acquired phonological dyslexia is that a selective impairment of the ability to read pronounceable non-words occurs although the ability to read familiar words is not affected. It has also been found that the ability to read non-words can be improved if the non-words belong to a family of pseudohomophones.[2][3] ## Contents * 1 Deep and phonological dyslexia * 2 Physiology * 3 Hyphenation * 4 Case study * 5 The dual route cascaded model * 6 See also * 7 References * 8 Further reading ## Deep and phonological dyslexia[edit] Individuals who suffer from phonological dyslexia have the opposite problem to surface dyslexics. These individuals are able to read using the whole word method. However, they struggle when it comes to sounding words out. Phonological dyslexics are able to read familiar words, but have difficulties when it comes to unfamiliar words or non-words that are pronounceable.[4] Several studies have found that many phonological dyslexics have a good reading ability if the individual has developed a large vocabulary prior to suffering from brain damage. These individuals seem to stop developing their vocabulary post-brain damage, which affects their reading capacity.[2] Phonological dyslexia is a reading disorder in which the patient has impaired reading of nonwords. The symptoms of phonological dyslexia are very similar to those of deep dyslexia. The major difference between these two dyslexias is that phonological dyslexics do not make semantic errors associated with deep dyslexia. Beauvois and Dérouesné (1979) studied the first case of phonological dyslexia and came up with this term.[5] The problem people with phonological dyslexia have is that they are able to read words using the whole word method; however, they are not able to sound words out. This means that they are able to read familiar words, but have difficulties reading new words. Initially it was believed that the factor causing phonological dyslexia was lexicality; however, other factors such as imageability and concreteness also play a critical role in reading. A study done by Crisp and Lambon Ralph concluded that imageability has a significant effect on phonological dyslexia. The study found that eleven out of the twelve patients had more accuracy when reading words with high imageability.[5] In that study, the patient who was the exception was the least severely damaged, contributing to a view of phonological dyslexia and deep dyslexia as points on a continuum rather than discrete disorders.[5] ## Physiology[edit] Several studies have found that different levels of brain damage can lead to the occurrence of varying forms of non-word reading disorders.[6][7] It has been found that during certain tasks, dyslexics had activated one of two regions of the brain: the Broca's area, which is responsible for speech, or the Wernicke's area, which is responsible for forming and understanding. Both areas were seldom active together. This study has led to the conclusion that there exist neural connection breakdowns between the language centers that may be causing dyslexia.[8] ## Hyphenation[edit] An investigation conducted by Harley, T. A., and O'Mara, D.A. (2006) found that hyphenation significantly improved a participant`s reading ability. The subject suffered from phonological dyslexia that was due to a deficiency in graphemic parsing. The study suggested that hyphenation might be generally useful as a strategy to assist phonological dyslexics.[9] ## Case study[edit] A study was done by Beauvois and Dérouesné on a 64-year-old man. The individual is described as right-handed, a retiree, and having formerly been an agricultural machinery representative. The individual had had surgery for a left parieto-occipital angioma. Scans showed a lesion at the left angular gyrus, the posterior part of the second temporal convolution, the inferior longitudinal fasciculus, the geniculostriate fibres and tapetum. The patient was also found to be suffering from neurological defects such as right inferior quadrantanopia, mild memory deficit, mild calculation impairment, minimal constructional apraxia, and astereognosia. It was found that the patient did not suffer from motor or sensory defects. He had been obliged to retire as the phonological dyslexia disrupted his ability to work. He had previously enjoyed reading, but was now unable to read his own or other pieces of writing. The diagnosis was confirmed with the Alouette reading test, which concluded that the patient suffered from a reading disability. He was found to have the reading ability of a 6-year-old child, which is considered to be the lowest reading level. The level of reading was not determined from the speed, rather from the fact that the patient was not able to read more than 62 of the stimuli presented in three minutes, while 40% of the represented stimuli were either read incorrectly or left unread. The reading errors included adjectives, possessive adjectives, conjunctions and verbs.[4] ## The dual route cascaded model[edit] Patients with phonological dyslexia have problem reading non-words and unfamiliar words. According to the dual route model, patients with phonological dyslexia use route 2 or 3 that have intact orthographic input lexicon which allow them to pronounce familiar words whether regular or irregular. However due to phonological dyslexia they are unable to use grapheme-phoneme conversion (Route 1), as route 1 is impaired, thus patients find it difficult to pronounce unfamiliar words and non-words.[citation needed] ## See also[edit] * Aphasia * Agnosia * Dual-route hypothesis to reading aloud * Developmental dyslexia * Surface dyslexia ## References[edit] 1. ^ Reiff Cherney, Leora (2 February 2015). "Aphasia, Alexia, and Oral Reading". Topics in Stroke Rehabilitation. 11 (1): 22–36. doi:10.1310/VUPX-WDX7-J1EU-00TB. PMID 14872397. 2. ^ a b Derouesne, J; Beauvois, M F (1 December 1979). "Phonological processing in reading: data from alexia". Journal of Neurology, Neurosurgery & Psychiatry. 42 (12): 1125–1132. doi:10.1136/jnnp.42.12.1125. PMC 490428. PMID 533851. 3. ^ Goodall, W. C.; Phillips, W. A. (16 August 2007). "Three routes from print to sound: Evidence from a case of acquired dyslexia". Cognitive Neuropsychology. 12 (2): 113–147. doi:10.1080/02643299508251993. 4. ^ a b Beauvois MF, Dérouesné J (December 1979). "Phonological alexia: three dissociations". J. Neurol. Neurosurg. Psychiatry. 42 (12): 1115–24. doi:10.1136/jnnp.42.12.1115. PMC 490427. PMID 533850. 5. ^ a b c Welbourne, Stephen R.; Lambon Ralph, Matthew A. (2006). "Phonological and Surface Dyslexia in a Single PDP Model of Reading" (PDF). Proceedings of the 28th Annual Conference of the Cognitive Science Society. Mahwah, New Jersey: Lawrence Erlbaum Associates. pp. 2359–64. ISBN 978-0-9768318-2-2. 6. ^ Berndt, Rita Sloan (September 1996). "An Investigation of Nonlexical Reading Impairments". Cognitive Neuropsychology. 13 (6): 763–801. doi:10.1080/026432996381809. 7. ^ Dérouesné, J; Beauvois, M.-F. (1985). "The 'Phonemic' Stage in the Non-lexical Reading Process: Evidence from a Case of Phonological Alexia". In Coltheart, Max; Patterson, Karalyn; Marshall, John F. (eds.). Surface Dyslexia. Hillsdale, N.J: Lawrence Erlbaum Associates. pp. 399–457. doi:10.4324/9781315108346-22. ISBN 978-0-86377-026-5. OCLC 789357383. 8. ^ Lishman, W A (1 December 2003). "Developmental dyslexia". Journal of Neurology, Neurosurgery & Psychiatry. 74 (12): 1603–1605. doi:10.1136/jnnp.74.12.1603. PMC 1757419. PMID 14638872. 9. ^ Harley, Trevor A.; O'Mara, David A. (August 2006). "Hyphenation can improve reading in acquired phonological dyslexia". Aphasiology. 20 (8): 744–761. doi:10.1080/02687030600591658. ## Further reading[edit] * Rohrer, Jonathan D.; Knight, William D.; Warren, Jane E.; Fox, Nick C.; Rossor, Martin N.; Warren, Jason D. (January 2008). "Word-finding difficulty: a clinical analysis of the progressive aphasias". Brain. 131 (Pt 1): 8–38. doi:10.1093/brain/awm251. PMC 2373641. PMID 17947337. * Sato, Hitomi; Patterson, Karalyn; Fushimi, Takao; Maxim, Jane; Bryan, Karen (26 November 2008). "Deep dyslexia for kanji and phonological dyslexia for kana: Different manifestations from a common source". Neurocase. 14 (6): 508–524. doi:10.1080/13554790802372135. PMID 19012171. * Tree, Jeremy J.; Kay, Janice (January 2006). "Phonological dyslexia and phonological impairment: An exception to the rule?". Neuropsychologia. 44 (14): 2861–2873. doi:10.1016/j.neuropsychologia.2006.06.006. PMID 16879843. * Tree, Jeremy J. (June 2008). "Two types of phonological dyslexia – A contemporary review". Cortex. 44 (6): 698–706. doi:10.1016/j.cortex.2006.11.003. PMID 18472039. * "Phonological Dyslexia: Past and Future Issues". Cognitive Neuropsychology. 13 (6): 749–762. September 1996. doi:10.1080/026432996381791. * v * t * e Dyslexia and related specific developmental disorders Conditions Speech, language, and communication * Expressive language disorder * Infantile speech * Landau–Kleffner syndrome * Language disorder * Lisp * Mixed receptive-expressive language disorder * Specific language impairment * Speech and language impairment * Speech disorder * Speech error * Speech sound disorder * Stuttering * Tip of the tongue Learning disability * Dyslexia * Dyscalculia * Dysgraphia * Disorder of written expression Motor * Developmental coordination disorder * Developmental verbal dyspraxia Sensory * Auditory processing disorder * Sensory processing disorder Related topics * Dyslexia research * Irlen filters * Learning Ally * Learning problems in childhood cancer * Literacy * Management of dyslexia * Multisensory integration * Neuropsychology * Reading acquisition * Spelling * Writing system Lists * Dyslexia in fiction * Languages by Writing System * People with dyslexia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Phonological dyslexia	c0454593	26,997	wikipedia	https://en.wikipedia.org/wiki/Phonological_dyslexia	2021-01-18T18:45:43	{"wikidata": ["Q7187290"]}
