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A number sign (#) is used with this entry because of evidence that brain small vessel disease-3 (BSVD3) is caused by compound heterozygous mutation in the COLGALT1 gene (617531) on chromosome 19p13. Description Brain small vessel disease-3 (BSVD3) is an autosomal recessive disorder resulting from fragility of cerebral vessels causing an increased risk of intracranial bleeding. The resultant phenotype is highly variable depending on timing and location of the intracranial bleed. Some patients may have onset in utero or early infancy, with subsequent global developmental delay, spasticity, and porencephaly on brain imaging. Other patients may have normal or mildly delayed development with sudden onset of intracranial hemorrhage causing acute neurologic deterioration (summary by Miyatake et al., 2018). For a discussion of genetic heterogeneity of brain small vessel disease, see BSVD1 (175780). Clinical Features Miyatake et al. (2018) reported 2 unrelated patients with small vessel disease with variable manifestations. The first patient was a 12-year-old boy with severe global developmental delay, hypotonia, spastic quadriplegia, and seizures who needed full support for daily living. He had severely impaired intellectual development with developmental quotient of 11 for cognitive function and 14 for language. CT brain imaging in infancy showed calcifications and an enlarged lateral ventricle, and subsequent MRI imaging showed left porencephaly and leukoencephalopathy with mild atrophy, suggesting subependymal hemorrhages. Miyatake et al. (2018) concluded that the severe developmental delay was secondary to cerebral vascular abnormalities. The other patient showed poor eye contact in infancy, and thereafter had mild developmental delay with walking at 18 months and 2-word sentences at 35 months. Brain imaging initially showed hyperintense white matter abnormalities on T2-weighted images, with later development of more extended leukoencephalopathy and microbleeds in the basal ganglia. His IQ was 92 and he was able to enter a normal school. At age 9 years, he was infected with influenza virus and developed severe neurologic decompensation associated with multiple acute intracranial hemorrhages resulting in death. Inheritance The transmission pattern of BSVD3 in the families reported by Miyatake et al. (2018) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 unrelated patients with BSVD3, Miyatake et al. (2018) identified compound heterozygous mutations in the COLGALT1 gene (617531.0001-617531.0004). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Knockdown of the COLGALT1 gene in human HT1080 cells resulted in significantly decreased amounts of intracellular and extracellular COL4A1 (120130) compared to controls. Mutant COLGALT1 was unable to restore proper COL4A1 production in cells with knockdown of COLGALT1. COL4A1 in cells transfected with the mutants showed diffuse distribution in the cytoplasm with a significantly decreased granular pattern, suggesting abnormal accumulation of collagen in the endoplasmic reticulum lumen instead of within secretory vesicles involved in intracellular trafficking. INHERITANCE \- Autosomal recessive CARDIOVASCULAR Vascular \- Cerebral small vessel disease and fragility \- Cerebral hemorrhage MUSCLE, SOFT TISSUES \- Hypotonia (patient A) NEUROLOGIC Central Nervous System \- Global developmental delay (patient A) \- Impaired intellectual development, severe (patient A) \- Normal development (patient B) \- Neurologic decompensation, acute, associated with infection (patient B) \- Poor language (patient A) \- Seizures (patient A) \- Spastic quadriplegia (patient A) \- Porencephaly (patient A) \- Cerebral atrophy (patient A) \- Lacunae (patient B) \- Cerebral microbleeds \- Intracranial calcifications \- Leukoencephalopathy MISCELLANEOUS \- Phenotypic variability \- Two unrelated patients have been reported (last curated March 2019) MOLECULAR BASIS \- Caused by mutation in the collagen beta(1-0)galactosyltransferase 1 gene (COLGALT1, 617531.0001 ) ▲ 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	BRAIN SMALL VESSEL DISEASE 3	None	26,800	omim	https://www.omim.org/entry/618360	2019-09-22T15:42:21	{"omim": ["618360"]}
Benign recurrent intrahepatic cholestasis (BRIC) is a hereditary liver disorder characterized by intermittent episodes of intrahepatic cholestasis, generally without progression to chronic liver damage. BRIC is now believed to belong to a clinical spectrum of intrahepatic cholestatic disorders that ranges from the mild intermittent attacks in BRIC to the severe, chronic and progressive cholestasis seen in progressive familial intrahepatic cholestasis (PFIC; see this term). ## Epidemiology The prevalence of BRIC is unknown. ## Clinical description The first cholestatic episode can occur at any age but onset within the first two decades of life is most common. Patients present with bouts of intense pruritus and jaundice that may last for several weeks or months before resolving spontaneously. Associated manifestations include fatigue, loss of appetite, dark urine and pale stools. Hepatomegaly is also a common finding. Between episodes patients show no symptoms and the interval between attacks varies from months to years. The factors triggering the onset of the cholestasis remain unclear but viral infections, pregnancy and oral contraceptives have all been implicated. Two forms of BRIC have been described (BRIC1 and BRIC2) (see these terms). Clinically, these forms are very similar; however, patients with BRIC1 can display extrahepatic features such as hearing loss, pancreatitis and diarrhea, whereas cholelithiasis is a common manifestation of BRIC2. Patients with BRIC2 also have an increased risk for hepatobiliary malignancy. ## Etiology BRIC1 is allelic to PFIC1 (see this term) and is caused by mutations in the ATP8B1 gene (18q21) encoding a P-type ATPase expressed at the canalicular membrane of hepatocytes as well as in other epithelia. BRIC2 is allelic to PFIC2 (see this term) and is caused by mutations in the ABCB11 gene (2q24) encoding the liver-specific bile salt export pump (BSEP). The disease-causing mutations in BRIC are generally missense mutations. ## Diagnostic methods Diagnosis is based on the clinical history (at least 2-3 episodes of cholestasis), serum biochemistry (low to normal serum gamma GT activity and cholesterol, elevated serum total bile acids and high levels of conjugated bilirubin during episodes), cholangiography (showing normal intra- and extrahepatic bile ducts), liver histology (revealing intrahepatic cholestasis with normal liver structure) and immunohistochemical analysis (absent or reduced BSEP staining in majority of BRIC2 patients). Molecular genetic testing confirms the diagnosis and discriminates between subtypes. ## Differential diagnosis Differential diagnoses include drug-induced cholestatic disease as well as intrahepatic cholestasis of pregnancy, primary biliary cirrhosis and primary sclerosing cholangitis (see these terms). BRIC can be differentiated from PFIC on the basis of the disease course and liver histology. ## Antenatal diagnosis Prenatal testing is available for families in which the disease-causing mutations have already been identified. ## Genetic counseling Both BRIC1 and BRIC2 are inherited in an autosomal recessive manner, although a BRIC family with seemingly autosomal dominant inheritance has been reported. ## Management and treatment Management is mainly symptomatic: rifampicin and cholestyramine can be used to reduce pruritus and to induce remission of a cholestatic episode in some patients. Plasmapheresis/MARS (Molecular Adsorbents Recirculation System) has also been shown to be of benefit in some cases. For individuals that are unresponsive to medical therapy, endoscopic nasobiliary drainage is generally effective. Partial external biliary diversion is also used to improve quality of life and prevent disease progression. Liver transplantation may eventually be indicated for patients with frequent and severe episodes. ## Prognosis The prognosis is generally good with a tendency for a reduction in the frequency of attacks with age. However, progression from BRIC to PFIC and cirrhosis has been reported in the literature, indicative of a clinical continuum. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Benign recurrent intrahepatic cholestasis	c0149841	26,801	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=65682	2021-01-23T19:01:40	{"gard": ["12185"], "omim": ["243300", "605479"], "umls": ["C0149841"], "icd-10": ["K83.1"], "synonyms": ["BRIC", "Summerskill-Walshe-Tygstrup syndrome"]}
Intellectual disability-myopathy-short stature-endocrine defect syndrome is a rare congenital myopathy syndrome characterized by nonprogressive myopathy (manifesting with mild facial and generalized weakness, bilateral ptosis, and severe lumbar lordosis), severe intellectual disability, short stature, and sexual infantilism (due to hypogonadotropic hypogonadism). The presence of a small pituitary fossa was also noted. There have been no further descriptions in the literature since 1985. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Intellectual disability-myopathy-short stature-endocrine defect syndrome	c1854663	26,802	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3068	2021-01-23T17:47:55	{"gard": ["1358"], "mesh": ["C535458"], "omim": ["253320"], "umls": ["C1854663"], "icd-10": ["Q87.8"], "synonyms": ["Chudley-Rozdilsky syndrome"]}
According to experts, the total number of individuals with HIV (including those who are undiagnosed) was estimated in 2016 to be between 0.85 and 1.5 million[1] (the lower estimate is from the Ministry of Healthcare of the Russian Federation). Prevalence of HIV in adult people is between 0.8 and 1%.[2] According to the UN, Russia has one of the fastest growing HIV/AIDS epidemics in the world.[3] Approximately 95,000 Russians were diagnosed with HIV in 2015, and approximately 75,000 in the first nine months of 2016.[3] Stigma surrounding the disease, and government indifference have contributed to the crisis.[4] As of 2016 the HIV/AIDS epidemic, despite successes with intravenous drug users, was poised to move into the general population of sexually active young people.[5] ## Contents * 1 USSR * 2 Russian Federation * 3 Recent data on the epidemics * 4 See also * 5 References * 6 External links ## USSR[edit] The first officially documented case of HIV in Russia (then the Soviet Union) was diagnosed in March 1987.[6] In 1984, one patient had been diagnosed with HIV by a Soviet doctor, but the record of her case was expunged. Prior to the diagnosis made in 1987, the Soviet Union denied that any HIV infections were occurring within its territory.[citation needed] Doctors were pressured to misdiagnose cases of HIV and AIDS as other ailments, and the government failed to take any steps to protect or warn the public about the nature of the disease and how to prevent its spread.[citation needed] The policy of denial and repression of HIV diagnoses not only inhibited an effective government response to the epidemic, but also inhibited the recording of accurate statistics. There is a lack of accurate data on people infected with HIV in the Soviet Union, as well as a lack of accurate data on the at-risk groups: injecting drug users (IDUs), men who have sex with men (MSM), and sex workers. In 1988, it was estimated that the incidence of homosexuality in the population was only 1 in 100,000,[7] and the existence of sex workers and drug addicts were also grossly underestimated. The size of the IDU population was even more underestimated than the other groups. In 1988, the incidence of intravenous drug use was considered to be extremely low, but in 1990 the veil of ignorance was partially lifted, and the official number of registered drug users measured 300,000. Nevertheless, this number is considered to be artificially low, with Soviet police having estimated the real number of addicts to be ten times as large.[8] The authorities’ neglect and near denial of the existence of these groups complicated the problems they faced as they came to grips with the existence of the HIV epidemic itself. Officials were unsure whom to test for HIV, due to never having kept track of the at-risk populations previously. Furthermore, individuals who belong to one of the at-risk groups were unlikely to independently seek treatment, due to both poor public awareness of the disease, as well as a fear of the stigma they would face if they came forward. ## Russian Federation[edit] Confirmed HIV mortality in the US and Russia per 100,000 population, 2014 projected based on 4 months In 2002, the Russian government collaborated with the World Bank to form a joint project to combat the rise of both tuberculosis and HIV/AIDS in the Russian Federation, funded in part by a loan from the bank of $150 million, and in part by the Russian treasury.[9] This project was stipulated to last from 2003–2008, with the aim of bridging the gap between needs and current practices in fighting both diseases.[10] The objectives of the project, as named by the World Bank in the original loan agreement, were to “contain the growth” of the epidemics in the short term, and to “halt and reverse” the course of the epidemics in the medium term.[9] A long-term objective is conspicuously absent. The fact that the project lacked a long-term objective is perhaps alarming, considering the obstacles the bank hopes to help Russia overcome through its loan. These obstacles were, in full: “inadequate response, both in scale and in technical quality, to tackle the large burden of TB and HIV/AIDS/STIs”, “the need for stronger management and institutional capacity for rapid implementation of large-scale programs, based on scientific evidence, across the vast expanse of Russia”, and last but not least “financial constraints”.[10] Little is said throughout the document on the exact nature of the “financial constraints” to be overcome. Russia must begin paying back the loan immediately in 2008, through 2020.[9] The long-term effect of the loan repayment on Russia's effort to combat these diseases may be significant, especially considering the fact that financial difficulties were an obstacle at the outset. One of the major areas in which the project intended to combat the spread of HIV was through interventions targeted at high risk sectors of the population. These interventions have been shown in the international literature to be highly effective at combating the spread of the disease, and the World Bank clearly communicated its intention to implement evidence-based programs, such as targeted interventions, through the project.[10] The key demographic to reach with targeted interventions is the population of intravenous drug users. At the time the agreement was made, various estimates placed the percentage of the HIV positive population that are IDUs at 70-95%,[9] making IDUs by far the most at-risk group. For this reason, interventions such as syringe exchange programs are listed as a high priority, with the goal of creating “approximately thirty (30) harm reduction programs for IDUs, and for the establishment of a federal HIV/AIDS and STI coordination center for training in high risk group prevention activities.”.[9] Despite these optimistic goals, even in the beginning, the project proposal makes clear that there will be significant cultural stigmas and prejudices to overcome, especially in relation to drug users and homosexuals, in order to implement targeted interventions. Contemporary Russia still possesses “a strong legacy of health services in the Soviet model, which is often at odds with contemporary approaches to evidence-based control of infectious diseases.” This vestigial approach to health care in the face of a rapidly growing epidemic has “contributed to a tension between a need for evidence-based disease control and traditional practices of doubtful effectiveness or potential harmfulness”.[10] Thus the World Bank expressed its doubts even before the project was implemented. In the review of the results of the loan agreement, the World Bank deemed the project to be overall a success.[11] This favorable appraisal was mainly due to the success of the TB portion of the project, as Russia conspicuously failed to establish targeted control interventions for IDUs to combat HIV/AIDS. The report reveals that the World Bank originally underestimated the “political and public reaction to harm reduction activities for high-risk groups such as IDUs”.[11] The attempts made by the bank to advocate for harm reduction programs failed to dispel the beliefs that IDUs are socially deviants, and that fighting HIV/AIDS within the IDU population is not worthwhile. “In fact, to some extent, this perception continues today”.[11] Therefore, in spite of the original plan to implement approximately 30 different harm reduction programs to help IDUs throughout Russia, the scope of targeted interventions was “limited to needs assessment of readiness of regional institutions to launch HIV prevention interventions in high risk groups (harm reduction programs) and development and approval of methodological recommendations”, in short, no new interventions or harm reduction programs for IDUs were effectively implemented.[11] Thus, the World Bank admitted that in retrospect its original plans may have been “over ambitious” and that “TB and HIV/AIDS remain significant threats to health and development in the Federation.”.[11] In 2007, 83% of HIV infections in Russia were registered among IDUs, 6% among sex workers, and 5% among prisoners.[12] \- though as of 2010 the share of IDUs had gone down to ca. 70%.[13] In 2007, 93.19% of adults and children with advanced HIV infection were receiving antiretroviral therapy.[14][15] The official number of registered HIV-infected people — 703,781 (22 November 2012)[16] Coordination of activities in responding to AIDS remains a challenge for Russia, despite increased efforts. In 2006, treatment for some patients was interrupted due to delays in tender procedures and unexpected difficulties with customs. Additionally, lack of full commitment to an in-depth program for education on sex and drugs in schools hinders effective prevention programs for children.[15] Education and knowledge in the general population surrounding HIV is limited. The Human Rights Commission comments that the low level of education may be an important determinant of discrimination and stigma experienced by people living with HIV/AIDs.[17] In addition, prevention programs for high risk groups implemented by Non-Governmental Organizations (NGO's) are impeded by lack of sustainability and government regulations, including difficult to meet requirements for reporting and severe penalties for non-compliance.[18] At the 2010 International AIDS Conference in Vienna, a representative of the Andrei Rylkov Foundation for Health and Social Justice, criticized Russian authorities for their harsh line on IDUs, which makes people in this high-risk group afraid of seeking out the health services they need, causing HIV rates to rise.[19] A research project by NIBR in 2010 revealed that despite Federal authorities' increased efforts, there remains a systemic reluctance to fund programs targeted at risk groups, with big regional differences in level of commitment to and way of organizing campaigns and treatment. Influence of individuals at the local level and personal relations between key stakeholders in different regions seem to be of core importance. The NIBR project found that the 'bottleneck' is at the elite level rather than the popular level: representative surveys in Arkhangelsk and St. Petersburg found that 90% supported education on sexual issues in the schools, more than 70% supported needle exchange-programs, and a majority supported methadone treatment - despite the latter being illegal in Russia today.[13] Because of official opposition to the dispensation of legal opioids for the treatment of heroin addiction, fearing diversion of such drugs, Russia approved the use of Vivitrol, an extended release version of the opioid antagonist naltrexone.[20] Another harm reduction program for IDUs, syringe exchange programs are currently not illegal in Russia, however, they face barriers to continued sustainability, primarily lack of funding.[21] The Russian government also declined to fund needle and syringe exchange programs after Global Fund support was discontinued in 2011, leading to the closure of many of the programs.[22] Estimated prevalence in % of HIV among young adults (15–49) per country as of 2011.[23] Current interventions that have been tested include targeted interventions that address the needs of specific populations, including gender specific interventions, and an intervention implemented in Orenburg, the “Follow the Voice of Life” program which is aimed at preventing HIV among MSM and empowering them to reduce their risk. The program uses peer counseling, community mobilization and advocacy to lobby for the needs of MSM around HIV.[24] Peer education is another model which has been found to show promise in reducing IDUs risk for HIV, and has been studied across several randomized control trials.[25] In these programs, IDUs are trained in harm reduction skills building and motivated to spread this message throughout their network, and as such, it an approach that capitalizes on both the social network of IDUs, as well as the credibility lent to information that comes from peers. Finally, programs that introduce brief HIV prevention counseling into settings that individuals are already frequenting, such as health clinics or STI clinics have been proven to show some level of efficacy in the literature.[26] All of the programs and interventions face barriers to sustainability however, primarily around issues of funding. According to Vadim Pokrovskiy from Federal HIV Center by 2019 the number of HIV infections will reach 2 million and infections are most prevalent among males aged 30–34, out of which 3% are infected. Infection rate among females in the same age range reaches 1.5%. Of those reported as infected throughout 2014, 57% acquired the infection through drug use, 1% through male homosexual contacts and 40% through heterosexual contacts.[27] Availability of HIV treatment drug also declined in 2013-2014 due to economic situation and systemic issues in the health care management and only 30% of those diagnosed with HIV who need medication actually receive it.[28] The conspiracy theories on HIV returned into the public discourse with the degradation of Russia–European Union relations in 2014–2015. Opinions of the medical community, like Vadim Pokrovskiy cited above, are countered by political activists who present HIV epidemics a "a tool of Western information war" and propose promotion of "traditional values" as an instrument to reduce number of infections rather than the "Western" methods such as "absolute priority for rights of the high-risk groups such as drug users and LGBT".[29] Russia is also targeted by conspiracy theories from the HIV denialism movement. While a small movement worldwide it has attracted significant public attention in recent times. In April 2019, two Siberian women had refused treatment and were reported to have died afterwards. A well-known activist from the Irkutsk region also refused treatment for her HIV positive child. Another Irkutsk woman was convicted of negligence for refusing treatment for her four-month-old daughter, who died of complications from Aids in 2018 it is reported. The movement is well-represented in social media. A popular group on Vkontakte called “HIV Aids is the greatest hoax of the XX century” with over 16 thousand followers. The page prominently links to House of Numbers, a 2009 documentary coming from the United States about HIV/Aids by filmmaker Brent Leung which is heavily criticized by media around the world.[30][31] A number of regions in Russian are officially classified as being in state of generalized epidemic, which is announced when over 1% of overall inhabitants are HIV-positive - 1.7% for example in Sverdlovsk Oblast. Other regions include Kemerovo, Tomsk, Novosibirsk, Chelyabinsk, Samara, Irkutsk, Kurgan oblasts, Altai, Perm and Krasnoyarsk krais.[32] ## Recent data on the epidemics[edit] In 2015 44% of new infections occurred through heterosexual sex. Experts predict that heterosexual sex may soon overtake injecting drug use as the main means of HIV transmission. This means the HIV epidemic may be shifting from mainly affecting key populations including people who inject drugs, sex workers, prisoners and men who have sex with men, to affecting the general population.[1] According to data published in 2019 amount of infected reached 1.06 million, there were 37 thousand deaths from AIDS in 2018. Infection rate in male population aged 30–40 is estimated about 4%. 57% acquired infection in heterosexual contacts, 2-3% in MSM contacts and 40-41% from drug use.[33] ## See also[edit] * Health in Russia ## References[edit] 1. ^ a b "HIV and AIDS in Russia". Retrieved 2017-03-04. 2. ^ "Russia's record-breaking HIV epidemic: what you need to know". The Independent. 2016-01-23. Retrieved 2016-11-18. 3. ^ a b "Russia Wishes Away Its HIV Epidemic". Retrieved 2016-11-18. 4. ^ Macfarquhar, Neil (2016-12-28). "H.I.V. Cases Surpass a Million in Russia, but Little Is Done". The New York Times. ISSN 0362-4331. Retrieved 2016-12-28. 5. ^ Neil MacFarquhar (December 28, 2016). "H.I.V. Cases Surpass a Million in Russia, but Little Is Done". The New York Times. Retrieved December 28, 2016. 6. ^ Twigg, Judyth (2006). HIV/AIDS in Russia and Eurasia, Volume 1. Gordonsville: Palgrave Macmillan. p. 9. 7. ^ Twigg, Judyth (2006). HIV/AIDS in Russia and Eurasia, Volume 1. Gordonsville: Palgrave Macmillan. p. 16. 8. ^ Twigg, Judyth (2006). HIV/AIDS in Russia and Eurasia, Volume 1. Gordonsville: Palgrave Macmillan. p. 17. 9. ^ a b c d e World Bank. "Loan Agreement for Tuberculosis and AIDS Control Project between Russian Federation and the International Bank for Reconstruction and Development". Retrieved 5 April 2014. 10. ^ a b c d World Bank. "Project Appraisal Document". Retrieved 5 April 2014. 11. ^ a b c d e World Bank. "Implementation Completion and Results Report". Retrieved 5 April 2014. 12. ^ UNAIDS Russia UNAIDS Retrieved on July 11, 2008 13. ^ a b Aasland, Aadne & Mikkel Berg-Nordlie: Situation critical for HIV/AIDS prevention in Russia, NIBR International Blog 12.11.2010 Archived 2011-04-30 at the Wayback Machine 14. ^ Eastern Europe and Central Asia AIDS epidemic update UNAIDS Retrieved on May 3, 2008 15. ^ a b UNAIDS: Russian Federation Archived 2008-04-09 at the Wayback Machine UNAIDS 16. ^ Federal HIV center. 17. ^ Human Rights Watch. Lessons not learned: Human rights abuses and HIV/AIDS in the Russian Federation. 2004; 16(5) Available from: https://www.hrw.org/sites/default/files/reports/russia0404.pdf. 18. ^ The International Center for Not-for-Profit Law. NGO Law Monitor: Russia. February 17, 2015. Available from: http://www.icnl.org/research/monitor/russia.html. 19. ^ Aasland, Aadne: ”Rights here, right now!” – the reality of injecting drug users in Russia? Archived 2011-04-30 at the Wayback Machine (NIBR International Blog 20.07.2010) 20. ^ Ed Holt (2010)."Russian injected drug use soars in face of political inertia". Lancet 3;376(9734):13-14. doi:10.1016/S0140-6736(10)61041-0 21. ^ Lunze, K., Raj, A., Cheng, DM. et al. Punitive policing and associated substance use risk among HIV-positive people in Russia who inject drugs. Journal of International AIDS Society. 2014;17:19043 22. ^ Degenhardt L, Mathers BM, Wirtz AL, et al. What has been achieved in HIV prevention, treatment and care for people who inject drugs, 2010-2012? A review of the six highest burden countries. Int J Drug Policy. 2014;25(1):53-60. 23. ^ "AIDSinfo". UNAIDS. Retrieved 4 March 2013. 24. ^ 1\. USAID. AIDSTAR One case study series: “Follow the voice of Life”. Available from: http://www.aidstar-one.com/sites/default/files/AIDSTAROne_Case_Study_GENDERMARPS_NewLife_Russia.pdf. 25. ^ Hoffman IF, Latkin C, Kukhareva PV, et al. A peer educator network HIV prevention intervention among injection drug users: results of a randomized control trial in St. Petersburg, Russia. AIDS Behav. 2013;17:2510-2520. 26. ^ Abdala N, Zhan W, Shabolitas A, et al. Efficacy of a brief HIV prevention counseling intervention among STI clinic patients in Russia: a randomized controlled trial. AIDS Behav. 2013; 17:1016-1024. 27. ^ "В России количество вставших на учет ВИЧ-инфицированных больше, чем во всей Европе вместе взятой". Kommersant. 14 May 2015. Retrieved June 13, 2015. 28. ^ "Awash in AIDS \| How Russia's economic crisis is skyrocketing HIV infections again". Retrieved 2015-09-17. 29. ^ "Kremlin Experts Blame Condoms for Russian HIV Epidemic \| News". The Moscow Times. Retrieved 2016-06-04. 30. ^ Roth, Andrew (May 3, 2019). "Russia wants to make HIV/AIDS denialism illlegal to halt epidemic". The Guardian. Retrieved 18 March 2020. 31. ^ "Aids Deadly Doubt, Tagespiegel 2010". Retrieved 18 March 2020. 32. ^ "Эпидемия ВИЧ в Екатеринбурге. Вопросы и ответы — Meduza". Meduza (in Russian). Retrieved 2016-11-28. 33. ^ "Число инфицированных ВИЧ в России превысило 1 млн человек". Interfax.ru (in Russian). Retrieved 2019-12-01. ## External links[edit] * 2008 UNAIDS Russia report * HealthRight International - NGO working to address HIV/AIDS in Russia * Russian Federal HIV center. * v * t * e HIV/AIDS topics HIV/AIDS HIV * HIV * Lentivirus * structure and genome * subtypes * CDC classification * disease progression rates * HIV/AIDS * diagnosis * management * pathophysiology * prevention * research * vaccination * PrEP * WHO disease staging system for HIV infection and disease * Children * Teens / Adults * Countries by AIDS prevalence rate Conditions * Signs and symptoms * AIDS-defining clinical condition * Diffuse infiltrative lymphocytosis syndrome * Lipodystrophy * Nephropathy * Neurocognitive disorders * Pruritus * Superinfection * Tuberculosis co-infection * HIV Drug Resistance Database * Innate resistance to HIV * Serostatus * HIV-positive people * Nutrition * Pregnancy History * History * Epidemiology * Multiple sex partners * Timeline * AIDS Museum * Timothy Ray Brown * Women and 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* Indonesia * Iran * Iraq * Israel * Japan * Jordan * Kazakhstan * North Korea * South Korea * Kuwait * Kyrgyzstan * Laos * Lebanon * Malaysia * Maldives * Mongolia * Myanmar * Nepal * Oman * Pakistan * Philippines * Qatar * Russia * Saudi Arabia * Singapore * Sri Lanka * Syria * Tajikistan * Thailand * Turkey * Turkmenistan * United Arab Emirates * Uzbekistan * Vietnam * Yemen States with limited recognition * Abkhazia * Artsakh * Northern Cyprus * Palestine * South Ossetia * Taiwan Dependencies and other territories * British Indian Ocean Territory * Christmas Island * Cocos (Keeling) Islands * Hong Kong * Macau * Book * Category * Asia portal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	HIV/AIDS in Russia	None	26,803	wikipedia	https://en.wikipedia.org/wiki/HIV/AIDS_in_Russia	2021-01-18T18:36:54	{"wikidata": ["Q2406363"]}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) The topic of this article may not meet Wikipedia's general notability guideline. Please help to demonstrate the notability of the topic by citing reliable secondary sources that are independent of the topic and provide significant coverage of it beyond a mere trivial mention. If notability cannot be shown, the article is likely to be merged, redirected, or deleted. Find sources: "Sleep emailing" – news · newspapers · books · scholar · JSTOR (January 2020) (Learn how and when to remove this template message) 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: "Sleep emailing" – news · newspapers · books · scholar · JSTOR (January 2020) (Learn how and when to remove this template message) Sleep messaging (or sleep emailing or sleep texting) is a phenomenon related to sleepwalking where people send emails or other textual communications to co-workers in a combined state of sleep and wakefulness.[1][secondary medical source needed][2][3] ## References[edit] 1. ^ Siddiqui, Fouzia; Osuna, Edgar; Chokroverty, Sudhansu (2009). "Writing emails as part of sleepwalking after increase in Zolpidem". Sleep Medicine. 10 (2): 262–264. doi:10.1016/j.sleep.2008.09.008. PMID 19059805. 2. ^ Stross, Randall (2009-01-10). "You've Been Talking (or Pressing 'Send') in Your Sleep". The New York Times. ISSN 0362-4331. Retrieved 2020-01-29. 3. ^ Hare, Breeanna. "Don't recall sending that message? Maybe you're 'sleep texting'". CNN. Retrieved 2020-01-29. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Sleep emailing	None	26,804	wikipedia	https://en.wikipedia.org/wiki/Sleep_emailing	2021-01-18T18:45:46	{"wikidata": ["Q85801575"]}
Hereditary breast–ovarian cancer syndrome Other namesHBOC Ovarian and breast cancer patients in a pedigree chart of a family SpecialtyObstetrics and gynaecology, endocrinology, dermatology, oncology, medical genetics Hereditary breast–ovarian cancer syndromes (HBOC) are cancer syndromes that produce higher than normal levels of breast cancer, ovarian cancer and additional cancers in genetically related families (either one individual had both, or several individuals in the pedigree had one or the other disease). It accounts for 90% of the hereditary cancers.[1] The hereditary factors may be proven or suspected to cause the pattern of breast and ovarian cancer occurrences in the family.[2] The name HBOC may be misleading because it implies that this genetic susceptibility to cancer is mainly in women. In reality, all sexes have the same rates of gene mutations and HBOC can predispose to other cancers including prostate cancer and pancreatic cancer.[3] For this reason, the term "King syndrome" has recently come into use. The new name references Mary-Claire King who identified the genes BRCA1 and BRCA2. ## Contents * 1 Causes * 2 Prevention * 3 References * 4 External links ## Causes[edit] A number of genes are associated with HBOC.[4] The most common of the known causes of HBOC are: * BRCA mutations:[4] Harmful mutations in the BRCA1 and BRCA2 genes can produce very high rates of breast and ovarian cancer, as well as increased rates of other cancers. Mutations in BRCA1 are associated with a 39-46% risk of ovarian cancer and mutations in BRCA2 are associated with a 10-27% risk of ovarian cancer.[5] Other identified genes include: * MLH1, MSH2, MSH6, PMS2: mutations in genes that lead to Lynch Syndrome put individuals at risk for ovarian cancer.[6] * TP53: Mutations cause Li-Fraumeni syndrome. It produces particularly high rates of breast cancer among younger women with mutated genes, and despite being rare, 4% of women with breast cancer under age 30 have a mutation in this gene.[4] * PTEN: Mutations cause Cowden syndrome, which produces hamartomas (benign polyps) in the colon, skin growths, and other clinical signs, as well as an increased risk for many cancers.[4] * CDH1: Mutations are associated with lobular breast cancer and gastric cancer.[4] * STK11: Mutations produce Peutz–Jeghers syndrome. It is extremely rare, and creates a predisposition to breast cancer, intestinal cancer, and pancreatic cancer.[4] * CHEK2: Approximately one out of 40 northern Europeans have a mutation in this gene, making it a common mutation. It is also one of the most frequently mutated genes after BRCA among Hispanics in the United States.[7] Considered a moderate-risk mutation, it may double or triple the carrier's lifetime risk of breast cancer, and also increase the risk of colon cancer and prostate cancer.[4] * ATM: Mutations cause ataxia telangectasia; female carriers have approximately double the normal risk of developing breast cancer.[4] * PALB2: Studies vary in their estimate of the risk from mutations in this gene and the frequency of mutations in this gene may be different among different populations.[7] It may be moderate risk, or as high as BRCA2.[4] Approximately 45% of HBOC cases involve unidentified genes, or multiple genes.[4] ## Prevention[edit] People with BRCA1 and BRCA2 mutations are recommended to have a transvaginal ultrasound 1-2 times per year. Screening with CA-125 is also recommended. Prophylactic salpingo-oophorectomy (removal of the ovaries and Fallopian tubes to prevent cancer) is recommended at age 35-40 for people with BRCA1 mutations and at age 40-45 for people with BRCA2 mutations.[5] ## References[edit] 1. ^ Bickerstaff, Helen (2017). Gynaecology by Ten Teachers. United Kingdom: CRC Press. p. 330. ISBN 978-1-4987-4428-7. 2. ^ "Hereditary Breast Ovarian Cancer Syndrome (BRCA1 / BRCA2)". Stanford University. Retrieved 2008-09-02. 3. ^ Pritchard, Colin C. (July 2019). "New name for breast-cancer syndrome could help to save lives". Nature. 571 (7763): 27–29. Bibcode:2019Natur.571...27P. doi:10.1038/d41586-019-02015-7. PMID 31270479. 4. ^ a b c d e f g h i j Morris, Joi L.; Gordon, Ora K. (Ora Karp) (2010). Positive results : making the best decisions when you're at high risk for breast or ovarian cance. Amherst, N.Y.: Prometheus Books. pp. 337–340. ISBN 978-1-59102-776-8. 5. ^ a b Ring, Kari L.; Garcia, Christine; Thomas, Martha H.; Modesitt, Susan C. (November 2017). "Current and future role of genetic screening in gynecologic malignancies". American Journal of Obstetrics and Gynecology. 217 (5): 512–521. doi:10.1016/j.ajog.2017.04.011. ISSN 1097-6868. PMID 28411145. 6. ^ Woolderink, J. M.; De Bock, G. H.; de Hullu, J. A.; Hollema, H.; Zweemer, R. P.; Slangen, B. F. M.; Gaarenstroom, K. N.; van Beurden, M.; van Doorn, H. C. (August 2018). "Characteristics of Lynch syndrome associated ovarian cancer". Gynecologic Oncology. 150 (2): 324–330. doi:10.1016/j.ygyno.2018.03.060. hdl:1887/96199. ISSN 1095-6859. PMID 29880284. 7. ^ a b Weitzel, Jeffrey N.; Neuhausen, Susan L.; Adamson, Aaron; Tao, Shu; Ricker, Charité; Maoz, Asaf; Rosenblatt, Margalit; Nehoray, Bita; Sand, Sharon (2019-06-17). "Pathogenic and likely pathogenic variants in PALB2, CHEK2, and other known breast cancer susceptibility genes among 1054 BRCA-negative Hispanics with breast cancer". Cancer. 125 (16): 2829–2836. doi:10.1002/cncr.32083. ISSN 1097-0142. PMC 7376605. PMID 31206626. ## External links[edit] Classification D * ICD-10: C50 C56 * OMIM: 604370 * MeSH: D061325 External resources * Orphanet: 145 * 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 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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 breast–ovarian cancer syndrome	c0677776	26,805	wikipedia	https://en.wikipedia.org/wiki/Hereditary_breast%E2%80%93ovarian_cancer_syndrome	2021-01-18T18:53:46	{"mesh": ["D061325"], "umls": ["C0677776"], "orphanet": ["145"], "wikidata": ["Q19000660"]}
A rare, genetic, syndromic intellectual disability disease characterized by progressive postnatal microcephaly and global developmental delay, as well as moderate to profound intellectual disability, difficulty or inability to walk, pyramidal signs (including spasticity, hyperreflexia and extensor plantar response) and thin corpus callosum revealed by brain imaging. Ophthalmologic signs (including nystagmus, strabismus and abnormal retinal pigmentation), foot deformity and genital anomalies 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	Microcephaly-thin corpus callosum-intellectual disability syndrome	c3810080	26,806	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=397951	2021-01-23T16:52:38	{"omim": ["615599"], "icd-10": ["Q87.8"]}
A number sign (#) is used with this entry because of evidence that Menke-Hennekam syndrome-1 (MKHK1) is caused by heterozygous mutation in exon 30 or 31 of the CREBBP gene (600140) on chromosome 16p13. Mutation elsewhere in the CREBBP gene results in Rubinstein-Taybi syndrome-1 (RSTS1; 180849), which is phenotypically distinct. Description Menke-Hennekam syndrome-1 (MKHK1) is a congenital disorder characterized by variable impairment of intellectual development and facial dysmorphisms. Feeding difficulties, autistic behavior, recurrent upper airway infections, hearing impairment, short stature, and microcephaly are also frequently seen. Although mutations in the same gene cause Rubinstein-Taybi syndrome-1 (RSTS1; 180849), patients with MKHK1 do not resemble the striking phenotype of RSTS1. ### Genetic Heterogeneity of Menke-Hennekam Syndrome Menke-Hennekam syndrome-2 (MKHK2; 618333) is caused by heterozygous mutation in exons 30 or 31 of the EP300 gene (602700). Mutation elsewhere in that gene results in RSTS2 (613684). Clinical Features Menke et al. (2016) reported 11 patients carrying mutations in CREBBP (exon 30 or 31) whose phenotype differed substantially from Rubinstein-Taybi syndrome (RSTS1; 180849). None had broad thumbs or characteristic facial features, and 3 had only somewhat broadened halluces. All had developmental delay or intellectual disability, 5 had short stature, and 7 had microcephaly. Facial characteristics were variable and included short palpebral fissures, telecanthus, depressed nasal bridge, short nose, anteverted nares, short columella, and long philtrum. Six of the 11 had autistic behavior and 2 had self-injurious behavior. Other symptoms were recurrent upper airway infection in 5, feeding problems in 7, and impaired hearing in 7. No major malformations occurred. Menke et al. (2018) reported an additional 11 patients with MKHK1 and compared them to the previously reported patients. Almost all patients had impaired intellectual development, with autistic behavior in more than half. Short stature, microcephaly, feeding problems, and vision and hearing impairment were frequent. Malformations were uncommon and included cleft palate, congenital heart anomaly, renal anomaly, malrotation, and cryptorchidism. Cerebral anomalies (white matter atrophy, hypoplasia or agenesis of corpus callosum) were seen in 3 of 4 previously unreported patients tested. Facial features were variable but patients with mutations in a restricted 3-prime region resembled each other (see GENOTYPE/PHENOTYPE CORRELATIONS). Only 2 had broad halluces. None of the patients had broad or angulated thumbs, or any other characteristic typical of RSTS. Inheritance In all MKHK1 patients but 1 included in the reports of Menke et al. (2016), Menke et al. (2018), and Angius et al. (2019), the mutations were shown to have arisen de novo. The only patient in which mode of inheritance could not be established was patient C16 of Menke et al. (2018), whose parents were deceased. Genotype/Phenotype Correlations Menke et al. (2018) noted that MKHK1 patients with mutations at the 3-prime end of CREBBP between basepairs 5,595 and 5,614 share facial characteristics consisting of ptosis, telecanthus, short and upslanting palpebral fissures, depressed nasal bridge, short nose, anteverted nares, short columella, and long philtrum. The facial characteristics change with age and are best recognized in infancy. Molecular Genetics Menke et al. (2016) reported 10 novel missense variants (e.g., 600140.0009-600140.0012) in CREBBP, all in the last part of exon 30 or the first part of exon 31, in 11 patients with Menke-Hennekam syndrome. All mutations occurred de novo. Menke et al. (2018) reported 9 different mutations (e.g., 600140.0010-600140.0012), 6 of them novel, in exon 30 or 31 of the CREBBP gene in 11 previously unreported patients with MKHK1. Eight mutations were missense and 1 was a 3-bp deletion; all but 1, in a patient whose parents were deceased, were shown to have occurred de novo. Menke et al. (2018) also reported 2 patients with MKHK2 (618333) with mutations in EP300 (602700) in locations homologous to those found in CREBBP. Angius et al. (2019) reported a 17-year-old Sardinian boy with MKHK1 who carried a novel de novo missense variant (E1724K; 600140.0013) in exon 30 of CREBBP. He presented with mild intellectual impairment and dysmorphisms as well as obesity, and did not resemble patients with classical Rubinstein-Taybi syndrome. Angius et al. (2019) noted that obesity had also been reported in 3 of the patients of Menke et al. (2018). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	MENKE-HENNEKAM SYNDROME 1	None	26,807	omim	https://www.omim.org/entry/618332	2019-09-22T15:42:28	{"omim": ["618332"]}
A number sign (#) is used with this entry because of evidence that variation at or near the C2 (613927) and CFB (138470) genes on chromosome 6p21 influences susceptibility to age-related macular degeneration. For a phenotypic description and a discussion of genetic heterogeneity of age-related macular degeneration (ARMD), see 603075. Molecular Genetics Because CFH (134370) haplotypes are associated with age-related macular degeneration (ARMD4; 610698), Gold et al. (2006) hypothesized that the same may be true for activators of the same pathway. Gold et al. (2006) screened the CFB (138470) and C2 (613927) genes for genetic variation in 2 independent cohorts comprising approximately 900 individuals with ARMD and approximately 400 matched controls. Haplotype analyses identified a statistically significant common risk haplotype and 2 protective haplotypes. Haplotype H10, consisting of the L9H variant (138470.0003) of CFB and the E318D variant (613927.0004) of C2, and haplotype H7, consisting of the variant in intron 10 (613927.0005) of C2 and the R32Q variant (138470.0004) of CFB, conferred a significantly reduced risk of ARMD (OR = 0.36 and 0.45, respectively). Combined analysis of the C2/CFB haplotypes and CFH variants showed that variation in the 2 loci can predict the clinical outcome in 74% of affected individuals and 56% of controls. Fritsche et al. (2013) executed a collaborative genomewide association study, including more than 17,100 advanced ARMD cases and more than 60,000 controls of European and Asian ancestry. They identified 19 loci associated at p less than 5 x 10(-8). These loci showed enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling, and angiogenesis. Fritsche et al. (2013) identified association of the G allele of rs429608, near the C2 and CFB genes on chromosome 6p21.3, with increased risk of age-related macular degeneration (OR 1.74, 95% CI 1.68-1.79, combined p = 4 x 10(-89)). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MACULAR DEGENERATION, AGE-RELATED, 14	c3809653	26,808	omim	https://www.omim.org/entry/615489	2019-09-22T15:51:55	{"omim": ["615489"]}
A number sign (#) is used with this entry because of evidence that X-linked susceptibility to autism-4 (AUTS4) is caused by mutation in the PTCHD1 gene (300828) on chromosome Xp22. Patients with a similar phenotype have been found to have a contiguous gene deletion on chromosome Xp22 that disrupts the PTCHD1 gene. Description Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypical, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Clinical Features Marshall et al. (2008) reported a boy with autism who inherited a hemizygous deletion of chromosome Xp22.11 encompassing the PTCHD1 gene from his unaffected mother. His dizygotic twin brother, who had developmental delay, also carried the deletion. The proband was ascertained from a larger group of 427 probands with autism spectrum disorder who were studied for genomewide copy number variation (CNV). Noor et al. (2010) stated that the deletion in this family was 167 kb and included exon 1 of PTCHD1. Analysis of the mother showed highly skewed X inactivation (94:6). Filges et al. (2011) reported 2 Italian brothers who inherited a 200-kb interstitial deletion of Xp22.11 including the PTCHD1 gene from their unaffected mother. The proband was a 6.5-year-old boy with significantly delayed psychomotor development, hypotonia, autistic features, and no expressive speech. He had limited emotional nonverbal contact, but stereotyped or compulsive behavior was not observed. His 20-year-old brother had mental retardation and hypotonia, but no autistic features. Both patients had a history of transient ataxia in early childhood, and neither had dysmorphic features. Chaudhry et al. (2015) reported 23 patients from 16 families with intellectual disability and/or features of ASD associated with heterozygous deletions of chromosome Xp22 disrupting the PTCHD1 gene. The cohort included 5 individuals from 3 unrelated families who had point mutations in the PTCHD1 gene resulting in premature termination. Four of the families had previously been reported (Marshall et al., 2008; Filges et al., 2011; Noor et al., 2010; Pinto et al., 2010; Whibley et al., 2010). The only female in the cohort was a 5-year-old girl with speech delay and ASD. Eighteen patients (78%) had global developmental delay in early childhood, and 9 patients (39%) were formally diagnosed with mild to severe intellectual disability. Fifteen patients (65%) had behavioral and/or psychiatric diagnoses including autism; other behavioral issues included vocal and motor tics, anxiety, attention deficit and/or hyperactivity, impulsivity, aggressive behaviors, and sleep disorder. Six patients (26%) had generalized hypotonia, especially of facial muscles, and 8 patients (35%) had mild vision problems. Although some patients had subtle dysmorphic features, there was not a recognizable pattern of congenital anomalies or growth abnormalities. None were reported to have seizures in childhood. Cytogenetics In a study of CNV among 996 ASD patients, Pinto et al. (2010) found that 7 patients had maternally inherited deletions at PTCHD1 (300828), implicating this gene in the disorder. When compared with 4,964 controls, the association was significant (p = 3.6 x 10(-6)). Among 251 families with X-linked intellectual disability (mental retardation) and autism, Whibley et al. (2010) found 1 family in which a 90-kb deletion upstream of the PTCHD1 gene from 23,239,008-23,329,210 segregated in 2 affected brothers and an affected uncle. The deletion was not found in 447 controls. Noor et al. (2010) reported a boy with intellectual disability and dysmorphic features who had a 146-kb deletion spanning PTCHD1 and upstream regions (23,146,927-23,293,273). Noor et al. (2010) also identified several variants in the PTCHD1 gene that were transmitted from an unaffected mother to a son with X-linked intellectual disability or autism, but functional characterization was not performed and the variants did not fully segregate with the phenotype in all families. Finally, Noor et al. (2010) found 11 deletions mapping upstream of the PTCHD1 gene in patients with autism and/or intellectual disability. Overall, the findings suggested that CNV at Xp22 may confer susceptibility to various disorders of cognitive impairment. Chaudhry et al. (2015) identified heterozygous deletions that disrupted the PTCHD1 gene in affected individuals from 13 families with a neurodevelopmental disorder and/or AUTSX4. The deletions ranged from 46 to 963 kb, and most were inherited from unaffected mothers. There were no apparent genotype/phenotype correlations and functional studies were not performed. Molecular Genetics In 5 male members of 3 unrelated families of European origin with AUTSX4, Chaudhry et al. (2015) identified 3 different truncating mutations in the PTCHD1 gene (300828.0001-300828.0003). Functional studies of the variants and studies of patient cells were not performed. Animal Model Wells et al. (2016) found that Ptchd1 in postnatal mice was selectively expressed in the thalamic reticular nucleus (TRN), a group of GABAergic neurons that regulate thalamocortical transmission, sleep rhythms, and attention. Ptchd1-null male mice showed increased distractibility, hyperactivity, impaired learning, hypotonia, hyperaggression, and hyperfragmented sleep compared to wildtype. These changes were associated with a significant decrease in repetitive burst firing in the neurons in the TRN, which resulted from a decrease in small conductance calcium-activated potassium (SK) channels. TRN neurons in mutant mice also showed reduced burst firing in sleep and an overall reduction in sleep spindle count, which may have led to sleep instability. Conditional knockdown of the Ptchd1 gene specifically in the TRN resulted in attention deficits and hyperactivity, but did not cause learning impairment, hypotonia, or hyperaggression. Pharmacologic boosting of SK currents mitigated impaired sensory-evoked thalamic inhibition and improved distractibility and hyperactivity in germline knockout mice. The findings suggested that decreased TRN neuronal activity resulted in diminished overall thalamic inhibition, and supported SK channel dysfunction as a cellular mechanism for certain behavioral abnormalities. Wells et al. (2016) suggested that a 'leaky thalamus' caused by impaired TRN function could underlie attention deficits, hyperactivity, and sleep disruption across various neurodevelopmental disorders. INHERITANCE \- X-linked recessive HEAD & NECK Eyes \- Visual problems, mild Mouth \- Orofacial hypotonia MUSCLE, SOFT TISSUES \- Hypotonia (in some patients) NEUROLOGIC Central Nervous System \- Global development delay \- Intellectual disability \- Learning disability \- Motor tics Behavioral Psychiatric Manifestations \- Autism spectrum disorder \- Attention deficit-hyperactivity disorder \- Impulsivity \- Aggressive behavior MISCELLANEOUS \- Onset in infancy \- Variable severity \- Nonspecific subtle dysmorphic facial features may be present \- Most patients have contiguous gene deletion syndrome involving Xp22 MOLECULAR BASIS \- Caused by mutation in the patched domain-containing protein 1 gene (PTCHD1, 300828.0001 ) ▲ 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	AUTISM, SUSCEPTIBILITY TO, X-LINKED 4	c0795888	26,809	omim	https://www.omim.org/entry/300830	2019-09-22T16:19:32	{"omim": ["300830"], "synonyms": ["Alternative titles", "CHROMOSOME Xp22 DELETION SYNDROME"]}