Cancer that originates in the mammary gland Breast cancer Mammograms showing a normal breast (left) and a breast with cancer (right) SpecialtyOncology SymptomsA lump in a breast, a change in breast shape, dimpling of the skin, fluid from the nipple, a newly inverted nipple, a red scaly patch of skin on the breast[1] Risk factorsBeing female, obesity, lack of exercise, alcohol, hormone replacement therapy during menopause, ionizing radiation, early age at first menstruation, having children late in life or not at all, older age, prior breast cancer, family history of breast cancer, Klinefelter syndrome[1][2][3] Diagnostic methodTissue biopsy[1] Mammography TreatmentSurgery, radiation therapy, chemotherapy, hormonal therapy, targeted therapy[1] PrognosisFive-year survival rate ≈85% (US, UK)[4][5] Frequency2.1 million affected as of 2018[6] Deaths627,000 (2018)[6] Breast cancer is cancer that develops from breast tissue.[7] Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, fluid coming from the nipple, a newly-inverted nipple, or a red or scaly patch of skin.[1] In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin.[8] Risk factors for developing breast cancer include being female, obesity, a lack of physical exercise, alcoholism, hormone replacement therapy during menopause, ionizing radiation, an early age at first menstruation, having children late in life or not at all, older age, having a prior history of breast cancer, and a family history of breast cancer.[1][2] About 5–10% of cases are the result of a genetic predisposition inherited from a person's parents,[1] including BRCA1 and BRCA2 among others.[1] Breast cancer most commonly develops in cells from the lining of milk ducts and the lobules that supply these ducts with milk.[1] Cancers developing from the ducts are known as ductal carcinomas, while those developing from lobules are known as lobular carcinomas.[1] There are more than 18 other sub-types of breast cancer.[2] Some, such as ductal carcinoma in situ, develop from pre-invasive lesions.[2] The diagnosis of breast cancer is confirmed by taking a biopsy of the concerning tissue.[1] Once the diagnosis is made, further tests are done to determine if the cancer has spread beyond the breast and which treatments are most likely to be effective.[1] The balance of benefits versus harms of breast cancer screening is controversial. A 2013 Cochrane review found that it was unclear if mammographic screening does more harm than good, in that a large proportion of women who test positive turn out not to have the disease.[9] A 2009 review for the US Preventive Services Task Force found evidence of benefit in those 40 to 70 years of age,[10] and the organization recommends screening every two years in women 50 to 74 years of age.[11] The medications tamoxifen or raloxifene may be used in an effort to prevent breast cancer in those who are at high risk of developing it.[2] Surgical removal of both breasts is another preventive measure in some high risk women.[2] In those who have been diagnosed with cancer, a number of treatments may be used, including surgery, radiation therapy, chemotherapy, hormonal therapy, and targeted therapy.[1] Types of surgery vary from breast-conserving surgery to mastectomy.[12][13] Breast reconstruction may take place at the time of surgery or at a later date.[13] In those in whom the cancer has spread to other parts of the body, treatments are mostly aimed at improving quality of life and comfort.[13] Outcomes for breast cancer vary depending on the cancer type, the extent of disease, and the person's age.[13] The five-year survival rates in England and the United States are between 80 and 90%.[14][4][5] In developing countries, five-year survival rates are lower.[2] Worldwide, breast cancer is the leading type of cancer in women, accounting for 25% of all cases.[15] In 2018 it resulted in 2 million new cases and 627,000 deaths.[6] It is more common in developed countries[2] and is more than 100 times more common in women than in men.[14][16] ## Contents * 1 Signs and symptoms * 2 Risk factors * 2.1 Lifestyle * 2.2 Genetics * 2.3 Medical conditions * 3 Pathophysiology * 4 Diagnosis * 4.1 Classification * 5 Screening * 6 Prevention * 6.1 Lifestyle * 6.2 Pre-emptive surgery * 6.3 Medications * 7 Management * 7.1 Surgery * 7.2 Medication * 7.2.1 Hormonal therapy * 7.2.2 Chemotherapy * 7.2.3 Monoclonal antibodies * 7.3 Radiation * 7.4 Follow-up care * 8 Prognosis * 8.1 Prognostic factors * 8.2 Psychological aspects * 9 Epidemiology * 10 History * 11 Society and culture * 11.1 Pink ribbon * 11.2 Breast cancer culture * 11.3 Emphasis * 12 Racial Differences in Breast Cancer Incidence / Mortality * 13 Pregnancy * 14 Hormones * 14.1 Birth control * 14.2 Menopausal hormone replacement * 15 Research * 15.1 Cryoablation * 15.2 Breast cancer cell lines * 15.3 Molecular markers * 15.3.1 Metabolic markers * 16 Other animals * 17 References * 18 External links ## Signs and symptoms[edit] Breast cancer Breast cancer showing an inverted nipple, lump, and skin dimpling. Breast cancer most commonly presents as a lump that feels different from the rest of the breast tissue. More than 80% of cases are discovered when a person detects such a lump with the fingertips.[17] The earliest breast cancers, however, are detected by a mammogram.[18][19] Lumps found in lymph nodes located in the armpits[17] may also indicate breast cancer. Indications of breast cancer other than a lump may include thickening different from the other breast tissue, one breast becoming larger or lower, a nipple changing position or shape or becoming inverted, skin puckering or dimpling, a rash on or around a nipple, discharge from nipple/s, constant pain in part of the breast or armpit and swelling beneath the armpit or around the collarbone.[20] Pain ("mastodynia") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.[17][18][21] Another symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as skin changes resembling eczema; such as redness, discoloration or mild flaking of the nipple skin. As Paget's disease of the breast advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half the women diagnosed with Paget's disease of the breast also have a lump in the breast.[22][23] Inflammatory Breast Cancer presents with similar effects. Inflammatory Breast Cancer is a rare (only seen in less than 5% of breast cancer diagnosis) yet aggressive form of breast cancer characterized by the swollen, red areas formed on the top of the Breast. The visual effects of Inflammatory Breast Cancer is a result of a blockage of lymph vessels by cancer cells. This type of breast cancer is seen in more commonly diagnosed in younger ages, obese women and African American women. As inflammatory breast cancer does not present as a lump there can sometimes be a delay in diagnosis.[24] In rare cases, what initially appears as a fibroadenoma (hard, movable non-cancerous lump) could in fact be a phyllodes tumor. Phyllodes tumors are formed within the stroma (connective tissue) of the breast and contain glandular as well as stromal tissue. Phyllodes tumors are not staged in the usual sense; they are classified on the basis of their appearance under the microscope as benign, borderline or malignant.[25] Malignant tumors can result in metastatic tumors— secondary tumors (originating from the primary tumor) that spread beyond the site of origination. The symptoms caused by metastatic breast cancer will depend on the location of metastasis. Common sites of metastasis include bone, liver, lung, and brain.[26] When cancer has reached such an invasive state, it is categorized as a stage 4 cancer, cancers of this state are oftentimes fatal.[27] Common symptoms of stage 4 cancer include unexplained weight loss, bone and joint pain, jaundice and neurological symptoms. These symptoms are called non-specific symptoms because they could be manifestations of many other illnesses.[28] Rarely breast cancer can spread to exceedingly uncommon sites such as peripancreatic lymph nodes causing biliary obstruction leading to diagnostic difficulties.[29] Most symptoms of breast disorders, including most lumps, do not turn out to represent underlying breast cancer. Less than 20% of lumps, for example, are cancerous,[30] and benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms.[31] ## Risk factors[edit] Main article: Risk factors of breast cancer Risk factors can be divided into two categories: * modifiable risk factors (things that people can change themselves, such as consumption of alcoholic beverages), and * fixed risk factors (things that cannot be changed, such as age and biological sex).[32] The primary risk factors for breast cancer are being female and older age.[33] Other potential risk factors include genetics,[34] lack of childbearing or lack of breastfeeding,[35] higher levels of certain hormones,[36][37] certain dietary patterns, and obesity. One study indicates that exposure to light pollution is a risk factor for the development of breast cancer.[38] ### Lifestyle[edit] See also: List of breast carcinogenic substances Obesity and drinking alcoholic beverages are among the most common modifiable risk factors.[39] However, the correlation between these factors and breast cancer is anything but linear. Studies show that those who rapidly gain weight in adulthood are at higher risk than those who have been overweight since childhood. Likewise excess fat in the midsection seems to induce a higher risk than excess weight carried in the lower body. This implies that the food one eats is of greater importance than one's BMI.[40] The consumption of alcohol is linked to the risk for breast cancer. Drinking alcoholic beverages increases the risk of breast cancer, even at relatively low (one to three drinks per week) and moderate levels.[41] The risk is highest among heavy drinkers.[41] Dietary factors that may increase risk include a high-fat diet[42] and obesity-related high cholesterol levels.[43][44] Dietary iodine deficiency may also play a role.[45] Evidence for fiber is unclear. A 2015 review found that studies trying to link fiber intake with breast cancer produced mixed results.[46] In 2016 a tentative association between low fiber intake during adolescence and breast cancer was observed.[47] Smoking tobacco appears to increase the risk of breast cancer, with the greater the amount smoked and the earlier in life that smoking began, the higher the risk.[48] In those who are long-term smokers, the risk is increased 35% to 50%.[48] A lack of physical activity has been linked to about 10% of cases.[49] Sitting regularly for prolonged periods is associated with higher mortality from breast cancer. The risk is not negated by regular exercise, though it is lowered.[50] There is an association between use of hormonal birth control and the development of premenopausal breast cancer,[32][51] but whether birth control pills actually cause premenopausal breast cancer is a matter of debate.[52] If there is indeed a link, the absolute effect is small.[52][53] Additionally, it is not clear if the association exists with newer hormonal birth controls.[53] In those with mutations in the breast cancer susceptibility genes BRCA1 or BRCA2, or who have a family history of breast cancer, use of modern oral contraceptives does not appear to affect the risk of breast cancer.[54][55] The association between breast feeding and breast cancer has not been clearly determined; some studies have found support for an association while others have not.[56] In the 1980s, the abortion–breast cancer hypothesis posited that induced abortion increased the risk of developing breast cancer.[57] This hypothesis was the subject of extensive scientific inquiry, which concluded that neither miscarriages nor abortions are associated with a heightened risk for breast cancer.[58] Other risk factors include radiation[59] and circadian disruptions related to shift-work[60] and routine late-night eating.[61] A number of chemicals have also been linked, including polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and organic solvents[62] Although the radiation from mammography is a low dose, it is estimated that yearly screening from 40 to 80 years of age will cause approximately 225 cases of fatal breast cancer per million women screened.