A number sign (#) is used with this entry because Shields type III dentinogenesis imperfecta can be caused by mutation in the DSPP gene (125485). This disorder was found in the Brandywine triracial isolate in southern Maryland (Hursey et al., 1956; Witkop et al., 1966). The crowns of the deciduous and permanent teeth wear rapidly after eruption and multiple pulp exposures may occur. The dentin is amber and smooth. Radiographs of the deciduous dentition show very large pulp chambers and root canals, at least during the first few years, although they may become reduced in size with age. The permanent teeth have pulpal spaces that are either smaller than normal or completely obliterated. Patients with Shields type III, or the Brandywine type, do not have stigmata of osteogenesis imperfecta; see 166200. The disorder reported by Schimmelpfennig and McDonald (1953) as 'enamel and dentin aplasia' is likely the same condition, since their patient was related to the Brandywine kindred with opalescent dentin (Witkop, 1971). Other cases have been reported by Pike (1972), Kamen et al. (1980), and Nayar et al. (1981). This disorder may be a separate mutation from dentinogenesis imperfecta (DGI1; 125490; also called Shields type II (DGI-II), or dentinogenesis imperfecta without osteogenesis imperfecta): Shields et al. (1973) stated that multiple pulp exposures and markedly enlarged pulp chambers in the deciduous teeth do not occur in DGI; however, Witkop (1975) suggested that the 2 disorders are the same because of a surname common to individuals with both disorders as well as clinical similarities. Levin et al. (1983) presented evidence that the Brandywine type of DGI is different from Shields type II: in type III, they found enamel pitting, enlarged pulps early in tooth development, and radiolucencies at the apices of teeth without pulp exposures. Anterior open bites were found in all persons with complete permanent dentitions. Linkage studies in the Brandywine kindreds, reviewed under 170650, are consistent with identity or at least allelism of types II and III (Boughman et al., 1986). MacDougall et al. (1999) performed linkage analysis in a 'new' branch of the Brandywine kindred. Segregation analysis allowed identification of flanking markers that defined the critical region for DGI-III. This 6.6-cM critical region overlapped the region on 4q that had the highest probability of containing the DGI1 locus (Crosby et al., 1995). A maximum 2-point lod score of 4.87 was obtained with a marker for dentin matrix acidic phosphoprotein-1 (DMP1; 600980). These results again were consistent with the hypothesis that DGI-II and DGI-III are allelic or the result of mutations in 2 tightly linked genes. MacDougall (1998) provided information on the intervals separating 4 genes that map to this same region, all 4 of which are involved in dental development: DSPP (125485), DMP1 (600980), IBSP (147563), and SPP1 (166490). MacDougall et al. (1999) stated that the manifestations of DGI-III can differ from those of DGI-II by the presence of multiple pulp exposures, normal nonmineralized pulp chambers and canals, and a general appearance of 'shell teeth.' They illustrated the amber discoloration of the teeth, attrition, and fractured enamel, as well as the classic 'shell teeth' appearance on radiographs. In a Korean patient and affected members of a Caucasian family displaying clinical and radiographic features of a classic DGI-III or DGI-II phenotype, respectively, Kim et al. (2005) identified a val18-to-phe mutation in the DSPP gene (V18F; 125485.0004). As the V18F mutation had been reported as causing dentinogenesis imperfecta in combination with deafness (605594) in a Chinese family, Kim et al. (2005) proposed that it represents a mutation hotspot; they noted that 'there was no apparent hearing loss symptom in either kindred' they described. The finding that a single mutation causes both phenotypic patterns suggested to Kim et al. (2005) that DGI-II and DGI-III are not separate diseases but rather the phenotypic variation of a single disease. INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Anterior openbite Teeth \- Primary and secondary teeth affected \- Amber-opalescent colored teeth (primary and secondary) \- Marked attrition (primary and secondary) \- Enamel pitting (secondary) \- Normal-to-enlarged pulp chamber (primary) \- Obliterated pulp chamber (secondary) \- Periapical radiolucencies \- Pulp exposures \- Incisal notching \- Shell teeth \- Bulbous tooth crowns MISCELLANEOUS \- Occurs in a Southern Maryland tri-racial inbred population known as the "Brandywine isolate" \- Shields classification - \- Type 1 - associated with osteogenesis imperfecta ( 125490 ) \- Type 2 - hereditary opalescent dentin, not associated with bone defect ( 125490 ) \- Type 3 - Brandywine isolate opalescent dentin ( 125500 ) MOLECULAR BASIS \- Caused by mutations in the dentin sialophosphoprotein gene (DSPP, 125485.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	DENTINOGENESIS IMPERFECTA, SHIELDS TYPE III	c0399378	26,810	omim	https://www.omim.org/entry/125500	2019-09-22T16:42:22	{"doid": ["4154"], "mesh": ["C538216"], "omim": ["125500"], "orphanet": ["166265"], "synonyms": ["Alternative titles", "DGI-III", "BRANDYWINE TYPE DENTINOGENESIS IMPERFECTA"]}
Beeturia is the urinary excretion of beet pigment (betacyanin) after oral ingestion of beets. Allison and McWhirter (1956) suggested that the trait is unifactorial and polymorphic. They concluded that 'nonexcreter' is dominant to 'excreter.' Penrose (1957) challenged this idea. Watson et al. (1963) found beeturia in 14% of the general population, but in 80% of iron-deficient subjects. They suggested that iron and betacyanin may compete for an intestinal mucosal acceptor substance, perhaps apoferritin. Thus, iron deficiency interferes with the usefulness of beeturia as a genetic trait. Eastwood and Nyhlin (1995) showed that betalaine is decolorized by hydrochloric acid, ferric ions, and colonic bacteria but not by pancreatic or mucosal enzymes. Oral betalaine together with oxalic acid produced beeturia in non-beeturic individuals. The authors concluded that beeturia results from colonic absorption of betalaine. Lab \- Urinary excretion of beet pigment (betacyanin) after oral ingestion of beets 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	BEETURIA	c1862292	26,811	omim	https://www.omim.org/entry/109600	2019-09-22T16:44:29	{"omim": ["109600"], "synonyms": ["Alternative titles", "BETACYANINURIA"]}
A number sign (#) is used with this entry because of evidence that lethal congenital contracture syndrome-6 (LCCS6) is caused by homozygous mutation in the ZBTB42 gene (613915) on chromosome 14q32. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of LCCS, see LCCS1 (253310). Clinical Features Patel et al. (2014) studied a consanguineous Saudi Arabian family in which 3 of 8 children were stillborn with arthrogryposis. The prenatal course of the proposita was complicated by reduced fetal movements, and antenatal ultrasound showed severe polyhydramnios, absent stomach, and multiple contracture deformities, without major renal or central nervous system malformations. Multiple sessions of reductive amniocentesis were required due to the severity of the polyhydramnios. The infant had no respiratory effort at birth, and the parents requested that no resuscitation be undertaken. There was no major craniofacial dysmorphism apart from macrocephaly. The hips were fixed in flexion and associated with severely adducted lower limbs, symmetric fixed extension deformity of the knees, fixed flexion of both hands, and dorsiflexion of the feet. No apparent digital defects were noted, and full-body x-ray showed no gross bony abnormality. Muscle biopsy and autopsy were denied by the parents. Molecular Genetics In a consanguineous Saudi Arabian family in which 3 sibs had lethal congenital contracture syndrome, Patel et al. (2014) excluded linkage to known LCCS loci. By combined autozygome analysis and whole-exome sequencing, they identified a homozygous missense mutation in the ZBTB42 gene (R397H; 613915.0001) that segregated with the disease in the family. The mutation was not found in the 1000 Genomes Project or Exome Variant Server databases, in 300 Saudi controls, or in 485 Saudi exomes. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Macrocephaly RESPIRATORY \- No respiratory effort at birth ABDOMEN Gastrointestinal \- Absent stomach SKELETAL Skull \- Macrocephaly Limbs \- Fixed-flexion deformity at hips \- Severely adducted lower limbs \- Fixed extension deformity of knees Hands \- Fixed flexion of hands Feet \- Dorsiflexion of feet PRENATAL MANIFESTATIONS Movement \- Reduced fetal movements Amniotic Fluid \- Severe polyhydramnios MISCELLANEOUS \- Based on report of 1 Saudi Arabian family (last curated February 2015) MOLECULAR BASIS \- Caused by mutation in the zinc finger- and BTB domain-containing protein-42 (ZBTB42, 613915.0001 ) ▲ 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	LETHAL CONGENITAL CONTRACTURE SYNDROME 6	c4015686	26,812	omim	https://www.omim.org/entry/616248	2019-09-22T15:49:28	{"omim": ["616248"]}
Skin and skin structure infections (SSSIs), also referred to as skin and soft tissue infections (SSTIs),[1] or acute bacterial skin and skin structure infections (ABSSSIs),[2] are infections of skin and associated soft tissues (such as loose connective tissue and mucous membranes).[citation needed] Historically, the pathogen involved has most frequently been a bacterial species—always, since redescription of SSSIs as ABSSSIs—and as such, these infections require treatment by antibiotics.[citation needed] ## Contents * 1 Types * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 Further reading * 7 External links ## Types[edit] Until 2008, a distinction was made between two types: complicated SSSIs (cSSSIs) and uncomplicated SSSIs (uSSSIs),[3] which had different regulatory approval requirements.[4][needs update] Uncomplicated SSSIs included "simple abscesses, impetiginous lesions, furuncles, and cellulitis."[4] Complicated SSSIs included "infections either involving deeper soft tissue or requiring significant surgical intervention, such as infected ulcers, burns, and major abscesses or a significant underlying disease state that complicates the response to treatment."[4] The FDA further noted that "[s]uperficial infections or abscesses in an anatomical site, such as the rectal area, where the risk of anaerobic or Gram-negative pathogen involvement is higher, [were also] considered complicated infections."[4] The uncomplicated category (uSSSI) is most frequently caused by Staphylococcus aureus and Streptococcus pyogenes, whereas the complicated category (cSSSI) might also be caused by a number of other pathogens.[4][verification needed] As of 2013, the pathogen involved in cases of cSSSI were known about 40% of the time.[4][needs update][verification needed] ## Diagnosis[edit] As of 2014, physicians were reported as generally not culturing to identify the infecting bacterial pathogen during diagnosis of SSSIs[5] ## Treatment[edit] Common treatment is empirical, with choice of an antibiotic agent based on presenting symptoms and location, and further followup based on trial and error.[5][verification needed] To achieve efficacy against SSSIs, physicians most often use broad-spectrum antibiotics,[citation needed] a practice contributing to increasing prevalence of antibiotic resistance,[citation needed] a trend related to the widespread use of antibiotics in medicine in general.[citation needed] The increased prevalence of antibiotic resistance is evident in MRSA species commonly involved in SSSIs, which worsen prognoses and limit treatment options.[citation needed] For less severe infections, microbiologic evaluation using tissue culture has been demonstrated to have high utility in guiding management decisions.[5] There is no evidence to support or oppose the use of Chinese herbal medicines in treating SSTIs.[6] ## See also[edit] * List of cutaneous conditions * Linezolid * Tedizolid ## References[edit] 1. ^ SSTI is the preferred description of the Infectious Diseases Society of America (IDSA), see Stevens, D. L.; Bisno, A. L.; Chambers, H. F.; Dellinger, E. P.; Goldstein, E. J. C.; Gorbach, S. L.; Hirschmann, J. V.; Kaplan, S. L.; Montoya, J. G.; Wade, J. C. (18 June 2014). "Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America". Clinical Infectious Diseases. 59 (2): e10–e52. doi:10.1093/cid/ciu296. PMID 24947530. 2. ^ The U.S. Food and Drug Administration began referring to this category of infection as acute bacterial SSSIs (ABSSSI) in 2008. See "Guidance for Industry Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment" (PDF). Aug 2010. 3. ^ Rosen, T (2005). "Update on treating uncomplicated skin and skin structure infections". Journal of Drugs in Dermatology. 4 (6 Suppl): s9–14. PMID 16300224. 4. ^ a b c d e f "Guidance for Industry - Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment" (PDF). Food and Drug Administration. October 2013. Retrieved 2014-11-23. 5. ^ a b c Xia, Fan Di; Song, Philip; Joyce, Cara; Mostaghimi, Arash (2017). "The Utility of Microbiological Studies in Diagnosis and Management of Suspected Dermatological Infection". JAMA Dermatology. 153 (11): 1190–1192. doi:10.1001/jamadermatol.2017.3057. PMC 5817467. PMID 28854298. 6. ^ Wang, Yun Fei; Que, Hua Fa; Wang, Yong-Jun; Cui, Xue Jun (2014-07-25). Cochrane Wounds Group (ed.). "Chinese herbal medicines for treating skin and soft-tissue infections". Cochrane Database of Systematic Reviews (7): CD010619. doi:10.1002/14651858.CD010619.pub2. PMID 25061914. ## Further reading[edit] * Lee, Su Young; Kuti, Joseph L.; Nicolau, David P. (September 1, 2005). "Antimicrobial Management of Complicated Skin and Skin Structure Infections in the Era of Emerging Resistance". Surgical Infections. 6 (3): 283–295. doi:10.1089/sur.2005.6.283. PMID 16201938 – via liebertpub.com (Atypon). ## External links[edit] This section is empty. You can help by adding to it. (September 2019) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Skin and skin structure infection	c0852000	26,813	wikipedia	https://en.wikipedia.org/wiki/Skin_and_skin_structure_infection	2021-01-18T18:33:46	{"mesh": ["D018461"], "umls": ["C0852000"], "wikidata": ["Q7535374"]}
A number sign (#) is used with this entry because autosomal recessive spastic paraplegia-54 (SPG54) is caused by homozygous or compound heterozygous mutation in the DDHD2 gene (615003) on chromosome 8p11. Description Spastic paraplegia-54 is a complicated form of spastic paraplegia, a neurodegenerative disorder affecting fibers of the corticospinal tract. Affected individuals have delayed psychomotor development, intellectual disability, and early-onset spasticity of the lower limbs. Brain MRI shows a thin corpus callosum and periventricular white matter lesions. Brain magnetic resonance spectroscopy shows an abnormal lipid peak (summary by Schuurs-Hoeijmakers et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800. Clinical Features Schuurs-Hoeijmakers et al. (2012) reported 2 unrelated families in which 2 sibs in each family had early-onset spastic paraplegia and intellectual disability. Subsequently, a large Omani family and an unrelated Iranian patient with a similar disorder were ascertained. The phenotype among all 4 families was relatively homogeneous. Affected individuals showed delayed psychomotor development that evolved into mental retardation, and early onset of progressive spasticity before age 2 years. Other features included foot contractures, dysarthria, dysphagia, and strabismus. Three of 5 patients examined had optic hypoplasia. Brain imaging showed thin corpus callosum and subtle periventricular white matter hyperintensities. Five individuals from 3 families showed an abnormal lipid peak on magnetic resonance spectroscopy (MRS) of cerebral tissue, with the highest intensity around the basal ganglia and thalamus. This peak was similar to that observed in Sjogren-Larssen syndrome (SLS; 270200) and is indicative of abnormal brain lipid accumulation. Two unrelated males had a syrinx on spinal MRI. Gonzalez et al. (2013) identified 2 unrelated families with SPG54 among a cohort of 79 probands with autosomal recessive SPG who underwent exome sequencing. The first family contained 2 affected sibs, born of consanguineous Iranian parents. Both sibs developed a spastic gait disorder in early childhood, but were still able to walk unsupported at ages 19 and 25 years. Both had mental retardation requiring special schooling, as well as short stature, high-arched palate, and dysgenesis of the corpus callosum on brain imaging. The second family was of Indian origin with no known consanguinity, but the parents originated from the same village and were part of the Muslim community. These brothers developed spasticity of the lower limbs in the first year of life. They also had mental retardation, short stature, and thin corpus callosum. One had dysmorphic features, with telecanthus and slanted palpebral fissures. The phenotype in these patients was similar to that reported by Schuurs-Hoeijmakers et al. (2012). Novarino et al. (2014) identified 2 additional, consanguineous families with SPG54. In 1 family (family 1314), 4 individuals presented with tiptoe walking between 15 and 18 months of age. All developed spasticity and dysarthria, and all had mild to moderate intellectual disability. When last examined, the oldest patient (23 years of age) was nonambulatory, whereas the other 3 (aged 2 to 20 years) could walk unsupported. In the other family (family 1675), 3 sibs presented in early infancy. When last examined, all 3 (aged 7 to 10 years) displayed spasticity, dysarthria, abnormal gait, strabismus, periventricular leukomalacia, high lipid peak on brain MRI, and moderate intellectual disability. All could walk unsupported with abnormal gait. Inheritance The transmission pattern of SPG54 in the families reported by Schuurs-Hoeijmakers et al. (2012) was consistent with autosomal recessive inheritance. Molecular Genetics By exome sequencing in 2 unrelated families with a complex form of autosomal recessive spastic paraplegia, Schuurs-Hoeijmakers et al. (2012) identified biallelic mutations in the DDHD2 gene (615003.0001-615003.0004). The mutations segregated with the phenotype in both families. Different homozygous mutations in the DDHD2 gene were found in affected individuals from a large Omani family with a similar disorder, originally reported as family A by Al-Yahyaee et al. (2006), an in an unrelated Iranian patient (see 615003.0005 and 615003.0006). Knockdown of the Drosophila ortholog resulted in a reduction of the number of active zones at the synaptic terminal, suggesting that the DDHD2 gene plays a role in synaptic function. The DDHD2 gene was found to be highly expressed in various human brain regions. In affected members of 2 unrelated families with SPG54, Gonzalez et al. (2013) identified homozygous truncating mutations in the DDHD2 gene (615003.0006 and 615003.0007). The 2 families were identified from a larger cohort of 79 probands with autosomal recessive SPG who underwent exome sequencing. In affected members of 2 consanguineous families with SPG54, Novarino et al. (2014) identified homozygous mutations in the DDHD2 gene: a previously identified nonsense mutation (615003.0006) and a splice site mutation (615003.0008). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Eyes \- Strabismus \- Telecanthus \- Optic nerve hypoplasia (in some patients) Mouth \- High-arched palate (in some patients) ABDOMEN Gastrointestinal \- Dysphagia \- Constipation (in some patients) \- Fecal incontinence (rare) GENITOURINARY Bladder \- Urinary incontinence (rare) SKELETAL Feet \- Foot contractures NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mental retardation \- Spastic paraplegia \- Hyperreflexia \- Extensor plantar responses \- Lower limb weakness \- Dysarthria \- Thin corpus callosum \- Periventricular white matter abnormalities \- Abnormal lipid peak on brain MRS \- Spinal cord syrinx (in 2 patients) MISCELLANEOUS \- Onset of spasticity by age 2 years \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the DDHD domain-containing protein 2 gene (DDHD2, 615003.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SPASTIC PARAPLEGIA 54, AUTOSOMAL RECESSIVE	c3539495	26,814	omim	https://www.omim.org/entry/615033	2019-09-22T15:53:27	{"doid": ["0110806"], "omim": ["615033"], "orphanet": ["320380"], "synonyms": ["SPG54"]}
Papulosquamous disorder SpecialtyDermatology A papulosquamous disorder is a condition which presents with both papules and scales,[1] or both scaly papules and plaques.[2] Examples include psoriasis, lichen planus,[3] and pityriasis rosea.[4] ## Contents * 1 See also * 2 References * 3 Further reading * 4 External links ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ "Definition: papulosquamous from Online Medical Dictionary". Retrieved 2007-11-18. 2. ^ "Dermatology Lectures Online". Retrieved 2007-11-18. 3. ^ "Papulosquamous Disorders". Archived from the original on March 20, 2005. Retrieved 2007-11-18. 4. ^ González LM, Allen R, Janniger CK, Schwartz RA (2005). "Pityriasis rosea: an important papulosquamous disorder". Int J Dermatol. 44 (9): 757–64. doi:10.1111/j.1365-4632.2005.02635.x. PMID 16135147. ## Further reading[edit] * Norman RA, Blanco PM (2003). "Papulosquamous diseases in the elderly". Dermatologic Therapy. 16 (3): 231–42. doi:10.1046/j.1529-8019.2003.01633.x. PMID 14510880. * http://www.emedicine.com/derm/index.shtml#papulosquamous ## External links[edit] Classification D * ICD-10: L40-L45 * MeSH: D017444 * v * t * e Papulosquamous disorders Psoriasis Pustular * Generalized pustular psoriasis (Impetigo herpetiformis) * Acropustulosis/Pustulosis palmaris et plantaris (Pustular bacterid) * Annular pustular psoriasis * Localized pustular psoriasis Other * Guttate psoriasis * Psoriatic arthritis * Psoriatic erythroderma * Drug-induced psoriasis * Inverse psoriasis * Napkin psoriasis * Seborrheic-like psoriasis Parapsoriasis * Pityriasis lichenoides (Pityriasis lichenoides et varioliformis acuta, Pityriasis lichenoides chronica) * Lymphomatoid papulosis * Small plaque parapsoriasis (Digitate dermatosis, Xanthoerythrodermia perstans) * Large plaque parapsoriasis (Retiform parapsoriasis) Other pityriasis * Pityriasis rosea * Pityriasis rubra pilaris * Pityriasis rotunda * Pityriasis amiantacea Other lichenoid Lichen planus * configuration * Annular * Linear * morphology * Hypertrophic * Atrophic * Bullous * Ulcerative * Actinic * Pigmented * site * Mucosal * Nails * Peno-ginival * Vulvovaginal * overlap synromes * with lichen sclerosus * with lupus erythematosis * other: * Hepatitis-associated lichen planus * Lichen planus pemphigoides Other * Lichen nitidus * Lichen striatus * Lichen ruber moniliformis * Gianotti–Crosti syndrome * Erythema dyschromicum perstans * Idiopathic eruptive macular pigmentation * Keratosis lichenoides chronica * Kraurosis vulvae * Lichen sclerosus * Lichenoid dermatitis * Lichenoid reaction of graft-versus-host disease This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Papulosquamous disorder	c0162818	26,815	wikipedia	https://en.wikipedia.org/wiki/Papulosquamous_disorder	2021-01-18T18:29:35	{"mesh": ["D017444"], "icd-10": ["L45", "L40"], "wikidata": ["Q7133237"]}
Basilar skull fracture Other namesBasal skull fracture, skull base fractures[1] A subtle temporal bone fracture as seen on CT in a person with a severe head injury SpecialtyEmergency medicine, neurosurgery SymptomsBruising behind the ears, bruising around the eyes, blood behind the ear drum[1] ComplicationsCerebrospinal fluid leak, facial fracture, meningitis[2][1] TypesAnterior, central, posterior[1] CausesTrauma[1] Diagnostic methodCT scan[1] TreatmentBased on injuries inside the skull[1] Frequency≈12% of severe head injuries[1] A basilar skull fracture is a break of a bone in the base of the skull.[1] Symptoms may include bruising behind the ears, bruising around the eyes, or blood behind the ear drum.[1] A cerebrospinal fluid (CSF) leak occurs in about 20% of cases and can result in fluid leaking from the nose or ear.[1] Meningitis is a complication in about 14% of cases.[2] Other complications include cranial nerve or blood vessel injury.[1] They typically require a significant degree of trauma to occur.[1] The break is of at least one of the following bones: temporal bone, occipital bone, sphenoid bone, frontal bone, or ethmoid bone.[1] They are divided into anterior fossa, middle fossa, and posterior fossa fractures.[1] Facial fractures often also occur.[1] Diagnosis is typically by CT scan.[1] Treatment is generally based on the injury to structures inside the head.[1] Surgery may be done for a CSF leak that does not stop or an injury to a blood vessel or nerve.[1] Preventive antibiotics are of unclear use.[3][2] It occurs in about 12% of people with a severe head injury.[1] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Management * 4 Prognosis * 4.1 Temporal bone fractures * 5 Society and culture * 6 References * 7 External links ## Signs and symptoms[edit] Bilateral raccoon eyes * Battle's sign – bruising of the mastoid process of the temporal bone. * Raccoon eyes – bruising around the eyes, i.e. "black eyes" * Cerebrospinal fluid rhinorrhea * Cranial nerve palsy * Bleeding (sometimes profuse) from the nose and ears * Hemotympanum * Conductive or perceptive deafness, nystagmus, vomiting * In 1–10% of patients, optic nerve entrapment occurs.[4] The optic nerve is compressed by the broken skull bones, causing irregularities in vision. * Serious cases usually result in death ## Pathophysiology[edit] A basilar skull fracture as seen on CT Diagram showing bones that may be involved in a basilar skull fracture Basilar skull fractures include breaks in the posterior skull base or anterior skull base. The former involve the occipital bone, temporal bone, and portions of the sphenoid bone; the latter, superior portions of the sphenoid and ethmoid bones. The temporal bone fracture is encountered in 75% of all basilar skull fractures and may be longitudinal, transverse or mixed, depending on the course of the fracture line in relation to the longitudinal axis of the pyramid.[5] Bones may be broken around the foramen magnum, the hole in the base of the skull through which the brain stem exits and becomes the spinal cord, creating the risk that blood vessels and nerves exiting the hole may be damaged.[6] Due to the proximity of the cranial nerves, injury to those nerves may occur.[4] This can cause loss of function of the facial nerve or oculomotor nerve or hearing loss due to damage of cranial nerve VIII.[4] ## Management[edit] Evidence does not support the use of preventive antibiotics regardless of the presence of a cerebrospinal fluid leak.[3][2] ## Prognosis[edit] Non-displaced fractures usually heal without intervention. Patients with basilar skull fractures are especially likely to get meningitis.[7] Unfortunately, the efficacy of prophylactic antibiotics in these cases is uncertain.[8] ### Temporal bone fractures[edit] Acute injury to the internal carotid artery (carotid dissection, occlusion, pseudoaneurysm formation) may be asymptomatic or result in life-threatening bleeding. They are almost exclusively observed when the carotid canal is fractured, although only a minority of carotid canal fractures result in vascular injury. Involvement of the petrous segment of the carotid canal is associated with a relatively high incidence of carotid injury.[9] ## Society and culture[edit] Basilar skull fractures are a common cause of death in many motor racing accidents. Drivers who have died as a result of basilar skull fractures include Formula One driver Roland Ratzenberger; IndyCar drivers Bill Vukovich Sr., Tony Bettenhausen Sr., Floyd Roberts, and Scott Brayton; NASCAR drivers Dale Earnhardt Sr., Adam Petty, Tony Roper, Kenny Irwin Jr., Neil Bonnett, John Nemechek, J.D. McDuffie, and Richie Evans; CART drivers Jovy Marcelo, Greg Moore, and Gonzalo Rodriguez; and ARCA drivers Blaise Alexander and Slick Johnson.[citation needed] Ernie Irvan happens to be a survivor of basilar skull fracture after suffering an accident during practice in 1994 at the Michigan International Speedway.[10] To prevent this injury, many motorsports sanctioning bodies mandate the use of head and neck restraints, such as the HANS device.[11][12][13][14] The HANS device has demonstrated its life-saving abilities multiple times, including Jeff Gordon at the 2006 Pocono 500, Michael McDowell at the Texas Motor Speedway in 2008,[15] Robert Kubica at the 2007 Canadian Grand Prix, and Elliott Sadler at the 2010 Sunoco Red Cross Pennsylvania 500.[16] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t Baugnon, KL; Hudgins, PA (August 2014). "Skull base fractures and their complications". Neuroimaging Clinics of North America. 24 (3): 439–65, vii–viii. doi:10.1016/j.nic.2014.03.001. PMID 25086806. 2. ^ a b c d Nellis, JC; Kesser, BW; Park, SS (January 2014). "What is the efficacy of prophylactic antibiotics in basilar skull fractures?". The Laryngoscope. 124 (1): 8–9. doi:10.1002/lary.23934. PMID 24122671. 3. ^ a b Ratilal, Bernardo O; Costa, João; Pappamikail, Lia; Sampaio, Cristina; Ratilal, Bernardo O (2015). "Antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures". The Cochrane Database of Systematic Reviews. 4 (4): CD004884. doi:10.1002/14651858.CD004884.pub4. PMID 25918919. 4. ^ a b c Pediatric Head Trauma at eMedicine 5. ^ Skull Fracture at eMedicine 6. ^ "About Brain Injury". Brain Injury Association of America. October 12, 2012. 7. ^ Dagi, T.Forcht; Meyer, Frederick B.; Poletti, Charles A. (1983). "The incidence and prevention of meningitis after basilar skull fracture". The American Journal of Emergency Medicine. 1 (3): 295–8. doi:10.1016/0735-6757(83)90109-2. PMID 6680635. 8. ^ Butler, John. "Antibiotics in base of skull fractures". BestBets. Retrieved 2014-03-22. 9. ^ Resnick, Daniel K.; Subach, Brian R.; Marion, Donald W. (1997). "The Significance of Carotid Canal Involvement in Basilar Cranial Fracture". Neurosurgery. 40 (6): 1177–81. doi:10.1097/00006123-199706000-00012. PMID 9179890. 10. ^ https://www.youtube.com/watch?v=ckT7z-XwKUo Dale Jr. Download: Ernie Irvan's Horrific Crash 11. ^ "FIA makes HANS device mandatory". Autosport. Autosport Media UK. 9 December 2005. Retrieved 2 January 2018. 12. ^ "NASCAR mandates HANS for 3 series". The Washington Times. The Washington Times LLC. 18 October 2001. Retrieved 2 January 2018. 13. ^ "MSA confirms Motor Sports Council decisions regarding Frontal Head Restraints". MSA. Motor Sports Association. Retrieved 2 January 2018. 14. ^ "Head and Neck Restraints Mandatory!". NNJR SCCA. Sports Car Club of America. Retrieved 2 January 2018. 15. ^ ANDERSON, LARS. "HOW SAFE IS RACING?". SI.com. Retrieved 2018-04-04. 16. ^ "Sadler: Sunday's crash hardest in Cup history". ESPN.com. 2010-08-03. Retrieved 2018-04-04. ## External links[edit] Classification D * ICD-10: S02.1 * ICD-9-CM: 801.1 * MeSH: D020205 External resources * eMedicine: med/2894 * v * t * e Fractures and cartilage damage General * Avulsion fracture * Chalkstick fracture * Greenstick fracture * Open fracture * Pathologic fracture * Spiral fracture Head * Basilar skull fracture * Blowout fracture * Mandibular fracture * Nasal fracture * Le Fort fracture of skull * Zygomaticomaxillary complex fracture * Zygoma fracture Spinal fracture * Cervical fracture * Jefferson fracture * Hangman's fracture * Flexion teardrop fracture * Clay-shoveler fracture * Burst fracture * Compression fracture * Chance fracture * Holdsworth fracture Ribs * Rib fracture * Sternal fracture Shoulder fracture * Clavicle * Scapular Arm fracture Humerus fracture: * Proximal * Supracondylar * Holstein–Lewis fracture Forearm fracture: * Ulna fracture * Monteggia fracture * Hume fracture * Radius fracture/Distal radius * Galeazzi * Colles' * Smith's * Barton's * Essex-Lopresti fracture Hand fracture * Scaphoid * Rolando * Bennett's * Boxer's * Busch's Pelvic fracture * Duverney fracture * Pipkin fracture Leg Tibia fracture: * Bumper fracture * Segond fracture * Gosselin fracture * Toddler's fracture * Pilon fracture * Plafond fracture * Tillaux fracture Fibular fracture: * Maisonneuve fracture * Le Fort fracture of ankle * Bosworth fracture Combined tibia and fibula fracture: * Trimalleolar fracture * Bimalleolar fracture * Pott's fracture Crus fracture: * Patella fracture Femoral fracture: * Hip fracture Foot fracture * Lisfranc * Jones * March * Calcaneal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Basilar skull fracture	c0748830	26,816	wikipedia	https://en.wikipedia.org/wiki/Basilar_skull_fracture	2021-01-18T19:01:58	{"mesh": ["D020205"], "icd-9": ["801.1"], "icd-10": ["S02.1"], "wikidata": ["Q1937676"]}
Progressive rubella panencephalitis SpecialtyInfectious disease Progressive rubella panencephalitis (PRP) is a neurological disorder which may occur in a child with congenital rubella.[1] It is a slow viral infection of the brain characterized by chronic encephalitis, usually manifesting between 8–19 years of age. It is believed to be due to a persistence or reactivation of rubella virus infection. ## Contents * 1 Cause * 2 Diagnosis * 3 Treatment * 4 Incidence * 5 See also * 6 References * 7 Further reading ## Cause[edit] It develops 6 months to 4 years after the primary rubella infection, which in most cases is a congenital rubella. In children with congenital rubella infection the deficits remain stable; neurological deterioration after the first few years of life is not believed to occur.[citation needed] Progression of the disease can be divided into two stages: * 1st stage: Behavioural Changes * insidious onset * subtle changes in behaviour and declining school work * 2nd stage: Neurological Changes * seizures – sometimes myoclonic * cerebellar ataxia * spastic weakness * retinopathy, optic atrophy * frank dementia leading to coma * spasticity and brainstem involvement with death in 2–5 years ## Diagnosis[edit] The diagnosis is considered when a child with congenital rubella develops progressive spasticity, ataxia, mental deterioration, and seizures. Testing involves at least CSF examination and serology. Elevated CSF total protein and globulin and elevated rubella antibody titers in CSF and serum occur. CT may show ventricular enlargement due to cerebellar atrophy and white matter disease. Brain biopsy may be necessary to exclude other causes of encephalitis or encephalopathy. Rubella virus cannot usually be recovered by viral culture or immunohistologic testing.[citation needed] ## Treatment[edit] Although no specific treatment exists, the disease can be managed with anticonvulsants, physiotherapy, etc.[citation needed] ## Incidence[edit] PRP is very rare and similar to SSPE but without intracellular inclusion bodies. Only 20 patients have been identified since first recognized in 1974.[citation needed] ## See also[edit] * Subacute sclerosing panencephalitis ## References[edit] 1. ^ Moore, David P. (2008). Textbook of clinical neuropsychiatry (2nd ed.). London: Hodder Arnold. p. 507. ISBN 9780340939536. Retrieved 6 August 2017. ## Further reading[edit] * Townsend JJ, Baringer JR, Wolinsky JS, Malamud N, Mednick JP, Panitch HS, Scott RA, Oshiro L, Cremer NE (1975). "Progressive rubella panencephalitis. Late onset after congenital rubella". N. Engl. J. Med. 292 (19): 990–3. doi:10.1056/NEJM197505082921902. PMID 1117960. * "Rubella". Merck Manual. * Haukenes, G. (2002). "40. Slow viruses: Conventional Slow Virus Infections – Subacute Sclerosing Panencephalitis (SSPE)". In Haaheim, L. R.; Pattison, J. R.; Whitley, R. J. (eds.). A Practical Guide to Clinical Virology (2nd ed.). Wiley. ISBN 9780470844298. Archived from the original on 2011-02-08. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Progressive rubella panencephalitis	c1305924	26,817	wikipedia	https://en.wikipedia.org/wiki/Progressive_rubella_panencephalitis	2021-01-18T19:02:09	{"orphanet": ["83616"], "synonyms": [], "wikidata": ["Q7248868"]}
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1HH is caused by heterozygous mutation in the BAG3 gene (603883) on chromosome 10q26.11. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy (CMD), see CMD1A (115200). Clinical Features Norton et al. (2011) reported 17 individuals from 8 families with dilated cardiomyopathy who carried heterozygous mutations in the BAG3 gene. The age at onset or diagnosis of the CMD phenotype ranged from 21 years to 64 years (median, 44). Disease severity varied considerably: although 9 of the 17 mutation carriers with CMD underwent heart transplant or died with advanced heart failure, there were 4 mutation carriers who had no disease and 1 who was asymptomatic with only mild left ventricular dysfunction. Norton et al. (2011) noted that similar phenotypic variability had been widely seen in pedigrees with CMD due to mutation in various genes. Molecular Genetics In a large 3-generation family segregating autosomal dominant dilated cardiomyopathy and that was negative for mutation in 15 known CMD-associated genes, Norton et al. (2011) performed whole-exome sequencing and genomewide analysis of copy number variation and identified an 8,733-bp deletion in the BAG3 gene (603883.0002) that was present in all 7 affected family members and absent from 355 controls. Norton et al. (2011) then sequenced exons 2, 3, and 4 of BAG3 in an additional 311 CMD probands who were also negative for mutation in 15 known CMD-associated genes, and identified heterozygous point mutations in 7 unrelated probands that were not found in 2,644 control chromosomes (see, e.g., 603883.0003-603883.0006). Knockdown of bag3 in a zebrafish model recapitulated CMD and heart failure. Arimura et al. (2011) analyzed the BAG3 gene in 72 Japanese probands with familial CMD and identified heterozygosity for 2 missense mutations in 2 probands: R218W (603883.0007) and L462P (603883.0008). Functional studies at the cellular level showed that these CMD-associated mutations impaired the Z-disc assembly and increased sensitivities to stress-induced apoptosis. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Dilated left ventricle \- Heart failure MOLECULAR BASIS \- Caused by mutation in the BCL2-associated athanogene 3 gene (BAG3, 603883.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CARDIOMYOPATHY, DILATED, 1HH	c0340427	26,818	omim	https://www.omim.org/entry/613881	2019-09-22T15:57:15	{"doid": ["0110448"], "mesh": ["C536231"], "omim": ["613881"], "orphanet": ["154"], "genereviews": ["NBK1309"]}
This article's lead section may be too short to adequately summarize its key points. Please consider expanding the lead to provide an accessible overview of all important aspects of the article. (December 2020) Vietnam faces a concentrated HIV epidemic. ## Contents * 1 Reporting * 2 Current State * 3 Major Causes * 4 Injection of Drugs * 5 Sexual Transmission * 6 Others * 7 Challenges * 8 References ## Reporting[edit] HIV prevalence data in Vietnam is based primarily on HIV/AIDS case reporting and on the HIV Sentinel Surveillance conducted annually in 40 of Vietnam’s 64 provinces. The government now reports HIV cases in all provinces, 93 percent of all districts, and 49 percent of all communes, although many high prevalence provinces report cases in 100 percent of communes. Even though Vietnam has implemented HIV/AIDS case reporting, the general lack of HIV testing thus far suggests that the actual number of people living with HIV/AIDS is much higher.[1] ## Current State[edit] The first HIV case was detected in 1990.[2] The estimated number of people living with HIV then rose drastically from 3,000 in 1992 [3] to 220,000 in 2007, and is projected to be 280,000 in 2012. Among these, 5,670 are children.[4] According to the IMF, this trend is placing Vietnam at the threshold of moving the disease from the high-risk groups of drug users and sex workers to the general population.[5] Among those who inject drugs, 19% are infected by HIV (up to 30% in some provinces.) [6] ## Major Causes[edit] This section is empty. You can help by adding to it. (January 2014) ## Injection of Drugs[edit] Injecting drug users (IDU) account for up to 65% of people living with HIV.[7] The HIV prevalence among male IDU is estimated to be 23.1%.[4] Drug injection is reported as the major cause for doubling the number of HIV/AIDS patients from 2000 to 2005.[8] Although there appears widespread awareness of using sterile needles among IDU (88% reported doing so in the last injection[4]) sharing needles is common among those who have already contracted HIV/AIDS. In a survey of 20 provinces in Vietnam, 35% of IDU living with HIV shared needles and syringes. [9] Besides, IDU often engage in risky sexual behaviours. 25% of male IDU in Hanoi is reported to buy sex and do not use condoms. Meanwhile, female IDU often sell sex to finance their drug need.[7] This raises the risk of spreading HIV/AIDS to the general population. ## Sexual Transmission[edit] Another main cause of HIV/AIDS spread is sexual transmission through the sex workers. While 97.1% of female sex workers (FSW) reported using condoms with their most recent clients,[4] the rate is much lower at 41.1% among those who are living with HIV.[9] ## Others[edit] While HIV/AIDS remain an epidemic only within the high-risk groups, women in the general population may be more exposed to the risk of contracting HIV than reported. One study estimates that reported HIV transmission among women may reflect as low as 16% of the real number due to the lack of HIV screening. The number of women with HIV infection is estimated to increase from less than 30,000 in 2000 to 90,000 in 2007.[2] Women may contract HIV/AIDS through partners who are undisclosed IDU. Men having pre-marital or extra-marital sexual relationships with FSW inevitably expose their wives to HIV/AIDS risk. Particularly in provinces with mobile populations, migrant husbands who, being away from home, are likely buy sex and use drugs may contract HIV and transmit to their wives.[2] With potentially high HIV prevalence among women, perinatal transmission presents another channel of HIV transmission. It is reported that more than 1% of pregnant women in some provinces are found HIV positive.[3] ## Challenges[edit] Social stigma against HIV/AIDS patients presents a major obstacle to contain HIV/AIDS. HIV/AIDS patients are treated unequally in the hospitals and denied employment. Children with HIV are not welcomed in school. In 2009, parents in Ho Chi Minh City forced officials to expel children with HIV.[10] Discrimination thus discourages people to go for screening or to take medication in fear of revealing their HIV status. Funding for HIV/AIDS programmes in Vietnam is another pressing issue limiting the success of the effort to control the disease. Over the past 5 years, the available resource covered merely 50% of the demand.[11] Moreover, since 70% of this amount was received from international institutions while state funding accounted for only 13%,[11] there is no guarantee of future availability. The final challenge lies in the limited human resources. There is a shortage of helpers in provincial and district areas. Currently, there are approximately 1,300 health workers in preventive medicines nationwide, including anti-HIV work, or 21 on average for each city or district.[12] Dr. Nguyen Thanh Long, Chief of the Health Ministry’s HIV/AIDS Control Department, estimated that Vietnam has to increase the number of health workers to 20,000 by 2020 in order to be able to contain and reduce the increasing number of infected cases.[12] ## References[edit] 1. ^ "2008 Country Profile: Vietnam". U.S. Department of State (2008). Accessed September 7, 2008. This article incorporates text from this source, which is in the public domain. 2. ^ a b c Nguyen (2008). "A hidden HIV epidemic among women in Vietnam". BMC Public Health. 3. ^ a b "HIV/AIDS in Viet Nam" (PDF). Retrieved 2011-09-10. 4. ^ a b c d "UNAIDS Vietnam". Archived from the original on 2011-07-12. Retrieved 2011-09-10. 5. ^ "Vietnam's Health Care System: A Macroeconomic Perspective". IMF. 2008. 6. ^ "USAID HIV/AIDS Vietnam". 7. ^ a b Nguyen (2008). "Drugs, Sex and AIDS: Sexual relationships among injecting drug users and their sexual partners in Vietnam". Culture, Health and Sexuality. 8. ^ "HIVS and AIDS in Asia". Retrieved 2011-09-10. 9. ^ a b DuongV (2009). "HIV Risk Behaviours and Determinants Among People Living with HIV/AIDS in Vietnam". AIDS and Behaviour. 10. ^ "Love as harm reduction: fighting AIDS and stigma in Vietnam". Harm Reducation Journal. 2009. 11. ^ a b "HIV/AIDS fight needs more funding, VietNam Today". Retrieved 2011-09-10. 12. ^ a b "Vietnam needs 20,000 health workers for HIV/AIDS fight". 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Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	HIV/AIDS in Vietnam	None	26,819	wikipedia	https://en.wikipedia.org/wiki/HIV/AIDS_in_Vietnam	2021-01-18T18:42:33	{"wikidata": ["Q5629893"]}
A rare myelodysplastic/myeloproliferative neoplasm characterized by peripheral blood leukocytosis due to increased numbers of morphologically dysplastic neutrophils and their precursors, hypercellular bone marrow with granulocytic proliferation and dysplasia (with or without dysplasia in the erythroid and megakaryocytic lineages), and prominent dysgranulopoiesis, but no or minimal absolute basophilia or monocytosis. Blasts account for less than 20% of leukocytes in the blood and bone marrow. BCR-ABL1 fusion is absent, as well as PDGFRA, PDGFRB or FGFR1 rearrangement, or PCM1-JAK2. Patients may present with signs and symptoms related to splenomegaly, anemia, or thrombocytopenia. Prognosis is generally poor. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Atypical chronic myeloid leukemia	c1292772	26,820	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98824	2021-01-23T17:11:10	{"mesh": ["D054438"], "umls": ["C0349640", "C1292772"], "icd-10": ["C92.2"], "synonyms": ["Subacute myeloid leukemia"]}
Ritual cutting of female genitals in India Female genital mutilation (FGM) is practised in India by some Islamic groups. The procedure is generally performed when a girl is seven years old and involves the total or partial removal of the clitoral hood. Consequences of FGM may range from discomfort to sepsis. ## Contents * 1 Practice * 1.1 Occurrence * 1.2 Consequences * 2 Activism * 2.1 Opposition * 2.2 Support * 3 Supreme Court * 4 References * 5 See also ## Practice[edit] ### Occurrence[edit] Further information: Dawoodi Bohra § Female genital mutilation FGM is practised by the Dawoodi Bohra, a sect of Shia Islam with one million members in India.[1] Known as khatna, khafz, and khafd, the procedure is performed on six- or seven-year-old girls and involves the total or partial removal of the clitoral hood.[2][1] The spiritual leader of the Dawoodi Bohra, Syedna Mufaddal Saifuddin, stated in 2016: "Religious books, written over a thousand years ago, specify the requirements for both males and females as acts of religious purity." The statement also emphasized the need to "respect the law of the land".[3] Other Bohra sects including the Sulemani Bohras and the Alavi Bohras,[4] as well as some Sunni communities in Kerala, are reported as practising FGM.[5] ### Consequences[edit] Dr. Meghana Reddy J, a gynaecologist, reported in 2018 that khatna can lead to complications in later life, including difficult deliveries and urinary infections. In one case a girl had developed sepsis after having had khatna and great effort had been required to revive her.[6] In conjunction with a small study, the first of its kind in India, twenty Bohra women were examined by Dr. Sujaat Vali, an obstetrician and gynaecologist, who reported that only a specialist would be able to separate and cut the clitoral hood without also cutting the clitoris, and the clitoris had been cut in most cases examined.[7][1] According to Vali, "[h]alf of them feel some kind of irritation, while 30% either feel discomfort while walking/urinating or have lost sensitivity in the area." The study covered 83 women and 11 men from five Indian states and found that 75 percent of the respondents' daughters who were at least seven years old had been subjected to FGM.[1] ## Activism[edit] ### Opposition[edit] In November 2011 a Bohra woman posted an online petition requesting that Syedna Mohammed Burhanuddin, religious leader of the Dawoodi Bohras, ban FGM. A spokesman ruled out any change saying "Bohra women should understand that our religion advocates the procedure and they should follow it without any argument."[8] Two Mumbai-based groups, Sahiyo and We Speak Out, launched a campaign in February 2016 called "Each One Reach One"; the campaign was repeated during Ramadan in 2017. The campaign promoted conversations about female genital cutting.[9][10] In an online survey of Bohra women, Sahiyo found that khatna had been performed on 80 percent of participants, with most cut when aged six or seven; 81 percent wanted the practice to stop.[11] On 10 December 2016 (Human Rights Day), a group of Dawoodi Bohra women started an online petition calling for FGM to be banned. A similar petition was conducted by the group a year earlier; that petition was submitted to India's Women and Child Development Minister Maneka Gandhi.[12] Also that month, Dawoodi Bohra women petitioned the United Nations demanding that India be recognised as a country where Female Genital Mutilation (FGM) or Female Genital Cutting (FGC) is practised.[13] In September 2017, when the 36th regular session of the United Nations Human Rights Council (UNHRC) was conducting a Universal Periodic Review of India, a written submission on FGM in India was presented at a side event. That was the first time the issue of FGM in India had been raised at the United Nations.[5][14][15] ### Support[edit] The Dawoodi Bohra Women for Religious Freedom (DBWRF) was established in May 2017 by six Bohra women to support their "beliefs, customs, culture and religious rights". It claims to represent the views of nearly 75,000 women who are followers of Mufaddal Saifuddin. The DBWRF states that the form of FGM practiced by the Dawoodi Bohra is a harmless procedure and not mutilation.[16][17] DBWRF's stated mission is to "stand for the rights of Dawoodi Bohra women in India" to ensure they have the same freedom as other citizens,[18][19] particularly by defending women who are victimised for their religious beliefs, practices,[20][21] customs and culture. In the face of controversy,[22][23] DBWRF has taken the lead in ensuring that the practice of FGM is protected.[24][25][26][27] In July 2018, senior advocate Abhishek Manu Singhvi represented the DBWRF during proceedings in the Supreme Court and stated that "the practice of khafz is an essential part of the religion as practised by Dawoodi Bohra Community and their right to practise and propagate religion is protected under Articles 25 and 26 of the Constitution of India".[2] ## Supreme Court[edit] In May 2017 a public interest litigation (PIL) case was raised in India's Supreme Court. The case was filed by Sunita Tiwari, a lawyer based in Delhi, seeking a ban on FGM in India. The Supreme Court received the petition and sought responses from four states and four ministries of the central government.[28] An advocate for the petition claimed the practice violated children's rights under Article 14 (Right to Equality) and Article 21 (Right to Life) of the Constitution of India,[29] while an advocate opposing the petition argued that khafz is an essential part of the community's religion, and their right to practise the religion is protected under Articles 25 and 26.[2] The Ministry of Women and Child Development reported in December 2017 that "there is no official data or study which supports the existence of FGM in India."[30] Earlier, in May 2017, Women and Child Development Minister Maneka Gandhi announced that the government will ban FGM if it is not voluntarily stopped.[31] In April 2018 India's Attorney General K. K. Venugopal asked a bench of the Supreme Court to issue directions regarding the case, saying that FGM was already a crime under existing law. The bench adjourned the case and issued notices to Kerala and Telangana, having earlier notified Maharashtra, Gujarat, Rajasthan and Delhi.[29] In September 2018 the Supreme Court referred the PIL to a five-judge constitution bench at the request of Venugopal and the counsel for the Dawoodi Bohras.[32][33] In November 2019, the Supreme Court decided that the issue of FGM be referred to a larger seven-judge bench and that it be examined alongside other women's rights issues. The court said it was a "seminal issue" regarding the power of the court to decide whether a practice is essential to a religion.[34] ## References[edit] 1. ^ a b c d Cantera, Angel L Martínez (6 March 2018). "'I was crying with unbearable pain': study reveals extent of FGM in India". The Guardian. Retrieved 9 November 2018. 2. ^ a b c Neeraj, Vartika (23 July 2018). "Genital Mutilation Plagues Thousands of Bohra Women in India". The Wire. Retrieved 9 November 2018. 3. ^ Das, Mohua (7 June 2016). "Clarifying his stand - Circumcision a religious rite, but abide by law of country: Syedna". The Times of India. Mumbai. Archived from the original on 10 November 2018. Retrieved 9 November 2018. 4. ^ "Female Genital Mutilation: Guide to Eliminating the FGM practice in India" (PDF). Lawyers Collective. 21 May 2017. Retrieved 9 November 2018. 5. ^ a b Punwani, Jyoti (21 October 2017). "It was a memory I had blocked out, says activist Masooma Ranalvi". The Hindu. Retrieved 9 November 2018. 6. ^ Ravishanker, Reshma (8 February 2018). "Curbing women's sexual desire through genital mutilation: Reality of 'khatna' in India". Retrieved 9 November 2018. 7. ^ Anantnarayan, Lakshmi (31 January 2018). "The Clitoral Hood A Contested Site, Khafd or Female Genital Mutilation/Cutting (FGM/C) in India" (PDF). Retrieved 9 November 2018. 8. ^ "Female circumcision anger aired in India". Dawn. 23 April 2012. Retrieved 9 November 2018. 9. ^ "Female genital mutilation in India: Campaign aims to initiate dialogue with Bohras on issue during Ramadan". 30 May 2017. Retrieved 9 November 2018. 10. ^ Sahiyo (30 May 2017). "Announcing Each One Reach One 2: Let's discuss Khatna this Ramzan". Retrieved 9 November 2018. 11. ^ STP Team (18 February 2017). "Sahiyo is India's first collective against type of FGM called Khatna in the Dawoodi Bohra community". Retrieved 9 November 2018. 12. ^ "Human Rights Day: Dawoodi Bohra women launch petition to ban female genital mutilation". Firstpost. 10 December 2016. Retrieved 9 November 2018. 13. ^ Shelar, Jyoti (9 December 2016). "Declare India country with FGM prevalence". The Hindu. Retrieved 9 November 2018. 14. ^ "Campaigners against female genital mutilation call upon UNHRC to address issue". 23 September 2017. Retrieved 9 November 2018. 15. ^ "FGM campaigner knocks at UNHRC doors to address FGM in India". 22 September 2017. Retrieved 9 November 2018. 16. ^ Das, Mohua (2 June 2017). "2 women doctors promote female genital mutilation, may face action". Retrieved 9 November 2018. 17. ^ Julios, Christina (2018). Female Genital Mutilation and Social Media. Routledge. pp. 66–67. ISBN 9781351717618. 18. ^ "Dawoodi Bohra Women for Religious Freedom". Retrieved 9 November 2018. 19. ^ "Update: 7-judge Constitution Bench to Hear PIL of Sunita Tiwari vs Union of India". www.dbwrf.org. Retrieved 18 November 2019. 20. ^ "WHO's stance and the criminalization of female circumcision: The protection of or violation of human rights?". www.dbwrf.org. Retrieved 18 November 2019. 21. ^ Shelar, Jyoti (6 February 2019). "Khafz: circumcision or FGM?". The Hindu. ISSN 0971-751X. Retrieved 19 November 2019. 22. ^ The Stream - Female cutting among the Bohra community, retrieved 24 November 2019 23. ^ "Twitter backlash as tweet promoting FGM is seen 30,000 times". Metro. 20 September 2018. Retrieved 24 November 2019. 24. ^ "Women in India: Egalitarianism from a Bohra Women's Perspective". US Department of State Cables. 19 March 2009. 25. ^ Jun 2, Mohua Das \| TNN \| Updated; 2017; Ist, 9:37. "DBWRF doctors explain difference between female circumcision and FGM \| Mumbai News - Times of India". The Times of India. Retrieved 21 November 2019.CS1 maint: numeric names: authors list (link) 26. ^ "Bohra women's group defends 'khafz', says FGM should be banned". Business Standard India. Press Trust of India. 25 August 2018. Retrieved 20 November 2019. 27. ^ India 2016 Human Rights Report. https://www.state.gov/wp-content/uploads/2019/01/India-1.pdf: US Department of State. 2016. p. 38.CS1 maint: location (link) 28. ^ Shelar, Jyoti (11 May 2017). "Waging a legal battle to ban FGM". The Hindu. Retrieved 9 November 2018. 29. ^ a b "Female genital mutilation a crime: Centre to Supreme Court". 20 April 2018. Retrieved 9 November 2018. 30. ^ "No evidence of FGM, India government tells court, appalling activists". Reuters. 29 December 2017. Retrieved 9 November 2018. 31. ^ Gupta, Moushumi Das (29 May 2017). "Govt will end female genital mutilation if Bohras don't: Maneka Gandhi". Hindustan Times. Retrieved 9 November 2018. 32. ^ "SC refers to five-judge bench plea against female genital mutilation". 24 September 2018. Retrieved 30 May 2019. 33. ^ "Female Genital Mutilation Day 8". 24 September 2018. Retrieved 30 May 2019. 34. ^ "Female genital mutilation petition pending before Supreme Court", Hindustan Times, 15 November 2019. ## See also[edit] * Prevalence of female genital mutilation by country * v * t * e Female genital mutilation Health issues * Clitoridectomy * Dysmenorrhea * Dyspareunia * Gishiri cutting * Husband stitch * Infibulation * Keloid scars * Pelvic inflammatory disease * Rectovaginal fistula * Vesicovaginal fistula By country * Prevalence by country * Laws by country * FGM in India * colonial Kenya * Kurdistan * New Zealand * Nigeria * Sierra Leone * Sudan * United Kingdom * United States * Religious views on FGM Writers/groups Early writers and activists * Raqiya Haji Dualeh Abdalla * Janice Boddy * Mary Daly * Efua Dorkenoo * Asma El Dareer * Benoîte Groult * Rose Oldfield Hayes * Fran Hosken * Edna Adan Ismail * Nawal El Saadawi * Lilian Passmore Sanderson * Marion Scott Stevenson * Hulda Stumpf * Nahid Toubia * Amina Warsame Others * Fuambai Ahmadu * Ayaan Hirsi Ali * Ellen Gruenbaum * Waris Dirie * Gerry Mackie * Molly Melching * Layli Miller-Muro * Comfort Momoh * Alice Walker Groups * Babiker Bedri Scientific Association for Women's Studies * Equality Now * FORWARD * Inter-African Committee on Traditional Practices Affecting the Health of Women and Children * RAINBO * Tostan * Tahirih Justice Center * Zero Tolerance Day Media Books * Woman at Point Zero (1975) * Woman, Why Do You Weep? (1982) * Possessing the Secret of Joy (1992) * Desert Flower (1998) Films * Moolaadé (2004) * Desert Flower (2009) * My Body My Rules (2015) Legislation * Matter of Kasinga * Prohibition of Female Circumcision Act 1985 * Female Genital Mutilation Act 2003 * 2005 (Scotland) Act * Children Act 1989 (Amendment) (Female Genital Mutilation) Act 2019 Categories * Female genital mutilation * Activists against female genital mutilation [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Female genital mutilation in India	None	26,821	wikipedia	https://en.wikipedia.org/wiki/Female_genital_mutilation_in_India	2021-01-18T18:30:02	{"wikidata": ["Q59555074"]}
A number sign (#) is used with this entry because of evidence that spastic paraplegia-23 (SPG23) is caused by homozygous mutation in the DSTYK gene (612666) on chromosome 1q32. Description Spastic paraplegia-23 is an autosomal recessive neurologic disorder characterized by childhood-onset spastic paraplegia resulting in gait difficulties and associated with pigmentary abnormalities, including premature graying of the hair and vitiligo-like or hyperpigmented skin lesions. Some patients may also have a peripheral neuropathy (summary by Lee et al., 2017). Clinical Features Abdallat et al. (1980) and Lison et al. (1981) reported a consanguineous Jordanian family in which 2 brothers and a sister from first-cousin parents had progressive spastic paraparesis and peripheral neuropathy, as well as disordered skin and hair pigmentation, including vitiligo, hyperpigmentation, numerous lentigines, and premature graying of body hair. Sural nerve biopsy showed axonal degeneration; skin biopsy showed abnormal epidermal pigmentation. The proband had diffusely depigmented hair and skin at birth. From the age of 6 months, patchy pigmentation developed, especially in exposed areas of the skin, and his hair developed irregular pigmentation. Progressive paraparesis was first noted at age 6 years. The face was thin with 'sharp' features. The syndrome was considered to be autosomal recessive. Stewart et al. (1981) described 2 sisters and a brother and 2 daughters of 1 of the affected sisters who had spastic paraplegia, peroneal neuropathy and crural hypopigmentation mainly about the knees and in the upper pretibial area. Daras et al. (1983) described 2 brothers and a sister from first-cousin parents who had progressive spastic paraplegia and cerebellar ataxia together with large hyperpigmented nevi on the legs. In an inbred Arab family in Israel, Mukamel et al. (1985) observed 4 affected sibs. All 4 sibs had severe incapacitating spastic paraparesis from early childhood, combined with abnormalities of skin and hair pigmentation. Two other sibs with similar dermatologic findings died at the ages of 3 and 4 months of sepsis. The proband, a 13-year-old boy, had microcephaly, canities, many cafe-au-lait spots and freckles all over his body, and spastic paraplegia. White hair was present from birth. Blumen et al. (2003) presented follow-up information on the family reported by Mukamel et al. (1985). The 4 affected sibs ranged in age from 22 to 32 years, and all had a prematurely aged facial appearance, with white scalp from birth and premature graying of eyebrows and eyelashes. Skin was hypopigmented in covered areas, with patchy, vitiligo-like depigmentation in sun-exposed areas. All affected sibs had severe weakness and spasticity of the lower extremities and mild cognitive impairment. Bamforth (2003) described an 18-year-old girl of northern European ancestry with acquired hypopigmentation and neurologic abnormalities. Her parents were not consanguineous and had 4 other healthy children. The patient's features included vitiligo, diffuse lentigines, increased deep tendon reflexes, spastic gait, kyphoscoliosis, small stature, and normal intelligence. Mode of inheritance was not clear. Lee et al. (2017) reported 2 unrelated families with SPG23, including 4 individuals from a consanguineous family of Kuwaiti-Jordanian descent and 2 sisters from a consanguineous Israeli family. The 23-year-old proband in the first family was described in detail. He had onset of waddling gait around age 2 to 3 years followed by spastic paraplegia; he was wheelchair-bound from age 9. He had premature graying of the hair and vitiligo-like skin lesions, as well as a horseshoe kidney detected on imaging; brain imaging showed no abnormalities. He had normal intelligence and no evidence of epilepsy or sensory impairment, but he and his younger affected brother both had bowel urgency and incontinence. The younger brother had febrile convulsions at age 6 and no urogenital anomalies. Two Israeli sisters had spastic paraparesis with hyperreflexia and extensor plantar responses, premature graying of the hair, vitiligo-like and pigmented skin lesions, and flexion contractures of the toes. Inheritance The transmission pattern of SPG23 in the families reported by Lee et al. (2017) was consistent with autosomal recessive inheritance. Mapping In an inbred affected Arab family first reported by Mukamel et al. (1985), Blumen et al. (2003) found linkage of the disorder to a 25-cM region on chromosome 1q24-q32 (maximum lod score of 3.05 near marker D1S2692). Haplotype analysis showed allele homozygosity in all affected members. Molecular Genetics In affected members of 3 unrelated families of Middle Eastern descent with SPG23, including the family reported by Mukamel et al. (1985) and Blumen et al. (2003), Lee et al. (2017) identified a homozygous intragenic deletion/insertion in the DSTYK gene (612666.0005). The deletion, which was found by a combination of whole-exome sequencing, homozygosity analysis, and copy number variation analysis in the first family, segregated with the disorder in all 3 families. Haplotype analysis indicated a founder effect. Skin biopsy from 1 of the patients showed markedly decreased immunolabeling for DSTYK compared to controls, consistent with a loss-of-function effect. Transmission electron microscopy showed focal loss of melanocytes with some remaining melanocytes showing ultrastructural features of swollen mitochondria with abnormal cristae and cytoplasmic vacuoles. Other cell types also showed these changes, findings that were consistent with increased susceptibility to stress and cell death. Patient cells and mouse fibroblasts with siRNA-mediated knockdown of Dstyk showed increased signs of apoptosis and cell death after UV exposure compared to controls. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly (in some patients) Face \- Thin face \- Micrognathia \- Retrognathia SKIN, NAILS, & HAIR Skin \- Patchy vitiligo \- Hyperpigmentation of exposed areas \- Lentigines Hair \- Premature graying of body hair NEUROLOGIC Central Nervous System \- Spastic paraplegia, severe \- Lower limb weakness \- Hyperreflexia \- Extensor plantar responses \- Cognitive impairment, mild Peripheral Nervous System \- Peripheral neuropathy, mild, in some MISCELLANEOUS \- Pigmentary abnormalities apparent at birth or in infancy \- Onset of spasticity in childhood MOLECULAR BASIS \- Caused by mutation in the dual serine/threonine and tyrosine protein kinase gene (DSTYK, 612666.0005 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SPASTIC PARAPLEGIA 23, AUTOSOMAL RECESSIVE	c0796019	26,822	omim	https://www.omim.org/entry/270750	2019-09-22T16:22:14	{"doid": ["0110774"], "mesh": ["C536859"], "omim": ["270750"], "orphanet": ["101003"], "synonyms": ["Alternative titles", "SPASTIC PARAPLEGIA WITH PIGMENTARY ABNORMALITIES", "SPASTIC PARAPARESIS, VITILIGO, PREMATURE GRAYING, CHARACTERISTIC FACIES", "LISON SYNDROME"]}
Fucosidosis is a condition that affects many areas of the body, especially the brain. Affected individuals have intellectual disability that worsens with age, and many develop dementia later in life. People with this condition often have delayed development of motor skills such as walking; the skills they do acquire deteriorate over time. Additional signs and symptoms of fucosidosis include impaired growth; abnormal bone development (dysostosis multiplex); seizures; abnormal muscle stiffness (spasticity); clusters of enlarged blood vessels forming small, dark red spots on the skin (angiokeratomas); distinctive facial features that are often described as "coarse"; recurrent respiratory infections; and abnormally large abdominal organs (visceromegaly). In severe cases, symptoms typically appear in infancy, and affected individuals usually live into late childhood. In milder cases, symptoms begin at age 1 or 2, and affected individuals tend to survive into mid-adulthood. In the past, researchers described two types of this condition based on symptoms and age of onset, but current opinion is that the two types are actually a single disorder with signs and symptoms that range in severity. ## Frequency Fucosidosis is a rare condition; approximately 100 cases have been reported worldwide. This condition appears to be most prevalent in Italy, Cuba, and the southwestern United States. ## Causes Mutations in the FUCA1 gene cause fucosidosis. The FUCA1 gene provides instructions for making an enzyme called alpha-L-fucosidase. This enzyme plays a role in the breakdown of complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins) and fats (glycolipids). Alpha-L-fucosidase is responsible for cutting (cleaving) off a sugar molecule called fucose toward the end of the breakdown process. FUCA1 gene mutations severely reduce or eliminate the activity of the alpha-L-fucosidase enzyme. A lack of enzyme activity results in an incomplete breakdown of glycolipids and glycoproteins. These partially broken down compounds gradually accumulate within various cells and tissues throughout the body and cause cells to malfunction. Brain cells are particularly sensitive to the buildup of glycolipids and glycoproteins, which can result in cell death. Loss of brain cells is thought to cause the neurological symptoms of fucosidosis. Accumulation of glycolipids and glycoproteins also occurs in other organs such as the liver, spleen, skin, heart, pancreas, and kidneys, contributing to the additional symptoms of fucosidosis. ### Learn more about the gene associated with Fucosidosis * FUCA1 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Fucosidosis	c0016788	26,823	medlineplus	https://medlineplus.gov/genetics/condition/fucosidosis/	2021-01-27T08:24:43	{"gard": ["6473"], "mesh": ["D005645"], "omim": ["230000"], "synonyms": []}
Congenital anomalies of spine SpecialtyMedical genetics, orthopedics Congenital vertebral anomalies are a collection of malformations of the spine. Most, around 85%, are not clinically significant, but they can cause compression of the spinal cord by deforming the vertebral canal or causing instability. This condition occurs in the womb. Congenital vertebral anomalies include alterations of the shape and number of vertebrae. ## Contents * 1 Lumbarization and sacralization * 2 Hemivertebrae * 3 Block vertebrae * 3.1 Fossil record * 4 Butterfly vertebrae * 5 Transitional vertebrae * 6 Spina bifida * 7 Associations * 8 References * 9 External links ## Lumbarization and sacralization[edit] Lumbarization of sacral vertebra 1, seen as 6 vertebrae that do not connect to ribs. Lumbarization is an anomaly in the spine. It is defined by the nonfusion of the first and second segments of the sacrum. The lumbar spine subsequently appears to have six vertebrae or segments, not five. This sixth lumbar vertebra is known as a transitional vertebra. Conversely the sacrum appears to have only four segments instead of its designated five segments. Lumbosacral transitional vertebrae consist of the process of the last lumbar vertebra fusing with the first sacral segment. [1] While only around 10 percent of adults have a spinal abnormality due to genetics, a sixth lumbar vertebra is one of the more common abnormalities. [2] Sacralization of the L5 vertebra is seen at the lower right of the image. Sacralization of the fifth lumbar vertebra (or sacralization) is a congenital anomaly, in which the transverse process of the last lumbar vertebra (L5) fuses to the sacrum on one side or both, or to ilium, or both. These anomalies are observed at about 3.5 percent of people, and it is usually bilateral but can be unilateral or incomplete (ipsilateral or contralateral rudimentary facets) as well. Although sacralization may be a cause of low back pain, it is asymptomatic in many cases (especially bilateral type). Low back pain in these cases most likely occurs due to biomechanics. In sacralization, the L5-S1 intervertebral disc may be thin and narrow. This abnormality is found by X-ray.[citation needed] Sacralization of L6 means L6 attaches to S1 via a rudimentary joint. This L6-S1 joint creates additional motion, increasing the potential for motion-related stress and lower back pain/conditions. This condition can usually be treated without surgery, injecting steroid medication at the pseudoarticulation instead. Additionally, if L6 fuses to another vertebra this is increasingly likely to cause lower back pain. [3] The presence of a sixth vertebra in the space where five vertebrae normally reside also decreases the flexibility of the spine and increases the likelihood of injury. [4] ## Hemivertebrae[edit] Hemivertebrae are wedge-shaped vertebrae and therefore can cause an angle in the spine (such as kyphosis, scoliosis, and lordosis). Among the congenital vertebral anomalies, hemivertebrae are the most likely to cause neurologic problems.[5] The most common location is the midthoracic vertebrae, especially the eighth (T8).[6] Neurologic signs result from severe angulation of the spine, narrowing of the spinal canal, instability of the spine, and luxation or fracture of the vertebrae. Signs include rear limb weakness or paralysis, urinary or fecal incontinence, and spinal pain.[5] Most cases of hemivertebrae have no or mild symptoms, so treatment is usually conservative. Severe cases may respond to surgical spinal cord decompression and vertebral stabilization.[6] Associations Recognised associations are many and include: Aicardi syndrome, cleidocranial dysostosis, gastroschisis 3, Gorlin syndrome, fetal pyelectasis 3, Jarcho-Levin syndrome, OEIS complex, VACTERL association.[7] The probable cause of hemivertebrae is a lack of blood supply causing part of the vertebrae not to form. Hemivertebrae in dogs are most common in the tail, resulting in a screw shape.[citation needed] ## Block vertebrae[edit] Block vertebrae occur when there is improper segmentation of the vertebrae, leading to parts of or the entire vertebrae being fused. The adjacent vertebrae fuse through their intervertebral discs and also through other intervertebral joints so that it can lead to blocking or stretching of the exiting nerve roots from that segment. It may lead to certain neurological problems depending on the severity of the block. It can increase stress on the inferior and the superior intervertebral joints. It can lead to an abnormal angle in the spine, there are certain syndromes associated with block vertebrae; for example, Klippel–Feil syndrome. The sacrum is a normal block vertebra.[citation needed] ### Fossil record[edit] Main article: Paleopathology Evidence for block vertebrae found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. A block vertebra has been documented in T. rex. This suggests that the basic development pattern of vertebrae goes at least as far back as the most recent common ancestor of archosaurs and mammals. The tyrannosaur's block vertebra was probably caused by a "failure of the resegmentation of the sclerotomes".[8] * Block vertebrae of the cervical spine (vertebrae 4 and 5). Probably based on degenerative or inflammatory changes. * Several congenital block vertebrae in the transition from the thoracic to the lumbar spine and hemivertebrae. * Congenital block vertebra in the lumbar spine (partial vertebrae 3 and 4). The rear portion of the disc still exists. * Congenital block vertebra of the lumbar spine. CT volume rendering. * Congenital block vertebra of the lumbar spine. CT volume rendering. ## Butterfly vertebrae[edit] Butterfly vertebrae have a sagittal cleft through the body of the vertebrae and a funnel shape at the ends. This gives the appearance of a butterfly on an x-ray. It is caused by persistence of the notochord (which usually only remains as the center of the intervertebral disc) during vertebrae formation. There are usually no symptoms. There are also coronal clefts mainly in skeletal dysplasias such as chondrodysplasia punctata. In dogs, butterfly vertebrae occur most often in Bulldogs, Pugs, and Boston Terriers.[9] * Butterfly vertebra (red). Normal vertebra for comparison (blue). * Volume rendering of a CT scan of the lumbar vertebral column, showing butterfly vertebrae at several levels, most typically in L1. ## Transitional vertebrae[edit] Short ribs at the first lumbar vertebra, which is thus a transitional vertebra, since lumbar vertebrae normally do not have ribs attached to them. Transitional vertebrae have the characteristics of two types of vertebra. The condition usually involves the vertebral arch or transverse processes. It occurs at the cervicothoracic, thoracolumbar, or lumbosacral junction. For instance, the transverse process of the last cervical vertebra may resemble a rib. A transitional vertebra at the lumbosacral junction can cause arthritis, disk changes, or thecal sac compression. Back pain associated with lumbosacral transitional vertebrae (LSTV) is known as Bertolotti's syndrome. One study found that male German Shepherd Dogs with a lumbosacral transitional vertebra are at greater risk for cauda equina syndrome, which can cause rear limb weakness and incontinence.[10] ## Spina bifida[edit] Spina bifida is characterized by a midline cleft in the vertebral arch. It usually causes no symptoms in dogs. It is seen most commonly in Bulldogs and Manx cats.[5] In Manx it accompanies a condition known as sacrocaudal dysgenesis that gives these cats their characteristic tailless or stumpy tail appearance. It is inherited in Manx as an autosomal dominant trait.[11] ## Associations[edit] Vertebral anomalies is associated with an increased incidence of some other specific anomalies as well, together being called the VACTERL association:[citation needed] * V - Vertebral anomalies * A - Anal atresia * C - Cardiovascular anomalies * T - Tracheoesophageal fistula * E - Esophageal atresia * R - Renal (Kidney) and/or radial anomalies * L - Limb defects ## References[edit] 1. ^ Jancuska, JM; Spivak, JM; Bendo, JA (2015). "A Review of Symptomatic Lumbosacral Transitional Vertebrae: Bertolotti's Syndrome". Int J Spine Surg. 9: 42. doi:10.14444/2042. PMC 4603258. PMID 26484005. 2. ^ Dorland's Medical Dictionary 3. ^ "Spinal Cord, Inc". Retrieved November 27, 2016. 4. ^ "Laser Spine Institute". Archived from the original on November 28, 2016. Retrieved November 27, 2016. 5. ^ a b c Braund, K.G. (2003). "Developmental Disorders". Clinical Neurology in Small Animals: Localization, Diagnosis and Treatment. Retrieved 2007-02-04. 6. ^ a b Jeffery N, Smith P, Talbot C (2007). "Imaging findings and surgical treatment of hemivertebrae in three dogs". J Am Vet Med Assoc. 230 (4): 532–6. doi:10.2460/javma.230.4.532. PMID 17302550. 7. ^ http://radiopaedia.org/articles/hemivertebra 8. ^ Molnar, R. E., 2001, Theropod paleopathology: a literature survey: In: Mesozoic Vertebrate Life, edited by Tanke, D. H., and Carpenter, K., Indiana University Press, p. 337-363. 9. ^ Ettinger, Stephen J.; Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 0-7216-6795-3. 10. ^ Flückiger M, Damur-Djuric N, Hässig M, Morgan J, Steffen F (2006). "A lumbosacral transitional vertebra in the dog predisposes to cauda equina syndrome". Vet Radiol Ultrasound. 47 (1): 39–44. doi:10.1111/j.1740-8261.2005.00103.x. PMID 16429983. 11. ^ "Congenital and Inherited Anomalies of the Nervous System: Small Animals". The Merck Veterinary Manual. 2006. Retrieved 2007-02-04. ## External links[edit] Classification D * ICD-10: Q67.5, Q76.0-.4 * ICD-9-CM: 756.1 * v * t * e Congenital malformations and deformations of musculoskeletal system / musculoskeletal abnormality Appendicular limb / dysmelia Arms clavicle / shoulder * Cleidocranial dysostosis * Sprengel's deformity * Wallis–Zieff–Goldblatt syndrome hand deformity * Madelung's deformity * Clinodactyly * Oligodactyly * Polydactyly Leg hip * Hip dislocation / Hip dysplasia * Upington disease * Coxa valga * Coxa vara knee * Genu valgum * Genu varum * Genu recurvatum * Discoid meniscus * Congenital patellar dislocation * Congenital knee dislocation foot deformity * varus * Club foot * Pigeon toe * valgus * Flat feet * Pes cavus * Rocker bottom foot * Hammer toe Either / both fingers and toes * Polydactyly / Syndactyly * Webbed toes * Arachnodactyly * Cenani–Lenz syndactylism * Ectrodactyly * Brachydactyly * Stub thumb reduction deficits / limb * Acheiropodia * Ectromelia * Phocomelia * Amelia * Hemimelia multiple joints * Arthrogryposis * Larsen syndrome * RAPADILINO syndrome Axial Skull and face Craniosynostosis * Scaphocephaly * Oxycephaly * Trigonocephaly Craniofacial dysostosis * Crouzon syndrome * Hypertelorism * Hallermann–Streiff syndrome * Treacher Collins syndrome other * Macrocephaly * Platybasia * Craniodiaphyseal dysplasia * Dolichocephaly * Greig cephalopolysyndactyly syndrome * Plagiocephaly * Saddle nose Vertebral column * Spinal curvature * Scoliosis * Klippel–Feil syndrome * Spondylolisthesis * Spina bifida occulta * Sacralization Thoracic skeleton ribs: * Cervical * Bifid sternum: * Pectus excavatum * Pectus carinatum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Congenital vertebral anomaly	None	26,824	wikipedia	https://en.wikipedia.org/wiki/Congenital_vertebral_anomaly	2021-01-18T18:50:43	{"icd-10": ["Q76.4"], "wikidata": ["Q332343"]}
Pseudo-Meigs syndrome is a rare neoplastic disease characterized by the presence of a benign or malignant, pelvic or abdominal tumor (other than ovarian fibroma or fibroma-like and localized outside of the ovaries, fallopian tubes, and broad ligaments) associated with hydrothorax and ascites that resolve after tumor resection. Patients usually present with dyspnea, pelvic mass with or without a tender, distended abdomen and/or weight 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	Pseudo-Meigs syndrome	None	26,825	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314459	2021-01-23T16:54:38	{"icd-10": ["D39.1"], "synonyms": ["Pseudo-Demons-Meigs syndrome"]}
Venous thoracic outlet syndrome (VTOS) is a form of thoracic outlet syndrome (TOS; see this term) that manifests as unilateral (rarely bilateral) arm pain and cyanosis. ## Epidemiology Determination of incidence is difficult due to the lack of a confirmatory test for TOS. VTOS accounts for 2%-3% of all cases of TOS. ## Clinical description VTOS occurs in young adults, usually after excessive arm activity. The characteristic symptoms, caused by venous obstruction, are arm swelling, cyanosis, pain and mild paresthesias. Neck pain and headaches may rarely occur. The forearm fatigues within minutes of use. Visible subcutaneous veins over the shoulder and upper chest are often present. ## Etiology Repetitive arm motion and compression of the subclavian vein in the neck (between the clavicle and the first rib) leads to scar tissue that can predispose one to thrombosis due to narrowing of vessels. ## Diagnostic methods Diagnosis is based on findings of arm swelling, cyanosis and distended superficial veins. Radiographs may identify compressive sources including an elongated C7 transverse process or anomalous first rib. Subclavian vein stenosis or occlusion on dynamic ultrasonography, magnetic resonance or computed tomography venography supports the diagnosis. Provocative physical exam maneuvers such as the Roos (test is positive when patient is unable to maintain the position of opening and closing hands while arms are in an elevated position for 3 minutes) and Adson (test is positive if radial pulse disappears while turning the head with extended neck following deep inspiration) tests can also be helpful. ## Differential diagnosis Differential diagnoses include arterial (ATOS) and neurogenic TOS (NTOS) (see these terms), which are differentiated clinically. ATOS presents as upper extremity ischemia due to subclavian artery compression or thrombosis and can be ruled-out with magnetic resonance angiography. True NTOS usually presents as a lower trunk brachial plexopathy and is diagnosed with electrodiagnostics or MRI. Other causes of venous obstruction including tumors, congenital abnormalities and upper extremity deep venous thromboses must also be considered. ## Management and treatment When acute, treatment is thrombolytic therapy followed by decompressive surgery (first rib resection, pectoralis minor release or scalenectomy) to decrease recurrences. Angioplasty or surgical bypass is performed to repair damaged veins. If chronic, with heaviness and a swollen limb but with a patent subclavian vein, decompressive surgery, angioplasty or vascular reconstruction is recommended. Physical therapy is not generally helpful in treating VTOS, but may be helpful in less severe cases. ## Prognosis Patients undergoing successful thrombolysis followed by decompression have five-year secondary vein patency rates greater than 95% but residual edema may limit function. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Venous thoracic outlet syndrome	c1956396	26,826	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=357131	2021-01-23T18:54:09	{"mesh": ["D013901"], "umls": ["C1956396"], "icd-10": ["G54.0"], "synonyms": ["Effort subclavian vein thrombosis", "Paget-Schrotter disease", "VTOS", "Venous TOS", "Venous cervical rib syndrome", "Venous costoclavicular syndrome", "Venous hyperabduction syndrome", "Venous scalenus anticus syndrome", "Venous thoracic outlet compression syndrome"]}
Trousseau sign of latent tetany Trousseau's Sign of Latent Tetany. Note the flexed wrist and MCPs, and the extended DIPs and PIPs Differential diagnosislow calcium Trousseau sign of latent tetany is a medical sign observed in patients with low calcium.[1] From 1 to 4 percent of normal patients will test positive for Trousseau's sign of latent tetany.[2] This sign may be positive before other manifestations of hypocalcemia such as hyperreflexia and tetany, as such it is generally believed to be more sensitive (94%) than the Chvostek sign (29%) for hypocalcemia.[3][4] To elicit the sign, a blood pressure cuff is placed around the arm and inflated to a pressure greater than the systolic blood pressure and held in place for 3 minutes. This will occlude the brachial artery. In the absence of blood flow, the patient's hypocalcemia and subsequent neuromuscular irritability will induce spasm of the muscles of the hand and forearm. The wrist and metacarpophalangeal joints flex, the DIP and PIP joints extend, and the fingers adduct. The sign is also known as main d'accoucheur (French for "hand of the obstetrician") because it supposedly resembles the position of an obstetrician's hand in delivering a baby.[5] The sign is named after French physician Armand Trousseau who described the phenomenon in 1861.[6] It is distinct from the Trousseau sign of malignancy. ## References[edit] 1. ^ Kumar, Abbas, Fausto. Pathologic Basis of Disease, 7th edition. Philadelphia: Elsevier-Saunders, 2005. 1188. 2. ^ Dennis, Mark; Bowen, William Talbot; Cho, Lucy (2012). "Trousseau's sign". Mechanisms of Clinical Signs. Elsevier. p. 555. ISBN 978-0729540759; pbk 3. ^ Fonseca, OA; Calverley, JR (August 1967). "Neurological manifestations of hypoparathyroidism". Archives of Internal Medicine. 120 (2): 202–6. doi:10.1001/archinte.1967.00300020074009. PMID 4952674. 4. ^ Schaat M, Payne CA. Effect of diphenylhydantoin and phenobarbital on latent tetany 5. ^ "Main d'accoucheur - Oxford Reference". www.oxfordreference.com. doi:10.1093/oi/authority.20110803100127204. 6. ^ Trousseau a. Clinique médicale de l'Hôtel-Dieu de Paris. Paris, 1861. Volume 2: 112-114. * v * t * e Electrolyte imbalances Sodium * High * Salt poisoning * Low * Hypotonic * Isotonic * Cerebral salt-wasting syndrome Potassium * High * Low Chloride * High * Low Calcium * High * Low * Symptoms and signs * Chvostek sign * Trousseau sign * Milk-alkali syndrome * Disorders of calcium metabolism * Calcinosis (Calciphylaxis, Calcinosis cutis) * Calcification (Metastatic calcification, Dystrophic calcification) * Familial hypocalciuric hypercalcemia Phosphate * High * Low Magnesium * High * Low This medical sign 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	Trousseau sign of latent tetany	c0234181	26,827	wikipedia	https://en.wikipedia.org/wiki/Trousseau_sign_of_latent_tetany	2021-01-18T18:41:50	{"umls": ["C0234181"], "wikidata": ["Q1458077"]}
## Clinical Features In 3 generations of a Filipino family, Honig et al. (1971) demonstrated elliptocytosis with transverse slitlike areas of decreased density in the red cells. This was accompanied by no hemolysis in vivo and red cell survival was normal. Male-to-male transmission was observed. The elliptical stomatocytosis described by Harrison et al. (1976) bears some similarities to the cases of Honig et al. (1971); however, their patients showed increased osmotic fragility whereas Honig's cases showed decreased osmotic fragility. Inheritance \- Autosomal dominant Lab \- Transverse slitlike areas of decreased density in red cells \- Normal red cell survival Heme \- Elliptocytosis \- No hemolysis ▲ 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	RED CELL PERMEABILITY DEFECT	c1867340	26,828	omim	https://www.omim.org/entry/179650	2019-09-22T16:35:17	{"omim": ["179650"], "synonyms": ["Alternative titles", "ELLIPTOCYTOSIS WITH TRANSVERSE SLITLIKE CHANGES"]}
Bowel obstruction Other namesIntestinal obstruction, intestinal occlusion Upright abdominal X-ray demonstrating a small bowel obstruction. Note multiple air fluid levels. SpecialtyGeneral surgery SymptomsAbdominal pain, vomiting, bloating, not passing gas[1] ComplicationsSepsis, bowel ischemia, bowel perforation[1] CausesAdhesions, hernias, volvulus, endometriosis, inflammatory bowel disease, appendicitis, tumors, diverticulitis, ischemic bowel, tuberculosis, intussusception[2][1] Diagnostic methodMedical imaging[1] TreatmentConservative care, surgery[2] Frequency3.2 million (2015)[3] Deaths264,000 (2015)[4] Bowel obstruction, also known as intestinal obstruction, is a mechanical or functional obstruction of the intestines which prevents the normal movement of the products of digestion.[2][5] Either the small bowel or large bowel may be affected.[1] Signs and symptoms include abdominal pain, vomiting, bloating and not passing gas.[1] Mechanical obstruction is the cause of about 5 to 15% of cases of severe abdominal pain of sudden onset requiring admission to hospital.[1][2] Causes of bowel obstruction include adhesions, hernias, volvulus, endometriosis, inflammatory bowel disease, appendicitis, tumors, diverticulitis, ischemic bowel, tuberculosis and intussusception.[1][2] Small bowel obstructions are most often due to adhesions and hernias while large bowel obstructions are most often due to tumors and volvulus.[1][2] The diagnosis may be made on plain X-rays; however, CT scan is more accurate.[1] Ultrasound or MRI may help in the diagnosis of children or pregnant women.[1] The condition may be treated conservatively or with surgery.[2] Typically intravenous fluids are given, a tube is placed through the nose into the stomach to decompress the intestines, and pain medications are given.[2] Antibiotics are often given.[2] In small bowel obstruction about 25% require surgery.[6] Complications may include sepsis, bowel ischemia and bowel perforation.[1] About 3.2 million cases of bowel obstruction occurred in 2015 which resulted in 264,000 deaths.[3][4] Both sexes are equally affected and the condition can occur at any age.[6] Bowel obstruction has been documented throughout history, with cases detailed in the Ebers Papyrus of 1550 BC and by Hippocrates.[7] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Small bowel obstruction * 2.2 Large bowel obstruction * 2.2.1 Outlet obstruction * 3 Diagnosis * 3.1 Differential diagnosis * 4 Treatment * 4.1 Small bowel obstruction * 4.2 Children * 5 Prognosis * 6 Animals * 7 References * 8 External links ## Signs and symptoms[edit] Tinkly bowel sounds Tinkly bowel sounds as heard with a stethoscope in someone with a small bowel obstruction. * * * Problems playing this file? See media help. Depending on the level of obstruction, bowel obstruction can present with abdominal pain, swollen abdomen, abdominal distension, and constipation. Bowel obstruction may be complicated by dehydration and electrolyte abnormalities due to vomiting; respiratory compromise from pressure on the diaphragm by a distended abdomen, or aspiration of vomitus; bowel ischemia or perforation from prolonged distension or pressure from a foreign body.[citation needed] In small bowel obstruction, the pain tends to be colicky (cramping and intermittent) in nature, with spasms lasting a few minutes. The pain tends to be central and mid-abdominal. Vomiting may occur before constipation.[citation needed] In large bowel obstruction, the pain is felt lower in the abdomen and the spasms last longer. Constipation occurs earlier and vomiting may be less prominent. Proximal obstruction of the large bowel may present as small bowel obstruction.[citation needed] ## Causes[edit] ### Small bowel obstruction[edit] Upright abdominal X-ray demonstrating a small bowel obstruction. Note multiple air fluid levels. Causes of small bowel obstruction include:[2] * Adhesions from previous abdominal surgery (most common cause) * Barbed sutures[8] * Pseudoobstruction * Hernias containing bowel * Crohn's disease causing adhesions or inflammatory strictures * Neoplasms, benign or malignant * Intussusception * Volvulus * Superior mesenteric artery syndrome, a compression of the duodenum by the superior mesenteric artery and the abdominal aorta * Ischemic strictures * Foreign bodies (e.g. gallstones in gallstone ileus, swallowed objects such as expandable water toys) * Intestinal atresia After abdominal surgery, the incidence of small bowel obstruction from any cause is 9%. In those where the cause of the obstruction was clear, adhesions are the single most common cause (more than half).[9] ### Large bowel obstruction[edit] Upright abdominal X-ray of a person with a large bowel obstruction showing multiple air fluid levels and dilated loops of bowel. Causes of large bowel obstruction include:[citation needed] * Neoplasms / cancer * Diverticulitis / Diverticulosis * Hernias * Inflammatory bowel disease * Colonic volvulus (sigmoid, caecal, transverse colon) * Adhesions * Constipation * Fecal impaction * Fecaloma * Colon atresia * Intestinal pseudoobstruction * Endometriosis * Narcotic induced (especially with the large doses given to cancer or palliative care patients) #### Outlet obstruction[edit] Outlet obstruction is a sub-type of large bowel obstruction and refers to conditions affecting the anorectal region that obstruct defecation, specifically conditions of the pelvic floor and anal sphincters. Outlet obstruction can be classified into four groups.[10] * Functional outlet obstruction * Inefficient inhibition of the internal anal sphincter * Short-segment Hirschsprung's disease * Chagas disease * Hereditary internal sphincter myopathy * Inefficient relaxation of the striated pelvic floor muscles * Anismus (pelvic floor dyssynergia) * Multiple sclerosis * Spinal cord lesions * Mechanical outlet obstruction * Internal intussusception * Enterocele * Dissipation of force vector * rectocele * Descending perineum * Rectal prolapse * Impaired rectal sensitivity * Megarectum * Rectal hyposensitivity ## Diagnosis[edit] A small bowel obstruction as seen on CT Small bowel dilation on CT scan in adults[11] <2.5 cm Non-dilated 2.5-2.9 cm Mildly dilated 3-4 cm Moderately dilated >4 cm Severely dilated Average inner diameters and ranges of different sections of the large intestine.[12] The main diagnostic tools are blood tests, X-rays of the abdomen, CT scanning, and ultrasound. If a mass is identified, biopsy may determine the nature of the mass. Radiological signs of bowel obstruction include bowel distension and the presence of multiple (more than six) gas-fluid levels on supine and erect abdominal radiographs.[medical citation needed] Ultrasounds may be as useful as CT scanning to make the diagnosis.[13] Contrast enema or small bowel series or CT scan can be used to define the level of obstruction, whether the obstruction is partial or complete, and to help define the cause of the obstruction. The appearance of water-soluble contrast in the cecum on an abdominal radiograph within 24 hours of it being given by mouth predicts resolution of an adhesive small bowel obstruction with sensitivity of 97% and specificity of 96%.[14] Colonoscopy, small bowel investigation with ingested camera or push endoscopy, and laparoscopy are other diagnostic options. * Play media Small bowel obstruction on ultrasound.[15] * Play media Small bowel obstruction on ultrasound.[15] * Small bowel obstruction on ultrasound.[15] ### Differential diagnosis[edit] Differential diagnoses of bowel obstruction include: * Ileus * Pseudo-obstruction or Ogilvie's syndrome * Intra-abdominal sepsis * Pneumonia or other systemic illness[citation needed]. ## Treatment[edit] Some causes of bowel obstruction may resolve spontaneously;[16] many require operative treatment.[17] In adults, frequently the surgical intervention and the treatment of the causative lesion are required. In malignant large bowel obstruction, endoscopically placed self-expanding metal stents may be used to temporarily relieve the obstruction as a bridge to surgery,[18] or as palliation.[19] Diagnosis of the type of bowel obstruction is normally conducted through initial plain radiograph of the abdomen, luminal contrast studies, computed tomography scan, or ultrasonography prior to determining the best type of treatment.[20] Further research is needed to find out if parenteral nutrition is of benefit to people with an inoperable blockage of the bowel caused by advanced cancer.[21] ### Small bowel obstruction[edit] In the management of small bowel obstructions, a commonly quoted surgical aphorism is: "never let the sun rise or set on small-bowel obstruction"[22] because about 5.5%[22] of small bowel obstructions are ultimately fatal if treatment is delayed. Improvements in radiological imaging of small bowel obstructions allow for confident distinction between simple obstructions, that can be treated conservatively, and obstructions that are surgical emergencies (volvulus, closed-loop obstructions, ischemic bowel, incarcerated hernias, etc.).[2] A small flexible tube (nasogastric tube) may be inserted through the nose into the stomach to help decompress the dilated bowel. This tube is uncomfortable but relieves the abdominal cramps, distention, and vomiting. Intravenous therapy is utilized and the urine output is monitored with a catheter in the bladder.[23] Most people with SBO are initially managed conservatively because in many cases, the bowel will open up. Some adhesions loosen up and the obstruction resolves. The patient is examined several times a day, and X-ray images are made to ensure he or she is not getting clinically worse.[24] Conservative treatment involves insertion of a nasogastric tube, correction of dehydration and electrolyte abnormalities. Opioid pain relievers may be used for patients with severe pain. Antiemetics may be administered if the patient is vomiting. Adhesive obstructions often settle without surgery. If the obstruction is complete a surgery is usually required. Most patients improve with conservative care in 2–5 days. When the obstruction is cancer, surgery is the only treatment. Those with bowel resection or lysis of adhesions usually stay in the hospital a few more days until they can eat and walk.[25] Small bowel obstruction caused by Crohn's disease, peritoneal carcinomatosis, sclerosing peritonitis, radiation enteritis, and postpartum bowel obstruction are typically treated conservatively, i.e. without surgery. ### Children[edit] Main article: Neonatal bowel obstruction Fetal and neonatal bowel obstructions are often caused by an intestinal atresia, where there is a narrowing or absence of a part of the intestine. These atresias are often discovered before birth via an ultrasound, and treated with using laparotomy after birth. If the area affected is small, then the surgeon may be able to remove the damaged portion and join the intestine back together. In instances where the narrowing is longer, or the area is damaged and cannot be used for a period of time, a temporary stoma may be placed.[citation needed] ## Prognosis[edit] The prognosis for non-ischemic cases of SBO is good with mortality rates of 3–5%, while prognosis for SBO with ischemia is fair with mortality rates as high as 30%.[26] Cases of SBO related to cancer are more complicated and require additional intervention to address the malignancy, recurrence, and metastasis, and thus are associated with poorer prognosis.[citation needed] All cases of abdominal surgical intervention are associated with increased risk of future small-bowel obstructions. Statistics from U.S. healthcare report 18.1% re-admittance rate within 30 days for patients who undergo SBO surgery.[27] More than 90% of patients also form adhesions after major abdominal surgery.[28] Common consequences of these adhesions include small-bowel obstruction, chronic abdominal pain, pelvic pain, and infertility.[28] ## Animals[edit] Main article: Impaction (animals) ## References[edit] 1. ^ a b c d e f g h i j k l Gore RM, Silvers RI, Thakrar KH, Wenzke DR, Mehta UK, Newmark GM, Berlin JW (November 2015). "Bowel Obstruction". Radiologic Clinics of North America. 53 (6): 1225–40. doi:10.1016/j.rcl.2015.06.008. PMID 26526435. 2. ^ a b c d e f g h i j k Fitzgerald JE (2010). "Small Bowel Obstruction". Emergency Surgery. Oxford: Wiley-Blackwell. pp. 74–79. doi:10.1002/9781444315172.ch14. ISBN 9781405170253. Archived from the original on September 8, 2017. 3. ^ a b Vos, Theo; Allen, Christine; Arora, Megha; Barber, Ryan M.; Bhutta, Zulfiqar A.; Brown, Alexandria; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Z.; Coggeshall, Megan; Cornaby, Leslie; Dandona, Lalit; Dicker, Daniel J.; Dilegge, Tina; Erskine, Holly E.; Ferrari, Alize J.; Fitzmaurice, Christina; Fleming, Tom; Forouzanfar, Mohammad H.; Fullman, Nancy; Gething, Peter W.; Goldberg, Ellen M.; Graetz, Nicholas; Haagsma, Juanita A.; Hay, Simon I.; Johnson, Catherine O.; Kassebaum, Nicholas J.; Kawashima, Toana; et al. (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282. 4. ^ a b Wang, Haidong; Naghavi, Mohsen; Allen, Christine; Barber, Ryan M.; Bhutta, Zulfiqar A.; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Zian; Coates, Matthew M.; Coggeshall, Megan; Dandona, Lalit; Dicker, Daniel J.; Erskine, Holly E.; Ferrari, Alize J.; Fitzmaurice, Christina; Foreman, Kyle; Forouzanfar, Mohammad H.; Fraser, Maya S.; Fullman, Nancy; Gething, Peter W.; Goldberg, Ellen M.; Graetz, Nicholas; Haagsma, Juanita A.; Hay, Simon I.; Huynh, Chantal; Johnson, Catherine O.; Kassebaum, Nicholas J.; Kinfu, Yohannes; et al. (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/s0140-6736(16)31012-1. PMC 5388903. PMID 27733281. 5. ^ Adams JG (2012). Emergency Medicine: Clinical Essentials (Expert Consult -- Online). Elsevier Health Sciences. p. 331. ISBN 978-1455733941. Archived from the original on September 8, 2017. 6. ^ a b Ferri FF (2014). Ferri's Clinical Advisor 2015: 5 Books in 1. Elsevier Health Sciences. p. 1093. ISBN 9780323084307. Archived from the original on September 8, 2017. 7. ^ Yeo CJ, McFadden DW, Pemberton JH, Peters JH, Matthews JB (2012). Shackelford's Surgery of the Alimentary Tract. Elsevier Health Sciences. p. 1851. ISBN 978-1455738076. Archived from the original on September 8, 2017. 8. ^ Segura-Sampedro JJ, Ashrafian H, Navarro-Sánchez A, Jenkins JT, Morales-Conde S, Martínez-Isla A (November 2015). "Small bowel obstruction due to laparoscopic barbed sutures: an unknown complication?". Revista Espanola de Enfermedades Digestivas. 107 (11): 677–80. doi:10.17235/reed.2015.3863/2015. PMID 26541657. 9. ^ ten Broek RP, Issa Y, van Santbrink EJ, Bouvy ND, Kruitwagen RF, Jeekel J, et al. (October 2013). "Burden of adhesions in abdominal and pelvic surgery: systematic review and met-analysis". BMJ. 347 (oct03 1): f5588. doi:10.1136/bmj.f5588. PMC 3789584. PMID 24092941. 10. ^ Zbar AP, Wexner SD (2010). Coloproctology. New York: Springer. p. 140. ISBN 978-1-84882-755-4. 11. ^ Jacobs SL, Rozenblit A, Ricci Z, Roberts J, Milikow D, Chernyak V, Wolf E (April 2007). "Small bowel faeces sign in patients without small bowel obstruction". Clinical Radiology. 62 (4): 353–7. doi:10.1016/j.crad.2006.11.007. PMID 17331829. 12. ^ Nguyen H, Loustaunau C, Facista A, Ramsey L, Hassounah N, Taylor H, et al. (July 2010). "Deficient Pms2, ERCC1, Ku86, CcOI in field defects during progression to colon cancer". Journal of Visualized Experiments (41). doi:10.3791/1931. PMC 3149991. PMID 20689513. 13. ^ Gottlieb M, Peksa GD, Pandurangadu AV, Nakitende D, Takhar S, Seethala RR (February 2018). "Utilization of ultrasound for the evaluation of small bowel obstruction: A systematic review and meta-analysis". The American Journal of Emergency Medicine. 36 (2): 234–242. doi:10.1016/j.ajem.2017.07.085. PMID 28797559. S2CID 24769945. 14. ^ Abbas S, Bissett IP, Parry BR (July 2007). "Oral water soluble contrast for the management of adhesive small bowel obstruction". The Cochrane Database of Systematic Reviews (3): CD004651. doi:10.1002/14651858.CD004651.pub3. PMC 6465054. PMID 17636770. 15. ^ a b c "UOTW #20 - Ultrasound of the Week". Ultrasound of the Week. October 1, 2014. Archived from the original on May 9, 2017. Retrieved May 27, 2017. 16. ^ Ludmir J, Samuels P, Armson BA, Torosian MH (December 1989). "Spontaneous small bowel obstruction associated with a spontaneous triplet gestation. A case report". The Journal of Reproductive Medicine. 34 (12): 985–7. PMID 2621741. 17. ^ "Abdominal Adhesions and Bowel Obstruction". University of California San Francisco. Archived from the original on August 2, 2013. Retrieved August 11, 2013. 18. ^ Young CJ, Suen MK, Young J, Solomon MJ (October 2011). "Stenting large bowel obstruction avoids a stoma: consecutive series of 100 patients". Colorectal Disease. 13 (10): 1138–41. doi:10.1111/j.1463-1318.2010.02432.x. PMID 20874797. S2CID 12724976. 19. ^ Mosler P, Mergener KD, Brandabur JJ, Schembre DB, Kozarek RA (February 2005). "Palliation of gastric outlet obstruction and proximal small bowel obstruction with self-expandable metal stents: a single center series". Journal of Clinical Gastroenterology. 39 (2): 124–8. PMID 15681907. 20. ^ Holzheimer, Rene G. (2001). Surgical Treatment. NCBI Bookshelf. ISBN 3-88603-714-2. Archived from the original on August 27, 2011. 21. ^ Sowerbutts AM, Lal S, Sremanakova J, Clamp A, Todd C, Jayson GC, et al. (August 2018). "Home parenteral nutrition for people with inoperable malignant bowel obstruction". The Cochrane Database of Systematic Reviews. 8: CD012812. doi:10.1002/14651858.cd012812.pub2. PMC 6513201. PMID 30095168. 22. ^ a b Maglinte DD, Kelvin FM, Rowe MG, Bender GN, Rouch DM (January 2001). "Small-bowel obstruction: optimizing radiologic investigation and nonsurgical management". Radiology. 218 (1): 39–46. doi:10.1148/radiology.218.1.r01ja5439. PMID 11152777. Archived from the original on April 18, 2008. Retrieved June 6, 2008. 23. ^ Small Bowel Obstruction overview Archived February 12, 2010, at the Wayback Machine. Retrieved February 19, 2010. 24. ^ Small Bowel Obstruction: Treating Bowel Adhesions Non-Surgically Archived February 27, 2010, at the Wayback Machine. Clear Passage treatment center online portal Retrieved February 19, 2010 25. ^ Small Bowel Obstruction Archived July 5, 2010, at the Wayback Machine The Eastern Association for the Surgery of Trauma. February 19, 2010 26. ^ Kakoza R, Lieberman G (May 2006). "Mechanical Small Bowel Obstruction" (PDF). Archived from the original (PDF) on May 7, 2013. Retrieved October 9, 2012. Cite journal requires `\|journal=` (help) 27. ^ "Readmissions to U.S. Hospitals by Procedure" (PDF). Agency for Healthcare Research and Quality. April 2013. Archived (PDF) from the original on October 20, 2013. Retrieved August 27, 2013. 28. ^ a b Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL (2001). "Peritoneal adhesions: etiology, pathophysiology, and clinical significance. Recent advances in prevention and management". Digestive Surgery. 18 (4): 260–73. doi:10.1159/000050149. PMID 11528133. S2CID 30816909. ## External links[edit] * Obstruction, Small Bowel at eMedicine * Obstruction, Large Bowel at eMedicine Classification D * ICD-10: K56 * ICD-9-CM: 560 * MeSH: D007415 * DiseasesDB: 15838 External resources * MedlinePlus: 000260 * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Bowel obstruction	c0021843	26,829	wikipedia	https://en.wikipedia.org/wiki/Bowel_obstruction	2021-01-18T19:10:40	{"mesh": ["D007415"], "umls": ["C0021843"], "wikidata": ["Q16244733"]}