[63] ### Genetics[edit] Genetics is believed to be the primary cause of 5–10% of all cases.[64] Women whose mother was diagnosed before 50 have an increased risk of 1.7 and those whose mother was diagnosed at age 50 or after has an increased risk of 1.4.[65] In those with zero, one or two affected relatives, the risk of breast cancer before the age of 80 is 7.8%, 13.3%, and 21.1% with a subsequent mortality from the disease of 2.3%, 4.2%, and 7.6% respectively.[66] In those with a first degree relative with the disease the risk of breast cancer between the age of 40 and 50 is double that of the general population.[67] In less than 5% of cases, genetics plays a more significant role by causing a hereditary breast–ovarian cancer syndrome.[68] This includes those who carry the BRCA1 and BRCA2 gene mutation.[68] These mutations account for up to 90% of the total genetic influence with a risk of breast cancer of 60–80% in those affected.[64] Other significant mutations include p53 (Li–Fraumeni syndrome), PTEN (Cowden syndrome), and STK11 (Peutz–Jeghers syndrome), CHEK2, ATM, BRIP1, and PALB2.[64] In 2012, researchers said that there are four genetically distinct types of the breast cancer and that in each type, hallmark genetic changes lead to many cancers.[69] Other genetic predispositions include the density of the breast tissue and hormonal levels. Women with dense breast tissue are more likely to get tumors and are less likely to be diagnosed with breast cancer - because the dense tissue makes tumors less visible on mammograms. Furthermore, women with naturally high estrogen and progesterone levels are also at higher risk for tumor development.[70][71] ### Medical conditions[edit] Breast changes like atypical ductal hyperplasia[72] and lobular carcinoma in situ,[73][74] found in benign breast conditions such as fibrocystic breast changes, are correlated with an increased breast cancer risk. Diabetes mellitus might also increase the risk of breast cancer.[75] Autoimmune diseases such as lupus erythematosus seem also to increase the risk for the acquisition of breast cancer.[76] Hormone therapy to treat menopause is also associated with an increase risk of breast cancer.[77] ## Pathophysiology[edit] See also: Carcinogenesis Ducts and lobules, the main locations of breast cancers. Overview of signal transduction pathways involved in programmed cell death. Mutations leading to loss of this ability can lead to cancer formation. Breast cancer, like other cancers, occurs because of an interaction between an environmental (external) factor and a genetically susceptible host. Normal cells divide as many times as needed and stop. They attach to other cells and stay in place in tissues. Cells become cancerous when they lose their ability to stop dividing, to attach to other cells, to stay where they belong, and to die at the proper time. Normal cells will self-destruct (programmed cell death) when they are no longer needed. Until then, cells are protected from programmed death by several protein clusters and pathways. One of the protective pathways is the PI3K/AKT pathway; another is the RAS/MEK/ERK pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of self-destructing when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the PTEN protein turns off the PI3K/AKT pathway when the cell is ready for programmed cell death. In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not self-destruct.[78] Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.[79] Additionally, G-protein coupled estrogen receptors have been associated with various cancers of the female reproductive system including breast cancer.[80] Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth.[81][82] In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.[83] In the United States, 10 to 20 percent of people with breast cancer and people with ovarian cancer have a first- or second-degree relative with one of these diseases. The familial tendency to develop these cancers is called hereditary breast–ovarian cancer syndrome. The best known of these, the BRCA mutations, confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. Some mutations associated with cancer, such as p53, BRCA1 and BRCA2, occur in mechanisms to correct errors in DNA. These mutations are either inherited or acquired after birth. Presumably, they allow further mutations, which allow uncontrolled division, lack of attachment, and metastasis to distant organs.[59][84] However, there is strong evidence of residual risk variation that goes well beyond hereditary BRCA gene mutations between carrier families. This is caused by unobserved risk factors.[85] This implicates environmental and other causes as triggers for breast cancers. The inherited mutation in BRCA1 or BRCA2 genes can interfere with repair of DNA cross links and DNA double strand breaks (known functions of the encoded protein).[86] These carcinogens cause DNA damage such as DNA cross links and double strand breaks that often require repairs by pathways containing BRCA1 and BRCA2.[87][88] However, mutations in BRCA genes account for only 2 to 3 percent of all breast cancers.[89] Levin et al. say that cancer may not be inevitable for all carriers of BRCA1 and BRCA2 mutations.[90] About half of hereditary breast–ovarian cancer syndromes involve unknown genes. Furthermore, certain latent viruses, may decrease the expression of the BRCA1 gene and increase the risk of breast tumors.[91] GATA-3 directly controls the expression of estrogen receptor (ER) and other genes associated with epithelial differentiation, and the loss of GATA-3 leads to loss of differentiation and poor prognosis due to cancer cell invasion and metastasis.[92] ## Diagnosis[edit] Most types of breast cancer are easy to diagnose by microscopic analysis of a sample - or biopsy \- of the affected area of the breast. Also, there are types of breast cancer that require specialized lab exams. The two most commonly used screening methods, physical examination of the breasts by a healthcare provider and mammography, can offer an approximate likelihood that a lump is cancer, and may also detect some other lesions, such as a simple cyst.[93] When these examinations are inconclusive, a healthcare provider can remove a sample of the fluid in the lump for microscopic analysis (a procedure known as fine needle aspiration, or fine needle aspiration and cytology, FNAC) to help establish the diagnosis. A needle aspiration can be performed in a healthcare provider's office or clinic. A local anesthetic may be used to numb the breast tissue to prevent pain during the procedure, but may not be necessary if the lump isn't beneath the skin. A finding of clear fluid makes the lump highly unlikely to be cancerous, but bloody fluid may be sent off for inspection under a microscope for cancerous cells. Together, physical examination of the breasts, mammography, and FNAC can be used to diagnose breast cancer with a good degree of accuracy. Other options for biopsy include a core biopsy or vacuum-assisted breast biopsy,[94] which are procedures in which a section of the breast lump is removed; or an excisional biopsy, in which the entire lump is removed. Very often the results of physical examination by a healthcare provider, mammography, and additional tests that may be performed in special circumstances (such as imaging by ultrasound or MRI) are sufficient to warrant excisional biopsy as the definitive diagnostic and primary treatment method.[95][non-primary source needed] Early signs of possible breast cancer * MRI showing breast cancer * Excised human breast tissue, showing an irregular, dense, white stellate area of cancer 2 cm in diameter, within yellow fatty tissue. * High-grade invasive ductal carcinoma, with minimal tubule formation, marked pleomorphism, and prominent mitoses, 40x field. * Micrograph showing a lymph node invaded by ductal breast carcinoma, with an extension of the tumor beyond the lymph node. * Neuropilin-2 expression in normal breast and breast carcinoma tissue. * F-18 FDG PET/CT: A breast cancer metastasis to the right scapula * Needle breast biopsy. * Elastography shows stiff cancer tissue on ultrasound imaging. * Ultrasound image shows irregularly shaped mass of breast cancer. * Infiltrating (Invasive) breast carcinoma. ### Classification[edit] Main article: Breast cancer classification Breast cancers are classified by several grading systems. Each of these influences the prognosis and can affect treatment response. Description of a breast cancer optimally includes all of these factors. Histopathologic types of breast cancer, with relative incidences and prognoses. * Histopathology. Breast cancer is usually classified primarily by its histological appearance. Most breast cancers are derived from the epithelium lining the ducts or lobules, and these cancers are classified as ductal or lobular carcinoma. Carcinoma in situ is growth of low-grade cancerous or precancerous cells within a particular tissue compartment such as the mammary duct without invasion of the surrounding tissue. In contrast, invasive carcinoma does not confine itself to the initial tissue compartment.[96] * Grade. Grading compares the appearance of the breast cancer cells to the appearance of normal breast tissue. Normal cells in an organ like the breast become differentiated, meaning that they take on specific shapes and forms that reflect their function as part of that organ. Cancerous cells lose that differentiation. In cancer, the cells that would normally line up in an orderly way to make up the milk ducts become disorganized. Cell division becomes uncontrolled. Cell nuclei become less uniform. Pathologists describe cells as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade) as the cells progressively lose the features seen in normal breast cells. Poorly differentiated cancers (the ones whose tissue is least like normal breast tissue) have a worse prognosis. * Stage. Breast cancer staging using the TNM system is based on the size of the tumor (T), whether or not the tumor has spread to the lymph nodes (N) in the armpits, and whether the tumor has metastasized (M) (i.e. spread to a more distant part of the body). Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis. The main stages are: * Stage 0 is a pre-cancerous or marker condition, either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS). * Stages 1–3 are within the breast or regional lymph nodes. * Stage 4 is 'metastatic' cancer that has a less favorable prognosis since it has spread beyond the breast and regional lymph nodes. * Stage T1 breast cancer * Stage T2 breast cancer * Stage T3 breast cancer * Metastatic or stage 4 breast cancer Where available, imaging studies may be employed as part of the staging process in select cases to look for signs of metastatic cancer. However, in cases of breast cancer with low risk for metastasis, the risks associated with PET scans, CT scans, or bone scans outweigh the possible benefits, as these procedures expose the person to a substantial amount of potentially dangerous ionizing radiation.