A number sign (#) is used with this entry because of evidence that Meier-Gorlin syndrome-3 (MGORS3) is caused by homozygous or compound heterozygous mutation in the ORC6 gene (607213) on chromosome 16q11. For a general phenotypic description and a discussion of genetic heterogeneity of Meier-Gorlin syndrome, see 224690. Clinical Features Lacombe et al. (1994) reported 5 patients, including a brother and sister, who had short stature, very small external ears, cryptorchidism in males, and various bone defects including absent or nonossified patellae, femoral asymmetry, coxa valga, abnormal ribs, sacral hypoplasia, skull defect, and abnormal development of sternum. All of the patients had similar facies, with marked micrognathia. The sibs were born to second-cousin Turkish Kurd parents and had 1 healthy sib. At 7 years of age, the brother had marked growth retardation, whereas his 6-year-old sister had only mild growth retardation. On follow-up of the Turkish Kurd family reported by Lacombe et al. (1994), Bicknell et al. (2011) noted that the brother and sister and another affected brother all had microtia, and the sister and 1 brother had abnormally formed ears; the sister and 1 brother had absent patellae, whereas the other brother had hypoplasia of the patellae. In addition, the sister had hypoplasia of the mammary glands. Shalev (2007) described 3 fetuses from 3 consecutive pregnancies of first-cousin Ashkenazi Jewish parents. The fetuses exhibited abnormal nuchal translucency; growth restriction; small flat ears; dislocation of the knees, with patellar aplasia noted in 1; gracile bones; clubfeet; and abnormal growth of other skeletal components, in particular shortening of the femurs, small thorax, and hypoplastic mandible. Molecular Genetics In 3 sibs with Meier-Gorlin syndrome from a consanguineous Turkish Kurd family reported by Lacombe et al. (1994), Bicknell et al. (2011) identified compound heterozygosity for a 2-bp deletion and a missense mutation in the ORC6 gene (607213.0001 and 607213.0002). De Munnik et al. (2012) reported 4 patients with Meier-Gorlin syndrome who were compound heterozygous for a missense and a splice site mutation in the ORC6 gene (607213.0003-607213.0004). The authors noted that 1 of the patients had microtia and short stature but no patellar abnormalities, and 1 exhibited conductive hearing loss. In 2 affected fetuses and 3 unaffected individuals from an Ashkenazi Jewish family originally described by Shalev (2007), Shalev et al. (2015) performed exome analysis and identified homozygosity for a 4-bp deletion in the ORC6 gene in the 2 patients (607213.0005). The mutation was present in heterozygosity in the first-cousin parents and in 2 healthy sisters, and was not found in the ExAC database. Shalev et al. (2015) noted that in contrast to the previously reported relatively mild ORC6-associated MGORS phenotype, these patients with homozygous null mutations in the ORC6 gene exhibited severely abnormal embryologic development, expanding the clinical phenotype and suggesting a genotype-phenotype correlation in this disease. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature \- Birth length less than 3rd percentile Weight \- Birth weight less than 3rd percentile Other \- Failure to thrive \- Intrauterine growth retardation (IUGR) HEAD & NECK Head \- Microcephaly Face \- Triangular face \- Maxillary hypoplasia \- Mandibular hypoplasia \- Microretrognathia Ears \- Microtia, bilateral \- Ears abnormally formed \- Low-set ears \- Posteriorly rotated ears Eyes \- Downslanting palpebral fissures Nose \- Convex nasal profile \- High nasal bridge Mouth \- Full lips \- Small mouth RESPIRATORY Larynx \- Laryngomalacia Airways \- Tracheomalacia \- Bronchomalacia Lung \- Pulmonary infections, recurrent \- Dyspnea secondary to thorax morphology CHEST Ribs Sternum Clavicles & Scapulae \- Narrow chest \- Short thorax \- Short ribs \- Lack of sternal ossification Breasts \- Breast hypoplasia ABDOMEN Gastrointestinal \- Gastroesophageal reflux \- Feeding problems in early infancy GENITOURINARY External Genitalia (Male) \- Cryptorchidism \- Hypoplastic scrotum \- Micropenis \- Hypospadias External Genitalia (Female) \- Hypertrophic clitoris \- Hypoplastic labia minora/majora SKELETAL \- Delayed bone age Skull \- Frontal circular lacuna Limbs \- Slender long bones \- Abnormal humeral epiphyses with flat metaphyses \- Abnormal femoral epiphyses with flat metaphyses \- Abnormal tibial epiphyses \- Coxa vara \- Absent or hypoplastic patellae \- Genu varum Hands \- Clinodactyly, fifth finger Feet \- Club feet SKIN, NAILS, & HAIR Hair \- Absent or sparse axillary hair \- Absent or sparse pubic hair NEUROLOGIC Central Nervous System \- Delayed motor development (in some patients) \- Delayed speech development (in some patients) MOLECULAR BASIS \- Caused by mutation in origin recognition complex, subunit 6, gene (ORC6, 607213.0001 ) ▲ 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	MEIER-GORLIN SYNDROME 3	c1868684	26,830	omim	https://www.omim.org/entry/613803	2019-09-22T15:57:29	{"doid": ["0080514"], "mesh": ["C538012"], "omim": ["613803"], "orphanet": ["2554"]}
Primary carnitine deficiency is a genetic condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). The nature and severity of signs and symptoms may vary, but they most often appear during infancy or early childhood and can include severe brain dysfunction (encephalopathy), cardiomyopathy, confusion, vomiting, muscle weakness, and hypoglycemia. Some individuals may only have fatigability in adulthood, or no symptoms at all. This condition is caused by mutations in the SLC22A5 gene and is inherited in an autosomal recessive manner. Treatment and prevention of symptoms typically includes oral L-carnitine supplementation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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 carnitine deficiency	c0342788	26,831	gard	https://rarediseases.info.nih.gov/diseases/5104/primary-carnitine-deficiency	2021-01-18T17:58:12	{"mesh": ["C536778"], "omim": ["212140"], "umls": ["C0342788"], "orphanet": ["158"], "synonyms": ["Systemic primary carnitine deficiency", "Carnitine uptake defect", "Carnitine deficiency, systemic, due to defect in renal reabsorption of carnitine", "Carnitine plasma-membrane transporter deficiency", "Carnitine transporter deficiency", "Carnitine uptake deficiency"]}
Psoriatic erythroderma Other namesErythrodermic psoriasis or Von Zumbusch Psoriasis SpecialtyDermatology Psoriatic erythroderma represents a form of psoriasis that affects all body sites, including the face, hands, feet, nails, trunk, and extremities.[1]:410–411[2]:195 This specific form of psoriasis affects 3 percent of persons diagnosed with psoriasis.[3] First-line treatments for psoriatic erythroderma include immunosuppressive medications such as methotrexate, acitretin, or ciclosporin.[4] ## See also[edit] * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. 3. ^ "Psoriasis types: Erythrodermic \| National Psoriasis Foundation". www.psoriasis.org. Retrieved 2019-10-25. 4. ^ Zattra E, Belloni Fortina A, Peserico A, Alaibac M (May 2012). "Erythroderma in the era of biological therapies". Eur J Dermatol. 22 (2): 167–71. doi:10.1684/ejd.2011.1569. PMID 22321651. ## External links[edit] Classification D * ICD-10: L40.8 (ILDS L40.850) * v * t * e Papulosquamous disorders Psoriasis Pustular * Generalized pustular psoriasis (Impetigo herpetiformis) * Acropustulosis/Pustulosis palmaris et plantaris (Pustular bacterid) * Annular pustular psoriasis * Localized pustular psoriasis Other * Guttate psoriasis * Psoriatic arthritis * Psoriatic erythroderma * Drug-induced psoriasis * Inverse psoriasis * Napkin psoriasis * Seborrheic-like psoriasis Parapsoriasis * Pityriasis lichenoides (Pityriasis lichenoides et varioliformis acuta, Pityriasis lichenoides chronica) * Lymphomatoid papulosis * Small plaque parapsoriasis (Digitate dermatosis, Xanthoerythrodermia perstans) * Large plaque parapsoriasis (Retiform parapsoriasis) Other pityriasis * Pityriasis rosea * Pityriasis rubra pilaris * Pityriasis rotunda * Pityriasis amiantacea Other lichenoid Lichen planus * configuration * Annular * Linear * morphology * Hypertrophic * Atrophic * Bullous * Ulcerative * Actinic * Pigmented * site * Mucosal * Nails * Peno-ginival * Vulvovaginal * overlap synromes * with lichen sclerosus * with lupus erythematosis * other: * Hepatitis-associated lichen planus * Lichen planus pemphigoides Other * Lichen nitidus * Lichen striatus * Lichen ruber moniliformis * Gianotti–Crosti syndrome * Erythema dyschromicum perstans * Idiopathic eruptive macular pigmentation * Keratosis lichenoides chronica * Kraurosis vulvae * Lichen sclerosus * Lichenoid dermatitis * Lichenoid reaction of graft-versus-host disease This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Psoriatic erythroderma	None	26,832	wikipedia	https://en.wikipedia.org/wiki/Psoriatic_erythroderma	2021-01-18T18:41:28	{"icd-10": ["L40.8"], "wikidata": ["Q10355322"]}
A rare genetic disease characterized by infantile or childhood onset of abnormal growth of hyalinized fibrous tissue, giving rise to multiple cutaneous nodules and/or pearly papules predominantly affecting the scalp, ears, neck, face, hands, and feet. Involvement of other organs results in gingiva hyperplasia, osteolytic bone lesions, and joint contractures. Some patients exhibit visceral involvement with intractable diarrhea, increased susceptibility to infections, and severe failure to thrive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Hyaline fibromatosis syndrome	c2745948	26,833	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=498474	2021-01-23T17:24:02	{"mesh": ["D057770"]}
## Clinical Features Malekpour et al. (2007) described 5 Iranian brothers, born of healthy first-cousin Kurdish parents, who had late-onset progressive hearing loss, posterior subcapsular cataract, pigmentary changes consistent with retinitis pigmentosa, and a spectrum of sperm abnormalities. The 2 unaffected sisters in the family had no hearing, vision, or fertility problems. All of the brothers first noted hearing loss at 18 or 19 years of age, followed by rapid progression to profound deafness within 5 to 6 years; vestibular reflexes were normal. All had posterior subcapsular cataract, and 2 brothers had undergone intraocular lens replacement surgery; all had pigmentary changes of the retina noted upon examination. Two of the brothers were infertile, and examination of sperm revealed misshapen sperm with impaired motility to varying degrees in all 5 brothers. Inheritance Malekpour et al. (2007) noted that the occurrence of the condition they described in 5 brothers suggested X-linked recessive rather than autosomal recessive inheritance. INHERITANCE \- X-linked recessive HEAD & NECK Ears \- Deafness, bilateral with postpubertal onset and rapid progression to profound deafness within 5 to 6 years Eyes \- Cataract, posterior subcapsular \- Pigmentary changes consistent with retinitis pigmentosa GENITOURINARY Internal Genitalia (Male) \- Infertility \- Misshapen sperm with decreased motility ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DEAFNESS, CATARACT, RETINITIS PIGMENTOSA, AND SPERM ABNORMALITIES	c2678011	26,834	omim	https://www.omim.org/entry/300719	2019-09-22T16:19:41	{"mesh": ["C567467"], "omim": ["300719"]}
LECT2 amyloidosis Example of amyloid deposits under Congo Red staining LECT2 Amyloidosis (ALECT2) is a form of amyloidosis caused by the LECT2 protein. It was found to be the third most common (~3% of total) cause of amyloidosis in a set of more than 4,000 individuals studied at the Mayo Clinic; the first and second most common forms the disorder were AL amyloidosis and AA amyloidosis, respectively. Amyloidosis is a disorder in which the abnormal deposition of a protein in organs and/or tissues gradually leads to organ failure and/or tissue injury.[1][2][3] Although more than 30 different proteins can cause amyloidosis, the disorder caused by LECT2 is distinctive in three ways. First, it has an unusually high incidence in certain ethnic populations. Second, it is a systemic form of amyloidosis (i.e. amyloid deposited in multiple organs), as opposed to a localized form (amyloid deposits limited to a single organ) but nonetheless injures the kidney without or rarely injuring the other organs in which it is deposited. Third, LECT2 amyloidosis is diagnosed almost exclusively in elderly individuals.[2] Given its relatively recent discovery, exceptionally strong ethnic bias, limitation to causing kidney disease, and restriction to elderly individuals, LECT2 amyloidosis appears at present to be an under-recognized cause of chronic kidney disease particularly in the ethnic groups that exhibit a high incidence of the disorder.[4] ## Contents * 1 Presentation * 2 Cause * 2.1 Gene * 2.2 Protein * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 Prognosis * 7 See also * 8 References * 9 External links ## Presentation[edit] Most individuals diagnosed with LECT2 amyloidosis in the United States (88%) are of Mexican descent and reside in Southwest region of the United States (New Mexico, Arizona, far Western Texas). Other groups with higher incidence rates of the disorder include First Nation Peoples in Canada, Punjabis, South Asians, Sudanese, Native Americans, and Egyptians. In Egyptians, for example, LECT2 is second most common cause of renal amyloidosis, accounting for nearly 31% of all cases.[5][6][7][8][9] LECT2 amyloidosis (ALECT2) is generally diagnosed in individuals between the ages 40 and 90, with a mean age of 67 years old. The disorder commonly presents with renal disease that in general is advanced or at an end stage. Associated signs and symptoms of their renal disease may include fatigue, dehydration, blood in urine, and/or other evidence for the presence of the nephrotic syndrome or renal failure. Further studies may find that these individuals have histological or other evidence of LECT2 amyloid deposition in the liver, lung, spleen, kidney, and/or adrenal glands but nonetheless they rarely show any symptoms or signs attributable to dysfunction in these organs. Unlike many other forms of systemic amyloidosis, LECT2 deposition has not been reported to be deposited in the myocardium or brain of affected individuals. Thus, LECT2 amyloidosis, while classified as a form of systemic amyloidosis, almost exclusively manifests clinically as renal amyloidosis.[10][6][7][11][12][13][14] No familial link has been found in the disorder although there have been several cases described among siblings.[10] ## Cause[edit] ### Gene[edit] The human LECT2 gene, LECT2, is located on the long, i.e, "q", arm of chromosome 5 at position q31.1 (notated as 5q31.1). This location is close to several immune modulating genes including interleukins 3, 5, and 9 and granulocyte-macrophage colony stimulating factor. LECT2 is conserved in zebrafish, chichen, rat, mouse, cow. dog, Rhesus monkey, and chimpanzee. Human LECT2 is composed of 4 exons, 3 introns, and ~8,000 base pairs. The gene has numerous single nucleotide variants as well as other variations, two of which (see Pathophysiology section) have been associated with human disease. Human LECT2 has several different transcriptional initiation sights and codes for a mRNA composed of 1,000 to 1,300 ribonucleotides. mRNA for LECT2 is highly expressed in liver tissue and expressed at far lower levels in a wide range of other tssues.[2][15] ### Protein[edit] The LECT2 protein consists of 133`amino acids Its structure is similar to that of the M23 family of metalloendopeptidases. Unlike this family of peptidases, however, LECT2 has not been found to possess enzymatic activity and does not appear to share any functions with M23 metalloendopeptidases.[2][16] It is widely expressed in vascular tissues, smooth muscle cells, adipocytes, cerebral neurons, apical squamous epithelia, parathyroid tissues, the epithelial cells of sweat and sebaceous glands, Hassall bodies, and monocytes. The liver hepatocyte is considered to be the source of the LECT2 circulating in blood. However, its expression in these cells is extremely low or undetectable even though these cells express very high levels of LECT2 mRNA. This implies that hepatocytes secrete LECT2 almost immediately after they make it. Using very sensitive methods, LECT2 protein can also be detected at low levels in the endothelial cells of hepatic arteries and veins including central veins. Several cell types or tissues, e.g. osteoblasts, chondrocytes, cardiac tissue, gastrointestinal smooth muscle cells, and epithelial cells of some tissues normally do not express LECT2 but do so under a variety of disease conditions.[2] ## Pathophysiology[edit] LECT2 as a hepatokine, a substance made and released into the circulation by liver hepatocyte cells that acts as a hormone or signaling agent to regulate the function of other cells.[2] While the pathogenesis of LECT2 amyloidosis is unclear, the intact LECT2 protein may have a tendency to fold abnormally thereby forming non-soluble fibrils that are deposited in tissues. It has been suggested that individuals with the disease have an increase in LECT2 production and/or a decrease in LECT2 catabolism (i.e. breakdown) which may increase its tendency to deposit in tissues. On the other hand, there are genetic variations which appear to cause the deposition of LECT2 in tissues. Studies to date have failed to obtain evidence for LECT2 gene mutations in the disorder but most cases examined in the United States are associated with a particular homozygous single nucleotide polymorphism (i.e. SNP) in the LECT2 gene. This SNP occurs in exon 3 at codon 58 of the gene, contains a guanine rather than adenine nucleotide at this site, and consequently codes for the amino acid valine rather than isoleucine. Although not yet proven to occur in vivo, the Val58Ile variant of LECT2 may have a propensity to fold abnormally, form insoluble fibrils, and therefore deposits in tissues. The Val58Ile LECT2 variant is common in Hispanics and appears to be the cause of their high incidence of LECT2 amyloidosis. However, not all homozygous Hispanic carriers of the variant ever exhibit LECT2 amyloidosis. This suggests that another factor(s) besides the variant Val58Ile protein's structure is involved in its organ/tissue deposition.[2] A second SNP which is also commonly found in Mexicans occurs at codon 172 of the LECT2 gene. This variant is homozygous for a G nucleotide at this codon position and is associated with an increased incidence of LECT2 amyloidosis. A reason for this association has not yet been proposed.[2][17] It has been found repeatedly that the mere presence of LECT2 amyloid tissue deposits does not necessarily indicate the presence of LECT2 amyloidosis disease. For example, autopsy studies find that up to 3.1% of Hispanics have these deposits in their kidneys but no history of signs or symptoms that could be attributed to LECT2 amyloidosis. This finding suggests that the LECT2 amyloidosis and its ethnic bias reflect multiple poorly understood factors.[2] ## Diagnosis[edit] LECT2 amyloidosis is diagnosed by a kidney biopsy which reveals two key findings: a) histological evidence of Congo red staining material deposited in the interstitial, mesangial, glomerular, and/or vascular areas of the kidney and b) the identification of these deposits as containing mainly LECT2 as identified by proteomics methodologies. Kidney biopsy shows the presence of LECT2-based amyloid predominantly in the renal cortex interstitium, glomeruli, and arterioles.[17][1] LECT2 amyloidosis can be distinguished from AL amyloidosis, the most common form of amyloidosis (~85% of total cases), by testing their blood for the presence of high levels of a clonal immunoglobulin light chain. If the patient tests negative for this light chain, positive Congo Red staining of the kidney biopsy strongly suggests LECT2 amyloidosis.[1][11] ## Treatment[edit] There has too little experience on the treatment of LECT2 amyloidosis to establish recommendations other than offering methods to support kidney function and dialysis. Nonetheless, it is important to accurately diagnose ALECT2-based amyloid disease in order to avoid treatment for other forms of amyloidosis.[1][17] ## Prognosis[edit] ALECT2 Patient Survival Based on Creatine Levels' Based on studies conducted in the United States, the prognosis for individuals with ALECT2 is guarded, particularly because they are elderly and their kidney disease is usually well-advanced at the time of presentation.[17] End-stage renal disease develops in 1 out of 3 patients and has a median renal survival of 62 months.[10] A suggested prognostic tool is to track creatinine levels in ALECT2 patients. The attached Figure gives survival plotss for individuals with LECT2 renal amyloidosis and serum creatinine levels less than 2 mg/100 ml versus 2 mg/100 ml or greater than 2 mg/100 ml. The results show that afflicted individuals with lower creatinine levels have a ~four-fold higher survival rate. ## See also[edit] * Amyloidosis * LECT2 ## References[edit] * Holanda DG, Acharya VK, Dogan A, Racusen LC and Atta MG. Atypical Presentation of Atypical Amyloid. Nephrology dialysis transplantation.2011; 26(1):373-6. 1. ^ a b c d Picken, M. (Aug 2014). "Alect2 amyloidosis: Primum non nocere (first, do no harm)". Kidney Int. 86 (2): 229–232. doi:10.1038/ki.2014.45. PMID 25079018. 2. ^ a b c d e f g h i Slowik V, Apte U (2017). "Leukocyte Cell-Derived Chemotaxin-2: It's [sic] Role in Pathophysiology and Future in Clinical Medicine". Clinical and Translational Science. 10 (4): 249–259. doi:10.1111/cts.12469. PMC 5504477. PMID 28466965. 3. ^ Meex RC, Watt MJ (2017). "Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance". Nature Reviews. Endocrinology. 13 (9): 509–520. doi:10.1038/nrendo.2017.56. PMID 28621339. 4. ^ Larsen CP, Beggs ML, Wilson JD, Lathrop SL (2016). "Prevalence and organ distribution of leukocyte chemotactic factor 2 amyloidosis (ALECT2) among decedents in New Mexico". Amyloid. 23 (2): 119–23. doi:10.3109/13506129.2016.1145110. PMC 4898138. PMID 26912093. 5. ^ Dogan, A.; Theis, J.D.; Vrana, J.A.; Jimenez-epeda, V.H.; Lacy, M.Q.; Leung, N. (2010). "Clinical and pathological phenotype of leukocyte cell-derived chemotaxin-2 (LECT2) amyloidosis (ALECT2)". Amyloid: 69–70. 6. ^ a b Hutton, H.L.; DeMarco, M.L.; Magil, A.B.; Taylor, P. (2014). "Renal leukocyte chemotactic factor 2 (LECT2) amyloidosis in first nations people in northern british columbia, canada: A report of 4 cases". Am J Kidney Dis. 64 (5): 790–792. doi:10.1053/j.ajkd.2014.06.017. PMID 25064673. 7. ^ a b Murphy, C. L.; Wang, S.; Kestler, D.; Larsen, C.; Benson, D.; Weiss, D. T. (2010). "Leukocyte chemotactic factor 2 (LECT2)-associated renal amyloidosis: A case series". Am J Kidney Dis. 56 (6): 1100–1107. doi:10.1053/j.ajkd.2010.08.013. PMC 2991509. PMID 20951486. 8. ^ Sethi S, Theis JD (2017). "Pathology and diagnosis of renal non-AL amyloidosis". Journal of Nephrology. 31 (3): 343–350. doi:10.1007/s40620-017-0426-6. PMID 28828707. 9. ^ Larsen CP, Ismail W, Kurtin PJ, Vrana JA, Dasari S, Nasr SH (2016). "Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is a common form of renal amyloidosis among Egyptians". Modern Pathology. 29 (4): 416–20. doi:10.1038/modpathol.2016.29. PMC 5411489. PMID 26867784. 10. ^ a b c Said SM, Sethi S, Valeri AM, Chang A, Nast CC, Krahl L, Molloy P, Barry M, Fidler ME, Cornell LD, Leung N, Vrana JA, Theis JD, Dogan A, Nasr SH (2014). "Characterization and outcomes of renal leukocyte chemotactic factor 2-associated amyloidosis". Kidney International. 86 (2): 370–7. doi:10.1038/ki.2013.558. PMID 24451324. 11. ^ a b Dogan A (2017). "Amyloidosis: Insights from Proteomics". Annual Review of Pathology. 12: 277–304. doi:10.1146/annurev-pathol-052016-100200. PMID 27959636. 12. ^ Benson, M. D.; James, S.; Scott, K.; Liepnieks, J. J.; Kluve-Beckerman, B. (April 2008). "Leukocyte chemotactic factor 2: A novel renal amyloid protein". Kidney Int. 74 (2): 218–222. doi:10.1038/ki.2008.152. PMID 18449172. 13. ^ Holanda, D.G.; Acharya, V.K.; Dogan, A.; Racusen, L.C.; Atta, M.G. (Oct 2010). "Atypical presentation of atypical amyloid". Nephrol Dial Transplant. 26 (1): 373–376. doi:10.1093/ndt/gfq638. PMID 20940371. 14. ^ Larsen, C. P.; Walker, P.D.; Weiss, D. T.; Solomon, A. (February 2010). "Prevalence and morphology of leukocyte chemotactic factor 2-associated amyloid in renal biopsies". Kidney Int. 77 (9): 816–819. doi:10.1038/ki.2010.9. PMID 20182418. 15. ^ "Entrez Gene: LECT2 leukocyte cell-derived chemotaxin 2". 16. ^ Zheng H, Miyakawa T, Sawano Y, Asano A, Okumura A, Yamagoe S, Tanokura M (2016). "Crystal Structure of Human Leukocyte Cell-derived Chemotaxin 2 (LECT2) Reveals a Mechanistic Basis of Functional Evolution in a Mammalian Protein with an M23 Metalloendopeptidase Fold". The Journal of Biological Chemistry. 291 (33): 17133–42. doi:10.1074/jbc.M116.720375. PMC 5016117. PMID 27334921. 17. ^ a b c d Larsen CP, Kossmann RJ, Beggs ML, Solomon A, Walker PD (2014). "Clinical, morphologic, and genetic features of renal leukocyte chemotactic factor 2 amyloidosis". Kidney International. 86 (2): 378–82. doi:10.1038/ki.2014.11. PMID 24522497. ## External links[edit] * ALect2 Alliance [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	LECT2 amyloidosis	None	26,835	wikipedia	https://en.wikipedia.org/wiki/LECT2_amyloidosis	2021-01-18T19:01:19	{"orphanet": ["439224"], "synonyms": ["Leukocyte chemotactic factor-2 amyloidosis"], "wikidata": ["Q25326834"]}
A number sign (#) is used with this entry because of evidence that hereditary myopathy with lactic acidosis (HML), also known as Swedish-type myopathy with exercise intolerance, is caused by homozygous or compound heterozygous mutation in the ISCU gene (611911), encoding the iron-sulfur cluster scaffold protein, on chromosome 12q23. Description Hereditary myopathy with lactic acidosis is an autosomal recessive muscular disorder characterized by childhood onset of exercise intolerance with muscle tenderness, cramping, dyspnea, and palpitations. Biochemical features include lactic acidosis and, rarely, rhabdomyolysis. It is a chronic disorder with remission and exacerbation of the muscle phenotype (summary by Sanaker et al., 2010). Clinical Features Reporting from Umea in northern Sweden, Larsson et al. (1964) described 14 patients in 5 families with an apparently distinct form of myopathy. The disease appeared in childhood and ran a chronic course with exacerbations and remissions. It was characterized by low physical performance. Physical exertion caused early exhaustion, dyspnea, and palpitations. In continued work the muscles became hard and tender with development of cramps and sometimes weakness. In its most severe form there was widespread weakness, severe acidosis, and sometimes myoglobinuria. Concentrations of lactate and pyruvate in the blood increased disproportionately for the workload. All the affected individuals were in single sibships and there was consanguinity in some of the families; recessive inheritance was thought likely. Linderholm et al. (1969) reported further findings in the same families. Haller et al. (1991) evaluated a 22-year-old man from the same coastal area of northern Sweden as that identified by Larsson et al. (1964) and Linderholm et al. (1969) with an identical clinical history and similar exercise pathophysiology as that of previously described patients. He had had lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations as well as episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia (myoglobinuria). Cycle exercise testing revealed low maximal oxygen uptake with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake but low lactate/pyruvate ratios in maximal exercise. The patient studied by Schapira et al. (1990) showed some similarities; in that case (see 251945) it was speculated that iron-sulfur proteins of the mitochondrial respiratory chain may be encoded by nuclear genes and that a mutation in a single coding sequence might account for double deficiency. Haller et al. (1991) commented on the fact that myocardium and brain as well as vascular smooth muscle appeared to be spared in the deficiency of SDH/aconitase. Reichmann and Angelini (1993) studied 2 brothers, aged 25 and 19 years, with hypertrophic cardiomyopathy. Both showed proximal muscle weakness and myopathic features by EMG. CPK was elevated. Muscle histochemistry showed subsarcolemmal mitochondria and lipid accumulation. SDH staining was negative in all muscle fibers, regardless of whether cross-sections or longitudinal sections were performed. Biochemical investigation showed a complex II defect in the respiratory chain. Kollberg et al. (2009) reported 2 brothers with myopathy and lactic acidosis born of a Finnish mother. The boys had a more severe phenotype than other reported patients: both had progressive and severe muscle weakness and muscle wasting beginning at age 2 years. They also showed evidence of cardiac involvement, with EKG changes and mild cardiac hypertrophy without dilatation. Kollberg et al. (2009) noted that the boys did not complain of exercise intolerance, and suggested that they were too weak to even elicit symptoms such as tachycardia, palpitations, or shortness of breath. Biochemical Features Wahren et al. (1979) confirmed the marked increase in lactate and pyruvate concentrations with exercise, exceeding the small rise in healthy controls. Furthermore, arterial alanine concentration rose during exercise whereas no change was observed in controls working at the same workload. Linderholm et al. (1990) studied muscle biopsy specimens taken before and after exercise to exhaustion in a young woman with this condition. Marked glycogenolysis with lactate production was observed after exercise and almost all type I fibers were found to be depleted of glycogen. Succinate dehydrogenase (see 185470) was low, while the activities of 3-OH-acyl-CoA-dehydrogenase, phosphofructokinase, phosphorylase, and lactate dehydrogenase were normal. On electron microscopy, the mitochondria showed abnormalities typical of mitochondrial myopathy. In a 22-year-old Swedish patient, Haller et al. (1991) performed studies of isolated skeletal muscle mitochondria demonstrated markedly impaired succinate oxidation with normal glutamate oxidation, implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in complex II in skeletal muscle was confirmed by the finding of deficiency of succinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near-normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase (ACO2; 100850) assessed enzymatically and immunologically whereas activities of the other tricarboxylic acid cycle enzymes were increased compared to normal subjects. There was abnormal deposition of iron in the patient's mitochondria. Haller et al. (1991) postulated that the abnormal metabolic and circulatory responses to exercise in this disorder related to severely impaired muscle oxidative phosphorylation due to a low rate of generation of NADH by the tricarboxylic acid cycle attributable to deficiency of succinate dehydrogenase and aconitase activities. Complex II consists of 2 large subunits: a 70-kD flavoprotein and a 30-kD iron-sulfur containing protein which comprise SDH, and 2 smaller subunits believed to be involved in attaching SDH to the inner mitochondrial membrane. Unlike the other respiratory chain complexes, all of the subunits of complex II are coded on the nuclear genome. SDH and aconitase have in common iron-sulfur centers. The selective deficiency of the 30-kD iron-sulfur polypeptide of SDH suggests that a common defect related to the iron-sulfur centers is present in both enzymes. In a subsequent report, Hall et al. (1993) reported additional enzymatic and immunologic characterization of mitochondria for their patient (Haller et al., 1991). In addition to severe deficiency of complex II, manifested by reduction of succinate dehydrogenase and succinate:coenzyme Q oxidoreductase activities to 12 and 22% of normal, respectively, complex III activity was reduced to 37% and rhodanese activity to 48% of normal. Immunoblot analysis of complex I showed deficiency of several peptides, and immunoblots of complex III showed markedly reduced levels of the mature Rieske protein in mitochondria and elevated levels of its precursor in the cytosol, suggesting deficient uptake into mitochondria. Immunoreactive aconitase was also low. Hall et al. (1993) interpreted these data as indicating a generalized abnormality of the synthesis, import, processing, or assembly of a group of proteins containing iron-sulfur clusters. Sanaker et al. (2010) reported a Norwegian woman with the disorder who was homozygous for the 7044G-C mutation (611911.0001). Activities of mitochondrial complexes I, II, and III were decreased in skeletal muscle samples, whereas cultured myoblasts and fibroblasts had nearly normal activity. Western blot analysis showed decreased ISCU type I in muscle, myoblasts, and fibroblasts. The steady-state level of ISCU mRNA was significantly decreased in patient myoblasts (20% of controls), moderately decreased in muscle (54% of controls), and normal in fibroblasts. The mutant transcript containing exons 5, 5A, and 6 was the predominant (90%) species in patient muscle, although low levels (10%) of the normal transcript with exons 5 and 6 were also found. Control samples had low levels of the mutant transcript as well, suggesting that the mutation strengthens a preexisting weak splice site. Patient blood, myoblasts, and fibroblasts had equal amounts of both transcripts. Patient muscle also specifically showed an increase in mitochondrial content compared to controls, perhaps representing a compensatory mechanism. These findings suggested that the ratio between normally spliced and abnormally spliced transcript is important in determining tissue specificity of the defect. Inheritance Hereditary myopathy with lactic acidosis had been described in 19 members of 9 families who lived in 2 geographically separate areas in northern Sweden. By using the unique Swedish historical archives, including Catechetical Meeting Records from a number of northern Swedish parishes, Drugge et al. (1995) could trace ancestors of the 9 families, including all 9 cases, back to some key couples who lived as many as 300 years ago. No common single couple or common links between families in the past was found. The mode of inheritance was thought to be autosomal recessive. In the 9 affected sibships, 19 out of 45 sibs were affected. Clinical Management Kollberg and Holme (2009) demonstrated that an antisense oligonucleotide specifically targeting activated cryptic splice sites in the ISCU gene induced by mutation (611911.0001) was able to restore the correct reading frame in cultured fibroblasts derived from patients with homozygous mutation. The restoration in cells was stable, with correctly spliced mRNA remaining the dominant RNA species after 21 days. Mapping Mochel et al. (2008) found a common region of homozygosity in 3 patients with myopathy with lactic acidosis from 3 families originating from northern Sweden and confirmed a founder haplotype. One of these patients had been studied extensively by Haller et al. (1991) and Hall et al. (1993), and another was a member of a family studied by Drugge et al. (1995). Independently, Olsson et al. (2008) mapped the locus for Swedish myopathy to chromosome 12q23.2-q24.11 (maximum lod score of 5.26 at D12S84) in 15 affected members from 9 families reported by Larsson et al. (1964) and Linderholm et al. (1969, 1990). Molecular Genetics Within a common region of homozygosity on chromosome 12q24.1, Mochel et al. (2008) identified an intronic G-to-C transversion (7044G-C; 611911.0001) in the ISCU gene in 3 patients with myopathy with lactic acidosis. This homozygous mutation strengthened a weak splice acceptor site and resulted in reduced levels of ISCU mRNA and protein, leading to adverse effects on iron-sulfur proteins and intracellular iron homeostasis. In 15 affected members from 9 families reported by Larsson et al. (1964) and Linderholm et al. (1969, 1990), Olsson et al. (2008) independently identified homozygosity for the G-to-C transversion in intron 5 of the ISCU gene. In 2 brothers with myopathy and lactic acidosis, Kollberg et al. (2009) identified compound heterozygosity for the common intronic mutation (7044G-C) and a missense mutation (611911.0002) in the ISCU gene. Western blot analysis of skeletal muscle mitochondria showed only slightly reduced levels of ISCU protein in the 2 brothers, suggesting that the missense mutation gives rise to a nonfunctional protein. INHERITANCE \- Autosomal recessive MUSCLE, SOFT TISSUES \- Myopathy \- Exercise intolerance \- Premature exertional muscle weakness \- Muscles become hard and tender during exercise \- Muscle cramps \- Mitochondrial respiratory chain complex I, II, and III defect \- Rhabdomyolysis may occur \- Abnormal mitochondria in skeletal muscle biopsy \- Subsarcolemmal mitochondrial accumulation \- Lipid droplet accumulation \- Abnormal iron deposition in mitochondria \- Decreased muscle succinate dehydrogenase \- Decreased muscle mitochondrial aconitase METABOLIC FEATURES \- Lactic acidosis LABORATORY ABNORMALITIES \- Myoglobinuria \- Disproportionate work-related increase in blood lactate and pyruvate \- Low maximal oxygen uptake on exercise testing \- Increased serum creatine kinase during episodes MISCELLANEOUS \- Onset in childhood \- Chronic course with exacerbations and remissions \- Low physical performance \- Early exhaustion on exertion MOLECULAR BASIS \- Caused by mutation in the human homolog of the iron-sulfur cluster scaffold gene (ISCU, 611911.0001 ) ▲ 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	MYOPATHY WITH LACTIC ACIDOSIS, HEREDITARY	c1850718	26,836	omim	https://www.omim.org/entry/255125	2019-09-22T16:24:37	{"mesh": ["C564972"], "omim": ["255125"], "orphanet": ["43115"], "synonyms": ["Alternative titles", "MYOPATHY WITH EXERCISE INTOLERANCE, SWEDISH TYPE", "MYOPATHY WITH DEFICIENCY OF SUCCINATE DEHYDROGENASE AND ACONITASE", "MYOGLOBINURIA DUE TO ABNORMAL GLYCOLYSIS"], "genereviews": ["NBK5299"]}
Ocular albinism is a genetic condition that primarily affects the eyes. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina, which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision. Ocular albinism is characterized by severely impaired sharpness of vision (visual acuity) and problems with combining vision from both eyes to perceive depth (stereoscopic vision). Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include rapid, involuntary eye movements (nystagmus); eyes that do not look in the same direction (strabismus); and increased sensitivity to light (photophobia). Many affected individuals also have abnormalities involving the optic nerves, which carry visual information from the eye to the brain. Unlike some other forms of albinism, ocular albinism does not significantly affect the color of the skin and hair. People with this condition may have a somewhat lighter complexion than other members of their family, but these differences are usually minor. The most common form of ocular albinism is known as the Nettleship-Falls type or type 1. Other forms of ocular albinism are much rarer and may be associated with additional signs and symptoms, such as hearing loss. ## Frequency The most common form of this disorder, ocular albinism type 1, affects at least 1 in 60,000 males. The classic signs and symptoms of this condition are much less common in females. ## Causes Ocular albinism type 1 results from mutations in the GPR143 gene. This gene provides instructions for making a protein that plays a role in pigmentation of the eyes and skin. It helps control the growth of melanosomes, which are cellular structures that produce and store a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. In the retina, this pigment also plays a role in normal vision. Most mutations in the GPR143 gene alter the size or shape of the GPR143 protein. Many of these genetic changes prevent the protein from reaching melanosomes to control their growth. In other cases, the protein reaches melanosomes normally but mutations disrupt the protein's function. As a result of these changes, melanosomes in skin cells and the retina can grow abnormally large. Researchers are uncertain how these giant melanosomes are related to vision loss and other eye abnormalities in people with ocular albinism. Rare cases of ocular albinism are not caused by mutations in the GPR143 gene. In these cases, the genetic cause of the condition is often unknown. ### Learn more about the gene associated with Ocular albinism * GPR143 ## Inheritance Pattern Ocular albinism type 1 is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the GPR143 gene in each cell is sufficient to cause the characteristic features of ocular albinism. Because females have two copies of the X chromosome, women with only one copy of a GPR143 mutation in each cell usually do not experience vision loss or other significant eye abnormalities. They may have mild changes in retinal pigmentation that can be detected during an eye examination. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Ocular albinism	c0342684	26,837	medlineplus	https://medlineplus.gov/genetics/condition/ocular-albinism/	2021-01-27T08:25:21	{"gard": ["592", "8471"], "mesh": ["C537863"], "omim": ["300500", "300650", "606952"], "synonyms": []}
Hoyeraal–Hreidarsson syndrome Other namesProgressive pancytopenia-immunodeficiency-cerebellar hypoplasia syndrome[1] This condition is inherited in an X-linked recessive manner. SpecialtyMedical genetics Hoyeraal–Hreidasson syndrome[2]) is a very rare multisystem X-linked recessive disorder characterized by excessively short telomeres and is considered a severe form of dyskeratosis congenita.[2][3] Being an X-linked disorder, Hoyeraal–Hreidasson syndrome primarily affects males. Patients typically present in early childhood with cerebellar hypoplasia, immunodeficiency, progressive bone marrow failure, and intrauterine growth restriction.[2] The primary cause of death in Hoyeraal–Hreidasson syndrome is bone marrow failure, but mortality from cancer and pulmonary fibrosis is also significant.[4][5][6] ## Contents * 1 Presentation * 1.1 Overlap with dyskeratosis congenita * 2 Pathogenesis * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Presentation[edit] The currently recognized features are cerebellar hypoplasia, immunodeficiency, progressive bone marrow failure, and intrauterine growth restriction. Patients also commonly exhibit symptoms such as microcephaly, aplastic anemia, and intellectual disability.[3] ### Overlap with dyskeratosis congenita[edit] Patients with Hoyeraal–Hreidasson syndrome frequently present with the mucocutaneous triad of nail dysplasia, lacy skin pigmentation, and oral leukoplakia.[citation needed] ## Pathogenesis[edit] Although the pathogenesis remains unknown, it is strongly suspected that the clinical sequelae of Hoyeraal–Hreidasson syndrome arise from the accelerated telomere shortening.[2] It has been associated with mutations in the poly(A)-specific ribonuclease poly(A)-specific ribonuclease gene.[7] ## Diagnosis[edit] * Neuroimaging – cerebellar hypoplasia/atrophy, small brainstem, thin corpus callosum and cerebral calcifications * Molecular genetic testing – for confirmation ## Treatment[edit] Current treatment is supportive:[citation needed] * The aplastic anemia and immunodeficiency can be treated by bone marrow transplantation. * Supportive treatment for gastrointestinal complications and infections. * Genetic counselling. ## See also[edit] * Dyskeratosis congenita ## References[edit] 1. ^ "Orphanet: Hoyeraal Hreidarsson syndrome". www.orpha.net. Retrieved 15 June 2019. 2. ^ a b c d Glousker G, Touzot F, Revy P, Tzfati Y, Savage SA (August 2015). "Unraveling the pathogenesis of Hoyeraal–Hreidarsson syndrome, a complex telomere biology disorder". British Journal of Haematology. 170 (4): 457–71. doi:10.1111/bjh.13442. PMC 4526362. PMID 25940403. 3. ^ a b Knight SW, Heiss NS, Vulliamy TJ, Aalfs CM, McMahon C, Richmond P, et al. (November 1999). "Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal–Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1". British Journal of Haematology. 107 (2): 335–9. doi:10.1046/j.1365-2141.1999.01690.x. PMID 10583221. S2CID 23750791. 4. ^ Deng Z, Glousker G, Molczan A, Fox AJ, Lamm N, Dheekollu J, et al. (September 2013). "Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal–Hreidarsson syndrome". Proceedings of the National Academy of Sciences of the United States of America. 110 (36): E3408-16. Bibcode:2013PNAS..110E3408D. doi:10.1073/pnas.1300600110. PMC 3767560. PMID 23959892. 5. ^ Le Guen T, Jullien L, Touzot F, Schertzer M, Gaillard L, Perderiset M, et al. (August 2013). "Human RTEL1 deficiency causes Hoyeraal–Hreidarsson syndrome with short telomeres and genome instability". Human Molecular Genetics. 22 (16): 3239–49. doi:10.1093/hmg/ddt178. PMID 23591994. 6. ^ Jullien L, Kannengiesser C, Kermasson L, Cormier-Daire V, Leblanc T, Soulier J, Londono-Vallejo A, de Villartay JP, Callebaut I, Revy P (May 2016). "Mutations of the RTEL1 Helicase in a Hoyeraal–Hreidarsson Syndrome Patient Highlight the Importance of the ARCH Domain". Human Mutation. 37 (5): 469–72. doi:10.1002/humu.22966. PMID 26847928. S2CID 21314739. 7. ^ Benyelles M, Episkopou H, O'Donohue MF, Kermasson L, Frange P, Poulain F, Burcu Belen F, Polat M, Bole-Feysot C, Langa-Vives F, Gleizes PE, de Villartay JP, Callebaut I, Decottignies A, Revy P (July 2019). "Impaired telomere integrity and rRNA biogenesis in PARN-deficient patients and knock-out models". EMBO Molecular Medicine. 11 (7): e10201. doi:10.15252/emmm.201810201. PMC 6609912. PMID 31273937. ## External links[edit] * Hoyeraal–Hreidarsson syndrome on Orphanet Classification D * ICD-10: Q82.8 * ICD-9-CM: 757.39 * OMIM: 305000 * MeSH: C536068 * DiseasesDB: 32955 This genetic disorder 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	Hoyeraal–Hreidarsson syndrome	c1846142	26,838	wikipedia	https://en.wikipedia.org/wiki/Hoyeraal%E2%80%93Hreidarsson_syndrome	2021-01-18T19:02:05	{"gard": ["346"], "mesh": ["C536068"], "umls": ["C1846142"], "icd-10": ["D61.0"], "orphanet": ["3322"], "wikidata": ["Q9390252"]}
A number sign (#) is used with this entry because of evidence that molybdenum cofactor deficiency of complementation group C (MOCODC) is caused by homozygous mutation in the GPHN gene (603930) on chromosome 14q23. For a general phenotypic description and a discussion of genetic heterogeneity of molybdenum cofactor deficiency, see MOCODA (252150). Clinical Features Reiss et al. (2001) studied the last of 3 affected infants born to a Danish mother and father who were cousins. All 3 died in the neonatal period (at day 12, 29, and 3, respectively) with symptoms identical to those of molybdenum cofactor (MoCo) deficiency. Three other pregnancies of the mother resulted in 2 healthy sibs and 1 spontaneous abortion. The first affected infant was a boy; the other 2 were girls. All showed hypotonia combined with hyperreflexia, as well as tonic-clonic convulsions. Fibroblasts of the third infant were used to verify molybdenum cofactor deficiency by biochemical and in vitro complementation assays. Reiss et al. (2011) reported a female infant, born of consanguineous Algerian parents, with MOCODC. She presented in the neonatal period with global hypotonia, feeding difficulties, and generalized seizures. Brain MRI showed cortical and subcortical lesions, abnormalities in the basal ganglia, and hypoplastic pons and cerebellum. The cerebellum showed polymicrogyria. Laboratory studies showed a positive sulfite test and were consistent with MOCODC. The seizures remained intractable. At age 2 years, she had severe axial hypotonia and peripheral hypertonia, with no head control or visual contact. Inheritance The transmission pattern of molybdenum cofactor deficiency of complementation group C in the family reported by Reiss et al. (2001) was consistent with autosomal recessive inheritance. Molecular Genetics In a Dutch patient, born of consanguineous parents, with molybdenum cofactor deficiency of complementation group C, Reiss et al. (2001) identified a homozygous deletion in the GEPH gene (603930.0001). Reiss and Johnson (2003) collected a total of 32 different disease-causing mutations in the MOCS1, MOCS2, or GPHN genes, including several common to more than 1 family, that had been identified in molybdenum cofactor-deficient patients and their relatives. In an Algerian girl with MOCODC, Reiss et al. (2011) identified a homozygous mutation in the GPHN gene (D580A; 603930.0003). INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- No visual contact ABDOMEN Gastrointestinal \- Poor feeding MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development, severe \- Seizures, intractable \- Opisthotonus \- Axial hypotonia \- Limb hyperreflexia \- Cerebral atrophy \- Cerebellar hypoplasia \- Pontine hypoplasia \- Cerebellar polymicrogyria (1 patient) \- Cortical and subcortical white matter lesions seen on brain MRI LABORATORY ABNORMALITIES \- Hypouricemia \- Increased urinary S-sulfocysteine \- Increased urinary taurine \- Sulfite oxidase deficiency \- Decreased xanthine dehydrogenase activity \- Decreased aldehyde oxidase activity \- Molybdenum cofactor deficiency MISCELLANEOUS \- Two unrelated families have been reported (last curated October 2013) \- Onset at birth or early infancy \- Often results in death in childhood MOLECULAR BASIS \- Caused by mutation in the gephyrin gene (GPHN, 603930.0001 ) ▲ 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	MOLYBDENUM COFACTOR DEFICIENCY, COMPLEMENTATION GROUP C	c1854990	26,839	omim	https://www.omim.org/entry/615501	2019-09-22T15:51:53	{"doid": ["0111166"], "mesh": ["C565374"], "omim": ["615501"], "orphanet": ["833", "99732", "308400"], "synonyms": ["Combined deficiency of sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase", "MOCOD"]}