[97][98] * Receptor status. Breast cancer cells have receptors on their surface and in their cytoplasm and nucleus. Chemical messengers such as hormones bind to receptors, and this causes changes in the cell. Breast cancer cells may or may not have three important receptors: estrogen receptor (ER), progesterone receptor (PR), and HER2. ER+ cancer cells (that is, cancer cells that have estrogen receptors) depend on estrogen for their growth, so they can be treated with drugs to block estrogen effects (e.g. tamoxifen), and generally have a better prognosis. Untreated, HER2+ breast cancers are generally more aggressive than HER2- breast cancers,[99][100] but HER2+ cancer cells respond to drugs such as the monoclonal antibody trastuzumab (in combination with conventional chemotherapy), and this has improved the prognosis significantly.[101] Cells that do not have any of these three receptor types (estrogen receptors, progesterone receptors, or HER2) are called triple-negative, although they frequently do express receptors for other hormones, such as androgen receptor and prolactin receptor. * DNA assays. DNA testing of various types including DNA microarrays have compared normal cells to breast cancer cells. The specific changes in a particular breast cancer can be used to classify the cancer in several ways, and may assist in choosing the most effective treatment for that DNA type. * Stage 1A breast cancer * Stage 1B breast cancer * Stage 2A breast cancer * Stage 2A breast cancer * Stage 2B breast cancer * Stage 2B breast cancer * Stage 2B breast cancer * Stage 3A breast cancer * Stage 3A breast cancer * Stage 3A breast cancer * Stage 3B breast cancer * Stage 3B breast cancer * Stage 4 breast cancer ## Screening[edit] Main article: Breast cancer screening A mobile breast cancer screening unit in New Zealand Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to achieve an earlier diagnosis under the assumption that early detection will improve outcomes. A number of screening tests have been employed including clinical and self breast exams, mammography, genetic screening, ultrasound, and magnetic resonance imaging. A clinical or self breast exam involves feeling the breast for lumps or other abnormalities. Clinical breast exams are performed by health care providers, while self-breast exams are performed by the person themselves.[102] Evidence does not support the effectiveness of either type of breast exam, as by the time a lump is large enough to be found it is likely to have been growing for several years and thus soon be large enough to be found without an exam.[103][104] Mammographic screening for breast cancer uses X-rays to examine the breast for any uncharacteristic masses or lumps. During a screening, the breast is compressed and a technician takes photos from multiple angles. A general mammogram takes photos of the entire breast, while a diagnostic mammogram focuses on a specific lump or area of concern.[105] A number of national bodies recommend breast cancer screening. For the average woman, the U.S. Preventive Services Task Force and American College of Physicians recommends mammography every two years in women between the ages of 50 and 74,[11][106] the Council of Europe recommends mammography between 50 and 69 with most programs using a 2-year frequency,[107] while the European Commission recommends mammography from 45 to 75 every 2 to 3 years,[108] and in Canada screening is recommended between the ages of 50 and 74 at a frequency of 2 to 3 years.[109] These task force reports point out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation.[110] The Cochrane collaboration (2013) states that the best quality evidence neither demonstrates a reduction in cancer specific, nor a reduction in all cause mortality from screening mammography.[9] When less rigorous trials are added to the analysis there is a reduction in mortality due to breast cancer of 0.05% (a decrease of 1 in 2000 deaths from breast cancer over 10 years or a relative decrease of 15% from breast cancer).[9] Screening over 10 years results in a 30% increase in rates of over-diagnosis and over-treatment (3 to 14 per 1000) and more than half will have at least one falsely positive test.[9][111] This has resulted in the view that it is not clear whether mammography screening does more good or harm.[9] Cochrane states that, due to recent improvements in breast cancer treatment, and the risks of false positives from breast cancer screening leading to unnecessary treatment, "it therefore no longer seems beneficial to attend for breast cancer screening" at any age.[112] Whether MRI as a screening method has greater harms or benefits when compared to standard mammography is not known.[113][114] ## Prevention[edit] ### Lifestyle[edit] Women can reduce their risk of breast cancer by maintaining a healthy weight, reducing alcohol use, increasing physical activity, and breast-feeding.[115] These modifications might prevent 38% of breast cancers in the US, 42% in the UK, 28% in Brazil, and 20% in China.[115] The benefits with moderate exercise such as brisk walking are seen at all age groups including postmenopausal women.[115][116] High levels of physical activity reduce the risk of breast cancer by about 14%.[117] Strategies that encourage regular physical activity and reduce obesity could also have other benefits, such as reduced risks of cardiovascular disease and diabetes.[32] The American Cancer Society and the American Society of Clinical Oncology advised in 2016 that people should eat a diet high in vegetables, fruits, whole grains, and legumes.[118] High intake of citrus fruit has been associated with a 10% reduction in the risk of breast cancer.[119] Marine omega-3 polyunsaturated fatty acids appear to reduce the risk.[120] High consumption of soy-based foods may reduce risk.[121] ### Pre-emptive surgery[edit] Removal of both breasts before any cancer has been diagnosed or any suspicious lump or other lesion has appeared (a procedure known as "prophylactic bilateral mastectomy" or "risk reducing mastectomy") may be considered in people with BRCA1 and BRCA2 mutations, which are associated with a substantially heightened risk for an eventual diagnosis of breast cancer.[122][123] Evidence is not strong enough to support this procedure in anyone but those at the highest risk.[124] BRCA testing is recommended in those with a high family risk after genetic counseling. It is not recommended routinely.[125] This is because there are many forms of changes in BRCA genes, ranging from harmless polymorphisms to obviously dangerous frameshift mutations.[125] The effect of most of the identifiable changes in the genes is uncertain. Testing in an average-risk person is particularly likely to return one of these indeterminate, useless results. Removing the second breast in a person who has breast cancer (contralateral risk‐reducing mastectomy or CRRM) may reduce the risk of cancer in the second breast, however, it is unclear if removing the second breast in those who have breast cancer improves survival.[124] ### Medications[edit] The selective estrogen receptor modulators (such as tamoxifen) reduce the risk of breast cancer but increase the risk of thromboembolism and endometrial cancer.[126] There is no overall change in the risk of death.[126][127] They are thus not recommended for the prevention of breast cancer in women at average risk but it is recommended they be offered for those at high risk and over the age of 35.[128] The benefit of breast cancer reduction continues for at least five years after stopping a course of treatment with these medications.[129] Aromatase inhibitors (such as exemestane and anasatrozole) may be more effective than selective estrogen receptor modulators (such as tamoxifen) at reducing breast cancer risk and they are not associated with an increased risk of endometrial cancer and thromboembolism.[130] ## Management[edit] Main article: Breast cancer management The management of breast cancer depends on various factors, including the stage of the cancer and the person's age. Treatments are more aggressive when the cancer is more advanced or there is a higher risk of recurrence of the cancer following treatment. Breast cancer is usually treated with surgery, which may be followed by chemotherapy or radiation therapy, or both. A multidisciplinary approach is preferable.[131] Hormone receptor-positive cancers are often treated with hormone-blocking therapy over courses of several years. Monoclonal antibodies, or other immune-modulating treatments, may be administered in certain cases of metastatic and other advanced stages of breast cancer. Although this range of treatment is still being studied.[132] ### Surgery[edit] Chest after right breast mastectomy Surgery involves the physical removal of the tumor, typically along with some of the surrounding tissue. One or more lymph nodes may be biopsied during the surgery; increasingly the lymph node sampling is performed by a sentinel lymph node biopsy. Standard surgeries include: * Mastectomy: Removal of the whole breast. * Quadrantectomy: Removal of one-quarter of the breast. * Lumpectomy: Removal of a small part of the breast. Once the tumor has been removed, if the person desires, breast reconstruction surgery, a type of plastic surgery, may then be performed to improve the aesthetic appearance of the treated site. Alternatively, women use breast prostheses to simulate a breast under clothing, or choose a flat chest. Nipple prosthesis can be used at any time following the mastectomy. ### Medication[edit] Medications used after and in addition to surgery are called adjuvant therapy. Chemotherapy or other types of therapy prior to surgery are called neoadjuvant therapy. Aspirin may reduce mortality from breast cancer when used with other treatments.[133][134] There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone-blocking agents, chemotherapy, and monoclonal antibodies. #### Hormonal therapy[edit] Some breast cancers require estrogen to continue growing. They can be identified by the presence of estrogen receptors (ER+) and progesterone receptors (PR+) on their surface (sometimes referred to together as hormone receptors). These ER+ cancers can be treated with drugs that either block the receptors, e.g. tamoxifen, or alternatively block the production of estrogen with an aromatase inhibitor, e.g. anastrozole[135] or letrozole. The use of tamoxifen is recommended for 10 years.[136] Letrozole is recommended for 5 years. Aromatase inhibitors are only suitable for women after menopause; however, in this group, they appear better than tamoxifen.[137] This is because the active aromatase in postmenopausal women is different from the prevalent form in premenopausal women, and therefore these agents are ineffective in inhibiting the predominant aromatase of premenopausal women.[138] Aromatase inhibitors should not be given to premenopausal women with intact ovarian function (unless they are also on treatment to stop their ovaries from working).[139] CDK inhibitors can be used in combination with endocrine or aromatase therapy.[140] #### Chemotherapy[edit] Chemotherapy is predominantly used for cases of breast cancer in stages 2–4, and is particularly beneficial in estrogen receptor-negative (ER-) disease. The chemotherapy medications are administered in combinations, usually for periods of 3–6 months. One of the most common regimens, known as "AC", combines cyclophosphamide with doxorubicin. Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as "CAT". Another common treatment is cyclophosphamide, methotrexate, and fluorouracil (or "CMF"). Most chemotherapy medications work by destroying fast-growing and/or fast-replicating cancer cells, either by causing DNA damage upon replication or by other mechanisms. However, the medications also damage fast-growing normal cells, which may cause serious side effects. Damage to the heart muscle is the most dangerous complication of doxorubicin, for example.[citation needed] #### Monoclonal antibodies[edit] Trastuzumab, a monoclonal antibody to HER2, has improved the 5-year disease free survival of stage 1–3 HER2-positive breast cancers to about 87% (overall survival 95%).[141] Between 25% and 30% of breast cancers overexpress the HER2 gene or its protein product,[142] and overexpression of HER2 in breast cancer is associated with increased disease recurrence and worse prognosis. Trastuzumab, however, is very expensive, and its use may cause serious side effects (approximately 2% of people who receive it develop significant heart damage).[143] Another antibody pertuzumab prevents HER2 dimerization and is recommended together with trastuzumab and chemotherapy in severe disease.[144][145] ### Radiation[edit] Internal radiotherapy for breast cancer Radiotherapy is given after surgery to the region of the tumor bed and regional lymph nodes, to destroy microscopic tumor cells that may have escaped surgery. When given intraoperatively as Targeted intraoperative radiotherapy, it may also have a beneficial effect on tumor microenvironment.[146][147] Radiation therapy can be delivered as external beam radiotherapy or as brachytherapy (internal radiotherapy). Conventionally radiotherapy is given after the operation for breast cancer. Radiation can also be given at the time of operation on the breast cancer. Radiation can reduce the risk of recurrence by 50–66% (1/2 – 2/3 reduction of risk) when delivered in the correct dose[148] and is considered essential when breast cancer is treated by removing only the lump (Lumpectomy or Wide local excision). In early breast cancer, partial breast irradiation does not give the same cancer control in the breast as treating the whole breast and may cause worse side effects.[149] ### Follow-up care[edit] Care after primary breast cancer treatment, otherwise called 'follow-up care', can be intensive involving regular laboratory tests in asymptomatic people to try to achieve earlier detection of possible metastases. A review has found that follow-up programs involving regular physical examinations and yearly mammography alone are as effective as more intensive programs consisting of laboratory tests in terms of early detection of recurrence, overall survival and quality of life.[150] Multidisciplinary rehabilitation programmes, often including exercise, education and psychological help, may produce short-term improvements in functional ability, psychosocial adjustment and social participation in people with breast cancer.[151] ## Prognosis[edit] Breasts after double mastectomy followed by nipple-sparing reconstruction with implants An extreme example of an advanced recurrent breast cancer with an ulcerating axillary mass ### Prognostic factors[edit] The stage of the breast cancer is the most important component of traditional classification methods of breast cancer, because it has a greater effect on the prognosis than the other considerations. Staging takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the poorer the prognosis. The stage is raised by the invasiveness of disease to lymph nodes, chest wall, skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones and close-to-normal cell behaviour (grading). Size is not a factor in staging unless the cancer is invasive. For example, Ductal Carcinoma In Situ (DCIS) involving the entire breast will still be stage zero and consequently an excellent prognosis with a 10-year disease free survival of about 98%.[152] * Stage 1 cancers (and DCIS, LCIS) have an excellent prognosis and are generally treated with lumpectomy and sometimes radiation.[153] * Stage 2 and 3 cancers with a progressively poorer prognosis and greater risk of recurrence are generally treated with surgery (lumpectomy or mastectomy with or without lymph node removal), chemotherapy (plus trastuzumab for HER2+ cancers) and sometimes radiation (particularly following large cancers, multiple positive nodes or lumpectomy).[medical citation needed] * Stage 4, metastatic cancer, (i.e. spread to distant sites) has a poor prognosis and is managed by various combination of all treatments from surgery, radiation, chemotherapy and targeted therapies. Ten-year survival rate is 5% without treatment and 10% with optimal treatment.[154] The breast cancer grade is assessed by comparison of the breast cancer cells to normal breast cells. The closer to normal the cancer cells are, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear immature, will divide more rapidly, and will tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used). The most widely used grading system is the Nottingham scheme.[155] Younger women with an age of less than 40 years or women over 80 years tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts may change with their menstrual cycles, they may be nursing infants, and they may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. There may also be biologic factors contributing to a higher risk of disease recurrence for younger women with breast cancer.[156] ### Psychological aspects[edit] Not all people with breast cancer experience their illness in the same manner. Factors such as age can have a significant impact on the way a person copes with a breast cancer diagnosis. Premenopausal women with estrogen-receptor positive breast cancer must confront the issues of early menopause induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function.[157] In women with non-metastatic breast cancer, psychological interventions such as cognitive behavioral therapy can have positive effects on outcomes such as anxiety, depression and mood disturbance.[158] Physical activity interventions may also have beneficial effects on health related quality of life, anxiety, fitness and physical activity in women with breast cancer following adjuvant therapy.[159] ## Epidemiology[edit] Main article: Epidemiology of breast cancer Age-standardized death from breast cancer per 100,000 inhabitants in 2004.[160] no data <2 2–4 4–6 6–8 8–10 10–12 12–14 14–16 16–18 18–20 20–22 >22 Worldwide, breast cancer is the most-common invasive cancer in women.[161] Along with lung cancer, breast cancer is the most commonly diagnosed cancer, with 2.09 million cases each in 2018.[162] Breast cancer affects 1 in 7 (14%) of women worldwide.[163] (The most common form of cancer is non-invasive non-melanoma skin cancer; non-invasive cancers are generally easily cured, cause very few deaths, and are routinely excluded from cancer statistics.) Breast cancer comprises 22.9% of invasive cancers in women[164] and 16% of all female cancers.[165] In 2012, it comprised 25.2% of cancers diagnosed in women, making it the most-common female cancer.[166] In 2008, breast cancer caused 458,503 deaths worldwide (13.7% of cancer deaths in women and 6.0% of all cancer deaths for men and women together).[164] Lung cancer, the second most-common cause of cancer-related deaths in women, caused 12.8% of cancer deaths in women (18.2% of all cancer deaths for men and women together).[164] The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries and greatest in the more-developed countries. In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows: 18 in Eastern Asia, 22 in South Central Asia and sub-Saharan Africa, 26 in South-Eastern Asia, 26, 28 in North Africa and Western Asia, 42 in South and Central America, 42, 49 in Eastern Europe, 56 in Southern Europe, 73 in Northern Europe, 74 in Oceania, 78 in Western Europe, and 90 in North America.[167] Metastatic breast cancer affects between 19% (United States) and 50% (parts of Africa) of women with breast cancer.[168] The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles.[169][170] Breast cancer is strongly related to age with only 5% of all breast cancers occurring in women under 40 years old.[171] There were more than 41,000 newly diagnosed cases of breast cancer registered in England in 2011, around 80% of these cases were in women age 50 or older.[172] Based on U.S. statistics in 2015 there were 2.8 million women affected by breast cancer.[161] In the United States, the age-adjusted incidence of breast cancer per 100,000 women rose from around 102 cases per year in the 1970s to around 141 in the late-1990s, and has since fallen, holding steady around 125 since 2003. However, age-adjusted deaths from breast cancer per 100,000 women only rose slightly from 31.4 in 1975 to 33.2 in 1989 and have since declined steadily to 20.5 in 2014.[173] ## History[edit] Breast cancer surgery in 18th century Because of its visibility, breast cancer was the form of cancer most often described in ancient documents.[174] Because autopsies were rare, cancers of the internal organs were essentially invisible to ancient medicine. Breast cancer, however, could be felt through the skin, and in its advanced state often developed into fungating lesions: the tumor would become necrotic (die from the inside, causing the tumor to appear to break up) and ulcerate through the skin, weeping fetid, dark fluid.[174] The oldest discovered evidence of breast cancer is from Egypt and dates back 4200 years, to the Sixth Dynasty.[175] The study of a woman's remains from the necropolis of Qubbet el-Hawa showed the typical destructive damage due to metastatic spread.[175] The Edwin Smith Papyrus describes 8 cases of tumors or ulcers of the breast that were treated by cauterization. The writing says about the disease, "There is no treatment."[176] For centuries, physicians described similar cases in their practices, with the same conclusion. Ancient medicine, from the time of the Greeks through the 17th century, was based on humoralism, and thus believed that breast cancer was generally caused by imbalances in the fundamental fluids that controlled the body, especially an excess of black bile.[177] Alternatively it was seen as divine punishment.[178] Mastectomy for breast cancer was performed at least as early as AD 548, when it was proposed by the court physician Aetios of Amida to Theodora.[174] It was not until doctors achieved greater understanding of the circulatory system in the 17th century that they could link breast cancer's spread to the lymph nodes in the armpit. In the early 18th century the French surgeon Jean Louis Petit performed total mastectomies that included removing the axillary lymph nodes, as he recognized that this reduced recurrence.