Polymerase proofreading-associated polyposis Other namesPPAP SpecialtyMedical genetics, gastroenterology SymptomsAsymptomatic, often develop multiple colorectal adenomas ComplicationsColorectal, duodenal, & endometrial cancer Diagnostic methodColonoscopy Differential diagnosisFamilial adenomatous polyposis, MUTYH-associated polyposis TreatmentColonoscopy Polypectomy FrequencyRare Polymerase proofreading-associated polyposis (PPAP) is an autosomal dominant hereditary cancer syndrome, which is characterized by numerous polyps in the colon and an increased risk of colorectal cancer.[1] It is caused by germline mutations in DNA polymerase ε (POLE) and δ (POLD1).[1] Affected individuals develop numerous polyps called colorectal adenomas. Compared with other polyposis syndromes, Polymerase proofreading-associated polyposis is rare. Genetic testing can help exclude similar syndromes, such as Familial adenomatous polyposis and MUTYH-associated polyposis. Endometrial cancer, duodenal polyps and duodenal cancer may also occur.[2] ## References[edit] 1. ^ a b Church, JM (March 2014). "Polymerase proofreading-associated polyposis: a new, dominantly inherited syndrome of hereditary colorectal cancer predisposition". Diseases of the Colon and Rectum. 57 (3): 396–7. doi:10.1097/DCR.0000000000000084. PMID 24509466. S2CID 9561294. 2. ^ Tomlinson, Ian (April 2015). "An update on the molecular pathology of the intestinal polyposis syndromes". Diagnostic Histopathology. 21 (4): 147–151. doi:10.1016/j.mpdhp.2015.04.006. * v * t * e Digestive system neoplasia GI tract Upper Esophagus * Squamous cell carcinoma * Adenocarcinoma Stomach * Gastric carcinoma * Signet ring cell carcinoma * Gastric lymphoma * MALT lymphoma * Linitis plastica Lower Small intestine * Duodenal cancer * Adenocarcinoma Appendix * Carcinoid * Pseudomyxoma peritonei Colon/rectum * Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers Cronkhite–Canada * Polyposis syndromes: Juvenile * MUTYH-associated * Familial adenomatous/Gardner's * Polymerase proofreading-associated * Serrated polyposis * Neoplasm: Adenocarcinoma * Familial adenomatous polyposis * Hereditary nonpolyposis colorectal cancer Anus * Squamous cell carcinoma Upper and/or lower * Gastrointestinal stromal tumor * Krukenberg tumor (metastatic) Accessory Liver * malignant: Hepatocellular carcinoma * Fibrolamellar * Hepatoblastoma * benign: Hepatocellular adenoma * Cavernous hemangioma * hyperplasia: Focal nodular hyperplasia * Nodular regenerative hyperplasia Biliary tract * bile duct: Cholangiocarcinoma * Klatskin tumor * gallbladder: Gallbladder cancer Pancreas * exocrine pancreas: Adenocarcinoma * Pancreatic ductal carcinoma * cystic neoplasms: Serous microcystic adenoma * Intraductal papillary mucinous neoplasm * Mucinous cystic neoplasm * Solid pseudopapillary neoplasm * Pancreatoblastoma Peritoneum * Primary peritoneal carcinoma * Peritoneal mesothelioma * Desmoplastic small round cell tumor [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Polymerase proofreading-associated polyposis	None	26,840	wikipedia	https://en.wikipedia.org/wiki/Polymerase_proofreading-associated_polyposis	2021-01-18T18:53:07	{"umls": ["CL970978"], "orphanet": ["447877"], "synonyms": ["PPAP"], "wikidata": ["Q56014183"]}
Pediatric-type follicular lymphoma Other namesPediatric follicular lymphoma, pediatric-type nodular follicular lymphoma SpecialtyHematology, oncology Pediatric-type follicular lymphoma (PTFL) is a disease in which malignant B-cells (i.e. a lymphocyte subtype originating from the bone marrow) accumulate in, overcrowd, and cause the expansion of the lymphoid follicles in, and thereby enlargement of the lymph nodes in the head and neck regions[1] and, less commonly, groin and armpit regions.[2] The disease accounts for 1.5% to 2% of all the lymphomas that occur in the pediatric age group.[3] Initially, PTFL was found only in children and adolescents and termed Pediatric follicular lymphoma. More recently, however, the disease has been found to occur also in adults.[4][5] This lead the World health Organization (2016) to rename the disorder pediatric-type follicular lymphoma.[4] (The disease is also referred to as pediatric-type nodular follicular lymphoma.[6][7]) At the same time the World Health Organization also recognized PTFL as a clinical entity distinct from the follicular lymphoma disorders in which it was previously classified. This reclassification was based on fundamental differences between the two diseases.[4] PTFL differs from follicular lymphoma in its clinical manifestations, its pathophysiology including the genomic alterations (i.e. chromosome abnormalities and gene mutations) which occur in the diseases malignant cells, and its clinical course. Relative to the last point, PTFL often presents histologically as a high-grade malignancy but unlike the small percentage of follicular lymphoma cases that similarly present as a high grade malignancy, it almost invariably takes an indolent, relapsing and remitting course without progressing to a more aggressive and incurable form.[2] Recognition of PTFL as a distinct disease separate from follicular lymphoma is critical to avoid mistaking it for a more aggressive lymphoma that requires potentially toxic chemotherapy treatments.[4] This appears to be particularly the case when PTFL occurs in children, adolescents, and perhaps very young adults.[2] A significant percentage of cases that were once diagnosed as PTFL are now regarded as being large B-cell lymphoma with IRF4 rearrangements, a very rare disease that was provisionally defined by the World Health organization (2016) as distinctly separate from PTFL.[8] PTFL is here described based on this recently formulated and important distinction. ## Contents * 1 Presentation * 2 Pathophysiology * 3 Diagnosis * 3.1 Differential diagnosis * 4 Treatment * 5 References ## Presentation[edit] PTFL occurs in male (male to female ratio ~10;1) children or adolescents (ages 1–17 years, median age ~13-14), less frequently in young adults (ages 18–30 years), and occasionally in older adults.[3][7] In ~90% of cases, the diseases is diagnosed in an early stage (i.e. stage I or II) and localized to one or two adjacent lymph node chains.[3] Historically, PTFL has been described as commonly presenting with swollen lymph nodes and/or tonsils in the head and neck regions,[3] less commonly as swollen lymph nodes in the axillary and/or inguinal regions,[2] and/or rarely as swollen lymph nodes in the abdomen and/or infiltrations of the malignant cells into the testes, bone marrow, and/or central nervous system.[3] However, many if not all of the latter rare cases as well as cases that exhibit tonsil involvement are now regarded by the World Health Organization (2016) as due to a provisional entity termed large B-cell lymphoma with IRF4 rearrangement. This diseases is a follicular-type large B-cell lymphoma that also afflicts children, adolescents, and young adults but is otherwise distinguished from PTFL by its lack of a strong predominance in males, its common occurrence in extra-nodal sites, its histology, its clinical course, and the genomic alterations carried by its malignant B-cells, particularly the hallmark translocation of the IRF4 (interferon regulatory factor 4) gene (also termed the MUM1 or melanoma associated antigen (mutated) 1 gene) on the short (i.e. p) arm of chromosome 6 at position 25.3[9] near to the IGH@ immunoglobulin heavy locus on the long (i.e. q) arm of chromosome 14 at position 32.33[10] This acquired genomic abnormality forces the overexpression of interferon regulatory factor protein.[8] Excluding cases now regarded as being large B-cell lymphomas with IRF4 rearrangement, PTFL presents almost exclusively with enlargement of lymph nodes in the head, neck, axilla, or groin.[3][11] ## Pathophysiology[edit] PTFL is the proliferation of a clone (i.e. a group of genetically identical cells that share a common ancestry) of B-cells that act non-physiologically by invading and disrupting the structure and function of lymphoid tissues. This cell clone forms, increases in size, and spreads to other lymphoid tissues in association with its progressively increasing accumulation of numerous chromosome deletions and gene mutations, although different sets of these alterations occur in different individuals with the disease. These alterations are thought to promote the survival of the malignant cells by inhibiting their programmed cell death, blocking their maturation, increasing their ability to evade the immune system, and/or creating conditions favorable for the development of other genomic alterations that have these pro-malignancy effects. The most common chromosome deletion is the 1p36 deletion which occurs in 20-50% of PTFL cases. This alteration is a deletion in the q arm of chromosome 1 at position 36 that results in the lose of TNFAIP3, a gene that encodes tumor necrosis factor, alpha-induced protein 3. This protein functions to inhibit the activation of NF-κB, to block programmed cell death, and to regulate lymphocyte-based immune responses through its ubiquitin ligase activity.[12] Other alterations repeatedly seen in PTFL include mutations in the following genes: 1) TNFRSF14 (30-50% of cases) which encodes tumor necrosis factor receptor superfamily, member 14, a receptor that stimulates immune responses in T-cells, a set of non-B-cell lymphocytes;[13] 2) IRF8 (10-50% of cases) which encodes the interferon regulatory factor 8 protein, a protein that contributes to the maturation and function of B-cells;[14][15] 3) MAP2K1 (10-40% of cases), which encodes mitogen-activated protein kinase kinase 1, an enzyme which activates the MAPK/ERK cell signaling pathway that regulates cell proliferation and the expression of various genes;[16] and 4) scores of other genes that are found in up to 15% of cases.[2] Recent Whole exome sequencing studies in children and adolescents with PTFL have confirmed these results, found that many of these genomic alterations result in suppressing either the MAPK/ERK or G protein-coupled receptor signaling pathways, and suggest that the suppression of these pathways contributes to the development of PFFL.[17] ## Diagnosis[edit] The diagnosis of PTFL depends on a constellation of findings related to its presentation, tissue distribution, histology, and expression of certain proteins and genomic abnormalities. The disease occurs in males (~90% of cases) that are more often children, adolescents, or young adults who have enlargement of lymph nodes located in one or two nearby sites of the head or neck or less commonly, armpit or groin regions. Histopathological examination of the involved lymph nodes reveals medium- to large-sized lymphoblasts mixed with occasional macrophages and rare centrocytes and centroblasts that together form follicular structures that partially or completely replace the nodes' normal structure with irregularly shaped and merged follicles, abnormally attenuated mantle zones, and the presence of helper T-cells that are pushed to the periphery of the follicles. Its histology is most often rated as high grade and by this criterion defines the disease as an aggressive grade III lymphoma (see follicular lymphoma grading).[2] Nonetheless, PTFL almost always behaves as a non-aggressive or minimally aggressive malignancy. Immunohistiochemical analyses of the involved tissues indicates that the malignant cells express CD20, CD10, and BCL6 but not BCL2 or interferon regulatory factor protein. Genomic analyses of these cells indicate that they have a clonal rearrangement in their IgH genes in all cases and in many cases the Ip6 deletion and gene mutations cited in the above pathophysiology section.[2] These cells lack the t(14:18)(q32:q21.3) translocation which is characteristic of malignant cells in follicular lymphoma but in a small percentage of cases still overexpress the TNFRSF14 gene product which is a consequence of this translocation. The exact cause for this overexpression is unclear.[4] ### Differential diagnosis[edit] The following lymphocyte disorders may be confused with but can be distinguished from PTFL based on the following points: * Follicular lymphoma does not have a strong male-predominance; is most common in older adults; is usually associated with the involvement of other tissues (e.g. bone marrow) in addition to lymph nodes;[3][11] and has a histology that is usually dominated by centrocytes and centorblasts;[2] that in >85-90% of cases have the t(14:18)(q32:q21.3) translocation;[2] and in 10-40% of cases MAP2K1 mutations.[3] * Large B-cell lymphoma with IRF4 rearrangement often occurs in females (male to female ratio 1-1.2 to 1:1.5);[2] has not yet been reported to occur in adults;[3] almost always involves non-nodal tissues in addition to lymph nodes; has a histology in involved tissues that is similar to diffuse large cell lymphomas;[3] and has malignant cells that overexpress interferon regulatory factor protein in almost all cases, frequently express BC10, and in most cases exhibit overt rearrangements of the IRF4 gene.[2] * The pediatric form of Marginal zone B-cell lymphoma has lymph node lesions consisting of a mixed population of monocyte-like cells, plasma cells, and lymphoblasts; its malignant cells do not to express CD10 and BCL6 and have relatively few genomic abnormalities except for trisomy 18 (up to 20% of cases).[2] * Benign reactive lymph node and follicular hyperplasia's lymph nodes do not exhibit irregularly shaped and merged follicles, abnormally attenuated mantle zones, or the presence of helper T-cells that are pushed to the periphery of the follicles.[2] ## Treatment[edit] Virtually all cases of PTFL, even if treated with minimal interventions such as surgical removal or a watch-and-wait approach, have had a relatively benign and sometimes remitting and relapsing course. Thus, past recommendations that these patients need to be evaluated by bone marrow biopsy, lumbar puncture, or other invasive and/or expensive procedures requires revaluation. The evaluation of therapeutic regimens used to treat PTFL is complicated by their purely retrospective nature and inclusion of cases which in retrospect were likely cases of large B-cell lymphoma with IRF4 rearrangement.[3] In any event, many of these cases were treated with chemotherapeutic regimens, principally, CHOP (i.e. cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone) or R-CHOP (i.e. CHOP plus rituximab)[11] while others, which likely excluded large B-cell lymphoma with IRF4 rearrangement, were treated with surgical removal, localized radiation therapy, and/or watch-and-wait strategies.[2][3] All of these treatments have yielded in pediatric patients overall survival rates of 100% and relapse rates of 0 to 6% as observed over variable observation periods of up to 5 years. Among this group, 36 pediatric patients were treated with surgical resection alone followed by observation with all patients surviving and only one having a relapse.[3] Most adults with PTFL have been treated more vigorously with regimens consisting of immunochemotherapy (e.g. R-CHOP) and/or radiation therapy. This more vigorous approach has been used because the distinction between PTFL and aggressive follicular lymphoma is not as clear in adults as it is in younger patients.[3] Thus, current recommendations for the treatment of pediatric PTFL patients is watch-and-wait following radiation therapy or complete surgical resection; in cases were surgical resection is incomplete, immunechemotherapy is added to the regimen.[2] The recommended treatment of adults with PTFL is less clear. Currently used regimens rely on immunochemotherapy but might change if the issue of discriminating PTFL from follicular lymphoma can be resolved.[2] ## References[edit] 1. ^ Quintanilla-Martinez L, Sander B, Chan JK, Xerri L, Ott G, Campo E, Swerdlow SH (February 2016). "Indolent lymphomas in the pediatric population: follicular lymphoma, IRF4/MUM1+ lymphoma, nodal marginal zone lymphoma and chronic lymphocytic leukemia". Virchows Archiv. 468 (2): 141–57. doi:10.1007/s00428-015-1855-z. PMID 26416032. S2CID 531366. 2. ^ a b c d e f g h i j k l m n o p Koo M, Ohgami RS (May 2017). "Pediatric-type Follicular Lymphoma and Pediatric Nodal Marginal Zone Lymphoma: Recent Clinical, Morphologic, Immunophenotypic, and Genetic Insights". Advances in Anatomic Pathology. 24 (3): 128–135. doi:10.1097/PAP.0000000000000144. PMID 28277421. 3. ^ a b c d e f g h i j k l m n Woessmann W, Quintanilla-Martinez L (June 2019). "Rare mature B-cell lymphomas in children and adolescents". Hematological Oncology. 37 Suppl 1: 53–61. doi:10.1002/hon.2585. PMID 31187530. 4. ^ a b c d e Lynch RC, Gratzinger D, Advani RH (July 2017). "Clinical Impact of the 2016 Update to the WHO Lymphoma Classification". Current Treatment Options in Oncology. 18 (7): 45. doi:10.1007/s11864-017-0483-z. PMID 28670664. S2CID 4415738. 5. ^ Du XY, Huang R, Cao L, Wu W, Wang Z, Zhu HY, Wang L, Fan L, Xu W, Li JY (May 2019). "[Clinical observation of five pediatric-type follicular lymphoma in adult]". Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi (in Chinese). 40 (5): 393–397. doi:10.3760/cma.j.issn.0253-2727.2019.05.009. PMC 7342233. PMID 31207704. 6. ^ Yamaguchi J, Kato S, Iwata E, Aoki K, Kabeya R, Natsume A, Wakabayashi T (July 2018). "Pediatric-Type Follicular Lymphoma in the Dura: A Case Report and Literature Review". World Neurosurgery. 115: 176–180. doi:10.1016/j.wneu.2018.04.053. PMID 29678710. 7. ^ a b Louissaint A, Schafernak KT, Geyer JT, Kovach AE, Ghandi M, Gratzinger D, Roth CG, Paxton CN, Kim S, Namgyal C, Morin R, Morgan EA, Neuberg DS, South ST, Harris MH, Hasserjian RP, Hochberg EP, Garraway LA, Harris NL, Weinstock DM (August 2016). "Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations". Blood. 128 (8): 1093–100. doi:10.1182/blood-2015-12-682591. PMC 5000844. PMID 27325104. 8. ^ a b Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES (May 2016). "The 2016 revision of the World Health Organization classification of lymphoid neoplasms". Blood. 127 (20): 2375–90. doi:10.1182/blood-2016-01-643569. PMC 4874220. PMID 26980727. 9. ^ https://www.ncbi.nlm.nih.gov/gene/3662 10. ^ https://www.ncbi.nlm.nih.gov/gene/3492 11. ^ a b c Liu Q, Salaverria I, Pittaluga S, Jegalian AG, Xi L, Siebert R, Raffeld M, Hewitt SM, Jaffe ES (March 2013). "Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma". The American Journal of Surgical Pathology. 37 (3): 333–43. doi:10.1097/PAS.0b013e31826b9b57. PMC 3566339. PMID 23108024. 12. ^ EntrezGene 7128 13. ^ EntrezGene 8764 14. ^ Shukla V, Lu R (August 2014). "IRF4 and IRF8: Governing the virtues of B Lymphocytes". Frontiers in Biology. 9 (4): 269–282. doi:10.1007/s11515-014-1318-y. PMC 4261187. PMID 25506356. 15. ^ https://www.ncbi.nlm.nih.gov/gene/3394 16. ^ https://www.ncbi.nlm.nih.gov/gene/5604 17. ^ Lovisa F, Binatti A, Coppe A, Primerano S, Carraro E, Pillon M, Pizzi M, Guzzardo V, Buffardi S, Porta F, Farruggia P, De Santis R, Bulian P, Basso G, Lazzari E, d'Amore ES, Bortoluzzi S, Mussolin L (February 2019). "A high definition picture of key genes and pathways mutated in pediatric follicular lymphoma". Haematologica. 104 (9): e406–e409. doi:10.3324/haematol.2018.211631. PMC 6717562. PMID 30819919. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Pediatric-type follicular lymphoma	c2698750	26,841	wikipedia	https://en.wikipedia.org/wiki/Pediatric-type_follicular_lymphoma	2021-01-18T19:08:27	{"umls": ["C2698750"], "wikidata": ["Q85792633"]}
A number sign (#) is used with this entry because of evidence that vertebral, cardiac, renal, and limb defects syndrome-1 (VCRL1) is caused by homozygous mutation in the HAAO gene (604521) on chromosome 2p21. Description VCRL1 is an autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal defects, and distal mild limb defects. Additional features are variable (summary by Shi et al., 2017). ### Genetic Heterogeneity of vertebral, cardiac, renal, and limb defects syndrome See also VCRL2 (617661), caused by mutation in the KYNU gene (605197) on chromosome 2q22. Clinical Features Shi et al. (2017) reported 2 unrelated patients, each born of consanguineous parents of Iraqi (family A) and Lebanese (family B) descent, respectively, with VCRL1. Both patients had vertebral segmentation defects predominantly affecting the thoracolumbar spine and spinal lipoma; patient A had sacral agenesis and patient B had spinal dysraphism. Both had cardiac defects: atrial septal defect in patient A and hypoplastic left heart with mitral and aortic stenosis in patient B. Patient A had a cleft palate, bifid uvula, and laryngeal web with persistent tracheomalacia, and patient B had a left vocal cord palsy that was possibly iatrogenic with no other laryngeal defects. Additional features found in both patients included microcephaly, hypoplastic kidneys, and sensorineural hearing loss. Patient A had short stature, talipes, delayed development, moderate intellectual disability and behavioral issues at age 12 years, whereas patient B died at age 11 months from complications of hypoplastic left heart. Inheritance The transmission pattern of VCRL1 in the families reported by Shi et al. (2017) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 unrelated patients, each born of consanguineous parents, with VCRL1, Shi et al. (2017) identified homozygous truncating mutations in the HAAO gene (604521.0001 and 604521.0002). The mutations, which were found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. In vitro functional expression studies showed that both mutations essentially abolished HAAO enzymatic activity. Analysis of patient plasma showed increased levels of the upstream metabolite 3HAA and decreased levels of the downstream metabolites NAD and NAH(H). Both patients belonged to a pair of dizygotic twins; their twins were unaffected and heterozygous for the mutation. Studies in mice, which have different niacin levels compared to humans, indicated that the congenital malformations found in humans resulted from deficient NAD levels rather than increased 3HAA. Shi et al. (2017) noted that NAD is a cofactor with broad cellular effects, including ATP production, macromolecular biosynthesis, redox reactions, energy metabolism, DNA repair, and modulation of transcription factors, all of which play an important role in embryogenesis. Animal Model Shi et al. (2017) found that Haao-null mice were viable and normal. Plasma analysis showed increased 3HAA levels, but normal NAD levels. The authors noted that mice have increased niacin levels compared to humans and that mouse embryos may receive niacin from their mothers, resulting in a buffering effect on genetic-based NAD deficiency. These findings suggested that the congenital malformations found in humans with increased levels of 3HAA but decreased levels of NAD, resulted from the deficient NAD levels. Indeed, further studies in mutant mice born to mothers on a niacin-free diet showed that NAD deficiency due to lack of Haao resulted in multiple defects, including defects in vertebral segmentation, heart defects, small kidney, cleft palate, talipes, syndactyly, and caudal agenesis. Supplementation of Haao-null mouse embryos with niacin during gestation restored NAD levels and prevented the disruption of embryogenesis. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly Ears \- Hearing loss, sensorineural Mouth \- Cleft palate \- Bifid uvula CARDIOVASCULAR Heart \- Congenital cardiac defects \- Atrial septal defect \- Hypoplastic left heart \- Mitral stenosis \- Aortic stenosis RESPIRATORY Larynx \- Laryngeal web (1 patient) \- Laryngotracheomalacia (1 patient) CHEST Ribs Sternum Clavicles & Scapulae \- Irregular ribs GENITOURINARY Kidneys \- Hypoplastic kidneys Bladder \- Vesicoureteral reflux SKELETAL Spine \- Vertebral segmentation defects \- Butterfly vertebrae \- Spinal dysraphism \- Tethered cord \- Hypoplastic sacrum \- Sacral agenesis Feet \- Talipes SKIN, NAILS, & HAIR Skin \- Spinal lipoma NEUROLOGIC Central Nervous System \- Delayed psychomotor development (1 patient) \- Intellectual disability (1 patient) LABORATORY ABNORMALITIES \- Increased serum levels of 3-hydroxyanthranilic acid (3HAA) \- Decreased serum levels of nicotinaminde adenine dinucleotide (NAD) and NAD(H) MISCELLANEOUS \- Two unrelated patients (one Iraqi and one Lebanese) have been reported (last curated September 2017) \- One patient died before age 1 \- Slightly variable phenotype MOLECULAR BASIS \- Caused by mutation in the 3-alpha-hydroxyanthranilate 3,4-dioxygenase gene (HAAO, 604521.0001 ) ▲ 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	VERTEBRAL, CARDIAC, RENAL, AND LIMB DEFECTS SYNDROME 1	c4540004	26,842	omim	https://www.omim.org/entry/617660	2019-09-22T15:45:16	{"omim": ["617660", "617661"], "orphanet": ["521438"], "synonyms": ["Alternative titles", "Congenital NAD deficiency disorder", "3-HYDROXYANTHRANILIC ACIDEMIA", "CONGENITAL NAD DEFICIENCY DISORDER 1"]}
Periventricular nodular heterotopia (PNH) is a brain malformation, due to abnormal neuronal migration, in which a subset of neurons fails to migrate into the developing cerebral cortex and remains as nodules that line the ventricular surface. Classical PNH is a rare X-linked dominant disorder far more frequent in females who present normal intelligence to borderline intellectual deficit, epilepsy of variable severity and extra-central nervous system signs, especially cardiovascular defects or coagulopathy. The disorder is generally associated with prenatal lethality in males. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Periventricular nodular heterotopia	c1868720	26,843	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98892	2021-01-23T17:13:19	{"gard": ["12724"], "mesh": ["D054091"], "omim": ["300049", "608097", "608098", "612881", "615544", "617201", "618185", "618918"], "umls": ["C1868720"], "icd-10": ["Q04.8"], "synonyms": ["PVNH"]}
Preventive analgesia is a practice aimed at reducing short- and long-term post-surgery pain. Activity in the body's pain signalling system during surgery produces "sensitization"; that is, it increases the intensity of post-operative pain. Reducing activity in the body's pain-signalling system by the use of analgesics before, during and immediately after surgery is thought to reduce subsequent sensitization, and consequently the intensity of post-surgery pain. The types of nerve activity targeted in preventive analgesia include pre-surgery pain, all pain-system activity caused during surgery, and pain produced post-surgery by damage and inflammation.[1] A person's assessment of pain intensity from standard experimental stimuli prior to surgery is correlated with the intensity of their post-surgery pain. Pain intensity immediately post-surgery is correlated with pain intensity on release from hospital, and correlated with the likelihood of experiencing chronic post-surgery pain.[1] Different medications such as pregabalin, acetaminophen, naproxen and dextromethorphan have been tried in studies about preemptive analgesia.[2][3] It is not known what causes some cases of acute post-surgery pain to become chronic long term problems but pain intensity in the short- and long-term post-operative period is correlated with the amount of pain system activity during and around the time of the surgery. It is not known whether reducing post-operative sensitization by the use of preventive analgesia will affect the likelihood of acute post-operative pain becoming chronic.[1] ## References[edit] 1. ^ a b c Katz J & Clarke H. Preventive analgesia and beyond: Current status, evidence and future directions. In: Macintyre PE, Walker SM & Rowbotham DJ. Acute Pain. London: Hodder Arnold; 2008. ISBN 978-0-340-94009-9. p. 154–198. 2. ^ Amiri, Hamid Reza et al. “Multi-Modal Preemptive Analgesia With Pregabalin, Acetaminophen, Naproxen, and Dextromethorphan in Radical Neck Dissection Surgery: A Randomized Clinical Trial.” Anesthesiology and Pain Medicine 6.4 (2016): e33526. PMC. Web. 23 Nov. 2017. 3. ^ Amiri, Hamidreza et al. “Three -Agent Preemptive Analgesia, Pregabalin-Acetaminophen-Naproxen, in Laparotomy for Cancer: A Randomized Clinical Trial.” Anesthesiology and Pain Medicine 7.2 (2017): e33269. PMC. Web. 23 Nov. 2017. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Preventive analgesia	None	26,844	wikipedia	https://en.wikipedia.org/wiki/Preventive_analgesia	2021-01-18T19:07:38	{"wikidata": ["Q7242400"]}
## Summary ### Clinical characteristics. GRIN2A-related speech disorders and epilepsy are characterized by speech disorders in all affected individuals and a range of epilepsy syndromes present in about 90%. Severe speech disorders observed can include dysarthria and speech dyspraxia, and both receptive and expressive language delay/regression; more mildly affected individuals may display subtly impaired intelligibility of conversational speech. Epilepsy features include seizure onset usually between ages three and six years, focal epilepsy with language and/or global developmental regression, and electroencephalogram (EEG) showing continuous spike-and-wave discharges in sleep or very active centrotemporal discharges. Seizure types include seizures associated with aura of perioral paresthesia, focal or focal motor seizures (often evolving to generalized tonic-clonic), and atypical absence seizures. Epilepsy syndromes can include: Landau-Kleffner syndrome (LKS), epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), childhood epilepsy with centrotemporal spikes (CECTS), atypical childhood epilepsy with centrotemporal spikes (ACECTS), autosomal dominant rolandic epilepsy with speech dyspraxia (ADRESD), and infantile-onset epileptic encephalopathy. ### Diagnosis/testing. The diagnosis of a GRIN2A-related speech disorder and epilepsy is established in a proband by the identification of a GRIN2A heterozygous pathogenic variant on molecular genetic testing. ### Management. Treatment of manifestations: Significant speech/language deficits require therapy from a speech pathologist. Seizures should be treated with antiepileptic drugs (AEDs). Many different AEDs may be effective, and no one medication has been demonstrated to be effective specifically for these disorders. Prevention of secondary complications: Monitoring for possible adverse effects of AEDs. Surveillance: Developmental surveillance in all affected children; routine monitoring of speech and language by a speech pathologist should be considered for all children, particularly those diagnosed before reaching school age. Agents/circumstances to avoid: In individuals with ECSWS, phenytoin, barbiturates and carbamazepine should be avoided as they are rarely effective, may worsen the EEG, and have negative effects on neuropsychological outcomes. Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic at-risk relatives in order to identify as early as possible those who would benefit from prompt evaluation for speech disorders and/or seizures and institution of treatment. ### Genetic counseling. GRIN2A-related speech disorders and epilepsy are inherited in an autosomal dominant manner. The proportion of GRIN2A-related speech disorders and epilepsy caused by a de novo pathogenic variant is unknown. Each child of an individual with a GRIN2A-related speech disorder and epilepsy has a 50% chance of inheriting the GRIN2A pathogenic variant. Once the GRIN2A pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings In general, a GRIN2A pathogenic variant should be considered in an individual presenting with an otherwise unexplained combination of the following speech disorders and/or epilepsy features, seizure types, epilepsy syndromes [Tsai et al 2013]. Speech disorders * Acquired aphasia * Auditory agnosia (impaired recognition of sounds) * Dysarthria * Speech dyspraxia Epilepsy features * Onset in early childhood (usually age 3-6 years) * Focal epilepsy with language and/or global developmental regression * Electroencephalogram (EEG) showing continuous spike-and-wave discharges in sleep or very active centrotemporal discharges Seizure types * Most commonly, focal seizures * Sometimes occurring with an aura of perioral paresthesia, and often evolving to generalized tonic-clonic seizures Epilepsy syndromes * Landau-Kleffner syndrome (LKS) * Epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS) * Childhood epilepsy with centrotemporal spikes (CECTS) * Atypical childhood epilepsy with centrotemporal spikes (ACECTS) * Autosomal dominant rolandic epilepsy with speech dyspraxia (ADRESD) * Infantile-onset epileptic encephalopathy Note: Detailed descriptions of each epilepsy syndrome can be found in Clinical Description. ### Establishing the Diagnosis The diagnosis of GRIN2A-related speech disorder and epilepsy is established in a proband by identification of either a heterozygous pathogenic variant in GRIN2A or a heterozygous deletion involving GRIN2A using molecular genetic testing (see Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (multigene panel or single-gene testing) or genomic testing (chromosomal microarray analysis or comprehensive genomic sequencing). Gene-targeted testing requires that the clinician develop a hypothesis about which gene(s) are likely involved, whereas genomic testing may not. The phenotypes of many genetic epileptic encephalopathies overlap; thus, most children with a GRIN2A-related speech disorder and epilepsy are diagnosed by CMA or multigene panel (see Recommended Testing) or by comprehensive genomic sequencing (see Testing to Consider). #### Recommended Testing Chromosomal microarray analysis (CMA) using oligonucleotide or SNP arrays is recommended first when developmental impairment/intellectual disability and/or dysmorphic features are present. The ability to determine the size of the deletion depends on the type of microarray used and the density of probes in the 16p13.2 region. A multigene panel that incorporates both sequence analysis and deletion/duplication analysis and includes GRIN2A and other genes of interest (see Differential Diagnosis) is recommended when epilepsy associated with speech dyspraxia and dysarthria are the primary findings (see Table 1). Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Testing to Consider Comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered if the phenotype alone is insufficient to support gene-targeted testing). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. Single-gene testing (sequence analysis of GRIN2A, followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found may be considered first in individuals with features that are highly suggestive of GRIN2A-related speech disorder and epilepsy. However, because many of these features overlap with those of other genetic epileptic encephalopathies, multigene panels or comprehensive genomic testing are often performed in lieu of single-gene testing. ### Table 1. Molecular Genetic Testing Used in GRIN2A-Related Speech Disorders and Epilepsy View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method 3 GRIN2ASequence analysis 458/71 Gene-targeted deletion/duplication analysis 513/71 6 CMASee footnote 7 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\. Based on the combined results of published reports of GRIN2A-related disorders [Endele et al 2010, Reutlinger et al 2010, Lesca et al 2012, Carvill et al 2013, DeVries & Patel 2013, Lemke et al 2013, Lesca et al 2013, Conroy et al 2014, Dimassi et al 2014, Venkateswaran et al 2014, Yuan et al 2014, Allen et al 2016, Fainberg et al 2016]. In one proband, GRIN2A was disrupted by an inherited translocation detectable by karyotype [Endele et al 2010]; this was categorized as "detectable by sequence analysis." 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and gene-targeted microarray designed to detect single-exon deletions or duplications. These methods will detect from single-exon to whole-gene deletions; however, breakpoints of large deletions and/or deletion of adjacent genes may not be detected by these methods. 6\. Of these 13 probands: 9 had small losses of genetic material (<292 kb), resulting in partial deletion of GRIN2A; 3 had large deletions (>0.9 Mb) affecting multiple genes (in 2 of the 3 GRIN2A was entirely deleted); and 1 had a small intragenic duplication. 7\. CMA is appropriate to define breakpoints of large deletions. ## Clinical Characteristics ### Clinical Description The clinical spectrum of GRIN2A-related speech disorders and epilepsy is broad and may vary within a family (e.g., from mild isolated speech impairment to rolandic epilepsy with speech dyspraxia) [Turner et al 2015b]. Disease progression is variable: some individuals have normal development and spontaneous remission of seizures, while others develop medically refractory epilepsy and severe developmental impairment. Language and/or global developmental regression often occurs in those with the more severe epilepsy-aphasia disorders. Speech and language were impaired in 100% of individuals in a study of the speech manifestations of GRIN2A-related disorders [Turner et al 2015a]. Abnormalities included dysarthria and speech dyspraxia, and both receptive and expressive language delay/regression. Mildly affected individuals may display subtly impaired intelligibility of conversational speech, most commonly characterized by hypernasality, imprecise consonant production, and impaired pitch and prosody [Turner et al 2015a]. Intellectual disability, observed in 38%-67% of affected individuals, ranges from mild to severe [Carvill et al 2013, Lemke et al 2013]. Epilepsy occurs in approximately 90% of individuals [Lemke et al 2013, Lesca et al 2013]. Seizure onset is typically between ages three and six years (mean 4.6 years), although individuals may present from infancy to adolescence [Endele et al 2010, Lesca et al 2012, Carvill et al 2013, Lemke et al 2013, Venkateswaran et al 2014]. The most common seizure type overall is focal seizures. These are often associated with an aura of perioral paresthesia, and frequently evolve to generalized tonic-clonic convulsions. The predominant seizure type(s) in a given individual vary depending on which clinical syndrome is present. The most common GRIN2A-related speech disorder and epilepsy is epilepsy-aphasia syndromes (EAS), a spectrum of disorders that includes: Landau-Kleffner syndrome (LKS); epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS); childhood epilepsy with centrotemporal spikes (CECTS); atypical childhood epilepsy with centrotemporal spikes (ACECTS); and autosomal dominant rolandic epilepsy with speech dyspraxia (ADRESD) [Tsai et al 2013]. Other epilepsy phenotypes can be broadly divided into infantile-onset epileptic encephalopathy and unclassified childhood epilepsy. Landau-Kleffner syndrome (LKS) [Landau & Kleffner 1957, Wang et al 2006, Hughes 2011] * Onset in childhood (peak age range 5-8 years) * Acquired aphasia, with auditory agnosia (impaired recognition of sounds) frequently described as the earliest feature * Seizures in approximately 70% of cases, most commonly atypical absence, with focal motor, atonic, and focal seizures evolving to bilateral tonic-clonic seizures also described * Developmental regression limited to language domains * Normal development prior to onset of aphasia or isolated language impairment * EEG showing frequent, sleep-activated, bilateral sharp and slow wave discharges (centrotemporal or perisylvian field), eventually evolving to continuous spike-and-wave in sleep (CSWS) Epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS) [Van Bogaert 2013] * Onset in childhood (peak age range 4-5 years) * Seizures in approximately 80% of cases, most commonly hemiclonic or generalized tonic-clonic in sleep and atypical absence while awake * Global developmental regression (as distinct from the pure language regression of LKS) * EEG showing near-continuous (>85% of recording), bilateral sharp and slow wave discharges in slow wave sleep (i.e., CSWS) Childhood epilepsy with centrotemporal spikes (CECTS) [Guerrini & Pellacani 2012] * Onset is in childhood (peak age range 5-8 years; range 3-13 years). * Seizures have a characteristic aura of perioral paresthesia which may involve the tongue, cheeks, and mouth. There is often speech arrest and a motor component involving the oropharyngeal muscles, unilateral facial tonic or clonic activity, and (less commonly) an upper limb. The majority of events occur during sleep, and classically involve drooling. Bilateral tonic-clonic seizures are also commonly observed. * Seizure frequency is low: half of patients have fewer than six seizures in their lifetime. * Epilepsy follows a self-limited course with duration less than five years in the majority of individuals. * Development is essentially normal, though mild deficits in language, computation, and motor skills may be apparent when compared to healthy controls [Staden et al 1998, Lillywhite et al 2009, Garcia-Ramos et al 2015]. * EEG background is normal and shows focal epileptiform discharges from the centrotemporal regions, potentiated in sleep. In 40% of affected individuals, the centrotemporal discharges are bilateral and independent. Atypical childhood epilepsy with centrotemporal spikes (ACECTS) [Aicardi & Chevrie 1982] * Epilepsy course is similar to CECTS with onset and spontaneous remission occurring in childhood. * Seizures are different from those seen in CECTS, and include negative myoclonus and atypical absence seizures. * Developmental regression or slowing is coincident with seizure onset; however, long-term developmental outcome may be normal. * EEG is similar to CECTS in that focal centrotemporal discharges potentiated in sleep are seen; however, focal or diffuse background slowing is also often present. Autosomal dominant rolandic epilepsy with speech dyspraxia (ADRESD) [Scheffer 2000, Turner et al 2015b] * Seizure characteristics and epilepsy course are identical to CECTS in most family members. One individual had an encephalopathic presentation associated with cognitive regression. * Affected individuals have oral and speech dyspraxia with dysarthria. * Individuals may have isolated speech dysfunction without seizures. * Cognitive function is usually within the normal range. Infantile-onset epileptic encephalopathy [Endele et al 2010, Venkateswaran et al 2014, Yuan et al 2014, Allen et al 2016] * Multiple different seizure types may be present, including tonic seizures, focal impaired awareness with evolution to bilateral seizures, infantile spasms, and myoclonic seizures. * Severe intellectual disability was seen in the three individuals reported. * EEG findings vary in the few reported cases and include background slowing, hypsarrhythmia, and focal spikes. * Brain MRI may show bilateral parenchymal volume loss and thin corpus callosum. Unclassified childhood-onset epilepsy [Reutlinger et al 2010, DeVries & Patel 2013] * Focal seizures are the most commonly seen; myoclonic, eyelid myoclonia, and atypical absence have also been reported. * Development ranges from normal to severely impaired. * Mild dysmorphic features may be present in individuals with a contiguous gene deletion. * EEG usually shows multifocal epileptiform discharges. Contiguous gene deletions. Reutlinger et al [2010] described three individuals with 16p13 deletions involving multiple genes and complete or partial heterozygous deletion of GRIN2A. All had mild dysmorphic features, intellectual disability, and epilepsy involving the rolandic region. EEG most commonly shows bilateral epileptiform discharges (usually spike or spike-wave) in the central-temporal or temporal-parietal regions which may be independent or bilaterally synchronous. These abnormalities become more frequent in sleep, often evolving to continuous spike-and-wave in sleep (CSWS). CSWS is defined as near-continuous (>85% of non-REM sleep recording) bilateral sharp and slow wave discharges in slow wave sleep. CECTS is classically associated with a horizontal dipole; tangential dipole across the Sylvian fissure has been reported in LKS [Morrell et al 1995, Dalla Bernardina et al 2005]. Brain imaging. Brain MRI is normal in the vast majority. Severely affected individuals may have enlargement of extra-axial spaces and a thin corpus callosum [Reutlinger et al 2010, Pierson et al 2014, Venkateswaran et al 2014, Yuan et al 2014]. One individual with focal cortical dysplasia was reported [Lesca et al 2013]. Positron emission tomography (PET) showing diffuse cortical hypometabolism was reported in one individual [DeVries & Patel 2013]. ### Genotype-Phenotype Correlations Genotype-phenotype correlation is observed in a number of families in which all individuals heterozygous for the GRIN2A pathogenic variant have an epilepsy-aphasia syndrome (EAS) phenotype. However, the specific EAS phenotype may vary considerably within the family, including one individual with isolated speech dysfunction and another with epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS) [Carvill et al 2013, Lemke et al 2013, Lesca et al 2013, Turner et al 2015a]. For single-nucleotide variants (SNVs) and small intragenic copy number variants (CNVs), the genomic region in which the pathogenic variant occurs does not appear to have any relationship to the phenotype. Specifically, the pathogenic variants associated with infantile-onset epileptic encephalopathies do not cluster in a region distinct from the location of pathogenic variants associated with the epilepsy-aphasia syndromes (EAS). ### Penetrance GRIN2A-related speech disorders and epilepsy show incomplete but high penetrance and variable expressivity. Penetrance is not clearly different for males and females. ### Nomenclature Landau-Kleffner syndrome (LKS) has also been referred to as epileptic acquired aphasia. Epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS) has also been referred to as continuous spike-and-wave during slow-wave sleep (CSWS) and electrical status epilepticus during sleep (ESES). Childhood epilepsy with centrotemporal spikes (CECTS) has been commonly referred to as benign epilepsy with centrotemporal spikes (BECTS) and benign rolandic epilepsy of childhood (BREC). Atypical childhood epilepsy with centrotemporal spikes (ACECTS) has been known as atypical benign partial epilepsy (ABPE), pseudo-Lennox syndrome, and atonic-benign childhood epilepsy with centrotemporal spikes. ### Prevalence The prevalence of GRIN2A-related speech disorders and epilepsy in the general population is unknown; however, estimates can be made for some of the classic disorders. GRIN2A pathogenic variants account for 9%-20% of epilepsy-aphasia syndrome (EAS), with pathogenic variants more likely to be present in persons with more severe phenotypes and a positive family history [Lesca et al 2012, Carvill et al 2013]. GRIN2A pathogenic variants are present in [Lemke et al 2013, Conroy et al 2014, Allen et al 2016]: * 4.8%-7.7% of Landau-Kleffner syndrome (LKS) * 17.6% of epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS) * 0%-4.9% of childhood epilepsy with centrotemporal spikes (CECTS) * 13.5% of atypical childhood epilepsy with centrotemporal spikes (ACECTS) * 2% of early-onset epileptic encephalopathy ## Differential Diagnosis Non-GRIN2-related genetic epilepsy * Epilepsy-aphasia syndrome (EAS). While GRIN2A is the gene most commonly associated with EAS, the majority of individuals with this group of syndromes do not have an identified genetic cause. A number of CNVs have been associated with EAS in individual cases. Pathogenic variants in RBFOX1 and RBFOX3 may play a contributory role in some cases [Lal et al 2013, Turner et al 2015b]. At present, no clinical features differentiate GRIN2A-related EAS from EAS of other genetic causes. * Non-EAS childhood-onset focal epilepsy and infantile-onset epileptic encephalopathy. Each phenotype has only a small number of reported cases associated with a GRIN2A pathogenic variant. Clinical data currently available are insufficient to distinguish those with a GRIN2A pathogenic variant from those with other genetic causes. Non-genetic causes of epilepsy. Focal epilepsy and epileptic encephalopathy may have many non-genetic causes, including autoimmune and infectious processes. A non-genetic cause should be more strongly considered when a history of any of the following is present: * Maternal substance abuse during pregnancy * Significant complications in the perinatal period * Significant cerebral insult (e.g., central nervous system infection, hypoxic-ischemic injury, major head trauma, toxic ingestion/exposure) Non-GRIN2A-related genetic language impairment. A severe speech and language disorder that primarily involves developmental verbal dyspraxia is caused by pathogenic variants in FOXP2 (see FOXP2-Related Speech and Language Disorders) [Lai et al 2001]. FOXP2 regulates CNTNAP2, and CNTNAP2 missense variants and deletions have been associated with childhood apraxia of speech; however, evidence of a causative link is at present limited [Worthey et al 2013, Centanni et al 2015]. Hearing impairment is a common cause of language-specific developmental delay or regression, thus in children with delayed speech development or regression in speech, the auditory system should be assessed (see Hereditary Hearing Loss and Deafness Overview). Structural brain abnormality. Brain malformations and acquired structural brain anomalies can present with a constellation of symptoms that can mimic the GRIN2A-related disorders. Worster-Drought syndrome (OMIM 185480) involves congenital bilateral perisylvian lesions, most commonly polymicrogyria [Christen et al 2000]. Affected children typically have seizures, expressive language delay, dysarthria, and oromotor apraxia. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a GRIN2A-related speech disorder and epilepsy, the following evaluations are recommended: * Consultation with a speech and language pathologist * Epilepsy consultation (if not done at the time of initial assessment) * Sleep-deprived or sleep EEG with monitoring to capture slow-wave sleep (if not done at the time of initial assessment), as this is essential to diagnosing or excluding continuous spike-and-wave in sleep (CSWS). * Neuropsychological assessment * Hearing testing * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Speech/language deficits. Individuals with significant speech/language deficits may benefit from therapy by a speech pathologist. The therapies, which are individualized to the specific speech disorder, often include linguistic approaches and augmentative and alternative communication [Murray et al 2014]. Seizures, if present, should be treated with antiepileptic drugs (AEDs). Many different AEDs may be effective, and no one medication has been demonstrated to be effective specifically for GRIN2A-related disorders. In one individual a good response to refractory epilepsy was achieved with topiramate [Venkateswaran et al 2014]. In one individual seizure burden was reduced with the addition of memantine; however, cognitive function did not improve [Pierson et al 2014]. Ketogenic diet and vagal nerve stimulator may also be considered in patients with refractory epilepsy. Treatment for epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS) and Landau-Kleffner syndrome (LKS) includes AEDs such as valproic acid, benzodiazepines, and corticosteroids. Sulthiame, ethosuximide, and levetiracetam may also be effective. Of note, intravenous immunoglobulin has not been proven to be efficacious [Striano & Capovilla 2013, Van Bogaert 2013]. Caregivers. For information on non-medical interventions and coping strategies for parents or caregivers of children diagnosed with epilepsy, see Epilepsy & My Child Toolkit. ### Prevention of Secondary Complications AEDs are associated with possible adverse reactions (e.g., sedation, gastrointestinal symptoms, changes in appetite [increase or decrease], weight gain or loss, and rash) which vary according to the specific medication. Patients on AEDs should be monitored closely for adverse reactions and, if they develop, a change to an alternate AED should be considered. Corticosteroids are associated with a wide variety of possible adverse reactions, including weight gain with cushingoid appearance, skin thinning and purpura, alopecia, acne, posterior subscapular cataract, glaucoma, exophthalmos, cardiac arrhythmias, hypertension, gastrointestinal upset, pancreatitis, hypokalemia, osteoporosis, avascular necrosis, myopathy, behavioral/psychiatric disturbance, diabetes mellitus, adrenal insufficiency, and increased infection risk. If complications of corticosteroid therapy become of concern, gradual tapering and alternate therapy should be considered. ### Surveillance Routine monitoring of speech and language by a speech pathologist should be considered for all children, particularly those diagnosed before reaching school age. Developmental surveillance should be conducted in all affected children. ### Agents/Circumstances to Avoid In individuals with epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), phenytoin, barbiturates and carbamazepine should be avoided as they are rarely effective, may worsen the EEG, and have negative effects on neuropsychological outcomes [Striano & Capovilla 2013, Van Bogaert 2013]. ### Evaluation of Relatives at Risk Using molecular genetic testing for the GRIN2A pathogenic variant found in an affected family member, it is appropriate to evaluate apparently asymptomatic at-risk relatives in order to identify as early as possible those who would benefit from institution of treatment. Of note, some individuals heterozygous for a GRIN2A pathogenic variant who have only relatively mild speech dysfunction may benefit from early evaluation and intervention by a speech and language pathologist. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for 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	GRIN2A-Related Speech Disorders and Epilepsy	None	26,845	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK385627/	2021-01-18T21:24:26	{"synonyms": []}
Erythrokeratodermia is a group of keratinization disorders.[1] Types include: * Erythrokeratodermia variabilis * Erythrokeratodermia with ataxia * Progressive symmetric erythrokeratodermia ## References[edit] 1. ^ "Erythrokeratoderma - DermNet New Zealand". www.dermnet.org.nz. * v * t * e Congenital malformations and deformations of integument / skin disease Genodermatosis Congenital ichthyosis/ erythrokeratodermia AD * Ichthyosis vulgaris AR * Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis * Lamellar ichthyosis * Harlequin-type ichthyosis * Netherton syndrome * Zunich–Kaye syndrome * Sjögren–Larsson syndrome XR * X-linked ichthyosis Ungrouped * Ichthyosis bullosa of Siemens * Ichthyosis follicularis * Ichthyosis prematurity syndrome * Ichthyosis–sclerosing cholangitis syndrome * Nonbullous congenital ichthyosiform erythroderma * Ichthyosis linearis circumflexa * Ichthyosis hystrix EB and related * EBS * EBS-K * EBS-WC * EBS-DM * EBS-OG * EBS-MD * EBS-MP * JEB * JEB-H * Mitis * Generalized atrophic * JEB-PA * DEB * DDEB * RDEB * related: Costello syndrome * Kindler syndrome * Laryngoonychocutaneous syndrome * Skin fragility syndrome Ectodermal dysplasia * Naegeli syndrome/Dermatopathia pigmentosa reticularis * Hay–Wells syndrome * Hypohidrotic ectodermal dysplasia * Focal dermal hypoplasia * Ellis–van Creveld syndrome * Rapp–Hodgkin syndrome/Hay–Wells syndrome Elastic/Connective * Ehlers–Danlos syndromes * Cutis laxa (Gerodermia osteodysplastica) * Popliteal pterygium syndrome * Pseudoxanthoma elasticum * Van der Woude syndrome Hyperkeratosis/ keratinopathy PPK * diffuse: Diffuse epidermolytic palmoplantar keratoderma * Diffuse nonepidermolytic palmoplantar keratoderma * Palmoplantar keratoderma of Sybert * Meleda disease * syndromic * connexin * Bart–Pumphrey syndrome * Clouston's hidrotic ectodermal dysplasia * Vohwinkel syndrome * Corneodermatoosseous syndrome * plakoglobin * Naxos syndrome * Scleroatrophic syndrome of Huriez * Olmsted syndrome * Cathepsin C * Papillon–Lefèvre syndrome * Haim–Munk syndrome * Camisa disease * focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis * Focal palmoplantar and gingival keratosis * Howel–Evans syndrome * Pachyonychia congenita * Pachyonychia congenita type I * Pachyonychia congenita type II * Striate palmoplantar keratoderma * Tyrosinemia type II * punctate: Acrokeratoelastoidosis of Costa * Focal acral hyperkeratosis * Keratosis punctata palmaris et plantaris * Keratosis punctata of the palmar creases * Schöpf–Schulz–Passarge syndrome * Porokeratosis plantaris discreta * Spiny keratoderma * ungrouped: Palmoplantar keratoderma and spastic paraplegia * desmoplakin * Carvajal syndrome * connexin * Erythrokeratodermia variabilis * HID/KID Other * Meleda disease * Keratosis pilaris * ATP2A2 * Darier's disease * Dyskeratosis congenita * Lelis syndrome * Dyskeratosis congenita * Keratolytic winter erythema * Keratosis follicularis spinulosa decalvans * Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome * Keratosis pilaris atrophicans faciei * Keratosis pilaris Other * cadherin * EEM syndrome * immune system * Hereditary lymphedema * Mastocytosis/Urticaria pigmentosa * Hailey–Hailey see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder Developmental anomalies Midline * Dermoid cyst * Encephalocele * Nasal glioma * PHACE association * Sinus pericranii Nevus * Capillary hemangioma * Port-wine stain * Nevus flammeus nuchae Other/ungrouped * Aplasia cutis congenita * Amniotic band syndrome * Branchial cyst * Cavernous venous malformation * Accessory nail of the fifth toe * Bronchogenic cyst * Congenital cartilaginous rest of the neck * Congenital hypertrophy of the lateral fold of the hallux * Congenital lip pit * Congenital malformations of the dermatoglyphs * Congenital preauricular fistula * Congenital smooth muscle hamartoma * Cystic lymphatic malformation * Median raphe cyst * Melanotic neuroectodermal tumor of infancy * Mongolian spot * Nasolacrimal duct cyst * Omphalomesenteric duct cyst * Poland anomaly * Rapidly involuting congenital hemangioma * Rosenthal–Kloepfer syndrome * Skin dimple * Superficial lymphatic malformation * Thyroglossal duct cyst * Verrucous vascular malformation * Birthmark This Genodermatoses 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	Erythrokeratodermia	c0432330	26,846	wikipedia	https://en.wikipedia.org/wiki/Erythrokeratodermia	2021-01-18T18:41:38	{"umls": ["C0432330"], "orphanet": ["79355"], "wikidata": ["Q5396475"]}