[179] Petit's work built on the methods of the surgeon Bernard Peyrilhe, who in the 17th century additionally removed the pectoral muscle underlying the breast, as he judged that this greatly improved the prognosis.[180] But poor results and the considerable risk to the patient meant that physicians did not share the opinion of surgeons such as Nicolaes Tulp, who in the 17th century proclaimed "the sole remedy is a timely operation". The eminent surgeon Richard Wiseman documented in the mid 17th century that following 12 mastectomies, two patients died during the operation, eight patients died shortly after the operation from progressive cancer and only two of the 12 patients were cured.[181] Physicians were conservative in the treatment they prescribed in the early stages of breast cancer. Patients were treated with a mixture of detox purges, blood letting and traditional remedies that were suppose to lower acidity, such as the alkaline arsenic.[182] When in 1664 Anne of Austria was diagnosed with breast cancer, the initial treatment involved compresses saturated with hemlock juice. When the lumps increased the King's physician commenced a treatment with arsenic ointments.[183] The royal patient died 1666 in atrocious pain.[184] Each failing treatment for breast cancer led to the search for new treatments, spurning a market in remedies that were advertised and soled by quacks, herbalists, chemists and apothecaries.[185] The lack of anesthesia and antiseptics made mastectomy a painful and dangerous ordeal.[186] In the 18th century, a wide variety of anatomical discoveries were accompanied by new theories about the cause and growth of breast cancer. The investigative surgeon John Hunter claimed that neural fluid generated breast cancer. Other surgeons proposed that milk within the mammary ducts led to cancerous growths. Theories about trauma to the breast as cause for malignant changes in breast tissue were advanced. The discovery of breast lumps and swellings fueled controversies about hard tumors and whether lumps were benign stages of cancer. Medical opinion about necessary immediate treatment varied.[187] The surgeon Benjamin Bell advocated removal of the entire breast, even when only a portion was affected.[188] Radical mastectomy, Halsted's surgical papers. Breast cancer was uncommon until the 19th century, when improvements in sanitation and control of deadly infectious diseases resulted in dramatic increases in lifespan. Previously, most women had died too young to have developed breast cancer.[189] William Stewart Halsted started performing radical mastectomies in 1882, helped greatly by advances in general surgical technology, such as aseptic technique and anesthesia. The Halsted radical mastectomy often involved removing both breasts, associated lymph nodes, and the underlying chest muscles. This often led to long-term pain and disability, but was seen as necessary in order to prevent the cancer from recurring.[190] Before the advent of the Halsted radical mastectomy, 20-year survival rates were only 10%; Halsted's surgery raised that rate to 50%.[191] Breast cancer staging systems were developed in the 1920s and 1930s to determining the extent to which a cancer has developed by growing and spreading.[190] The first case-controlled study on breast cancer epidemiology was done by Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 controls of the same background and lifestyle for the British Ministry of Health.[192] Radical mastectomies remained the standard of care in the USA until the 1970s, but in Europe, breast-sparing procedures, often followed by radiation therapy, were generally adopted in the 1950s.[190] In 1955 George Crile Jr. published Cancer and Common Sense arguing that cancer patients needed to understand available treatment options. Crile became a close friend of the environmentalist Rachel Carson, who had undergone a Halsted radical mastectomy in 1960 to treat her malign breast cancer.[193] The US oncologist Jerome Urban promoted superradical mastectomies, taking even more tissue, until 1963, when the ten-year survival rates proved equal to the less-damaging radical mastectomy.[190] Carson died in 1964 and Crile went on to published a wide variety of articles, both in the popular press and in medical journals, challenging the widespread used of the Halsted radical mastectomy. In 1973 Crile published What Women Should Know About the Breast Cancer Controversy. When in 1974 Betty Ford was diagnosed with breast cancer, the options for treating breast cancer were openly discussed in the press.[194] During the 1970s, a new understanding of metastasis led to perceiving cancer as a systemic illness as well as a localized one, and more sparing procedures were developed that proved equally effective.[195] In the 1980s and 1990s, thousands of women who had successfully completed standard treatment then demanded and received high-dose bone marrow transplants, thinking this would lead to better long-term survival. However, it proved completely ineffective, and 15–20% of women died because of the brutal treatment.[196] The 1995 reports from the Nurses' Health Study and the 2002 conclusions of the Women's Health Initiative trial conclusively proved that hormone replacement therapy significantly increased the incidence of breast cancer.[196] ## Society and culture[edit] See also: Breast cancer awareness and List of people with breast cancer Before the 20th century, breast cancer was feared and discussed in hushed tones, as if it were shameful. As little could be safely done with primitive surgical techniques, women tended to suffer silently rather than seeking care. When surgery advanced, and long-term survival rates improved, women began raising awareness of the disease and the possibility of successful treatment. The "Women's Field Army", run by the American Society for the Control of Cancer (later the American Cancer Society) during the 1930s and 1940s was one of the first organized campaigns. In 1952, the first peer-to-peer support group, called "Reach to Recovery", began providing post-mastectomy, in-hospital visits from women who had survived breast cancer.[197] The breast cancer movement of the 1980s and 1990s developed out of the larger feminist movements and women's health movement of the 20th century.[198] This series of political and educational campaigns, partly inspired by the politically and socially effective AIDS awareness campaigns, resulted in the widespread acceptance of second opinions before surgery, less invasive surgical procedures, support groups, and other advances in care.[199] ### Pink ribbon[edit] The pink ribbon is a symbol to show support for breast cancer awareness Main article: Pink ribbon A pink ribbon is the most prominent symbol of breast cancer awareness. Pink ribbons, which can be made inexpensively, are sometimes sold as fundraisers, much like poppies on Remembrance Day. They may be worn to honor those who have been diagnosed with breast cancer, or to identify products that the manufacturer would like to sell to consumers that are interested in breast cancer.[200] In the 1990s breast cancer awareness campaigns were launched by US based corporations. As part of these cause related marketing campaigns corporations donated to a variety of breast cancer initiatives for every pink ribbon product that was purchased.[201] The Wall Street Journal noted "that the strong emotions provoked by breast cancer translate to a company's bottom line". While many US corporations donated to existing breast cancer initiatives others such as Avon established their own breast cancer foundations on the back of pink ribbon products.[202] Wearing or displaying a pink ribbon has been criticized by the opponents of this practice as a kind of slacktivism, because it has no practical positive effect. It has also been criticized as hypocrisy, because some people wear the pink ribbon to show good will towards women with breast cancer, but then oppose these women's practical goals, like patient rights and anti-pollution legislation.[203][204] Critics say that the feel-good nature of pink ribbons and pink consumption distracts society from the lack of progress on preventing and curing breast cancer.[205] It is also criticized for reinforcing gender stereotypes and objectifying women and their breasts.[206] In 2002 Breast Cancer Action launched the "Think Before You Pink" campaign against pinkwashing to target businesses that have co-opted the pink campaign to promote products that cause breast cancer, such as alcoholic beverages.[207] ### Breast cancer culture[edit] In her 2006 book Pink Ribbons, Inc.: Breast Cancer and the Politics of Philanthropy Samantha King claimed that breast cancer has been transformed from a serious disease and individual tragedy to a market-driven industry of survivorship and corporate sales pitch.[208] In 2010 Gayle Sulik argued that the primary purposes or goals of breast cancer culture are to maintain breast cancer's dominance as the pre-eminent women's health issue, to promote the appearance that society is doing something effective about breast cancer, and to sustain and expand the social, political, and financial power of breast cancer activists[209] In the same year Barbara Ehrenreich published an opinion piece in Harper's Magazine, lamenting that in breast cancer culture, breast cancer therapy is viewed as a rite of passage rather than a disease. To fit into this mold, the woman with breast cancer needs to normalize and feminize her appearance, and minimize the disruption that her health issues cause anyone else. Anger, sadness, and negativity must be silenced. As with most cultural models, people who conform to the model are given social status, in this case as cancer survivors. Women who reject the model are shunned, punished and shamed. The culture is criticized for treating adult women like little girls, as evidenced by "baby" toys such as pink teddy bears given to adult women.[210] ### Emphasis[edit] In 2009 the US science journalist Christie Aschwanden criticized that the emphasis on breast cancer screening may be harming women by subjecting them to unnecessary radiation, biopsies, and surgery. One-third of diagnosed breast cancers might recede on their own.[211] Screening mammography efficiently finds non-life-threatening, asymptomatic breast cancers and precancers, even while overlooking serious cancers. According to the cancer researcher H. Gilbert Welch screening mammography has taken the "brain-dead approach that says the best test is the one that finds the most cancers" rather than the one that finds dangerous cancers.[211] In 2002 it was noted that as a result of breast cancer's high visibility, the statistical results can be misinterpreted, such as the claim that one in eight women will be diagnosed with breast cancer during their lives—a claim that depends on the unrealistic assumption that no woman will die of any other disease before the age of 95.[212] By 2010 the breast cancer survival rate in Europe was 91% at one years and 65% at five years. In the USA the five-year survival rate for localized breast cancer was 96.8%, while in cases of metastases it was only 20.6%. Because the prognosis for breast cancer was at this stage relatively favorable, compared to the prognosis for other cancers, breast cancer as cause of death among women was 13.9% of all cancer deaths. The second most common cause of death from cancer in women was lung cancer, the most common cancer worldwide for men and women. The improved survival rate made breast cancer the most prevalent cancer in the world. In 2010 an estimated 3.6 million women worldwide have had a breast cancer diagnosis in the past five years, while only 1.4 million male or female survivors from lung cancer were alive.[213] ## Racial Differences in Breast Cancer Incidence / Mortality[edit] There are racial disparities in the mortality rates for breast cancer as well as in breast cancer treatment. Breast cancer is the most prevalent cancer affecting women of every ethnic group in the United States. Breast cancer incidence among black women aged 45 and older is higher than that of white women in the same age group. White women aged 60-84 have higher incidence rates of breast cancer than Black women. Despite this, Black women at every age are more likely to succumb to breast cancer.[214] Breast cancer treatment has improved greatly in recent years, but black women are still less likely to obtain treatment compared to white women. [215] Risk factors such as socioeconomic status, late-stage, or breast cancer at diagnosis, genetic differences in tumor subtypes, differences in health care access all contribute to these disparities. Socioeconomic determinants affecting the disparity in breast cancer illness include poverty, culture, as well as social injustice. In Hispanic women, the incidence of breast cancer is lower than in non-Hispanic women but is often diagnosed at a later stage than white women with larger tumors. Black women are usually diagnosed with breast cancer at a younger age than white women. The median age of diagnosis for Black women is 59, in comparison to 62 in White women. The incidence of breast cancer in Black women has increased by 0.4% per year since 1975 and 1.5% per year among Asian/Pacific Islander women since 1992. Incidence rates were stable for non-Hispanic White, Hispanics, and Native women. The five-year survival rate is noted to be 81% in Black women and 92% in White women. Chinese and Japanese women have the highest survival rates.[216] Poverty is a major driver for disparities related to breast cancer. Low-income women are less likely to undergo breast cancer screening and thus are more likely to have a late-stage diagnosis. [217] Ensuring women of all racial and ethnic groups receive equitable health care can positively affect these disparities. ## Pregnancy[edit] Pregnancy at an early age decreases the risk of developing breast cancer later in life.[218] The risk of breast cancer also declines with the number of children a woman has.[218] Breast cancer then becomes more common in the 5 or 10 years following pregnancy but then becomes less common than among the general population.[219] These cancers are known as postpartum breast cancer and have worse outcomes including an increased risk of distant spread of disease and mortality.[220] Other cancers found during or shortly after pregnancy appear at approximately the same rate as other cancers in women of a similar age.[221] Diagnosing new cancer in a pregnant woman is difficult, in part because any symptoms are commonly assumed to be a normal discomfort associated with pregnancy.[221] As a result, cancer is typically discovered at a somewhat later stage than average in many pregnant or recently pregnant women. Some imaging procedures, such as MRIs (magnetic resonance imaging), CT scans, ultrasounds, and mammograms with fetal shielding are considered safe during pregnancy; some others, such as PET scans are not.[221] Treatment is generally the same as for non-pregnant women.[221] However, radiation is normally avoided during pregnancy, especially if the fetal dose might exceed 100 cGy. In some cases, some or all treatments are postponed until after birth if the cancer is diagnosed late in the pregnancy. Early deliveries to speed the start of treatment are not uncommon. Surgery is generally considered safe during pregnancy, but some other treatments, especially certain chemotherapy drugs given during the first trimester, increase the risk of birth defects and pregnancy loss (spontaneous abortions and stillbirths).[221] Elective abortions are not required and do not improve the likelihood of the mother surviving or being cured.[221] Radiation treatments may interfere with the mother's ability to breastfeed her baby because it reduces the ability of that breast to produce milk and increases the risk of mastitis. Also, when chemotherapy is being given after birth, many of the drugs pass through breast milk to the baby, which could harm the baby.[221] Regarding future pregnancy among breast cancer survivors, there is often fear of cancer recurrence.[222] On the other hand, many still regard pregnancy and parenthood to represent normalcy, happiness and life fulfillment.[222] ## Hormones[edit] ### Birth control[edit] In breast cancer survivors, non-hormonal birth control methods such as the copper intrauterine device (IUD) should be used as first-line options.[223] Progestogen-based methods such as depot medroxyprogesterone acetate, IUD with progestogen or progestogen only pills have a poorly investigated but possible increased risk of cancer recurrence, but may be used if positive effects outweigh this possible risk.[224] ### Menopausal hormone replacement[edit] In breast cancer survivors, it is recommended to first consider non-hormonal options for menopausal effects, such as bisphosphonates or selective estrogen receptor modulators (SERMs) for osteoporosis, and vaginal estrogen for local symptoms. Observational studies of systemic hormone replacement therapy after breast cancer are generally reassuring. If hormone replacement is necessary after breast cancer, estrogen-only therapy or estrogen therapy with an intrauterine device with progestogen may be safer options than combined systemic therapy.[225] ## Research[edit] Treatments are being evaluated in clinical trials. This includes individual drugs, combinations of drugs, and surgical and radiation techniques Investigations include new types of targeted therapy,[226] cancer vaccines, oncolytic virotherapy,[227] gene therapy[228][229] and immunotherapy.[230] The latest research is reported annually at scientific meetings such as that of the American Society of Clinical Oncology, San Antonio Breast Cancer Symposium,[231] and the St. Gallen Oncology Conference in St. Gallen, Switzerland.[232] These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category. Fenretinide, a retinoid, is also being studied as a way to reduce the risk of breast cancer.[233][234] In particular, combinations of ribociclib plus endocrine therapy have been the subject of clinical trials.[235] A 2019 review found moderate certainty evidence that giving people antibiotics before breast cancer surgery helped to prevent surgical site infection (SSI). Further study is required to determine the most effective antibiotic protocol and use in women undergoing immediate breast reconstruction.[236] ### Cryoablation[edit] As of 2014 cryoablation is being studied to see if it could be a substitute for a lumpectomy in small cancers.[237] There is tentative evidence in those with tumors less than 2 centimeters.[238] It may also be used in those in who surgery is not possible.[238] Another review states that cryoablation looks promising for early breast cancer of small size.[239] ### Breast cancer cell lines[edit] See also: List of breast cancer cell lines Part of the current knowledge on breast carcinomas is based on in vivo and in vitro studies performed with cell lines derived from breast cancers. These provide an unlimited source of homogenous self-replicating material, free of contaminating stromal cells, and often easily cultured in simple standard media. The first breast cancer cell line described, BT-20, was established in 1958. Since then, and despite sustained work in this area, the number of permanent lines obtained has been strikingly low (about 100). Indeed, attempts to culture breast cancer cell lines from primary tumors have been largely unsuccessful. This poor efficiency was often due to technical difficulties associated with the extraction of viable tumor cells from their surrounding stroma. Most of the available breast cancer cell lines issued from metastatic tumors, mainly from pleural effusions. Effusions provided generally large numbers of dissociated, viable tumor cells with little or no contamination by fibroblasts and other tumor stroma cells. Many of the currently used BCC lines were established in the late 1970s. A very few of them, namely MCF-7, T-47D, and MDA-MB-231, account for more than two-thirds of all abstracts reporting studies on mentioned breast cancer cell lines, as concluded from a Medline-based survey. ### Molecular markers[edit] #### Metabolic markers[edit] Clinically, the most useful metabolic markers in breast cancer are the estrogen and progesterone receptors that are used to predict response to hormone therapy. New or potentially new markers for breast cancer include BRCA1 and BRCA2[240] to identify people at high risk of developing breast cancer, HER-2,[medical citation needed] and SCD1, for predicting response to therapeutic regimens, and urokinase plasminogen activator, PA1-1 and SCD1 for assessing prognosis.[medical citation needed] ## Other animals[edit] * Mammary tumor for breast cancer in other animals * Mouse models of breast cancer metastasis ## References[edit] 1. ^ a b c d e f g h i j k l m "Breast Cancer Treatment (PDQ®)". NCI. 23 May 2014. 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PMID 11522269. ## External links[edit] Classification D * ICD-10: C50 * ICD-9-CM: 174-175,V10.3 * ICD-O: M8502/3 * OMIM: 114480 * MeSH: D001943 * DiseasesDB: 1598 External resources * MedlinePlus: 000913 * eMedicine: med/2808 med/3287 radio/115 plastic/521 * Patient UK: Breast cancer * NCI: Breast cancer Library resources about Breast cancer * * * * Resources in your library * Resources in other libraries * Breast cancer at Curlie Portals Access related topics * Biology portal * Medicine portal * * * Find out more on Wikipedia's Sister projects * Media from Commons * Travel guides from Wikivoyage * News stories from Wikinews * Definitions from Wiktionary * Textbooks from Wikibooks * Quotations from Wikiquote * Source texts from Wikisource * Learning resources from Wikiversity * v * t * e Breast cancer Types Ductal * Ductal carcinoma in situ (DCIS): Paget's disease of the breast * Comedocarcinoma * Invasive ductal carcinoma (IDC) * Intraductal papilloma Lobular * Lobular carcinoma in situ (LCIS) * Invasive lobular carcinoma (ILC) Fibroepithelial/stromal * Fibroadenoma * Phyllodes tumor Other * Medullary carcinoma * Male breast cancer * Inflammatory breast cancer * Precursor lesions * Atypical ductal hyperplasia * Nipple adenoma General * Breast cancer * Classification * Risk factors * Alcohol * Hereditary breast—ovarian cancer syndrome * BRCA mutation * Screening * Treatment Other * Breast cancer awareness * Pink ribbon * National Breast Cancer Awareness Month * List of people with breast cancer Authority control * GND: 4008528-4 * LCCN: sh85016679 * NDL: 00568758 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Breast cancer	c0006142	26,998	wikipedia	https://en.wikipedia.org/wiki/Breast_cancer	2021-01-18T19:08:27	{"mesh": ["D001943"], "umls": ["C0006142"], "icd-10": ["C50"], "orphanet": ["180257"], "wikidata": ["Q128581"]}