Steroid acne SpecialtyDermatology Steroid acne is an adverse reaction to corticosteroids, and presents as small, firm follicular papules on the forehead, cheeks, and chest.[1]:137 Steroid acne presents with monomorphous pink paupules, as well as comedones, which may be indistinguishable from those of acne vulgaris.[2] Steroid acne is commonly associated with endogenous or exogenous sources of androgen, drug therapy, or diabetes and is less commonly associated with HIV infection or Hodgkin's disease.[3] ## Contents * 1 See also * 2 References * 3 External links * 4 External links ## See also[edit] * Medicine portal * List of cutaneous conditions * Steroid folliculitis ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. 2. ^ Plewig, Gerd; Kligman, Albert M. (6 December 2012). Acne and Rosacea. Springer Science & Business Media. p. 416. ISBN 9783642972348. "Acne vulgaris and steroid acne are quite different processes, although the comedones may be clinically indistinguishable." 3. ^ Dennis, Mark; Bowen, William Talbot; Cho, Lucy (2012). "Steroid acne". Mechanisms of Clinical Signs. Elsevier. p. 554. ISBN 978-0729540759; pbk ## External links[edit] Classification D * ICD-10: L70.8 (ILDS L70.816), Y42 * ICD-9-CM: E932 ## External links[edit] * v * t * e Disorders of skin appendages Nail * thickness: Onychogryphosis * Onychauxis * color: Beau's lines * Yellow nail syndrome * Leukonychia * Azure lunula * shape: Koilonychia * Nail clubbing * behavior: Onychotillomania * Onychophagia * other: Ingrown nail * Anonychia * ungrouped: Paronychia * Acute * Chronic * Chevron nail * Congenital onychodysplasia of the index fingers * Green nails * Half and half nails * Hangnail * Hapalonychia * Hook nail * Ingrown nail * Lichen planus of the nails * Longitudinal erythronychia * Malalignment of the nail plate * Median nail dystrophy * Mees' lines * Melanonychia * Muehrcke's lines * Nail–patella syndrome * Onychoatrophy * Onycholysis * Onychomadesis * Onychomatricoma * Onychomycosis * Onychophosis * Onychoptosis defluvium * Onychorrhexis * Onychoschizia * Platonychia * Pincer nails * Plummer's nail * Psoriatic nails * Pterygium inversum unguis * Pterygium unguis * Purpura of the nail bed * Racquet nail * Red lunulae * Shell nail syndrome * Splinter hemorrhage * Spotted lunulae * Staining of the nail plate * Stippled nails * Subungual hematoma * Terry's nails * Twenty-nail dystrophy Hair Hair loss/ Baldness * noncicatricial alopecia: Alopecia * areata * totalis * universalis * Ophiasis * Androgenic alopecia (male-pattern baldness) * Hypotrichosis * Telogen effluvium * Traction alopecia * Lichen planopilaris * Trichorrhexis nodosa * Alopecia neoplastica * Anagen effluvium * Alopecia mucinosa * cicatricial alopecia: Pseudopelade of Brocq * Central centrifugal cicatricial alopecia * Pressure alopecia * Traumatic alopecia * Tumor alopecia * Hot comb alopecia * Perifolliculitis capitis abscedens et suffodiens * Graham-Little syndrome * Folliculitis decalvans * ungrouped: Triangular alopecia * Frontal fibrosing alopecia * Marie Unna hereditary hypotrichosis Hypertrichosis * Hirsutism * Acquired * localised * generalised * patterned * Congenital * generalised * localised * X-linked * Prepubertal Acneiform eruption Acne * Acne vulgaris * Acne conglobata * Acne miliaris necrotica * Tropical acne * Infantile acne/Neonatal acne * Excoriated acne * Acne fulminans * Acne medicamentosa (e.g., steroid acne) * Halogen acne * Iododerma * Bromoderma * Chloracne * Oil acne * Tar acne * Acne cosmetica * Occupational acne * Acne aestivalis * Acne keloidalis nuchae * Acne mechanica * Acne with facial edema * Pomade acne * Acne necrotica * Blackhead * Lupus miliaris disseminatus faciei Rosacea * Perioral dermatitis * Granulomatous perioral dermatitis * Phymatous rosacea * Rhinophyma * Blepharophyma * Gnathophyma * Metophyma * Otophyma * Papulopustular rosacea * Lupoid rosacea * Erythrotelangiectatic rosacea * Glandular rosacea * Gram-negative rosacea * Steroid rosacea * Ocular rosacea * Persistent edema of rosacea * Rosacea conglobata * variants * Periorificial dermatitis * Pyoderma faciale Ungrouped * Granulomatous facial dermatitis * Idiopathic facial aseptic granuloma * Periorbital dermatitis * SAPHO syndrome Follicular cysts * "Sebaceous cyst" * Epidermoid cyst * Trichilemmal cyst * Steatocystoma * simplex * multiplex * Milia Inflammation * Folliculitis * Folliculitis nares perforans * Tufted folliculitis * Pseudofolliculitis barbae * Hidradenitis * Hidradenitis suppurativa * Recurrent palmoplantar hidradenitis * Neutrophilic eccrine hidradenitis Ungrouped * Acrokeratosis paraneoplastica of Bazex * Acroosteolysis * Bubble hair deformity * Disseminate and recurrent infundibulofolliculitis * Erosive pustular dermatitis of the scalp * Erythromelanosis follicularis faciei et colli * Hair casts * Hair follicle nevus * Intermittent hair–follicle dystrophy * Keratosis pilaris atropicans * Kinking hair * Koenen's tumor * Lichen planopilaris * Lichen spinulosus * Loose anagen syndrome * Menkes kinky hair syndrome * Monilethrix * Parakeratosis pustulosa * Pili (Pili annulati * Pili bifurcati * Pili multigemini * Pili pseudoannulati * Pili torti) * Pityriasis amiantacea * Plica neuropathica * Poliosis * Rubinstein–Taybi syndrome * Setleis syndrome * Traumatic anserine folliculosis * Trichomegaly * Trichomycosis axillaris * Trichorrhexis (Trichorrhexis invaginata * Trichorrhexis nodosa) * Trichostasis spinulosa * Uncombable hair syndrome * Wooly hair nevus Sweat glands Eccrine * Miliaria * Colloid milium * Miliaria crystalline * Miliaria profunda * Miliaria pustulosa * Miliaria rubra * Occlusion miliaria * Postmiliarial hypohidrosis * Granulosis rubra nasi * Ross’ syndrome * Anhidrosis * Hyperhidrosis * Generalized * Gustatory * Palmoplantar Apocrine * Body odor * Chromhidrosis * Fox–Fordyce disease Sebaceous * Sebaceous hyperplasia * v * t * e Adverse drug reactions Antibiotics * Penicillin drug reaction * Sulfonamide hypersensitivity syndrome * Urticarial erythema multiforme * Adverse effects of fluoroquinolones * Red man syndrome * Jarisch–Herxheimer reaction Hormones * Steroid acne * Steroid folliculitis Chemotherapy * Chemotherapy-induced acral erythema * Chemotherapy-induced hyperpigmentation * Scleroderma-like reaction to taxanes * Hydroxyurea dermopathy * Exudative hyponychial dermatitis Anticoagulants * Anticoagulant-induced skin necrosis * Warfarin necrosis * Vitamin K reaction * Texier's disease Immunologics * Adverse reaction to biologic agents * Leukotriene receptor antagonist-associated Churg–Strauss syndrome * Methotrexate-induced papular eruption * Adverse reaction to cytokines Other drugs * Anticonvulsant hypersensitivity syndrome * Allopurinol hypersensitivity syndrome * Vaccine adverse event * Eczema vaccinatum * Bromoderma * Halogenoderma * Iododerma General Skin and body membranes * Acute generalized exanthematous pustulosis * Bullous drug reaction * Drug-induced acne * Drug-induced angioedema * Drug-related gingival hyperplasia * Drug-induced lichenoid reaction * Drug-induced lupus erythematosus * Drug-induced nail changes * Drug-induced pigmentation * Drug-induced urticaria * Stevens–Johnson syndrome * Injection site reaction * Linear IgA bullous dermatosis * Toxic epidermal necrolysis * HIV disease-related drug reaction * Photosensitive drug reaction Other * Drug-induced pseudolymphoma * Fixed drug reaction * Serum sickness-like reaction This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Steroid acne	c0406479	26,847	wikipedia	https://en.wikipedia.org/wiki/Steroid_acne	2021-01-18T18:49:22	{"umls": ["C0406479"], "icd-9": ["E932"], "icd-10": ["L70.8"], "wikidata": ["Q7611605"]}
Parasitic ectoparasitic infectious disease caused by mites Not to be confused with Ascariasis an intestinal parasite. Acariasis SpecialtyInfectious disease Acariasis is an infestation with mites.[1] ## Contents * 1 Terminology * 2 Classification * 3 Diagnosis * 4 References * 5 External links ## Terminology[edit] There are several complications with the terminology: Acariasis is a term for a rash, caused by mites, sometimes with a papillae (pruritic dermatitis) or papule (papular urticaria), and usually accompanied by a hive (urticaria) and severe itching sensations. An example of such an infection is scabies or gamasoidosis. The closely related term, mange, is commonly used with domestic animals and also livestock and wild mammals, whenever hair-loss is involved. Sarcoptes and Demodex species are involved in mange, but both of these genera are also involved in human skin diseases (by convention only, not called mange). Sarcoptes in humans is especially severe symptomatically, and causes the condition scabies noted above. Another genus of mite which causing itching but rarely causes hair loss because it burrows only at the keratin level, is Cheyletiella. Various species of this genus of mite also affect a wide variety of mammals, including humans. Mite infestation sometimes implies an ectoparasitic, cutaneous condition such as dermatitis. However, it is possible for mites to invade the gastrointestinal and urinary tracts.[2] MeSH uses the term "Mite Infestations" as pertaining to Acariformes.[3] However, mites not in this grouping can be associated with human disease. (See "Classification", below.) The term Acari refers to ticks and mites together, which can cause ambiguity. (Mites are a paraphyletic grouping). Mites can be associated with disease in at least three different ways: (1) cutaneous dermatitis, (2) production of allergin, and (3) as a vector for parasitic diseases. The language used to describe mite infestation often does not distinguish among these.[citation needed] ## Classification[edit] Most of the mites which cause this affliction to humans are from the order Acari, hence the name Acariasis. The entire taxonomic classification to order would be: * Kingdom: Animalia * Phylum: Arthropoda * Subphylum: Chelicerata * Class: Arachnida * Order: Acari (At the order level, there is still substantial argument among researchers as to how to categorize Acari. Some call it a subclass, others a superorder, "Acarina".) Specific species involved include: * Acariformes * Trombidiformes * Trombicula species (Trombiculosis or chiggers) * Demodex species (Demodicosis) * Pyemotes tritici * Cheyletiella * Sarcoptiformes * Sarcoptes scabiei (Scabies) * Parasitiformes * Dermanyssus gallinae, Ornithonyssus bursa, Ornithonyssus sylviarum (Gamasoidosis) * Liponyssoides sanguineus, Laelaps echidnina, Ornithonyssus bacoti (Rodent mite dermatitis) * Another candidate is Androlaelaps casalis. However, based on this mite's life style as a predator on other mite species (such as the previously-mentioned Dermanyssus gallinae),[4] it is highly unlikely to be a cause of acariasis. Some of these reflect reports existing of human infestation by mites previously believed not to prey on humans.[5] ## Diagnosis[edit] Medical doctors and dermatologists can still misdiagnose this rash as many are unfamiliar with parasitism, not trained in it, or if they do consider it, cannot see the mites. Different methods for detection are recognized for different acariasis infections. Human acariasis with mites can occur in the gastrointestinal tract, lungs, urinary tracts and other organs which not have been well-studied. For intestinal acariasis with symptoms such as abdominal pain, diarrhea, and phohemefecia (is this hemafecia?), human acariasis is diagnosed by detection of mites in stools.[6] For pulmonary acariasis, the presence of mites in sputum is determined by identifying the presence and number of mites in the sputum of patients with respiratory symptoms. Both physical and chemical methods for liquefaction of sputum have been developed.[7] ## References[edit] 1. ^ "Acariasis" at Dorland's Medical Dictionary 2. ^ Li, CP; Cui, YB; Wang, J; Yang, QG; Tian, Y (2003). "Acaroid mite, intestinal and urinary acariasis". World Journal of Gastroenterology. 9 (4): 874–77. PMID 12679953. 3. ^ Mite+infestations at the US National Library of Medicine Medical Subject Headings (MeSH) 4. ^ Lesna, Izabela; Wolfs, Peter; Faraji, Farid; Roy, Lise; Komdeur, Jan; Sabelis, Maurice W. (2009). "Candidate predators for biological control of the poultry red mite Dermanyssus gallinae". Experimental and Applied Acarology. 48 (1–2): 63–80. doi:10.1007/s10493-009-9239-1. PMID 19184469. 5. ^ "Research and Reference Articles"[unreliable source?] 6. ^ Cui, YB; Ling, YZ; Zhou, Y; Feng, ZW; Xing, YR; Zhang, SW (2006). "An effective indirect fluorescent antibody test for diagnosis of intestinal acariasis". The Southeast Asian Journal of Tropical Medicine and Public Health. 37 (3): 452–55. PMID 17120963. 7. ^ Martínez-Girón, Rafael; Woerden, Hugo Cornelis; Ribas-Barceló, Andrés (2007). "Experimental method for isolating and identifying dust mites from sputum in pulmonary acariasis". Experimental and Applied Acarology. 42 (1): 55–59. doi:10.1007/s10493-007-9076-z. PMID 17549588. ## External links[edit] Classification D * ICD-10: B86, B88.0 * ICD-9-CM: 133 * MeSH: D008924 * v * t * e Arthropods and ectoparasite-borne diseases and infestations Insecta Louse * Body louse (pediculosis corporis) / Head louse (head lice infestation) * Crab louse (phthiriasis) Hemiptera * Bed bug (cimicosis) Fly * Dermatobia hominis / Cordylobia anthropophaga / Cochliomyia hominivorax (myiasis) * Mosquito (mosquito-borne disease) Flea * Tunga penetrans (tungiasis) Crustacea Pentastomida * Linguatula serrata (linguatulosis) * Porocephalus crotali / Armillifer armillatus (porocephaliasis) * For ticks and mites, see Template:Tick and mite-borne diseases and infestations [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Acariasis	c0026229	26,848	wikipedia	https://en.wikipedia.org/wiki/Acariasis	2021-01-18T18:52:27	{"mesh": ["D008924"], "umls": ["C0026229"], "icd-9": ["133"], "icd-10": ["B86", "B88.0"], "wikidata": ["Q337998"]}
For social philosophy, see objectification and dehumanization. Depersonalization can consist of a detachment within the self, regarding one's mind or body, or being a detached observer of oneself.[1] Subjects feel they have changed and that the world has become vague, dreamlike, less real, lacking in significance or being outside reality while looking in.[not verified in body] Chronic depersonalization refers to depersonalization/derealization disorder, which is classified by the DSM-5 as a dissociative disorder,[2] based on the findings that depersonalization and derealization are prevalent in other dissociative disorders including dissociative identity disorder.[3] Though degrees of depersonalization and derealization can happen to anyone who is subject to temporary anxiety or stress, chronic depersonalization is more related to individuals who have experienced a severe trauma or prolonged stress/anxiety. Depersonalization-derealization is the single most important symptom in the spectrum of dissociative disorders, including dissociative identity disorder and "dissociative disorder not otherwise specified" (DD-NOS). It is also a prominent symptom in some other non-dissociative disorders, such as anxiety disorders, clinical depression, bipolar disorder, schizophrenia,[4] schizoid personality disorder, hypothyroidism or endocrine disorders,[5] schizotypal personality disorder, borderline personality disorder, obsessive–compulsive disorder, migraines, and sleep deprivation; it can also be a symptom of some types of neurological seizure. In social psychology, and in particular self-categorization theory, the term depersonalization has a different meaning and refers to "the stereotypical perception of the self as an example of some defining social category".[6] ## Contents * 1 Description * 2 Prevalence * 3 Pharmacological and situational causes * 4 Depersonalization as a psychobiological mechanism * 5 Treatment * 6 Research * 7 See also * 8 References * 8.1 Other references ## Description[edit] Individuals who experience depersonalization feel divorced from their own personal self by sensing their body sensations, feelings, emotions, behaviors etc. as not belonging to the same person or identity.[7][permanent dead link] Often a person who has experienced depersonalization claims that things seem unreal or hazy. Also, a recognition of a self breaks down (hence the name). Depersonalization can result in very high anxiety levels, which further increase these perceptions.[8] Depersonalization is a subjective experience of unreality in one's self, while derealization is unreality of the outside world. Although most authors currently regard depersonalization (self) and derealization (surroundings) as independent constructs, many do not want to separate derealization from depersonalization.[9] ## Prevalence[edit] Depersonalization is a symptom of anxiety disorders, such as panic disorder.[10][11] It can also accompany sleep deprivation (often occurring when suffering from jet lag), migraine, epilepsy (especially temporal lobe epilepsy,[12] complex-partial seizure, both as part of the aura and during the seizure[13]), obsessive-compulsive disorder, severe stress or trauma, anxiety, the use of recreational drugs[14] —especially cannabis, hallucinogens, ketamine, and MDMA, certain types of meditation, deep hypnosis, extended mirror or crystal gazing, sensory deprivation, and mild-to-moderate head injury with little or loss of consciousness (less likely if unconscious for more than 30 mins).[13] Interoceptive exposure is a non-pharmacological method that can be used to induce depersonalization.[15][5] In the general population, transient depersonalization/derealization are common, having a lifetime prevalence between 26-74%. A random community-based survey of 1,000 adults in the US rural south found a 1-year depersonalization prevalence rate at 19%. Several studies, but not all, found age to be a significant factor: adolescents and young adults in the normal population reported the highest rate. In a study, 46% of college students reported at least one significant episode in the previous year. In another study, 20% of patients with minor head injury experience significant depersonalization and derealization. Several studies found that up to 66% of individuals in life-threatening accidents report transient depersonalization at minimum during or immediately after the accidents.[13] Depersonalization occurs 2-4 time more in women than in men.[16] A similar and overlapping concept called ipseity disturbance (ipse is Latin for "self" or "itself"[17]) may be part of the core process of schizophrenia spectrum disorders. However, specific to the schizophrenia spectrum seems to be "a dislocation of first-person perspective such that self and other or self and world may seem to be non-distinguishable, or in which the individual self or field of consciousness takes on an inordinate significance in relation to the objective or intersubjective world" (emphasis in original).[4] For the purposes of evaluation and measurement depersonalization can be conceived of as a construct and scales are now available to map its dimensions in time and space.[clarification needed][18] A study of undergraduate students found that individuals high on the depersonalization/derealization subscale of the Dissociative Experiences Scale exhibited a more pronounced cortisol response in stress. Individuals high on the absorption subscale, which measures a subject's experiences of concentration to the exclusion of awareness of other events, showed weaker cortisol responses.[19] In general infantry and special forces soldiers, measures of depersonalization and derealization increased significantly after training that include experiences of uncontrollable stress, semi-starvation, sleep deprivation, and lack of control over hygiene, movement, communications, and social interactions.[13] ## Pharmacological and situational causes[edit] Depersonalization has been described by some as a desirable state, particularly by those that have experienced it under the influence of mood-altering recreational drugs. It is an effect of dissociatives and psychedelics, as well as a possible side effect of caffeine, alcohol, amphetamine, and cannabis.[20][21][22][23][24] It is a classic withdrawal symptom from many drugs.[25][26][27][28] Benzodiazepine dependence, which can occur with long-term use of benzodiazepines, can induce chronic depersonalization symptomatology and perceptual disturbances in some people, even in those who are taking a stable daily dosage, and it can also become a protracted feature of the benzodiazepine withdrawal syndrome.[29][30] Lieutenant Colonel Dave Grossman, in his book On Killing, suggests that military training artificially creates depersonalization in soldiers, suppressing empathy and making it easier for them to kill other human beings.[31] Graham Reed (1974) claimed that depersonalization occurs in relation to the experience of falling in love.[32] ## Depersonalization as a psychobiological mechanism[edit] Depersonalization is a classic response to acute trauma, and may be highly prevalent in individuals involved in different traumatic situations including motor vehicle accident, and imprisonment.[3] Psychologically depersonalization can, just like dissociation in general, be considered a type of coping mechanism. Depersonalization is in that case unconsciously used to decrease the intensity of unpleasant experience, whether that is something as mild as stress or something as severe as chronically high anxiety and post-traumatic stress disorder.[33] The decrease in anxiety and psychobiological hyperarousal helps preserving adaptive behaviors and resources under threat or danger.[3] Depersonalization is an overgeneralized reaction in that it doesn't diminish just the unpleasant experience, but more or less all experience - leading to a feeling of being detached from the world and experiencing it in a more bland way. An important distinction must be made between depersonalization as a mild, short term reaction to unpleasant experience and depersonalization as a chronic symptom stemming from a severe mental disorder such as PTSD or Dissociative Identity Disorder.[33] Chronic symptoms may represent persistence of depersonalization beyond the situations under threat.[3] ## Treatment[edit] An attempt at a visual representation of depersonalization Treatment is dependent on the underlying cause, whether it is organic or psychological in origin. If depersonalization is a symptom of neurological disease, then diagnosis and treatment of the specific disease is the first approach. Depersonalization can be a cognitive symptom of such diseases as amyotrophic lateral sclerosis, Alzheimer's, multiple sclerosis (MS), or any other neurological disease affecting the brain.[citation needed] For those suffering from depersonalization with migraine, tricyclic antidepressants are often prescribed. If depersonalization is a symptom of psychological causes such as developmental trauma, treatment depends on the diagnosis. In case of dissociative identity disorder or DD-NOS as a developmental disorder, in which extreme developmental trauma interferes with formation of a single cohesive identity, treatment requires proper psychotherapy, and—in the case of additional (co-morbid) disorders such as eating disorders—a team of specialists treating such an individual. It can also be a symptom of borderline personality disorder, which can be treated in the long term with proper psychotherapy and psychopharmacology.[34] The treatment of chronic depersonalization is considered in depersonalization disorder. A recently completed study at Columbia University in New York City has shown positive effects from transcranial magnetic stimulation (TMS) to treat depersonalization disorder. Currently, however, the FDA has not approved TMS to treat DP.[citation needed] A 2001 Russian study showed that naloxone, a drug used to reverse the intoxicating effects of opioid drugs, can successfully treat depersonalization disorder. According to the study: "In three of 14 patients, depersonalization symptoms disappeared entirely and seven patients showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the endogenous opioid system in the pathogenesis of depersonalization."[35] The anti convulsion drug Lamotrigine has shown some success in treating symptoms of depersonalization, often in combination with a Selective serotonin reuptake inhibitor and is the first drug of choice at the depersonalisation research unit at King's College London.[34][36][37] ## Research[edit] The Depersonalisation Research Unit at the Institute of Psychiatry in London conducts research into depersonalization disorder.[38] Researchers there use the acronym DPAFU (Depersonalisation and Feelings of Unreality) as a shortened label for the disorder. In a 2020 article in the journal Nature, Vesuna, et al. describe experimental findings which show that layer 5 of the retrosplenial cortex is likely responsible for dissociative states of consciousness in mammals. ## See also[edit] * Alienation * Brain fog * Catatonic state * Cognition * Derealization * Dissociation (psychology) * Ego death * Falling (sensation) * Hallucinogen persisting perception disorder * Human spirit * Nina Searl * Out-of-body experience * Post-traumatic stress disorder * Psychedelic experience * Psychological trauma * Śūnyatā * Spiritual crisis * Weltschmerz ## References[edit] 1. ^ Sierra, M.; Berrios, G. E. (2001). "The phenomenological stability of depersonalization: Comparing the old with the new". The Journal of Nervous and Mental Disease. 189 (9): 629–36. doi:10.1097/00005053-200109000-00010. PMID 11580008. 2. ^ American Psychiatry Association (2013). "Dissociative Disorders". Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington: American Psychiatric Publishing. pp. 291-307. ISBN 978-0-89042-555-8. 3. ^ a b c d Dissociative Disorders (2017), CHANGES IN DIAGNOSTIC CRITERIA TO THE DISSOCIATIVE DISORDERS, Changes to the Diagnostic Criteria for Depersonalization Disorder 4. ^ a b Sass, Louis; Pienkos, Elizabeth; Nelson, Barnaby; Medford, Nick (2013). "Anomalous self-experience in depersonalization and schizophrenia: A comparative investigation". Consciousness and Cognition. 22 (2): 430–441. doi:10.1016/j.concog.2013.01.009. PMID 23454432. 5. ^ a b Sharma, Kirti; Behera, Joshil Kumar; Sood, Sushma; Rajput, Rajesh; Satpal; Praveen, Prashant (2014). "Study of cognitive functions in newly diagnosed cases of subclinical and clinical hypothyroidism". Journal of Natural Science, Biology, and Medicine. 5 (1): 63–66. doi:10.4103/0976-9668.127290. ISSN 0976-9668. PMC 3961955. PMID 24678200. 6. ^ Turner, John; Oakes, Penny (1986). "The significance of the social identity concept for social psychology with reference to individualism, interactionism and social influence". British Journal of Social Psychology. 25 (3): 237–52. doi:10.1111/j.2044-8309.1986.tb00732.x. 7. ^ Depersonalization Disorder at Merck Manual of Diagnosis and Therapy Home Edition 8. ^ Hall-Flavin, Daniel. "Depersonalization disorder: A feeling of being 'outside' your body". Retrieved 2007-09-08. 9. ^ Radovic F.; Radovic S. (2002). "Feelings of Unreality: A Conceptual and Phenomenological Analysis of the Language of Depersonalization". Philosophy, Psychiatry, & Psychology. 9 (3): 271–9. doi:10.1353/ppp.2003.0048. 10. ^ Sierra-Siegert M, David AS (December 2007). "Depersonalization and individualism: the effect of culture on symptom profiles in panic disorder". J. Nerv. Ment. Dis. 195 (12): 989–95. doi:10.1097/NMD.0b013e31815c19f7. PMID 18091192. 11. ^ Simeon D (2004). "Depersonalisation Disorder: A Contemporary Overview". CNS Drugs. 18 (6): 343–54. doi:10.2165/00023210-200418060-00002. PMID 15089102. 12. ^ Michelle V. Lambert; Mauricio Sierra; Mary L. Phillips; Anthony S. David (May 2002). "The Spectrum of Organic Depersonalization: A Review Plus Four New Cases". J Neuropsychiatry Clin Neurosci. 14 (2): 141–54. doi:10.1176/appi.neuropsych.14.2.141. PMID 11983788. 13. ^ a b c d Dissociative Disorders (2017), GENERAL POPULATION STUDIES OF DISSOCIATIVE DISORDERS, Epidemiology of Depersonalization and Derealization Symptoms. 14. ^ "Depersonalization-derealization disorder - Symptoms and causes". Mayo Clinic. Retrieved 2019-11-20. 15. ^ Lickel J; Nelson E; Lickel A H; Brett Deacon (2008). "Interoceptive Exposure Exercises for Evoking Depersonalization and Derealization: A Pilot Study". Journal of Cognitive Psychotherapy. 22 (4): 321–30. doi:10.1891/0889-8391.22.4.321. 16. ^ Sadock, BJ; Sadock, VA (2015). "12: Dissociative Disorders". Kaplan and Sadock's Synopsis of Psychiatry (11th ed.). Wolters Kluwer. DEPERSONALIZATION/DEREALIZATION DISORDER, Epidemiology, pp. 454-455. ISBN 978-1-60913-971-1. 17. ^ Louis A. Sass; Josef Parnas (2003). "Schizophrenia, Consciousness, and the Self". Schizophrenia Bulletin. 29 (3): 427–44. doi:10.1093/oxfordjournals.schbul.a007017. PMID 14609238. 18. ^ Sierra, Mauricio; Berrios, German E. (2000). "The Cambridge Depersonalisation Scale: A new instrument for the measurement of depersonalisation". Psychiatry Research. 93 (2): 153–164. doi:10.1016/S0165-1781(00)00100-1. PMID 10725532. 19. ^ Giesbrecht, T.; T. Smeets; H. Merckelbac; M. Jelicic (2007). "Depersonalization experiences in undergraduates are related to heightened stress cortisol responses". J. Nerv. Ment. Dis. 195 (4): 282–87. doi:10.1097/01.nmd.0000253822.60618.60. PMID 17435477. S2CID 9283387. 20. ^ Stein, M. B.; Uhde, TW (July 1989). "Depersonalization Disorder: Effects of Caffeine and Response to Pharmacotherapy". Biological Psychiatry. 26 (3): 315–20. doi:10.1016/0006-3223(89)90044-9. PMID 2742946. 21. ^ Raimo, E. B.; R. A. Roemer; M. Moster; Y. Shan (June 1999). "Alcohol-Induced Depersonalization". Biological Psychiatry. 45 (11): 1523–6. doi:10.1016/S0006-3223(98)00257-1. PMID 10356638. 22. ^ Cohen, P. R. (2004). "Medication-associated depersonalization symptoms: report of transient depersonalization symptoms induced by minocycline". Southern Medical Journal. 97 (1): 70–73. doi:10.1097/01.SMJ.0000083857.98870.98. PMID 14746427. 23. ^ "Medication-Associated Depersonalization Symptoms". medscape.com. 24. ^ Arehart-Treichel, Joan (2003-08-15). "Depersonalization Again Finds Psychiatric Spotlight". Psychiatric News. 38 (16): 18–30. doi:10.1176/pn.38.16.0018. 25. ^ Marriott, S.; P. Tyrer (1993). "Benzodiazepine dependence: avoidance and withdrawal". Drug Safety. 9 (2): 93–103. doi:10.2165/00002018-199309020-00003. PMID 8104417. 26. ^ Shufman, E.; A. Lerner; E. Witztum (2005). "Depersonalization after withdrawal from cannabis usage" [Depersonalization after withdrawal from cannabis usage]. Harefuah (in Hebrew). 144 (4): 249–51 and 303. PMID 15889607. 27. ^ Djenderedjian, A.; R. Tashjian (1982). "Agoraphobia following amphetamine withdrawal". The Journal of Clinical Psychiatry. 43 (6): 248–49. PMID 7085580. 28. ^ Mourad, I.; M. Lejoyeux; J. Adès (1998). "Evaluation prospective du sevrage des antidépresseurs" [Prospective evaluation of antidepressant discontinuation]. L'Encéphale (in French). 24 (3): 215–22. PMID 9696914. 29. ^ Ashton, Heather (1991). "Protracted withdrawal syndromes from benzodiazepines". Journal of Substance Abuse Treatment. 8 (1–2): 19–28. doi:10.1016/0740-5472(91)90023-4. PMID 1675688. 30. ^ Terao T; Yoshimura R; Terao M; Abe K (1992-01-15). "Depersonalization following nitrazepam withdrawal". Biol Psychiatry. 31 (2): 212–3. doi:10.1016/0006-3223(92)90209-I. PMID 1737083. 31. ^ Grossman, Dave (1996). On Killing: The Psychological Cost of Learning to Kill in War and Society. Back Bay Books. ISBN 978-0-316-33000-8. 32. ^ Reed, Graham (1972). The Psychology of Anomalous Experience. Hutchinson. p. 127. 33. ^ a b Cardeña, Etzel (1994). "The Domain of Dissociation". In Lynn, Steven J.; Rhue, Judith W. (eds.). Dissociation: Clinical and theoretical perspectives. New York: Guilford Press. pp. 15–31. ISBN 978-0-89862-186-0. 34. ^ a b Sierra, Mauricio; Baker, Dawn; Medford, Nicholas; Lawrence, Emma; Patel, Maxine; Phillips, Mary L.; David, Anthony S. (2006). "Lamotrigine as an Add-on Treatment for Depersonalization Disorder". Clinical Neuropharmacology. 29 (5): 253–258. doi:10.1097/01.WNF.0000228368.17970.DA. PMID 16960469. 35. ^ Nuller, Yuri L.; Morozova, Marina G.; Kushnir, Olga N.; Hamper, Nikita (2001). "Effect of naloxone therapy on depersonalization: A pilot study". Journal of Psychopharmacology. 15 (2): 93–95. doi:10.1177/026988110101500205. PMID 11448093. 36. ^ Somer, Eli; Amos-Williams, Taryn; Stein, Dan J. (2013). "Evidence-based treatment for Depersonalisation-derealisation Disorder (DPRD)". BMC Psychology. 1 (1): 20. doi:10.1186/2050-7283-1-20. PMC 4269982. PMID 25566370. 37. ^ Medford, Nick; Sierra, Mauricio; Baker, Dawn; David, Anthony S. (2005). "Understanding and treating depersonalisation disorder". Advances in Psychiatric Treatment. 11 (2): 92–100. doi:10.1192/apt.11.2.92. 38. ^ Depersonalisation Research Unit - Institute of Psychiatry, London ### Other references[edit] * Loewenstein, Richard J; Frewen, Paul; Lewis-Fernández, Roberto (2017). "20 Dissociative Disorders". In Sadock, Virginia A; Sadock, Benjamin J; Ruiz, Pedro (eds.). Kaplan & Sadock's Comprehensive Textbook of Psychiatry (10th ed.). Wolters Kluwer. ISBN 978-1-4511-0047-1. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Depersonalization	c0011551	26,849	wikipedia	https://en.wikipedia.org/wiki/Depersonalization	2021-01-18T18:32:56	{"mesh": ["D003861"], "umls": ["C0011551"], "wikidata": ["Q83177"]}
## Summary ### Clinical characteristics. Congenital dyserythropoietic anemia type I (CDA I) is characterized by moderate-to-severe macrocytic anemia presenting occasionally in utero as severe anemia associated with hydrops fetalis but more commonly in neonates as hepatomegaly, early jaundice, and intrauterine growth retardation. Some cases present in childhood or adulthood. After the neonatal period, most affected individuals have lifelong moderate anemia, usually accompanied by jaundice and splenomegaly. Secondary hemochromatosis develops with age as a result of increased iron absorption even in those who are not transfused. Distal limb anomalies occur in 4%-14% of affected individuals. ### Diagnosis/testing. Diagnosis of CDA I is suspected based on hematologic findings and established with identification of biallelic pathogenic variants in CDAN1 or CDIN1 (C15orf41). ### Management. Treatment of manifestations: Intramuscular or subcutaneous injections of interferon (IFN)-α2a or INF-α2b given two or three times a week increase hemoglobin and decrease iron overload in the majority of treated individuals. Successful allogenic bone marrow transplantation has been described in three children and should be considered only in those transfusion-dependent persons who are resistant to IFN therapy. Prevention of secondary complications: Treatment of iron overload using standard guidelines for regular phlebotomy and iron chelation as needed. Surveillance: Recommended monitoring for iron overload: * Measurement of hemoglobin, bilirubin, iron, transferrin and serum ferritin concentration every three months starting at age ten years. * Annual myocardial T2* MRI and hepatic R2* MRI (if available) starting at age ten years. Agents/circumstances to avoid: Any preparation containing iron. ### Genetic counseling. CDA I is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible options. ## Diagnosis ### Suggestive Findings Congenital dyserythropoietic anemia type I (CDA I) should be suspected in individuals with the following findings: * Moderate-to-severe macrocytic anemia with MCV >90 fL * Inappropriately low number of reticulocytes for the degree of anemia compared to other hemolytic anemias (secondary to ineffective erythropoiesis) * On peripheral blood smear: macrocytosis, elliptocytes, basophilic stippling, and occasional mature nucleated erythrocytes * In bone marrow aspirate: * On light microscopy: erythroid hyperplasia, few double-nucleated erythroblasts, and interchromatin bridges between erythroblasts (in 0.6%-2.8% of erythroblasts) * On electron microscopy: erythroid precursors with spongy appearance of heterochromatin (in ≤60% of erythroblasts) and invaginations of the nuclear membrane * Other: * Jaundice * Splenomegaly resulting from marrow expansion secondary to ineffective erythropoiesis * Anemia and distal limb dimorphism including hypoplastic nails and syndactyly ### Establishing the Diagnosis The diagnosis of CDA I is established in a proband with suggestive findings and identification of biallelic pathogenic variants in one of the genes listed in Table 1. Molecular testing approaches can include serial single-gene testing, use of a multigene panel, and more comprehensive genomic testing. Serial single-gene testing can be considered if (1) mutation of a particular gene accounts for a large proportion of the disease or (2) factors including clinical findings, laboratory findings, or ancestry indicate that mutation of a particular gene is most likely. Sequence analysis of the gene of interest is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found.* * Targeted analysis for the c.3124C>T pathogenic variant in CDAN1 can be performed first in individuals of Bedouin ancestry. * In all other ethnicities, full gene sequencing of CDAN1 should be performed first. * If no CDAN1 pathogenic variant is found, full sequencing of CDIN1 (C15orf41) should be performed in all populations. Note: The authors are not aware of deletion/duplication analysis having been performed on either CDAN1 or CDIN1. A multigene panel that includes CDIN1 and CDAN1 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered if serial single-gene testing (and/or use of a multigene panel that includes CDIN1 and CDAN1) fails to confirm a diagnosis in an individual with features of CDA 1. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Congenital Dyserythropoietic Anemia Type I (CDA I) View in own window Gene 1Proportion of CDA1 Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 2 Detectable by Method Sequence analysis 3Gene-targeted deletion/duplication analysis 4 CDIN1~1% 53/3Unknown 6 CDAN190% 797/97Unknown 6 Unknown 89%NA 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 5\. Author, personal observation 6\. No data on detection rate of gene-targeted deletion/duplication analysis are available. 7\. In 60% of affected individuals two pathogenic variants were identified by sequence analysis, in 28% only one pathogenic variant was identified, and in 11% no pathogenic variant was identified (Note: Testing to detect splice site variants and large deletions was not performed) [Authors and other labs, combined data, unpublished]. 8\. The existence of at least one additional locus is suggested by the absence of pathogenic variants in CDAN1 or CDIN1 in seven families with CDA I [Babbs et al 2013]. ## Clinical Characteristics ### Clinical Description Prenatal findings. Rarely, congenital dyserythropoietic anemia type I (CDA I) presents as severe in utero anemia that may be associated with hydrops fetalis, requiring intrauterine red blood cell (RBC) transfusion. Prenatal management of pregnancies at risk for complications of CDA I involves monitoring of fetal hemoglobin by Doppler ultrasonography and fetal transfusions to prevent hydrops fetalis if severe fetal anemia is detected. Neonatal presentation. Of 70 Bedouin neonates with CDA I, 45 (64%) were symptomatic [Shalev et al 2004]. Of those with symptoms, 65% had hepatomegaly, 53% had early jaundice, and 27% were small for gestational age. A few had persistent pulmonary hypertension, direct hyperbilirubinemia, and transient thrombocytopenia. The majority of affected infants required at least one blood transfusion during the neonatal period. Childhood and later Anemia. Most affected individuals have lifelong moderate anemia (mean hemoglobin levels 85±6 g/L). Anemia is usually accompanied by jaundice and splenomegaly, which was present in 17 of 21 (80%) individuals [Heimpel et al 2006]. Few are transfusion dependent; Heimpel et al [2006] found that only two of 21 individuals followed for up to 37 years were dependent on transfusion. Even in those with CDA I who are not transfused, secondary hemochromatosis develops with age as a result of increased iron absorption. Free iron precipitating in parenchymal organs and especially in the heart can cause congestive heart failure and arrhythmias. Low hepcidin levels have been documented in individuals with CDA I. * Splenomegaly may be absent in infants or young children, but develop later with age. * Gallstones were detected in four of 21 individuals before age 30 years. * Skeletal findings. Distal limb anomalies including syndactyly, hypoplastic nails, and duplication of fourth metatarsal bone were described in 4%-14% of affected individuals. Lumbar scoliosis resulting from a partly duplicated L3 vertebra was also described. * Ophthalmic concerns. Retinal angioid streaks with deterioration of vision have been reported is a rare complication of inherited hemolytic anemia in 4 adults aged 45-57 years [Roberts et al 2006, Tamary et al 2008, Frimmel & Kniestedt 2016]. Life span. Five (23%) of 21 adult patients described by Heimpel et al [2006] died, mainly as a result of iron overload. According to the authors’ recently published follow-up data, 9% (3/32) of adult patients died at age 46-59 years. Causes of death included sepsis and severe arterial pulmonary hypertension [Shalev et al 2017]. It should be noted that all deceased patients previously underwent splenectomy. ### Genotype-Phenotype Correlations No phenotype-genotype correlations are known. Marked clinical variability is observed even among individuals with the same pathogenic variants. ### Prevalence About 100 simplex cases (i.e., single occurrences in a family) mainly from Europe and about 70 consanguineous Israeli Bedouin families have been described in the literature. CDIN1 (C15orf41) variants have been described in one family originating in Kuwait and in two South Asian (Pakistani) families [Babbs et al 2013]. ## Differential Diagnosis The following congenital anemias are included in the differential diagnosis of CDA I: * Congenital dyserythropoietic anemia type II (CDA II; OMIM 224100) is the most common CDA. It is also known as HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum lysis test) because the RBCs of affected individuals are lysed by acidified sera of 40%-60% of healthy adults due to the presence of natural cold-reacting IgM antibody. CDA II is characterized by mild-to-severe anemia, jaundice, and (in 50%-60% of affected individuals) splenomegaly. Up to 15% of affected individuals are transfusion dependent [Heimpel et al 2003, Wickramasinghe & Wood 2005]. Beyond age 20 years most affected individuals develop iron overload. The diagnosis of CDA II requires evidence of congenital anemia, ineffective erythropoiesis, and typical bone marrow findings with binuclearity in 10%-50% of erythroblasts. CDA II is caused by mutation of SEC23B and inherited in an autosomal recessive manner [Schwarz et al 2009]. * Congenital dyserythropoietic anemia type III (CDA III; OMIM 105600) is the rarest CDA. It was first described in 1951 in an American family by Wolfe and von Hofe, and again in 1962 in a large family from northern Sweden [Wickramasinghe & Wood 2005]. The clinical presentation is similar to that of CDA I and CDA II; however, in the Swedish family, the anemia is not severe and transfusions are not required. The most marked anomaly in the bone marrow is the presence of giant multinucleated erythroblasts with up to 12 nuclei per cell. Additional findings include retinal angioid streaks, macular degeneration, and monoclonal gammopathy with or without multiple myeloma. The gene in which pathogenic variants were causative was mapped close to CDAN1 in a 4.5-cM interval between 15q21 and 15q25. CDA III has been described in fewer than 20 well-documented simplex cases (i.e., a single occurrence in a family). * Congenital dyserythropoietic anemia type IV (CDAN IV; OMIM 613673) is caused by mutation of KLF1 and inherited in an autosomal dominant manner. Other. The diagnosis of CDA should be considered following exclusion of other causes of macrocytosis (mainly B12 deficiency and folic acid deficiency) and dyserythropoiesis, including thalassemia syndromes and hereditary sideroblastic anemia. However, the latter two are associated with microcytic anemia. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with congenital dyserythropoietic anemia type I (CDA I), the following evaluations are recommended: * Hemoglobin concentration and serum bilirubin concentration * Serum ferritin concentration and other modalities used to assess iron overload including liver and myocardial T2* MRI and hepatic R2* MRI * Abdominal ultrasound examination to evaluate for biliary stones * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Intramuscular or subcutaneous injections of interferon (IFN)- α2a or INF- α2b given two or three times a week increase hemoglobin and decrease iron overload in the majority of treated individuals [Lavabre-Bertrand et al 2004]. Peginterferon-α2b has also been given once a week. The mechanism behind this response is unknown. To date, only a limited number of individuals, including infants, have been treated.Treatment should be given by a physician who is experienced in interferon administration. Successful allogenic bone marrow transplantation has been described in three children [Ayas et al 2002] and should be considered only in those transfusion-dependent persons who are resistant to IFN therapy. Splenectomy is of unproved value; failure of this procedure to increase hemoglobin levels and also thromboembolic complications may follow splenectomy. Therefore, splenectomy should be cautiously considered in patients with CDA I, as is recommended for non-transfusion-dependent thalassemia [Taher et al 2013]. ### Prevention of Secondary Complications Treatment of iron overload with regular phlebotomies, if possible, along with iron chelators as necessary, is indicated. Iron overload therapy should follow the guidelines used for non-transfusion dependent thalassemia [Taher et al 2013]. ### Surveillance Recommended monitoring for iron overload: * Measurement of hemoglobin, bilirubin, iron, transferrin and serum ferritin concentration every three months starting at age ten years * Annual myocardial T2* MRI and hepatic R2* MRI, if available, starting at age ten years ### Agents/Circumstances to Avoid Avoid any preparation containing iron. ### Evaluation of Relatives at Risk Evaluation of the younger sibs of a proband for early manifestations of CDA I is recommended so that monitoring of hemoglobin and ferritin levels and treatment can begin as soon as necessary in those who are affected. * Evaluation of at-risk family members should include CBC to identify macrocytic anemia as well as typical findings on blood smear including macrocytosis, elliptocytes, and basophilic stippling. * The diagnosis can be confirmed by molecular genetic testing if the pathogenic variants in the family have been identified. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Anemia places pregnancies of affected women at high risk for delivery-related and outcome complications [Shalev et al 2008]. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Congenital Dyserythropoietic Anemia Type I	c0271933	26,850	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK5313/	2021-01-18T21:33:30	{"mesh": ["D000742"], "synonyms": []}
A rare syndromic constitutional thrombocytopenia characterized by thrombocytopenia with increased bleeding tendency (leading to epistaxis, menorrhagia, and petechiae), in combination with myelofibrosis and splenomegaly. Platelets may be abnormally large or small and partly hypo- or agranular, plasma thrombopoietin is elevated, and the number of megakaryocytes in the bone marrow increased. Additional non-hematologic manifestations have been described in some patients, including mild bone abnormalities and facial dysmorphism with large forehead, hypertelorism, deep-set eyes, and wide nostrils. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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 thrombocytopenia with early-onset myelofibrosis	c4310789	26,851	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=480851	2021-01-23T17:49:00	{"omim": ["616937"]}