A number sign (#) is used with this entry because combined oxidative phosphorylation deficiency-11 (COXPD11) is caused by homozygous or compound heterozygous mutation in the RMND1 gene (614917) on chromosome 6q25. Description COXPD11 is a severe multisystemic autosomal recessive disorder characterized by neonatal hypotonia and lactic acidosis. Affected individuals may have respiratory insufficiency, foot deformities, or seizures, and all reported patients have died in infancy. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes (summary by Garcia-Diaz et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). Clinical Features Ferreiro-Barros et al. (2008) reported a male infant, born of consanguineous Saudi Arabian parents, with severe neonatal encephalopathy resulting in death at age 18 months. The infant was unresponsive at birth, but was successfully resuscitated and intubated. He had little spontaneous limb movement and required mechanical ventilation. Physical examination showed tongue fasciculations, equinus deformities of the feet, and profound limb hypotonia with absent reflexes. He developed myoclonic jerks at age 3 days. Laboratory studies showed increased serum and CSF lactate. EEG was severely abnormal with diffuse signal attenuation, low amplitude, and slow activity consistent with postanoxic encephalopathy. Brain MRI showed signs of immaturity with prominence of the cortical sulci, possible pachygyria of the anterior frontal and temporal lobes, and hypomyelination. Muscle biopsy showed diffuse mitochondrial complex IV deficiency with low-normal activities of mitochondrial complexes I+III and II+III. There were reductions in the steady-state of complexes I, IV, and V, whereas complex II was normal and complex III was increased. Immunoblot analysis in patient cells showed a decrease of mitochondrial proteins, consistent with a defect in mitochondrial protein synthesis. Sural nerve biopsy revealed sparse myelinated nerve fibers, indicating severe loss of fibers and endoneural fibrosis consistent with a peripheral neuropathy. Fusion of patient cells with normal nuclear DNA complemented the defect, indicating that it was of nuclear origin. The diagnosis was profound neonatal encephaloneuromyopathy with cytochrome c oxidase (COX) deficiency. Family history revealed an older sister with congenital arthrogryposis, short neck, breathing problems, breech presentation, and hypoventilation requiring intubation and mechanical ventilation. Garcia-Diaz et al. (2012) provided follow-up of the family reported by Ferreiro-Barros et al. (2008) and reported 4 additional affected family members. Three infants presented with severe neonatal encephaloneuromyopathy at birth and showed lethargy, respiratory failure, profound floppiness, hyporeflexia or areflexia, equinus deformities, lactic acidosis, and death in the first year of life, whereas the fifth affected individual was stillborn and did not have skeletal deformities. Fibroblast studies of 1 patient confirmed deficiencies in multiple mitochondrial respiratory chain enzymes. Janer et al. (2012) reported a female infant, born of consanguineous parents, with encephalopathy and lactic acidosis. She was normal at birth, but developed seizures on day 6 and had severe hypotonia requiring tube feeding. At 4 months of age, she had unremitting seizures and her head circumference was not increasing; she died at age 5 months. Laboratory studies showed increased serum and CSF lactate, and cultured fibroblasts showed severely decreased cytochrome c oxidase activity. There were also assembly defects in complexes I, III, IV, and V, suggesting a mitochondrial translation defect. Postmortem examination showed marked cortical atrophy, and atrophic cord, ventricular dilation, and a thin corpus callosum. Microscopic analysis showed widespread vacuolation of cortical gray matter and status spongiosus, and extensive loss of myelin in the brainstem. Family history revealed an older sister who developed intractable seizures at 2 months of age and died at age 13 months. Brain CT scan showed cerebral atrophy and microcephaly. Taylor et al. (2014) reported 5 unrelated children, born of consanguineous British Pakistani parents, with COXPD11. The patients developed symptoms in infancy, and 2 died. All patients had muscle involvement and deafness; additional features included central nervous system, renal, and cardiac involvement. Patient cells showed deficiencies of mitochondrial respiratory complexes I, III, and IV. A sixth patient with a similar disorder was also reported. Janer et al. (2015) reported a boy, born of unrelated Caucasian parents, with COXPD11. He had failure to thrive with severe feeding difficulties in the first month of life and presented with epileptic encephalopathy and lactic acidosis at age 8 weeks. Laboratory studies showed lactic acidosis, anemia, hyperkalemia, hyponatremia, and hypertension. Echocardiogram showed mild left ventricle hypertrophy secondary to high blood pressure. He developed progressive renal failure and by age 3 years, he had end-stage renal tubulopathy. He had delayed psychomotor development with absent language, hearing loss, and seizures. Brain imaging showed T2-weighted signal abnormalities in the white matter and delayed myelination. Skeletal muscle biopsy showed decreased activities of mitochondrial respiratory complexes I, III, IV, and V, suggestive of a mitochondrial translation defect. The patient died at 4 years of age: postmortem examination showed hypoplastic kidneys with cysts and focal medullary calcification, enlarged liver with microvesicular steatosis and absent glycogen, and nodular adrenal glands. Ravn et al. (2016) reported 2 sisters, born of unrelated parents, with a slightly milder form of COXPD11 and longer survival. The patients were 17 and 13 years of age. Both had progressive renal failure and underwent successful renal transplantation, which may have contributed to the survival. The girls had failure to thrive in infancy, hypotonia, hearing impairment, and intellectual disability. One patient had normal brain imaging, whereas the other had loss of white matter in the temporal lobe; the latter patient also had seizures. Respiratory chain enzyme analysis showed decreased activities of complexes I, II, and IV, which was more pronounced in skeletal muscle than in fibroblasts. Inheritance The transmission pattern of COXPD11 in the families reported by Ferreiro-Barros et al. (2008), Garcia-Diaz et al. (2012), and Janer et al. (2012) was consistent with autosomal recessive inheritance. Mapping By homozygosity mapping of a consanguineous Saudi Arabian family with COXPD11, Garcia-Diaz et al. (2012) found linkage to a 1-Mb region on chromosome 6q25 between SNPs rs519861 and rs926777. Molecular Genetics By homozygosity mapping followed by candidate gene sequencing of a family with COXPD11, Garcia-Diaz et al. (2012) identified a homozygous pathogenic mutation in the RMND1 gene (614917.0001) that segregated with the disorder. The unaffected parents were heterozygous for the mutation. Janer et al. (2012) identified a homozygous mutation in the RMND1 gene (R417Q; 614917.0002) in a girl with COXPD11. The mutation was found by exome sequencing and confirmed by Sanger sequencing. In 5 unrelated children, each born of consanguineous British Pakistani parents, with COXPD11, Taylor et al. (2014) identified a homozygous mutation in the RMND1 gene (614917.0003). Haplotype analysis indicated a founder effect. A sixth patient with a similar phenotype was compound heterozygous for 2 RMND1 mutations. Functional studies of the variants were not performed. The patients were part of a study of 53 patients with mitochondrial respiratory chain complex deficiencies who underwent whole-exome sequencing. In a boy with COXPD11, Janer et al. (2015) identified compound heterozygous mutations in the RMND1 gene (614917.0004 and 614917.0005). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient fibroblasts showed absence of the 240-kD RMND1 homopolymeric complex. Patient cells also showed decreased levels of mitochondrial ribosomal subunits and impaired translation of mitochondrial proteins, which could be rescued by expression of wildtype RMND1. In 2 sisters, born of unrelated parents, with COXPD11, Ravn et al. (2016) identified compound heterozygous mutations in the RMND1 gene (614917.0004 and 614917.0006). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient cells showed low amounts of the RMND1 homopolymeric complex and assembly defects of complexes I, IV, and V. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Deafness Mouth \- Tongue fasciculations (rare) CARDIOVASCULAR Heart \- Cardiomyopathy (in some patients) RESPIRATORY \- Respiratory insufficiency requiring mechanical ventilation (in 1 family) ABDOMEN Liver \- Hepatomegaly \- Liver dysfunction \- Steatosis Gastrointestinal \- Poor feeding GENITOURINARY Kidneys \- Dysplastic kidneys \- Hypoplastic kidneys \- Cystic kidneys \- Renal tubular acidosis \- Renal disease \- Renal failure SKELETAL Feet \- Equinus foot deformities MUSCLE, SOFT TISSUES \- Hypotonia \- Myopathy \- Deficiency of mitochondrial respiratory enzymes I, III, IV, and V NEUROLOGIC Central Nervous System \- Hypotonia, severe \- Floppiness \- Lethargy \- Little spontaneous limb movement \- Delayed psychomotor development \- Poor or absent speech \- Seizures \- Myoclonic jerks (rare) \- Cortical atrophy \- Atrophic spinal cord \- Thin corpus callosum \- Hypomyelination \- Pachygyria \- Prominent sulci \- Delayed myelination \- White matter abnormalities Peripheral Nervous System \- Hyporeflexia \- Areflexia \- Sural nerve biopsy shows lack of myelinated fibers (rare) \- Peripheral neuropathy (rare) METABOLIC FEATURES \- Lactic acidosis LABORATORY ABNORMALITIES \- Increased serum lactate \- Increased CSF lactate MISCELLANEOUS \- Onset at birth or early infancy \- Early death (in some patients) \- Variable severity MOLECULAR BASIS \- Caused by mutation in the required for meiotic nuclear division 1 homolog gene (RMND1, 614917.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 11	c3554067	26,999	omim	https://www.omim.org/entry/614922	2019-09-22T15:53:43	{"doid": ["0060286"], "omim": ["614922"], "orphanet": ["324535"], "synonyms": ["Alternative titles", "COXPD11", "ENCEPHALONEUROMYOPATHY, INFANTILE, DUE TO MITOCHONDRIAL TRANSLATION DEFECT"]}

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