Imerslund-Gräsbeck syndrome is a condition caused by low levels of vitamin B12 (also known as cobalamin). The primary feature of this condition is a blood disorder called megaloblastic anemia. In this form of anemia, which is a disorder characterized by the shortage of red blood cells, the red cells that are present are abnormally large. About half of people with Imerslund-Gräsbeck syndrome also have high levels of protein in their urine (proteinuria). Although proteinuria can be an indication of kidney problems, people with Imerslund-Gräsbeck syndrome appear to have normal kidney function. Imerslund-Gräsbeck syndrome typically begins in infancy or early childhood. The blood abnormality leads to many of the signs and symptoms of the condition, including an inability to grow and gain weight at the expected rate (failure to thrive), pale skin (pallor), excessive tiredness (fatigue), and recurring gastrointestinal or respiratory infections. Other features of Imerslund-Gräsbeck syndrome include mild neurological problems, such as weak muscle tone (hypotonia), numbness or tingling in the hands or feet, movement problems, delayed development, or confusion. Rarely, affected individuals have abnormalities of organs or tissues that make up the urinary tract, such as the bladder or the tubes that carry fluid from the kidneys to the bladder (the ureters). ## Frequency Imerslund-Gräsbeck syndrome is a rare condition that was first described in Finland and Norway; in these regions, the condition is estimated to affect 1 in 200,000 people. The condition has also been reported in other countries worldwide; its prevalence in these countries is unknown. ## Causes Mutations in the AMN or CUBN gene can cause Imerslund-Gräsbeck syndrome. The AMN gene provides instructions for making a protein called amnionless, and the CUBN gene provides instructions for making a protein called cubilin. Together, these proteins play a role in the uptake of vitamin B12 from food. Vitamin B12, which cannot be made in the body and can only be obtained from food, is essential for the formation of DNA and proteins, the production of cellular energy, and the breakdown of fats. This vitamin is involved in the formation of red blood cells and maintenance of the brain and spinal cord (central nervous system). The amnionless protein is embedded primarily in the membrane of kidney cells and cells that line the small intestine. Amnionless attaches (binds) to cubilin, anchoring cubilin to the cell membrane. Cubilin can interact with molecules and proteins passing through the intestine or kidneys. During digestion, vitamin B12 is released from food. As the vitamin passes through the small intestine, cubilin binds to it. Amnionless helps transfer the cubilin-vitamin B12 complex into the intestinal cell. From there, the vitamin is released into the blood and transported throughout the body. In the kidney, the amnionless and cubilin proteins are involved in the reabsorption of certain proteins that would otherwise be released in urine. Mutations in the AMN gene prevent cubilin from attaching to the cells in the small intestine and kidneys. Without cubilin function in the small intestine, vitamin B12 is not taken into the body. A shortage of this essential vitamin impairs the proper development of red blood cells, leading to megaloblastic anemia. Low levels of vitamin B12 can also affect the central nervous system, causing neurological problems. In addition, without cubilin function in the kidneys, proteins are not reabsorbed and are instead released in urine, leading to proteinuria. Like AMN gene mutations, some CUBN gene mutations impair cubilin's function in both the small intestine and the kidneys, leading to a shortage of vitamin B12 and proteinuria. Other CUBN gene mutations affect cubilin's function only in the small intestine, impairing uptake of vitamin B12 into the intestinal cells. Individuals with these mutations have a shortage of vitamin B12, which can lead to megaloblastic anemia and neurological problems, but not proteinuria. ### Learn more about the genes associated with Imerslund-Gräsbeck syndrome * AMN * CUBN ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Imerslund-Gräsbeck syndrome	c4551825	26,852	medlineplus	https://medlineplus.gov/genetics/condition/imerslund-grasbeck-syndrome/	2021-01-27T08:25:50	{"gard": ["7006"], "mesh": ["C538556"], "omim": ["261100"], "synonyms": []}
In a family on the Isle of Man, Michaels et al. (1999) described 2 brothers and 2 sisters, ranging in age from 33 to 45 years, who presented with low-grade malignant tumors of the submandibular gland in 3 and of the nasal cavities and maxillary sinuses in 1. The neoplasms were all of the same histologic type, apparently hitherto undescribed, showing well-differentiated neoplastic ducts, surrounded by neoplastic myoepithelial cells, together with sheets of epithelial cells expressing neuroendocrine markers by immunohistochemistry. Cervical neck node metastases had developed in all 4 cases. In the sib with the primary sinonasal neoplasm, widespread bloodstream metastases also became manifest and a single such metastasis was found in his brother. All 4 sibs had severe enamel hypoplasia, and the same dental abnormality was present in 5 of their 11 children. In the 2 male patients, severe sensorineural hearing loss developed in adult life, unilateral in one and bilateral in the other. In the brother with bilateral sensorineural hearing loss, MRI demonstrated a vestibular schwannoma (101000) on the left side. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Sensorineural hearing loss (males only) Teeth \- Enamel hypoplasia (amelogenesis imperfecta) NEOPLASIA \- Low-grade neuroendocrine carcinoma (submandibular glands, salivary glands, maxillary sinus, nasal cavity) \- Unilateral vestibular schwannoma MISCELLANEOUS \- Possible X-linked inheritance ▲ 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	NEUROENDOCRINE CARCINOMA OF SALIVARY GLANDS, SENSORINEURAL HEARING LOSS, AND ENAMEL HYPOPLASIA	c1863649	26,853	omim	https://www.omim.org/entry/603641	2019-09-22T16:12:49	{"mesh": ["C566352"], "omim": ["603641"]}
A rare bleeding disorder marked by the same biological anomalies as those seen in hereditary von Willebrand disease (VWD) but which occurs in association with another underlying pathology, generally in elderly patients without any personal or family history of bleeding anomalies. ## Epidemiology Prevalence is unknown, but Acquired von Willebrand syndrome (AVWS) is a rare disease that is underdiagnosed, with just over 300 cases reported in the literature so far. ## Clinical description The bleeding manifestations are similar to those occurring in hereditary VWD (prolonged bleeding after trauma, epistaxis, ecchymoses and gastrointestinal bleeding associated with angiodysplasia). ## Etiology Three principle pathogenic mechanisms have been described: 1) the presence of autoantibodies (inhibiting or noninhibiting) that form immune complexes with the von Willebrand factor (VWF) leading to rapid clearance of VWF from the circulation (the mechanism most commonly implicated in AVWS associated with monoclonal gammapathies and autoimmune diseases); 2) absorption of VWF onto malignant cell clones (the mechanism implicated in AVWS associated with neoplasia); 3) increased proteolysis of high molecular weight VWF multimers under abnormal hemorheologic conditions caused by cardiovascular malformations (such as aortic valve stenosis). ## Diagnostic methods The most accurate diagnostic tests rely on detection of abnormally low levels of VWF activity (ristocetin cofactor or collagen binding assays) in comparison to VWF antigen levels, and on demonstration of a selective deficiency of high molecular weight VWF multimers. Measurement of VWF propeptide levels may also be useful as they reflect the abnormally rapid clearance of VWF from the circulation. However, none of these tests allow AVWS to be distinguished from hereditary VWD. Detection of anti-VWF antibodies is pathognomonic of the acquired mechanism of VWF deficiency; however, these antibodies are only detected in 14% of suspected cases of AVWS. The finding of a monoclonal protein detected by serum protein electrophoresis is an argument for AVWS. Thus, it is the presentation of an acute bleeding disorder, in association with an underlying pathology (such as lympho- or myeloproliferative disorders, solid tumors, immunological or cardiovascular disorders) which generally leads to the diagnosis of acquired VWF deficiency. ## Management and treatment Management relies on identification and then treatment of the underlying pathology usually involving corticosteroids or immunosuppressors, chemotherapy, plasmapheresis or valve replacement. In cases when these treatments are not rapidly efficient, symptomatic treatment aiming to correct the VWF deficiency is used to prevent or to cure abnormal bleeding. The choice of treatment depends on the suspected physiopathology and clinical status: intravenous immunoglobulins (in case of IgG monoclonal gammopathy of undetermined significance), desmopressin or VWF concentrates (although pharmacokinetic studies may be required before any major surgical intervention as the half-life of endogenous or exogenous VWF may be significantly reduced), recombinant factor VIII concentrates (completely depleted of VWF) or, as a last-resort treatment option, recombinant activated factor VII. ## Prognosis The prognosis depends on the underlying pathology associated with 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	Acquired von Willebrand syndrome	c0272362	26,854	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99147	2021-01-23T18:48:53	{"gard": ["5573"], "umls": ["C0272362"], "icd-10": ["D68.4"], "synonyms": ["Acquired von Willebrand disease"]}
For a phenotypic description and a discussion of genetic heterogeneity of body mass index (BMI), see 606641. Mapping Obesity (see 601665) is a multifactorial trait with evidence of a genetic component. Obesity is very common in all westernized countries, including Finland, where 10% of the adult population has a body mass index of 32 kg/m(2) or more. Ohman et al. (2000) reported results from a 3-stage genomewide scan of obesity in 188 affected subjects (BMI, 32 kg/m(2) or more) from 87 Finnish families. Initially, 374 markers with an average density of 10 cM were genotyped. The strongest evidence for linkage to obesity was detected on chromosome Xq24, with the marker DXS6804 providing a maximum likelihood score (MLS) of 3.14 in a model-free 2-point sib pair analysis. Fine mapping in an extended sample set of 367 affected subjects from 166 families yielded a multipoint MLS of 3.48 over this X-chromosomal region. The Xq24 region contains a plausible candidate gene, that encoding the serotonin 2C receptor (312861), variants of which have been shown to predispose to obesity and type II diabetes (NIDDM; 125853) in mice. In 218 obese Finnish sib pairs, Suviolahti et al. (2003) genotyped microsatellite markers and SNPs for 11 positional and functional candidate genes in the 15-Mb region on Xq24 previously identified by Ohman et al. (2000) and narrowed the critical interval to 4 Mb between DXS8088 and DXS8067. Evidence of linkage emerged mainly from the obese male sib pairs, suggesting a gender-specific effect for the underlying gene. Suviolahti et al. (2003) detected significant associations between susceptibility to obesity and SNPs in exon 14 (22510C-G) and in intron 12 (20649C-T) of the SLC6A14 gene (300444) (p = 0.0002 and 0.07, respectively). The 22510C-G SNP, also designated exon 14 +326, is located in the 3-prime untranslated region and was the SNP that showed the strongest association with obesity in this study. An independent replication sample of 837 cases and 968 controls from Finland and Sweden also showed significant differences in allele frequencies between obese and nonobese individuals (p = 0.003). The association was predominantly in females and extended to SNP haplotypes of the SLC6A14 gene. Suviolahti et al. (2003) noted that gender-specific differences in the prevalence of severe obesity are well established, with females more often affected than males in Finland, and stated that SLC6A14 is an interesting candidate gene for obesity because it encodes an amino acid transporter which potentially regulates tryptophan availability for serotonin synthesis and thus possibly affects appetite control. Durand et al. (2004) genotyped 1,267 obese French adults and 649 lean controls for the SLC6A14 SNPs 22510C-G (rs2011162) and 20649C-T (rs2071877) and confirmed the association with obesity in the French population (OR, 1.23 and p = 0.013, and OR, 1.36 and p = 0.0001, respectively). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 11	c2678155	26,855	omim	https://www.omim.org/entry/300306	2019-09-22T16:20:28	{"omim": ["300306"], "synonyms": ["Alternative titles", "OBESITY, SUSCEPTIBILITY TO"]}
Endocapillary proliferative glomerulonephritis Renal corpuscle showing glomerulus capillaries. SpecialtyUrology Endocapillary proliferative glomerulonephritis is a form of glomerulonephritis that can be associated with nephritis.[1] It may be associated with Parvovirus B19.[2] ## References[edit] 1. ^ Katano K, Hayatsu Y, Matsuda T, et al. (November 2007). "Endocapillary proliferative glomerulonephritis with crescent formation and concurrent tubulointerstitial nephritis complicating retroperitoneal fibrosis with a high serum level of IgG4". Clin. Nephrol. 68 (5): 308–14. doi:10.5414/cnp68308. PMID 18044263. 2. ^ Iwafuchi Y, Morita T, Kamimura A, Kunisada K, Ito K, Miyazaki S (March 2002). "Acute endocapillary proliferative glomerulonephritis associated with human parvovirus B19 infection". Clin. Nephrol. 57 (3): 246–50. PMID 11924757. ## Further reading[edit] * Ito S, Kuriyama H, Iino N, et al. (December 2003). "Patient with diffuse mesangial and endocapillary proliferative glomerulonephritis with hypocomplementemia and elevated anti-streptolysin O treated with prednisolone, angiotensin-converting enzyme inhibitor, and angiotensin II receptor antagonist". Clin. Exp. Nephrol. 7 (4): 290–5. doi:10.1007/s10157-003-0244-0. PMID 14712359. * Kano K, Nishikura K, Kojima M, et al. (June 2003). "A patient with membranoproliferative glomerulonephritis diagnosed by the third biopsy via endocapillary proliferative glomerulonephritis and focal membranoproliferative glomerulonephritis". Clin. Exp. Nephrol. 7 (2): 157–62. doi:10.1007/s10157-003-0231-5. PMID 14586735. ## External links[edit] Classification D * ICD-10: N00-N08 with .4 suffix * v * t * e Disease of the kidney glomerules Primarily nephrotic Non-proliferative * Minimal change * Focal segmental * Membranous Proliferative * Mesangial proliferative * Endocapillary proliferative * Membranoproliferative/mesangiocapillary By condition * Diabetic * Amyloidosis Primarily nephritic, RPG Type I RPG/Type II hypersensitivity * Goodpasture syndrome Type II RPG/Type III hypersensitivity * Post-streptococcal * Lupus * diffuse proliferative * IgA Type III RPG/Pauci-immune * Granulomatosis with polyangiitis * Microscopic polyangiitis * Eosinophilic granulomatosis with polyangiitis General * glomerulonephritis * glomerulonephrosis This article about a disease, disorder, or medical condition 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	Endocapillary proliferative glomerulonephritis	c0403411	26,856	wikipedia	https://en.wikipedia.org/wiki/Endocapillary_proliferative_glomerulonephritis	2021-01-18T18:29:19	{"icd-10": ["N00", "N08"], "wikidata": ["Q5376224"]}
A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome. Clinical Features Ballif et al. (2010) reported 7 unrelated patients with chromosome 17q23.1-q23.2 deletion syndrome ranging in age from 8 months to 16.5 years. All individuals had mild to moderate developmental delay. Other common features included low birth weight (5 of 7), microcephaly or relative microcephaly (5 of 7), and postnatal growth retardation (5 of 7). Heart defects, either patent ductus arteriosus or atrial septal defect, were present in 6. All had hand and foot anomalies, including long, thin fingers and toes, and 4 had variable musculoskeletal anomalies, such as ossification defects, hypoplasia of the patellas, and deep or shallow acetabula. Two had aggressive behavior, and 2 had hearing loss. Five had eye anomalies, such as chalazion, stellate pattern of the irides, retinopathy of prematurity, and esotropia, but the authors concluded that the anomalies were incidental, since they affected different components of the eye. Although all individuals had at least mild dysmorphic facial features, there was no characteristic constellation of features that were specific to the disorder. Some of the musculoskeletal abnormalities were reminiscent of the small patella syndrome (147891). In 2 sibs with congenital clubfoot, both of whom were less than 3 years of age, Alvarado et al. (2010) identified a 2.2-Mb chromosome 17q23.1-q23.2 deletion. Neither sib had the heart defects, facial dysmorphism, or cognitive and behavioral abnormalities previously reported in patients with the same deletion. Alvarado et al. (2010) identified patients in 3 other families segregating clubfoot who had duplication of the same chromosome 17q region (613618). Ballif et al. (2010) identified 7 unrelated patients with a heterozygous deletion of chromosome 17q23.1-q23.2 using microarray-based comparative genomic hybridization. All deletions were confirmed by FISH and BAC analysis and were apparently de novo. One individual had a 2.8-Mb deletion, whereas the remaining 6 had 2.2-Mb deletions. The 2.2-Mb deletions were flanked by homologous segmental duplications in the same orientation, consistent with nonallelic homologous recombination. The proximal breakpoint of the 2.8-Mb deletion fell between 2 segmental duplications. The phenotype of the patient with the larger deletion did not appear to differ from that of those with the 2.2-Mb deletion. Ballif et al. (2010) postulated that the conserved transcription factors TBX2 (600747) and TBX4 (601719) located within this chromosome region may be involved, since they are known to play numerous roles in development. Nimmakayalu et al. (2011) reported a girl with a 17q22-q23 deletion who had congenital microcephaly, thyroglossal duct cyst, sensorineural hearing loss, dysmorphic features, developmental delay, and pulmonary hypertension. Kerstjens-Frederikse et al. (2013) studied 20 consecutive patients with idiopathic or heritable pulmonary arterial hypertension (PAH), 6 of whom had accompanying mental retardation and dysmorphic features. By array CGH, 3 of the 6 were found to have 17q23 deletions. German et al. (2019) reported a neonate with severe respiratory failure, bilateral clenched fists, posteriorly rotated and low-set ears, widely spaced and underdeveloped nipples, broad halluces, hypoplastic toenails, and bilateral clinodactyly of the second toes. By rapid exome sequencing, he was found to have a 2-Mb deletion (chr17:59,290,909-61,353,248, GRCh37) involving 14 genes, including TBX4. A lung biopsy on day 8 of life showed marked arrest of lung maturation consistent with acinar dysplasia. Suhrie et al. (2019) reported 2 neonates with pulmonary hypoplasia, one of whom (infant B) had the 2.2-Mb deletion on 17q with a missense variant (R288K; rs11760393) in the ABCA3 gene (601615) on the other allele. Of 26 patients with lethal lung disorders, Karolak et al. (2019) found that 8 had deletions on 17q that involved the TBX4 gene. Inheritance was de novo in 2 cases, inherited in 1 case, and unknown in the remaining 5 cases. Karolak et al. (2019) also reported 7 controls with the same deletion and identified an additional 6 patients who did not have pulmonary hypoplasia but had other issues, including developmental delay, hearing impairment, and variable dysmorphic features. One of the latter patients had a pneumothorax at birth and another developed severe childhood-onset pulmonary arterial hypertension and interstitial lung disease, in the setting of autism spectrum disorder and microcephaly. Karolak et al. (2019) argued that those affected with lung hypoplasia harbored at least one noncoding single nucleotide variant in the predicted lung-specific enhancer region, which was absent in 13 control individuals with overlapping deletions but without any structural lung disease. INHERITANCE \- Isolated cases GROWTH Weight \- Low birth weight Other \- Postnatal growth retardation HEAD & NECK Head \- Microcephaly Face \- Facial dysmorphism, mild, variable Ears \- Hearing loss (2 patients) CARDIOVASCULAR Heart \- Atrial septal defect \- Bicuspid aortic valve Vascular \- Patent ductus arteriosus \- Pulmonary hypertension SKELETAL \- Ossification defects (2 patients) Hands \- Long fingers \- Thin fingers Feet \- Clubfoot (in 2 sibs) \- Long toes \- Thin toes NEUROLOGIC Central Nervous System \- Developmental delay, mild to moderate Behavioral Psychiatric Manifestations \- Aggressive behavior (2 patients) MISCELLANEOUS \- 7 unrelated patients have been reported MOLECULAR BASIS \- Contiguous gene syndrome caused by deletion (2.2 Mb) of chromosome 17q23.1-q23 ▲ 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	CHROMOSOME 17q23.1-q23.2 DELETION SYNDROME	c3150607	26,857	omim	https://www.omim.org/entry/613355	2019-09-22T15:58:53	{"doid": ["0060405"], "omim": ["613355"], "orphanet": ["261279"], "synonyms": ["Del(17)(q23.1q23.2)", "Monosomy 17q23.1q23.2"]}
An aldosterone-producing adenoma is a noncancerous (benign) tumor that develops in an adrenal gland, which is a small hormone-producing gland located on top of each kidney. In most cases, individuals develop a single tumor in one of the adrenal glands. The adrenal tumor produces too much of the hormone aldosterone, which is a condition known as primary hyperaldosteronism. Aldosterone helps regulate the body's fluid levels and blood pressure by controlling the amount of salt retained by the kidneys. Excess aldosterone causes the kidneys to retain more salt than normal, which increases the body's fluid levels and blood pressure. People with an aldosterone-producing adenoma may develop severe high blood pressure (hypertension), and they have an increased risk of heart attack, stroke, or an irregular heart beat (atrial fibrillation). ## Frequency Aldosterone-producing adenomas cause up to 60 percent of cases of primary hyperaldosteronism. It is estimated that primary hyperaldosteronism accounts for 5 to 15 percent of cases of hypertension, which affects approximately 3 in 10 adults worldwide. However, the prevalence of aldosterone-producing adenomas is unknown. ## Causes Aldosterone-producing adenomas are caused by mutations in one of several genes. The most commonly mutated gene is KCNJ5, accounting for an estimated 40 percent of the tumors, followed by the CACNA1D and ATP1A1 genes, which are mutated in about 9 percent and 6 percent of aldosterone-producing adenomas, respectively. Changes in other genes cause a small percentage of cases. Only about 60 percent of affected individuals have a mutation in one of the identified genes; additional unidentified genes are also thought to be involved in the condition. The genes known to be involved in aldosterone-producing adenomas have roles in balancing the amounts of positively charged atoms (ions) of sodium (Na+), potassium (K+), and calcium (Ca2+) in cells. Each of the proteins produced from these genes transports certain ions across cell membranes. The flow of these ions creates an electrical charge across the cell membrane, which affects certain biochemical processes. In adrenal gland cells, this flow of ions helps control the production of aldosterone. Mutations in the KCNJ5, CACNA1D, or ATP1A1 gene lead to abnormal electrical charges across cell membranes. These abnormalities overactivate a biochemical process that increases adrenal cell growth and division (proliferation), which promotes adenoma formation. Overactivation of this biochemical process also increases aldosterone production, resulting in hyperaldosteronism and leading to hypertension. ### Learn more about the genes associated with Aldosterone-producing adenoma * ATP1A1 * CACNA1D * CTNNB1 * KCNJ5 Additional Information from NCBI Gene: * ATP2B3 ## Inheritance Pattern Aldosterone-producing adenomas are generally not inherited but arise from a mutation in the body's cells that occurs after conception. In particular, the alteration occurs in adrenal gland cells that give rise to the tumor. Such mutations are called somatic mutations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Aldosterone-producing adenoma	c0009777	26,858	medlineplus	https://medlineplus.gov/genetics/condition/aldosterone-producing-adenoma/	2021-01-27T08:24:37	{"mesh": ["D018246"], "synonyms": []}
## Description Confluent and reticulated papillomatosis is a dermatologic disorder characterized by onset in the teenage or young adult years of hyperkeratotic 1- to 2-mm papules that increase in size to 4 to 5 mm and coalesce to form a reticular pattern peripherally and a confluent pattern centrally. Early papules can be erythematous and later turn brown. Affected individuals are usually otherwise asymptomatic. The condition is distinct from acanthosis nigricans and tinea versicolor (infection with the yeast Pityrosporum), but can appear similar. Microscopic examination of skin biopsy shows epidermal undulation with hyperkeratosis, squat papillomatosis, and occasional acanthotic downward projections from the bases of the dells between papillomatous areas. Antibacterial agents such as minocycline and azithromycin are effective, perhaps due to their antiinflammatory and immunomodulatory properties (summary by Scheinfeld, 2006). Clinical Features Baden (1965) described a confluent, reticular type of papillomatosis in 2 sisters and the daughter of one. Henning and de Wit (1981) described the disorder in a 44-year-old woman and her 15-year-old daughter and 18-year-old son. The lesions became more pigmented during the premenstrual phase of the women's cycle. Inaloz et al. (2002) reported 2 brothers, aged 27 and 21 years, with a 5- and 2-year history, respectively, of an asymptomatic scaly rash. It first appeared on the chest and progressed to the flanks and axilla of the older brother and predominantly involved the upper back of the younger brother. Affected skin had a brownish rash forming confluent plaques in the center and a reticulated network at the periphery, consistent with CARP. Immunohistochemistry of skin biopsies showed increased suprabasal keratin-16 (KRT16; 148067) expression in the epidermis with intense focal staining in the stratum granulosum, and an increased number of cycling epidermal cells in the basal layer and stratum malpighii. Electron microscopy showed an increased number of transitional cells between the stratum granulosum and stratum corneum. There was no evidence of mycologic infection. Inaloz et al. (2002) postulated a hyperproliferative keratinocyte disorder. There was no family history of a similar disorder. Eisman and Rustin (2003) reported a sister and brother with CARP. The girl presented at age 12 years with a hyperpigmented ichthyotic rash over the upper back, upper arms, and chest. Treatment with UVB phototherapy was effective, but the condition returned with extension after treatment cessation. Treatment with minocycline was effective. Her brother had a sib-matched allogenetic bone marrow transplant from their older brother for leukemia at age 6 years. He presented at age 14 years with hyperpigmented, scaly skin lesions of the back and upper chest; treatment with minocycline was effective. Neither sib had a fungal skin infection. Eisman and Rustin (2003) supported a role for hyperkeratinization in this condition, and suggested that the benefit from minocycline may be attributed to the inhibition of rapid protein synthesis of keratinocytes. Thoms et al. (2006) reported 2 German brothers, ages 25 and 16 years, with a several-year history of reticular hyperpigmentation that was slowly increasing. The lesions were mildly pruritic. Examination showed punctiform and verrucose brown lesions mainly on the trunk, upper arms, and buttocks. The father reportedly had similar skin lesions. Laboratory studies confirmed that both were infected with the yeast Pityrosporum orbiculare. However, biopsy showed hyperkeratosis with focal parakeratosis, as well as subtle acanthosis between the papillae. The lesions did not respond to treatment with ketoconazole, but did respond to azithromycin. INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Papillomatosis, reticular on the periphery, 1 to 2-mm growing to 4-5-mm and coalescing \- Papillomatosis, confluent centrally, erythematous turning brown later \- Scaly rash Skin Histology \- Epidermal undulation \- Hyperkeratosis \- Squat papillomatosis \- Acanthotic downward projections from areas between the papillae Electron Microscopy \- Increased number of transitional cells between the stratum granulosum and stratum corneum MISCELLANEOUS \- Onset in teenage or young adult years \- Mode of inheritance is unclear \- Favorable response to treatment with minocycline or azithromycin ▲ 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	PAPILLOMATOSIS, CONFLUENT AND RETICULATED	c0263385	26,859	omim	https://www.omim.org/entry/167900	2019-09-22T16:36:45	{"mesh": ["C566832"], "omim": ["167900"], "icd-10": ["L83"], "synonyms": ["Alternative titles", "PAPILLOMATOSIS, RETICULATED AND CONFLUENT, OF GOUGEROT AND CARTEAUD", "PAPILLOMATOSIS, FAMILIAL CUTANEOUS"]}
Pharyngeal-cervical-brachial variant of Guillain-Barré syndrome is a rare, acquired peripheral neuropathy disease characterized by rapidly progressive oropharyngeal (facial palsy, dysarthria) and cervicobrachial weakness, associated with upper limb weakness and hypo/areflexia, in the absence of ophthalmoplegia, ataxia, altered consciousness, and prominent lower limb weakness. The presence of monospecific IgG anti-GT1a antibodies is 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	Pharyngeal-cervical-brachial variant of Guillain-Barré syndrome	None	26,860	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231426	2021-01-23T17:22:36	{"icd-10": ["G61.0"], "synonyms": ["PCB variant of GBS", "PCB variant of Guillain-Barré syndrome", "Pharyngeal-cervical-brachial weakness", "Pharyngo-cervico-brachial variant of GBS", "Pharyngo-cervico-brachial variant of Guillain-Barré syndrome"]}
A number sign (#) is used with this entry because immunodeficiency-18 (IMD18) is caused by homozygous or compound heterozygous mutation in the CD3E gene (186830) on chromosome 11q23. Description Immunodeficiency-18 is an autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18 (summary by de Saint Basile et al., 2004). Clinical Features Le Deist et al. (1991) reported a 4-year-old boy who presented at age 2 years with a mild immunodeficiency manifesting as recurrent bacterial pneumonia and otitis media. Lymphocyte counts were normal, and serum Ig levels were increased during the infection, but later returned to normal. There was some evidence of defective antibody production, with lack of antibodies to poliovirus or isohemagglutinin, but antibody levels to tetanus and diphtheria toxoids were normal. Patient lymphocytes showed significantly decreased CD3 expression on T cells (about 10% of normal) and decreased numbers of CD4 (186940)-positive T cells. B cells were normal and NK cells were increased. Functional studies showed defects in T-cell proliferation in response to CD2 (186990) stimulation, and cytotoxic T-cell activity was absent. De Saint Basile et al. (2004) reported 3 sibs, born of consanguineous parents, with recurrent multisystem infections due to SCID apparent in the first months of life. One child died of pneumonitis at age 5 months, and a second died at age 3 months. The third infant received a bone marrow transplant soon after birth, but died 25 days later. Laboratory studies of 2 of the patients showed T-cell lymphopenia, with a complete absence of CD3-positive T cells, but normal amounts of B cells and NK cells. The findings suggested a complete block of T-cell development in these patients. De Saint Basile et al. (2004) noted that the phenotype in their family was more severe than that of the patient reported by Le Deist et al. (1991), who had residual CD3-epsilon expression and unimpaired T-cell development. Inheritance Soudais et al. (1993) demonstrated that the mild form of IMD18 originally reported by Le Deist et al. (1991) was inherited in an autosomal recessive manner. The transmission pattern of the SCID form of IMD18 in the family reported by De Saint Basile et al. (2004) was consistent with autosomal recessive inheritance. Molecular Genetics In a 5-year-old boy with a mild primary immunodeficiency originally reported by Le Deist et al. (1991), Soudais et al. (1993) identified compound heterozygous mutations in the CD3E gene (186830.0001-186830.0002). Each unaffected parent was heterozygous for 1 of the mutations. Patient lymphocytes had decreased membrane expression of TCR/CD3. Thoenes et al. (1992) had shown that the CD3E mRNA was abnormally small and present at a reduced level in the patient's T cells. Soudais et al. (1993) showed that a small amount of normal-sized CD3E transcript was also expressed in the patient. In a child, born of consanguineous parents, with T-, B+, NK+ SCID, De Saint Basile et al. (2004) identified a homozygous deletion mutation in the CD3E gene (186830.0003). Two sibs were similarly affected, and all 3 patients died in infancy. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Otitis media, recurrent RESPIRATORY \- Respiratory infections, recurrent ABDOMEN Gastrointestinal \- Gastroenteritis, recurrent IMMUNOLOGY \- Primary immunodeficiency \- Decreased CD3 expression on T cells \- Decreased cytotoxic T cell activity \- Variably impaired T-cell proliferative responses \- Partially defective antibody production \- Lymphopenia (1 family) \- Absence of CD3+ T cells (1 family) \- Normal B cells \- Normal NK cells MISCELLANEOUS \- Two unrelated families have been reported (last curated January 2014) \- Onset in infancy \- Variable severity MOLECULAR BASIS \- Caused by mutation in the CD3 antigen, epsilon subunit gene (CD3E, 186830.0001 ) ▲ 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 18	c3810127	26,861	omim	https://www.omim.org/entry/615615	2019-09-22T15:51:32	{"omim": ["615615"], "orphanet": ["169160"], "synonyms": ["T-B+ SCID due to CD3delta/CD3epsilon/CD3zeta", "Alternative titles", "CD3-EPSILON DEFICIENCY"]}
A number sign (#) is used with this entry because susceptibility to the development of cystic renal dysplasia (CYSRD) can be conferred by heterozygous mutation in the BICC1 gene (614295) on chromosome 10q21. Clinical Features Sase et al. (1996) described a family in which 3 sibs, a male and 2 females, were affected with nonsyndromic diffuse cystic dysplasia of the kidneys. The parents were nonconsanguineous and had no renal abnormality. A possibly similar condition was reported by Cole et al. (1976) in 3 sibs (2 females and 1 male) who were born to nonconsanguineous parents with apparently normal kidneys. The first affected sib died soon after birth; the other 2 were found to have the disorder by ultrasonography and the pregnancies were terminated. Autopsies were performed in all 3 cases. There were no other external or internal malformations except for hypoplastic lungs related to the renal abnormality. Sase et al. (1996) suggested that the disorder is an autosomal recessive. Diffuse cystic renal dysplasia is often seen in malformation syndromes, of which the investigators listed a number. Kraus et al. (2012) reported 2 unrelated Caucasian boys with nonsyndromic cystic dysplasia. In the first boy, prenatal ultrasound at 22 weeks' gestation showed unilateral cystic dysplasia of the right kidney. After birth at age 38 weeks, sonography of the right kidney showed renal dysplasia with cysts, increased renal size, and hyperechogenicity. The left kidney was completely normal, and there were no other visceral abnormalities. Functional imaging showed hypofunction of the right kidney (34% of normal), but arterial hypertension was the only clinical manifestation. Last follow-up at 18 months of age showed normal psychomotor development, normal growth, and normal renal serum and urinary parameters. Both parents were asymptomatic, and there was no family history of a similar disorder. Prenatal ultrasound in the second boy showed a dysplastic left kidney and a hyperechogenic right kidney with normal size and shape. The boy was born at 32 weeks' gestation with normal renal function. Serial imaging showed that the right kidney became progressively normal, whereas the left kidney showed persistent abnormalities. He had a left low-grade vesicoureteral reflux and a nonfunctional left kidney, but no additional features. On last follow-up at age 5 years, the boy had normal growth and development. Family history was negative for renal failure and diabetes. Noting clinical overlap with the renal cyst and early-onset diabetes syndrome (RCAD; 137920), Kraus et al. (2012) could not exclude that these patients may later develop additional manifestations. Molecular Genetics In 2 (2%) of 92 children with isolated renal abnormalities who were negative for mutations in the HNF1B gene (189907), Kraus et al. (2012) identified 2 different heterozygous loss-of-function or hypomorphic mutations in the BICC1 gene (614295.0001 and 614295.0002, respectively). The authors examined the BICC1 gene because of a similar phenotype in murine knockout models. In each case, the mutation was inherited from an unaffected parent, suggesting that the disorder shows incomplete penetrance or that additional genetic or environmental factors are necessary for its development. No BICC1 mutation was found in 45 adults with kidney disease and early-onset diabetes. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Vascular \- Arterial hypertension (in 1 patient) GENITOURINARY Kidneys \- Renal dysplasia \- Renal cysts \- Hyperechogenic kidneys \- Decreased renal function Bladder \- Vesicoureteral reflux (in 1 patient) MISCELLANEOUS \- Two unrelated patients with confirmed mutations have been reported (as of January 2012) \- Onset in utero MOLECULAR BASIS \- Susceptibility conferred by mutation in the homolog of the Drosophila bicaudal C gene (BICC1, 614295.0001 ) ▲ 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	RENAL DYSPLASIA, CYSTIC, SUSCEPTIBILITY TO	c3275898	26,862	omim	https://www.omim.org/entry/601331	2019-09-22T16:15:11	{"omim": ["601331"]}
Hemimelia is a limb malformation characterized by the absence or gross shortening of the lower portion of one or more of the limbs. The condition is designated according to which bone of the distal arm or leg is absent or defective and includes fibular, radial, tibial, or ulnar hemimelia (see these terms). Hemimelia ranges in severity. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Hemimelia	c0018987	26,863	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2130	2021-01-23T18:18:57	{"mesh": ["D004480"], "umls": ["C0018987"], "icd-10": ["Q71.8", "Q72.8", "Q73.8"], "synonyms": ["Longitudinal meromelia"]}
Premature junctional contractions (PJCs), also called atrioventricular junctional premature complexes or junctional extrasystole, are premature cardiac electrical impulses originating from the atrioventricular node of the heart or "junction". This area is not the normal but only a secondary source of cardiac electrical impulse formation. These premature beats can be found occasionally in healthy people and more commonly in some pathologic conditions, typically in the case of drug cardiotoxicity, electrolyte imbalance, mitral valve surgery, and cold water immersion.[1] If more than two such beats are seen, then the condition is termed junctional rhythm. On the surface ECG, premature junctional contractions will appear as a normally shaped ventricular complex or QRS complex, not preceded by any atrial complex or P wave or preceded by an abnormal P wave with a shorter PR interval. Rarely, the abnormal P wave can follow the QRS.[2] ## See also[edit] * Premature atrial contraction * Premature ventricular contraction ## References[edit] 1. ^ Tipton MJ, Kelleher PC, Golden FS Institute of Naval Medicine, Gosport, Hants, UK. Undersea & Hyperbaric Medicine [1994, 21(3):305-313] 2. ^ "An introduction to clinical electrocardiography - Supraventricular Arrhythmias". ECG Learning Center. University of Utah. * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Premature junctional contraction	c0232209	26,864	wikipedia	https://en.wikipedia.org/wiki/Premature_junctional_contraction	2021-01-18T18:30:59	{"umls": ["C0232209"], "icd-10": ["I49.2"], "wikidata": ["Q22907909"]}
Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome, also known as Beare-Stevenson syndrome (BSS), is a severe form of syndromic craniosynostosis, characterized by a variable degree of craniosynostosis, with cloverleaf skull reported in over 50% of cases, cutis gyrata, corduroy-like linear striations in the skin, acanthosis nigricans, skin tags, and choanal stenosis or atresia). Additional features include facial features similar to Crouzon disease, ear defects (conductive hearing loss, posteriorly angulated ears, stenotic auditory canals, preauricular furrows, and narrow ear canals), hirsutism, a prominent umbilical stump, and genitorurinary anomalies (anteriorly placed anus, hypoplasic labia, hypospadias). BSS is associated with a poor outcome as patients present an elevated risk for sudden death in their first year of life. Significant developmental delay and intellectual disability are observed in most patients who survive infancy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome	c1852406	26,865	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1555	2021-01-23T19:05:33	{"gard": ["1635", "332"], "mesh": ["C565129"], "omim": ["123790"], "umls": ["C1852406"], "icd-10": ["Q87.8"], "synonyms": ["Beare-Stevenson cutis gyrata syndrome"]}
A number sign (#) is used with this entry because of evidence that early-onset severe spinocerebellar ataxia-42 with neurodevelopmental deficits (SCA42ND) is caused by heterozygous mutation in the CACNA1G gene (604065) on chromosome 17q22. Heterozygous mutation in the CACNA1G gene can also cause SCA42 (616795), a later-onset, less severe disorder with overlapping features. Clinical Features Chemin et al. (2018) reported 4 unrelated girls, ranging in age from 3 to 13 years, with a severe neurodevelopmental disorder associated with cerebellar atrophy on brain imaging. The patients presented soon after birth or in early infancy with severe hypotonia, and thereafter showed delayed psychomotor development with severe to profound intellectual disability and absent speech, although some had a few words. They had poor or absent eye contact and poor head control. There was severe axial hypotonia and variable spasticity, hypertonia, or dystonia of the limbs. None were able to walk independently. All had cerebellar ataxia and 2 had dysmetria. Three patients had oculomotor apraxia with strabismus and the fourth had hyperopia. Variable dysmorphic features included small or upslanted palpebral fissures, hypertelorism, deep-set eyes, enophthalmia, short nose, small nares, prognathism, anteverted ears, sparse hair, thick hair, low posterior hairline, and distal abnormalities of the fingers and toes. Two patients had mild microcephaly (-2 and -2.5 SD), and 2 had early-onset seizures consistent with epileptic encephalopathy. Molecular Genetics In 4 unrelated girls with SCA42ND, Chemin et al. (2018) identified de novo heterozygous missense mutations in the CACNA1G gene (A961T, 605065.0002 and M1531V, 605065.0003). Three patients carried the A961T variant, suggesting a mutation hotspot. The mutation in the first patient was found by whole-exome sequencing and confirmed by Sanger sequencing. The other patients were identified through collaborative data sharing of patients with a similar phenotype who underwent exome sequencing. Electrophysiologic studies in HEK293 cells showed that the mutant currents activated at more negative potentials and had markedly slowed inactivation kinetics compared to wildtype. This resulted in increased calcium influx, consistent with a gain of function. Computational modeling of the mutations confirmed that the mutations would promote increased firing activity in deep cerebellar neurons. These currents were blocked in vitro in the presence of TTA-P2, a selective T-type calcium channel blocker. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Microcephaly, mild (-2 to -2.5 SD) (in some patients) Face \- Dysmorphic features, variable \- Prognathism Ears \- Anteverted ears Eyes \- Oculomotor apraxia \- Strabismus \- Hyperopia \- Small palpebral fissures \- Upslanted palpebral fissures \- Hypertelorism \- Deep-set eyes \- Enophthalmia \- Poor or absent eye contact Nose \- Short nose \- Small nares SKELETAL Hands \- Distal abnormalities \- Clinodactyly Feet \- Distal abnormalities \- Syndactyly SKIN, NAILS, & HAIR Hair \- Hirsutism \- Sparse hair MUSCLE, SOFT TISSUES \- Axial hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development, severe \- Intellectual disability, severe to profound \- Hypotonia, axial \- Poor head control \- Inability to walk \- Ataxia \- Dysmetria \- Poor or absent language \- Spasticity \- Dystonia \- Hyperreflexia \- Seizures, early-onset (in some patients) \- Cerebellar hypoplasia MISCELLANEOUS \- Onset soon after birth or in early infancy \- De novo mutation \- Four unrelated girls have been reported (last curated August 2018) MOLECULAR BASIS \- Caused by mutation in the calcium channel, voltage-dependent, T type, alpha-1G subunit gene (CACNA1G, 604065.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SPINOCEREBELLAR ATAXIA 42, EARLY-ONSET, SEVERE, WITH NEURODEVELOPMENTAL DEFICITS	None	26,866	omim	https://www.omim.org/entry/618087	2019-09-22T15:44:07	{"omim": ["618087"]}
Central core disease (CCD) is an inherited condition that involves muscle weakness, skeletal abnormalities, and an increased chance of having a severe reaction to some anesthesia medications. Muscle weakness ranges from mild to severe and typically affects muscles in the trunk and upper legs, though muscles in the neck and face can also be affected. Skeletal abnormalities may include curving of the spine (scoliosis), dislocation of the hip, or restricted motion in certain joints (contractures). Some individuals with CCD have an increased chance of having a severe reaction to anesthesia, called malignant hyperthermia, which may cause muscle rigidity or break-down (rhabdomyolysis), a high fever, or a rapid heart beat. RYR1 is the only gene associated with CCD and clinical testing is available to look for disease-causing alterations in this gene known as pathogenic variants (mutations). Treatment depends on the severity of symptoms and is mainly supportive. Muscle weakness and skeletal abnormalities may benefit from physical therapy or surgery. Avoidance of inhaled anesthetics and succinylcholine can help prevent complications from malignant hyperthermia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	26,867	gard	https://rarediseases.info.nih.gov/diseases/6014/central-core-disease	2021-01-18T18:01:34	{"mesh": ["D020512"], "omim": ["117000"], "orphanet": ["597"], "synonyms": ["CCD", "CCO", "Central core disease of muscle", "Muscle core disease", "Muscular central core disease", "Myopathy, central fibrillar", "Myopathy, central core", "Shy-Magee syndrome"]}
Methanol toxicity Other namesMethanol poisoning Molecular structure of methanol SpecialtyEmergency medicine SymptomsDecreased level of consciousness, poor coordination, vomiting, abdominal pain, specific smell on the breath[1][2] ComplicationsBlindness, kidney failure[1] CausesMethanol (such as found in windshield washer fluid)[1][2] Diagnostic methodBlood acidosis, increased osmol gap, methanol blood level[1][2] Differential diagnosisInfections, exposure to other toxic alcohols, serotonin syndrome, diabetic ketoacidosis[2] TreatmentAntidote, hemodialysis[2] MedicationFomepizole, ethanol[2] PrognosisGood with early treatment[1] Frequency1,700 cases per year (US)[3] Methanol toxicity is poisoning from methanol, characteristically via ingestion.[1] Symptoms may include a decreased level of consciousness, poor or no coordination, vomiting, abdominal pain, and a specific smell on the breath.[1][2] Decreased vision may start as early as twelve hours after exposure.[2] Long-term outcomes may include blindness and kidney failure.[1] Toxicity and death may occur even after drinking a small amount.[1] Methanol poisoning most commonly occurs following the drinking of windshield washer fluid.[2] This may be accidental or as part of an attempted suicide.[1] Toxicity may also rarely occur through extensive skin exposure or breathing in fumes.[1] When methanol is broken down by the body it results in formaldehyde, formic acid, and formate which cause much of the toxicity.[2] The diagnosis may be suspected when there is acidosis or an increased osmol gap and confirmed by directly measuring blood levels.[1][2] Other conditions that can produce similar symptoms include infections, exposure to other toxic alcohols, serotonin syndrome, and diabetic ketoacidosis.[2] Early treatment increases the chance of a good outcome.[2] Treatment consists of stabilizing the person, followed by the use of an antidote.[2] The preferred antidote is fomepizole, with ethanol used if this is not available.[2] Hemodialysis may also be used in those where there is organ damage or a high degree of acidosis.[2] Other treatments may include sodium bicarbonate, folate, and thiamine.[2] Outbreaks of methanol ingestion have occurred due to contamination of drinking alcohol.[2] This is more common in the developing world.[2] In 2013 more than 1700 cases occurred in the United States.[3] Those affected are usually adult and male.[3] Toxicity to methanol has been described as early as 1856.[4] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Mechanism * 4 Treatment * 5 History * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] The initial symptoms of methanol intoxication include central nervous system depression, headache, dizziness, nausea, lack of coordination, and confusion. Sufficiently large doses cause unconsciousness and death. The initial symptoms of methanol exposure are usually less severe than the symptoms from the ingestion of a similar quantity of ethanol.[5] Once the initial symptoms have passed, a second set of symptoms arises, from 10 to as many as 30 hours after the initial exposure, that may include blurring or complete loss of vision, acidosis, and putaminal hemorrhages, an uncommon but serious complication.[6][7] These symptoms result from the accumulation of toxic levels of formate in the blood, and may progress to death by respiratory failure. Physical examination may show tachypnea, and eye examination may show dilated pupils with hyperemia of the optic disc and retinal edema. ## Cause[edit] Methanol has a high toxicity in humans. As little as 10 mL of pure methanol when drunk is metabolized into formic acid, which can cause permanent blindness by destruction of the optic nerve. 15 mL is potentially fatal,[1] although the median lethal dose is typically 100 mL (3.4 fl oz) (i.e. 1–2 mL/kg body weight of pure methanol[8]). Reference dose for methanol is 0.5 mg/kg/day.[9] Ethanol is sometimes denatured (adulterated), and made poisonous, by the addition of methanol. The result is known as methylated spirit, "meths" (British use) or "metho" (Australian slang). This is not to be confused with "meth", a common abbreviation for methamphetamine and for methadone in Britain and the United States. ## Mechanism[edit] Methanol is toxic by two mechanisms. First, methanol (whether it enters the body by ingestion, inhalation, or absorption through the skin) can be fatal due to its CNS depressant properties in the same manner as ethanol poisoning. Second, in a process of toxication, it is metabolized to formic acid (which is present as the formate ion) via formaldehyde in a process initiated by the enzyme alcohol dehydrogenase in the liver.[6] Methanol is converted to formaldehyde via alcohol dehydrogenase and formaldehyde is converted to formic acid (formate) via aldehyde dehydrogenase. The conversion to formate via ALDH proceeds completely, with no detectable formaldehyde remaining.[10] Formate is toxic because it inhibits mitochondrial cytochrome c oxidase, causing hypoxia at the cellular level, and metabolic acidosis, among a variety of other metabolic disturbances.[11] ## Treatment[edit] Methanol poisoning can be treated with fomepizole, or if unavailable, ethanol.[6][12][13] Both drugs act to reduce the action of alcohol dehydrogenase on methanol by means of competitive inhibition. Ethanol, the active ingredient in alcoholic beverages, acts as a competitive inhibitor by more effectively binding and saturating the alcohol dehydrogenase enzyme in the liver, thus blocking the binding of methanol. Methanol is excreted by the kidneys without being converted into the very toxic metabolites formaldehyde and formic acid. Alcohol dehydrogenase instead enzymatically converts ethanol to acetaldehyde, a much less toxic organic molecule.[6][14] Additional treatment may include sodium bicarbonate for metabolic acidosis, and hemodialysis or hemodiafiltration to remove methanol and formate from the blood.[6] Folinic acid or folic acid is also administered to enhance the metabolism of formate.[6] ## History[edit] See also: List of methanol poisoning incidents There are cases of methanol resistance, such as that of Mike Malloy, whom someone tried and failed to poison by methanol in the early 1930s.[15] In December 2016, 78 people died in Irkutsk, Russia from methanol poisoning after ingesting a counterfeit body lotion that was primarily methanol rather than ethanol as labeled. The body lotion, prior to the event, had been used as a cheap substitute for vodka by the impoverished people in the region despite warnings on the lotion's bottles that it was not safe for drinking and long-standing problems with alcohol poisoning across the country.[16] During the COVID-19 pandemic, Iranian media reported that nearly 300 people had died and over a thousand became ill due to methanol poisoning in the belief that drinking the alcohol could help with the disease.[17] In the United States, the Food and Drug Administration discovered that a number of brands of hand sanitizer manufactured in Mexico during the pandemic contained methanol, and urged the public to avoid using the affected products.[18] ## See also[edit] * Ethylene glycol poisoning ## References[edit] 1. ^ a b c d e f g h i j k l m Kruse, JA (October 2012). "Methanol and ethylene glycol intoxication". Critical Care Clinics. 28 (4): 661–711. doi:10.1016/j.ccc.2012.07.002. PMID 22998995. 2. ^ a b c d e f g h i j k l m n o p q r s Beauchamp, GA; Valento, M (September 2016). "Toxic Alcohol Ingestion: Prompt Recognition And Management In The Emergency Department". Emergency Medicine Practice. 18 (9): 1–20. PMID 27538060. 3. ^ a b c Ferri, Fred F. (2016). Ferri's Clinical Advisor 2017: 5 Books in 1. Elsevier Health Sciences. p. 794. ISBN 9780323448383. Archived from the original on 2017-09-08. 4. ^ Clary, John J. (2013). The Toxicology of Methanol. John Wiley & Sons. p. 3.4.1. ISBN 9781118353103. Archived from the original on 2017-09-08. 5. ^ National Institute for Occupational Safety and Health (22 August 2008). "The Emergency Response Safety and Health Database: Methanol". Archived from the original on 23 April 2009. Retrieved 17 March 2009. 6. ^ a b c d e f Schep LJ, Slaughter RJ, Vale JA, Beasley DM (2009). "A seaman with blindness and confusion". BMJ. 339: b3929. doi:10.1136/bmj.b3929. PMID 19793790. S2CID 6367081. Archived from the original on 2009-10-08. 7. ^ Permpalung N, Cheungpasitporn W, Chongnarungsin D, Hodgdon TM (Oct 2013). "Bilateral putaminal hemorrhages: serious complication of methanol intoxication". N Am J Med Sci. 5 (10): 623–4. doi:10.4103/1947-2714.120804. PMC 3842708. PMID 24350079. 8. ^ "Methanol Poisoning Overview". Antizol. Archived from the original on 5 October 2011. 9. ^ Methanol (CASRN 67-56-1) Archived 2012-12-05 at the Wayback Machine 10. ^ McMartin KE, Martin-Amat G, Noker PE, Tephly TR (1979). "Lack of a role for formaldehyde in methanol poisoning in the monkey". Biochem. Pharmacol. 28 (5): 645–9. doi:10.1016/0006-2952(79)90149-7. PMID 109089. 11. ^ Liesivuori J, Savolainen H (September 1991). "Methanol and formic acid toxicity: biochemical mechanisms". Pharmacol. Toxicol. 69 (3): 157–63. doi:10.1111/j.1600-0773.1991.tb01290.x. PMID 1665561. 12. ^ Casavant MJ (Jan 2001). "Fomepizole in the treatment of poisoning". Pediatrics. 107 (1): 170–171. doi:10.1542/peds.107.1.170. PMID 11134450. Archived from the original on 2005-06-29. 13. ^ Brent J (May 2009). "Fomepizole for ethylene glycol and methanol poisoning". N Engl J Med. 360 (21): 2216–23. doi:10.1056/NEJMct0806112. PMID 19458366. 14. ^ Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. 5th ed. Hoboken, NJ: Wiley, 2008. Print 15. ^ Blum, Deborah (2011). The Poisoner's Handbook. Penguin Books. p. 231. ISBN 014311882X. 16. ^ Isachenkov, Vladimir (19 December 2016). "Alcohol poisoning death toll in Russian city rises to 49". Associated Press. Archived from the original on 20 December 2016. Retrieved 19 December 2016. 17. ^ Associated Press. "In Iran, false belief a poison fights virus kills hundreds". Associated Press. Associated Press. Retrieved 27 March 2020. 18. ^ "FDA Updates on Hand Sanitizers with Methanol". U.S. Food and Drug Administration. Retrieved 28 July 2020. ## External links[edit] Classification D * ICD-10: T51.1 * ICD-9-CM: E980.9 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Methanol toxicity	c0161680	26,868	wikipedia	https://en.wikipedia.org/wiki/Methanol_toxicity	2021-01-18T18:58:03	{"icd-10": ["T51.1"], "orphanet": ["31825"], "synonyms": [], "wikidata": ["Q3631225"]}
Unverricht-Lundborg disease is a rare inherited form of epilepsy. Affected individuals usually begin showing signs and symptoms of the disorder between the ages of 6 and 15. Unverricht-Lundborg disease is classified as a type of progressive myoclonus epilepsy. People with this disorder experience episodes of involuntary muscle jerking or twitching (myoclonus) that increase in frequency and severity over time. Episodes of myoclonus may be brought on by physical exertion, stress, light, or other stimuli. Within 5 to 10 years, the myoclonic episodes may become severe enough to interfere with walking and other everyday activities. Affected individuals also usually have seizures involving loss of consciousness, muscle rigidity, and convulsions (tonic-clonic or grand mal seizures). Like the myoclonic episodes, these may increase in frequency over several years but may be controlled with treatment. After several years of progression, the frequency of seizures may stabilize or decrease. Eventually people with Unverricht-Lundborg disease may develop problems with balance and coordination (ataxia), involuntary rhythmic shaking called intention tremor because it worsens during movement, difficulty speaking (dysarthria), depression, and a slow, mild decline in intellectual functioning. People with Unverricht-Lundborg disease typically live into adulthood. Depending on the severity of the condition and a person's response to treatment, life expectancy may be normal. ## Frequency Progressive myoclonus epilepsy is a rare condition. Unverricht-Lundborg disease is believed to be the most common cause of this type of epilepsy, but its worldwide prevalence is unknown. Unverricht-Lundborg disease occurs most frequently in Finland, where approximately 4 in 100,000 people are affected. ## Causes Mutations in the CSTB gene cause Unverricht-Lundborg disease. The CSTB gene provides instructions for making a protein called cystatin B. This protein reduces the activity of enzymes called cathepsins. Cathepsins help break down certain proteins in the lysosomes (compartments in the cell that digest and recycle materials). While the specific function of cystatin B is unclear, it may help protect the cells' proteins from cathepsins that leak out of the lysosomes. In almost all affected individuals, Unverricht-Lundborg disease is caused by an increase in size of the CSTB gene. One region of the CSTB gene has a particular repeating sequence of 12 DNA building blocks (nucleotides). This sequence is normally repeated two or three times within the gene and is called a dodecamer repeat. Most people with this disorder have more than 30 repeats of the dodecamer sequence in both copies of the CSTB gene. A small number of people with Unverricht-Lundborg disease carry other mutations. The increased number of dodecamer repeats in the CSTB gene seems to interfere with the production of the cystatin B protein. Levels of cystatin B in affected individuals are only 5 to 10 percent of normal, and cathepsin levels are significantly increased. These changes are believed to cause the signs and symptoms of Unverricht-Lundborg disease, but it is unclear how a reduction in the amount of cystatin B leads to the features of this disorder. ### Learn more about the gene associated with Unverricht-Lundborg disease * CSTB ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Unverricht-Lundborg disease	c0751785	26,869	medlineplus	https://medlineplus.gov/genetics/condition/unverricht-lundborg-disease/	2021-01-27T08:25:49	{"gard": ["3876"], "mesh": ["D020194"], "omim": ["254800"], "synonyms": []}
A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome on chromosome Xq28. Description This multisystem disorder is characterized by moyamoya disease, short stature, hypergonadotropic hypogonadism, and facial dysmorphism. Other variable features include dilated cardiomyopathy, premature graying of the hair, and early-onset cataracts. Moyamoya disease is a progressive cerebrovascular disorder characterized by stenosis or occlusion of the internal carotid arteries and the main branches, leading to the development of small collateral vessels (moyamoya vessels) at the base of the brain. Affected individuals can develop acute neurologic events due to stroke-like episodes (summary by Miskinyte et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of moyamoya disease, see MYMY1 (252350). Clinical Features Herve et al. (2010) reported an Algerian family in which 5 males were affected with a multisystem disorder characterized by moyamoya angiopathy, short stature, hypergonadotropic hypogonadism, facial dysmorphism, and early-onset cataracts. The proband developed repeated episodes of sudden right arm weakness at age 22 years, and was later found to have cortical and subcortical infarcts associated with moyamoya disease on brain imaging. He had facial dysmorphism, with mild congenital ptosis, long philtrum, retrognathia, and premature graying of the hair. He also had short stature, hypergonadotropic hypogonadism, decreased testicular volume, and azoospermia. Cardiac function was compromised due to dilated cardiomyopathy. He had recurrent episodes of heart failure and neurologic deficits, and died at age 34 years of heart failure. Miskinyte et al. (2011) described the family reported by Herve et al. (2010) and 2 additional unrelated families with a similar disorder. There were 9 affected males in all. The age at onset of acute neurologic events ranged between 4 and 36 years of age, and both cerebral infarcts and hemorrhages occurred. All had short stature and facial dysmorphism, which variably included wide nose, deep-set eyes, low-set ears, hypertelorism, ptosis, long philtrum, and flared nares. Other features included hypergonadotropic hypogonadism (7/9 patients), hypertension (3/9 patients), partial growth hormone deficiency (4/9 patients), dilated cardiomyopathy (3/9 patients), premature coronary heart disease (1/9 patients), and premature hair graying (6/9 patients). Gonadal failure was associated with azoospermia. Four patients in 1 family had early-onset cataracts, and 2 patients from another family had developmental delay. Inheritance The transmission pattern of syndromic moyamoya disease in the families reported by Herve et al. (2010) and Miskinyte et al. (2011) was consistent with X-linked recessive inheritance. Molecular Genetics In affected members of 3 families with X-linked recessive syndromic moyamoya disease, Miskinyte et al. (2011) identified 3 different deletions on chromosome Xq28. The critical region of overlap was a 3.4-kb region including exon 1 of the MTCP1/MTCP1NB gene (300116) and the first 3 exons of the BRCC3 gene (300617), resulting in loss of BRCC3 and MTCP1NB expression in patient lymphoblastoid cell lines. Morpholino knockdown of Brcc3 in zebrafish resulted in defective angiogenesis that could be rescued by endothelial expression of Brcc3, suggesting that loss of BRCC3 function was responsible for the human disorder. Miskinyte et al. (2011) noted that some of the features of the disorder were reminiscent of chromosome breakage syndromes. INHERITANCE \- X-linked recessive GROWTH Height \- Short stature HEAD & NECK Face \- Long philtrum \- Retrognathia Ears \- Low-set ears Eyes \- Early-onset cataracts (1 family) \- Ptosis \- Hypertelorism \- Deep-set eyes Nose \- Wide nose \- Broad nose \- Flared nares CARDIOVASCULAR Heart \- Dilated cardiomyopathy (variable) \- Left ventricular enlargement (variable) Vascular \- Moyamoya disease \- Cerebrovascular disease GENITOURINARY External Genitalia (Male) \- Decreased testicular volume Internal Genitalia (Male) \- Azoospermia SKELETAL Hands \- Small hands \- Short, broad fingers SKIN, NAILS, & HAIR Hair \- Premature graying NEUROLOGIC Central Nervous System \- Acute neurologic deficits due to cerebrovascular disease \- Cerebral infarcts \- Cerebral hemorrhages \- Stroke-like symptoms \- Seizures (less common) \- Developmental delay (1 family) ENDOCRINE FEATURES \- Hypergonadotropic hypogonadism \- Growth hormone deficiency MISCELLANEOUS \- Three families have been reported (as of 28 June 2011) \- Onset of neurologic events can occur between 4 and 35 years of age \- Facial dysmorphic features are variable MOLECULAR BASIS \- Contiguous gene deletion syndrome caused by deletion (3.4 kb) of chromosome Xq28 ▲ 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	MOYAMOYA DISEASE 4 WITH SHORT STATURE, HYPERGONADOTROPIC HYPOGONADISM, AND FACIAL DYSMORPHISM	c3151857	26,870	omim	https://www.omim.org/entry/300845	2019-09-22T16:19:29	{"doid": ["13099"], "omim": ["300845"], "orphanet": ["280679"], "synonyms": ["Moyamoya disease-short stature-facial dysmorphism-hypergonadotropic hypogonadism", "Alternative titles", "SYNDROMIC MOYAMOYA DISEASE", "CHROMOSOME Xq28 DELETION SYNDROME, 3.4-KB"]}
Treponematosis SpecialtyInfectious disease Treponematosis is a term used to individually describe any of the diseases caused by four members of the bacterial genus Treponema. The four diseases are collectively referred to as treponematoses:[1] * Syphilis (Treponema pallidum pallidum) * Yaws (Treponema pallidum pertenue) * Bejel (Treponema pallidum endemicum) * Pinta (Treponema carateum) Traditional laboratory tests cannot distinguish the treponematoses.[2] However, sequence differences among the T. pallidum subspecies have been identified. Molecular approaches involving PCR to identify these sequences are being developed.[3] ## References[edit] 1. ^ Giacani, L.; Lukehart, S. A. (2014). "The Endemic Treponematoses". Clinical Microbiology Reviews. 27 (1): 89–115. doi:10.1128/CMR.00070-13. PMC 3910905. PMID 24396138. 2. ^ Marks M, Solomon AW, Mabey DC (October 2014). "Endemic treponemal diseases". Transactions of the Royal Society of Tropical Medicine and Hygiene. 108 (10): 601–7. doi:10.1093/trstmh/tru128. PMC 4162659. PMID 25157125. 3. ^ Mitjà O, Šmajs D, Bassat Q (2013). "Advances in the diagnosis of endemic treponematoses: yaws, bejel, and pinta". PLoS Neglected Tropical Diseases. 7 (10): e2283. doi:10.1371/journal.pntd.0002283. PMC 3812090. PMID 24205410. ## External links[edit] Classification D * MeSH: D014211 External resources * eMedicine: article/230403 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	Treponematosis	c0040843	26,871	wikipedia	https://en.wikipedia.org/wiki/Treponematosis	2021-01-18T19:08:36	{"gard": ["7798"], "mesh": ["D014211"], "wikidata": ["Q1243869"]}
Danes et al. (1970) described 6 families in which metachromasia could be traced through normal individuals in at least 3 generations. The basis for the metachromasia was not known. Increased concentrations of mucopolysaccharides was not the explanation. Possibly this cellular characteristic was an expression of the heterozygous state of some recessive disorders. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	METACHROMASIA OF FIBROBLASTS	c1835008	26,872	omim	https://www.omim.org/entry/156300	2019-09-22T16:38:17	{"omim": ["156300"]}
Pinnae fistula or cyst is a rare otorhinolaryngological malformation characterized by the presence of a, usually unilateral, sinus tract or cyst located in the vicinity of the auricle (most frequently identified by a small pit near the anterior margin of the first ascending portion of the helix). Typically, patients are asymptomatic and usually only present symptoms (pain, erythema, discharge from pit) in relation to infection. Renal and inner ear anomalies may 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	Pinnae fistula or cyst	None	26,873	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=155838	2021-01-23T17:07:34	{"icd-10": ["Q18.8"]}
Familial retinal arterial macroaneurysm is a rare, genetic cardiac disease characterized by an early onset of retinal artery macroaneurysms formation and concomitant supravalvular pulmonic stenosis, often requiring surgical correction. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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 retinal arterial macroaneurysm	c3280205	26,874	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=284247	2021-01-23T18:42:22	{"gard": ["12779"], "omim": ["614224"], "synonyms": ["FRAM", "Retinal arterial macroaneurysm and supravalvular pulmonic stenosis"]}
Kniest dysplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities and problems with vision and hearing. It is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. 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. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Kniest dysplasia	c0265279	26,875	gard	https://rarediseases.info.nih.gov/diseases/6841/kniest-dysplasia	2021-01-18T17:59:35	{"mesh": ["C537207"], "omim": ["156550"], "umls": ["C0265279"], "orphanet": ["485"], "synonyms": []}
## Summary ### Clinical characteristics. Krabbe disease comprises a spectrum ranging from infantile-onset disease (i.e., onset of extreme irritability, spasticity, and developmental delay before age 12 months) to later-onset disease (i.e., onset of manifestations after age 12 months and as late as the seventh decade). Although historically 85%-90% of symptomatic individuals with Krabbe disease diagnosed by enzyme activity alone have infantile-onset Krabbe disease and 10%-15% have later-onset Krabbe disease, the experience with newborn screening (NBS) suggests that the proportion of individuals with possible later-onset Krabbe disease is higher than previously thought. Infantile-onset Krabbe disease is characterized by normal development in the first few months followed by rapid severe neurologic deterioration; the average age of death is 24 months (range 8 months to 9 years). Later-onset Krabbe disease is much more variable in its presentation and disease course. ### Diagnosis/testing. The two diagnostic scenarios are the following: * Scenario 1. The diagnosis of Krabbe disease, suspected in a symptomatic proband based on clinical findings (by age) and other supportive laboratory, neuroimaging, and electrophysiologic findings, is established by detection of deficient GALC enzyme activity in leukocytes. Abnormal results require follow-up molecular genetic testing of GALC; elevated psychosine levels can also help establish the diagnosis. * Scenario 2. In an asymptomatic newborn with low GALC enzyme activity on dried blood spot specimens on NBS urgent time-critical measurement of blood psychosine levels and GALC molecular genetic testing is necessary to identify – before age 14 days – those newborns with evidence of infantile-onset Krabbe disease who are candidates for early treatment with hematopoietic stem cell transplantation (HSCT). ### Management. Treatment of manifestations: Treatment of a child who is symptomatic before age six months is supportive and focused on increasing the quality of life and avoiding complications. For older individuals, treatment with HSCT is individualized based on disease burden and manifestations. Prevention of primary manifestations: Consensus guidelines recommend that asymptomatic newborns identified by either prenatal/neonatal evaluation because of a positive family history of Krabbe disease or an abnormal NBS result undergo additional testing to identify those with infantile-onset Krabbe disease. Those with laboratory findings consistent with infantile-onset Krabbe disease are candidates for HSCT before age 30 days. Surveillance: Monitor symptomatic individuals with Krabbe disease for development of: hydrocephalus, swallowing difficulties and chronic microaspiration, scoliosis, hip subluxation, and osteopenia, decreased vision, and corneal ulcerations. Agents/circumstances to avoid: Atypical antipsychotics and multiple medications for seizures can cause over-sedation (affecting cognition, respiratory drive, and rate of neurologic decline). Routine childhood vaccinations can accelerate disease progression. Evaluation of relatives at risk: Couples who have had one child with molecularly confirmed infantile-onset Krabbe disease may choose prenatal molecular genetic testing in subsequent pregnancies so that newborns with biallelic GALC pathogenic variants can be promptly tested and – if appropriate -- referred for HSCT. ### Genetic counseling. Krabbe disease is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the GALC pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic diagnosis are possible. ## Diagnosis Krabbe disease (also known as galactocerebrosidase [GALC] deficiency) has two major phenotypes that constitute a continuum: * Infantile-onset Krabbe disease (onset <12 months), characterized by progressive neurologic deterioration in infancy and death before age two years (85%-90% of affected individuals) * Later-onset Krabbe disease (onset >12 months), with slower disease progression (10%-15%) ### Suggestive Findings The two different scenarios in which Krabbe disease could be suspected in a proband: * Scenario 1. A symptomatic individual * Scenario 2. An asymptomatic newborn with a positive result on NBS #### Scenario 1 Krabbe disease should be suspected in a symptomatic proband based on clinical findings (by age) and other supportive laboratory, neuroimaging, and electrophysiologic findings. Clinical findings Age <12 months (infantile-onset Krabbe disease) * Excessive crying to extreme irritability * Feeding difficulties, gastroesophageal reflux disease * Spasticity of lower extremities and fisting, with axial hypotonia * Loss of acquired milestones (smiling, cooing, and head control) * Staring episodes * Peripheral neuropathy Age >12 months (later-onset Krabbe disease) * Slow development of motor milestones or loss of milestones (e.g., sitting without support, walking), slurred speech * Spasticity of extremities with truncal hypotonia * Vision loss, esotropia * Seizures * Peripheral neuropathy Other supportive findings * Increased cerebrospinal fluid (CSF) protein concentration. Ranges vary by age and laboratory, normal infant range reported at 48-72 mg/dL [Shah et al 2011]. Adult range: 18-58 mg/dL. Note: CSF protein concentration is already increased in Stage I infantile-onset Krabbe disease (see Clinical Description). * MRI (infantile-onset Krabbe disease) observed within the first few months of age * Abnormal brain MRI, consistent with demyelination. T2-weighted images show involvement of periventricular white matter, deep gray matter, and centrum semiovale as well as enhancement of cranial nerves. Subcortical U-fibers may be spared until late in the disease course [Gupta et al 2014]. * Abnormal spine MRI (enhancement of spinal nerve roots) * Abnormal electrophysiologic studies (nerve conduction velocity, brain stem auditory evoked response, visual evoked potentials) #### Scenario 2 Krabbe disease should be suspected in an asymptomatic newborn with a positive result on NBS. Currently, seven states (Illinois, Kentucky, Missouri, New York, Ohio, Pennsylvania, and Tennessee) perform NBS for GALC deficiency using dried blood spots. While the approaches to testing and cut-off values indicating a positive newborn screen vary by state, all results suggesting GALC deficiency require immediate follow-up studies (see Establishing the Diagnosis, Scenario 2). ### Establishing the Diagnosis #### Scenario 1 The testing required to establish the diagnosis Krabbe disease in a symptomatic proband. In individuals with some or all of the suggestive findings of infantile-onset Krabbe disease or later-onset Krabbe disease, the diagnosis is established by detection of deficient GALC enzyme activity in leukocytes. Abnormal results require follow-up molecular genetic testing of GALC. For children with infantile-onset Krabbe disease, elevated psychosine levels in dried blood spot specimens confirm the diagnosis; however, in individuals who have later-onset Krabbe disease or have progressed to the later stages of the infantile form of disease, it is not yet known if psychosine concentrations are consistently elevated. Galactocerebrosidase (GALC) enzyme activity is measured in leukocytes isolated from whole heparinized blood or cultured skin fibroblasts. The substrate used (i.e., radiometric substrate, fluorescent substrate, or mass spectrometry substrate) depends on the laboratory. * Very low GALC enzyme activity (0%-5% of normal activityl) is observed in all individuals with Krabbe disease who are symptomatic. Note: Low GALC activity can result from pseudodeficiency alleles (benign GALC variants that reduce enzyme activity in vitro but do not cause disease), carrier status for a GALC pathogenic variant, or saposin A deficiency (see Molecular Genetics). * If GALC enzyme activity in leukocytes is completely normal, no additional biochemical testing is required to exclude Krabbe disease. However, if psychosine was elevated in such cases, a diagnosis of saposin A deficiency should be considered. Psychosine concentration * Infantile-onset Krabbe disease. Very elevated concentrations of psychosine (usually >10 nmol/L) are strongly supportive of early symptomatic Krabbe disease [Turgeon et al 2015, Escolar et al 2017, Minter Baerg et al 2018]. Note that psychosine concentrations may drop significantly in the later stages of infantile-onset Krabbe disease and that psychosine may also be elevated in individuals with saposin A deficiency. * Later-onset Krabbe disease. Psychosine concentrations may not be markedly elevated and may depend on how long the patient has been symptomatic [Escolar et al 2017]. Molecular testing involves single-gene testing. Sequence analysis of GALC and targeted analysis for the common GALC 30-kilobase deletion (30kb del) is performed [Luzi et al 1995, Rafi et al 1995]. Gene-targeted deletion/duplication analysis should also be performed, at least when the suspicion of Krabbe disease is high and only one GALC pathogenic variant has been detected by sequence analysis. See Table 1. ### Table 1. Molecular Genetic Testing Used in Krabbe Disease (Galactosylcerebrosidase Deficiency) View in own window Gene 1Test MethodProportion of Probands with Pathogenic Variants 2 Detectable by This Method GALCSequence analysis 355%-65% 4 Targeted analysis for 30kb del35%-45% 5 Gene-targeted deletion/duplication analysis 6See footnote 7 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\. Wenger et al [2013], Orsini et al [2016] 5\. This large deletion accounts for approximately 35% of the pathogenic variants in individuals with Krabbe disease of Mexican heritage [D.Wenger, personal experience] and 45% of the pathogenic variants in individuals with Krabbe disease of European ancestry [Luzi et al 1995, Rafi et al 1995]. 6\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single exon deletions or duplications. 7\. Deletions involving single exons and multiple exons, other than the common 30-kb deletion, are rare but have been reported [Wenger et al 2001, Tanner et al 2012]. #### Scenario 2 The testing required to establish the diagnosis Krabbe disease in an asymptomatic infant identified on NBS. Presumptive positive newborn screening results for Krabbe disease must be followed up urgently with time-critical biochemical and molecular genetic studies to identify those newborns with biochemical and molecular genetic evidence of infantile-onset Krabbe disease before age 14 days who are candidates for early treatment with hematopoietic stem cell transplantation (HSCT) (see Management, Prevention of Primary Manifestations) [Wasserstein et al 2016, Kwon et al 2018]. Note that regardless of the method used to assay GALC enzyme activity, low GALC activity in dried blood spots and/or leukocytes in asymptomatic newborns is not sufficiently specific to diagnose Krabbe disease, let alone to distinguish between infantile-onset and later-onset Krabbe disease. In addition to certain environmental factors, low GALC activity can result from pseudodeficiency alleles (benign GALC variants that reduce enzyme activity in vitro but do not cause disease), heterozygosity (i.e., carrier state) for one GALC pathogenic variant, and GALC variants observed in later-onset Krabbe disease. * The first step in testing an asymptomatic newborn with low GALC enzyme activity identified on NBS. Measurement of concentration of psychosine in the blood (either a punch from the original NBS dried blood spot specimen or a subsequent sample). Very elevated concentration of psychosine (>10 nmol/L) appears to be specific for severe infantile Krabbe disease [Turgeon et al 2015, Escolar et al 2017, Minter Baerg et al 2018] and warrants next-step testing [Kwon et al 2018]. * Testing for an asymptomatic newborn with low GALC enzyme activity and very elevated concentration of psychosine identified on NBS * Sequence analysis of GALC to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants * Gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications including the common 30kb deletion (Table 1). Note: (1) The common 30-kb deletion may be tested for by allele-specific or breakpoint PCR as part of the first-tier sequencing assay [Luzi et al 1995, Rafi et al 1995]. (2) The necessary turn-around time for sequencing and deletion/duplication analysis in this scenario is shorter than routinely offered for diagnostic purposes; therefore, specific arrangements need to be made to ensure expedited testing. Identification of biallelic GALC pathogenic variants known to be associated with infantile-onset Krabbe disease or classified as pathogenic or likely pathogenic further confirms the diagnosis of infantile-onset Krabbe disease [Orsini et al 2016]. Of note, the vast majority of infants identified through the New York State NBS program who have low GALC enzyme activity and two presumptive pathogenic GALC variants do not have signs or symptoms of infantile-onset disease [Wasserstein et al 2016] and thus are considered to be at risk for later-onset Krabbe disease. A revised definition of risk for infantile-onset Krabbe disease based on results of psychosine concentration and GALC molecular genetic testing that is under review is expected to significantly decrease the proportion of infants designated as at risk for infantile-onset Krabbe disease identified by NBS [Author, personal communication]. ## Clinical Characteristics ### Clinical Description Historically, 85%-90% of symptomatic individuals with Krabbe disease diagnosed by enzyme activity alone had infantile-onset Krabbe disease (i.e., onset of extreme irritability, spasticity, and developmental delay before age 12 months) and 10%-15% had later-onset Krabbe disease (i.e., onset of manifestations after age 12 months and as late as the seventh decade). In contrast, the vast majority of infants identified through the New York State newborn screening (NBS) program who have low GALC enzyme activity and two presumptive pathogenic GALC variants do not have signs or symptoms of infantile-onset disease [Wasserstein et al 2016]; thus, it is likely that the proportion of individuals with later-onset Krabbe disease is higher than previously thought [Author, personal communication]. #### Infantile-Onset Krabbe Disease Infantile-onset Krabbe disease typically has four stages: * Stage I. The infant, apparently normal for the first few months after birth, begins to cry frequently without apparent cause. Many keep their hands tightly fisted. Feeding difficulties and gastroesophageal reflux may result in progressive weight loss leading to emaciation. In some infants, peripheral neuropathy is a presenting feature with no other neurologic features appreciated for several months [Korn-Lubetzki et al 2003]. * Stage II is characterized by rapid severe neurologic deterioration with decorticate posturing (marked hypertonicity with extended and crossed legs, flexed arms, and trunk hyperextension [opisthotonus]). Tendon reflexes are absent. Staring episodes and minor muscle spasms occur. Optic atrophy and sluggish pupillary reactions to light are common. * Stage III is characterized by poor control of temperature and heart rate, as well as blindness, deafness, and seizures. * Stage IV is characterized by very low muscle tone and absence of voluntary movement. The average age of death in children with infantile-onset Krabbe disease is 24 months; however, some succumb by age eight months from infections and respiratory failure, while others live up to age nine years. Symptoms and signs are confined to the nervous system. No visceromegaly is present. Head size may be large or small; hydrocephalus with increased intracranial pressure has been observed. Macular cherry-red spots were described in one individual. One infant, diagnosed with GALC deficiency in utero, had normal psychomotor development for the first two months of life but lost deep tendon reflexes by age five weeks, had markedly reduced nerve conduction velocities at age seven weeks, and developed neck muscle weakness at age three months [Lieberman et al 1980]. These findings suggest that detailed examination could reveal clinical manifestations of infantile-onset Krabbe disease earlier than the reported age of onset. Some infants with a positive NBS (and subsequently confirmed to have infantile-onset Krabbe disease) had at least one of the following in the first weeks of life: clonus in the lower extremities, difficulty feeding, abnormal nerve conduction velocity, elevated CSF protein, abnormal brain MRI. #### Later-Onset Krabbe Disease Children with onset between ages 12 months and three years can be clinically normal until they manifest gait changes, hemiplegia/diplegia, visual impairment, febrile seizures, and/or tremors. Because myelination occurs very rapidly between birth and age two years, symptoms develop more rapidly at this age than after age two years. Children with disease onset between ages 24 months and four years can initially manifest loss of milestones and vision (including rapid loss of vision) or gait changes and seizures. Although disease progression is variable, children who develop symptoms between ages nine months and four years may have rapid worsening of symptoms shortly after presentation. In most instances death occurs approximately four to six years after onset [M Escolar, personal communication]. Initial manifestations in children older than age six years may be behavioral difficulties (attention-deficit/hyperactivity disorder and mood disorders) followed by motor difficulty. They often decline rapidly soon after disease onset [Fiumara et al 2011]. Some individuals with onset in adolescence and adulthood present with loss of manual dexterity, burning paresthesias in their extremities, and weakness without intellectual deterioration; others become bedridden and continue to deteriorate mentally and physically [Kolodny et al 1991, Satoh et al 1997, Jardim et al 1999, Wenger 2003]. Presenting manifestations in adult-onset disease can also include unilateral upper-limb weakness and lower-limb hypoesthesia [Debs et al 2013]. Disease progression is generally slower in the adult-onset disease than in adolescent-onset disease. The adult-onset group includes individuals in whom the diagnosis was first made in adulthood (because the subtle symptoms present earlier in life did not prompt biochemical testing) as well as individuals considered completely normal until manifestations began after age 20 years [Kolodny et al 1991, Satoh et al 1997, Wenger 2003]. An example of the former is a woman reported by Kolodny et al [1991] (case 15) who had been "shaky" in childhood, walked slowly with a stiff and wide-based gait, and had progressive, generalized neurologic deterioration after age 40 years. She died of pneumonia at age 73 years. An example of the latter is a woman who developed slowly progressive spastic paraparesis at age 38 years. Demyelination identified on MRI was confined to the corticospinal tract [Satoh et al 1997]. Peripheral neuropathy is less common in later-onset disease (affecting about half of affected individuals) than in infantile-onset disease (affecting nearly all affected individuals) [Husain et al 2004, Siddiqi et al 2006, Debs et al 2013]. Survival varies widely among persons with later-onset disease; the median age is eight years after symptom onset [Bascou et al 2018]. Neurophysiologic findings in later-onset Krabbe disease include the following: * Electroencephalogram (EEG). While normal in the initial stages, the EEG gradually becomes abnormal. Background activity becomes slow and disorganized, with changes that may be asymmetric. * Cerebrospinal fluid protein levels can vary widely but are always elevated in the infantile-onset disease. * Electrophysiologic studies. Although motor nerve conduction velocities are generally low, they are normal in some adults with an enzymatically confirmed diagnosis. MRI. In general, brain MRI detects demyelination in the brain stem and cerebellum more clearly than CT in the early stage of later-onset Krabbe disease; however, some infants younger than age six months have a deceptively normal MRI because of the low contrast between gray and white matter in this period of brain development. Of note, scoring of atrophy of the midbrain assists in evaluating general disease progression [Zuccoli et al 2015]. Diffusion tensor imaging (DTI) of the brain. DTI is the preferred imaging modality for evaluating asymptomatic infants with Krabbe disease detected by NBS [Gupta et al 2014] (see Management, Prevention of Primary Manifestations). ### Genotype-Phenotype Correlations Infantile-onset Krabbe disease results from severe loss of galactocerebrosidase activity due to: * Homozygosity for the common GALC 30-kb deletion; * Compound heterozygosity for either the common GALC 30-kb deletion and a severe GALC pathogenic variant (most frequently nonsense or frameshift variants, but also some missense variants) or two severe pathogenic variants [Tappino et al 2010]. Later-onset Krabbe disease. The following genotypes have been observed in individuals with later-onset disease: * p.Gly286Asp+30kb del [Furuya et al 1997, De Gasperi et al 1999] * p.Gly286Asp+p.Pro318Arg [Tappino et al 2010] * p.Gly286Asp + another severe allele * p.Thr112Ala+p.Asp187Val [Luzi et al 1996] * p.Leu634Ser + another severe allele or homozygous p.Leu634Ser [Hossain et al 2014, Zhang et al 2018] The p.Gly57Ser variant, a founder variant common in Catania, Italy, is associated with late-onset Krabbe disease in both the homozygous and compound heterozygous states [Lissens et al 2007]. Note that although p.Gly286Asp has been observed in individuals with a milder phenotype, to date it is not possible to predict the clinical course in a given individual. ### Nomenclature The protein encoded by GALC is termed galactocerebrosidase in UniProt, the standard reference for GeneReviews (see Table A). Because additional terms for this protein are used in the published literature, Krabbe disease may also be referred to as: * Galactosylceramidase deficiency * Galactosylcerebrosidase deficiency * β-galactocerebrosidase deficiency ### Prevalence Krabbe disease occurs in approximately one in 250,000 births in the United States [Barczykowski et al 2012] and approximately one in 100,000 births in Europe [Wenger et al 2013]; with the median prevalence varying widely between countries [Tappino et al 2010]. A very high incidence of Krabbe disease is found in a Druze community in northern Israel and two Muslim Arab villages located near Jerusalem where the carrier rate is estimated at one in six [Rafi et al 1996]. ### Genetically Related (Allelic) Disorders No phenotypes other than those discussed in this GeneReview are known to be associated with pathogenic variants in GALC. ## Differential Diagnosis Although a history of normal development for the first few months after birth followed by psychomotor deterioration differentiates Krabbe disease from non-progressive CNS disorders of congenital or perinatal origin, it is nonetheless often difficult to differentiate Krabbe disease from other degenerative diseases. Individuals of any age with progressive deterioration of the central or peripheral nervous system should be evaluated for galactocerebrosidase (GALC) deficiency. The following disorders, ordered by mode of inheritance, should be considered in the differential diagnosis. ### Autosomal Recessive Arylsulfatase A deficiency (metachromatic leukodystrophy, MLD) is characterized by three clinical subtypes that can closely resemble late-onset Krabbe disease: * Late-infantile MLD (50%-60% of individuals) with onset between age one and three years * Juvenile MLD (~20%-30%) with onset between age four years and sexual maturity (12-14 years) * Adult MLD (~15%-20%) with onset after sexual maturity Biallelic pathogenic variants in ARSA are causative. Hexosaminidase A deficiency results in a group of neurodegenerative disorders caused by the intralysosomal storage of the specific glycosphingolipid, GM2 ganglioside. Tay-Sachs disease, the prototype hexosaminidase A deficiency, is characterized by loss of motor skills beginning between ages three and six months with progressive evidence of neurodegeneration, including seizures, macular cherry-red spots, and blindness. Total incapacitation and death usually occur before age four years. The juvenile, chronic, and adult-onset variants of hexosaminidase A deficiency have later onset, slower progression, and more variable neurologic findings, including progressive dystonia, spinocerebellar degeneration, motor neuron disease, and in some individuals with adult-onset disease, a bipolar form of psychosis. Biallelic pathogenic variants in HEXA are causative. Canavan disease. Neonatal/infantile (severe) Canavan disease is characterized by evidence of developmental delays by age three to five months with severe hypotonia and failure to achieve independent sitting, ambulation, or speech. Hypotonia evolves into spasticity and assistance with feeding becomes necessary. Life expectancy is usually into the second decade. Most individuals with Canavan disease have macrocephaly, which is a variable finding in individuals with Krabbe disease. MRI shows prominent involvement of subcortical white matter. Biallelic pathogenic variants in ASPA are causative. Saposin A deficiency (OMIM 611722). An infant from a consanguineous union who demonstrated abnormal myelination resembling Krabbe disease was found to be homozygous for a pathogenic variant in the saposin A region of PSAP, which codes prosaposin, a heat-stable protein that interacts with the GALC enzyme to catalyze the hydrolysis of the natural lipid substrates [Spiegel et al 2005]. Saposin A deficiency may also be associated with reduced GALC enzyme activity and elevated psychosine concentrations. Biallelic pathogenic variants in PSAP are causative. ### X-Linked X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and the adrenal cortex. The childhood cerebral form of X-ALD is in the differential diagnosis of Krabbe disease. It manifests most commonly between age four and eight years. It initially resembles attention deficit disorder; progressive impairment of cognition, behavior, vision, hearing, and motor function follow the initial symptoms and often lead to total disability within two years. A hemizygous ABCD1 pathogenic variant is causative. Pelizaeus-Merzbacher disease (PMD) is part of the phenotypic spectrum of PLP1-related disorders of central nervous system myelin formation. The phenotypes that can be observed in males with this disorder range from PMD to spastic paraplegia 2 (SPG2); a wide range of phenotypes can be observed in members of the same family. PMD typically manifests in infancy or early childhood with nystagmus, hypotonia, and cognitive impairment and progresses to severe spasticity and ataxia. Life span is shortened. A hemizygous PLP1 pathogenic variant is causative. ### Autosomal Dominant Alexander disease is a progressive disorder of cerebral white matter that predominantly affects infants and children and has variable life expectancy. The later-onset forms present with a slower clinical course. The infantile form comprises about 42% of affected individuals, the juvenile form about 22%, and the adult form about 33%. A neonatal form is also recognized. The neonatal form leads to severe disability or death within two years. The infantile form presents in the first two years of life typically with progressive psychomotor retardation with loss of developmental milestones, megalencephaly, frontal bossing, and seizures. Affected individuals survive a few weeks to several years. The juvenile form usually presents between age four and ten years, occasionally in the mid-teens. Survival is variable, ranging from the early teens to the 20s-30s. Affected individuals can present with bulbar/pseudobulbar signs, poor coordination (ataxia), gradual loss of intellectual function, seizures, normocephaly or megalencephaly, and breathing problems. A heterozygous pathogenic variant in GFAP is causative. Autosomal dominant leukodystrophy with dysautonomia is a slowly progressive disorder of central nervous system white matter characterized by onset of autonomic dysfunction in the fourth to fifth decade, followed in months to years by pyramidal and cerebellar involvement. Autonomic dysfunction can include bladder dysfunction, constipation, postural hypotension, feeding difficulties, erectile dysfunction, and (less often) impaired sweating. Pyramidal signs are often more prominent in the lower extremities (i.e., spastic weakness, hypertonia, clonus, brisk deep tendon reflexes, and bilateral Babinski signs). Cerebellar signs typically appear at the same time as the pyramidal signs and can include gait ataxia, dysdiadochokinesia, intention tremor, dysmetria, and nystagmus. Although cognitive function is usually preserved or only mildly impaired early in the disease course, dementia and psychiatric manifestations can occur as late manifestations. Affected individuals may survive for decades after onset. Either an LMNB1 duplication or (more rarely) a large heterozygous deletion upstream of the LMNB1 promoter is causative. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of a symptomatic individual diagnosed with Krabbe disease (i.e., Scenario 1), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended: * Neurologic and developmental examination * Brain stem auditory evoked response to assess hearing and auditory neuropathy * Brain MRI (DTI preferred) to understand disease progression and anticipate care needs (e.g., atrophy of brain stem is likely associated with apnea and temperature instability). * Nerve conduction velocity to help understand the peripheral nerve involvement and development of muscle weakness * Visual evoked potential to help understand the best approach to visual and developmental therapy * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Symptomatic individual. For a child younger than age six months who is in Stage II or III of infantile-onset Krabbe disease (see Clinical Description), treatment is supportive and focused on increasing the quality of life and avoiding complications (Table 2) [Escolar et al 2016]. ### Table 2. Treatment of Manifestations in Individuals with Krabbe Disease Who Have NOT Undergone Hematopoietic Stem Cell Transplantation (HSCT) View in own window System/ConcernManifestationTreatment GastrointestinalVomiting & gastroesophageal reflux disease (GERD) * Maintainence of upright positioning during & after feeding * Consideration of proton pump inhibitors in those age >1 yr * Nissen fundoplication w/gastrostomy tube (G-tube) placement. Dysphagia * Modifying texture & thickness of foods using commercial thickening agents can help w/swallowing difficulties. * Swallowing ability may be improved by providing tiny tastes of food or juice several times per day in non-feeders. * Consideration of nasogastric tube or gastric tube placement Constipation * Maintain appropriate fluid intake. * Consideration of osmotic laxatives &/or use of stimulant medication in those w/refractory constipation NeurologicSpasticity * Baclofen & clonazepam may improve global spasticity * Botox injections at specific sites may be considered; spasticity typically decreases for 3-5 mos after each injection. Neuropathic pain; seizures * Standard anti-pileptic medications; monotherapy is preferred, if possible. * Gabapentin may decrease neuropathic pain & can be used for control of seizures in some. MusculoskeletalContractures * Positioning devices (wedges, rolls, and cushions) to decrease spasticity & prevent contractures * Physical therapy RespiratoryExcessive airway secretions * Chest physiotherapy * Postural drainage * Suctioning device GenitourinaryUrinary tract infections * Bladder massage (Crede maneuver) to encourage complete bladder emptying * Intermittent catheterization EyesDelayed pupillary response, difficulty w/upward gaze & palpebral weakness Corneal ulcers * Dark glasses to help reduce photophobia * Eye lubricants or protective ointments DentalDelayed dentition Table adapted from Escolar et al [2016] Older individuals with mild manifestations. Treatment (based on standard practice) is tailored to the manifestations in each individual. ### Prevention of Primary Manifestations Escolar et al [2005] reported that all 11 asymptomatic newborns (diagnosed prenatally or shortly after birth because of a family history of Krabbe disease) who underwent HSCT between ages 12 and 44 days had stable engraftment of donor hematopoietic stem cells that provided a long-term source of GALC enzyme. Follow up over four months to six years has thus far revealed that while most children had normal cognitive ability and receptive language, they eventually developed speech and motor difficulties (including spasticity). Wasserstein et al [2016] reported outcomes for five infants from four families detected by the New York State newborn screening program. Two of the five were sibs. All but the first-born in the sib pair underwent HSCT between days 24 and 41 of life. Outcomes for the four who underwent HSCT were not ideal, likely due to disease severity at the time of the transplantation. More recently, several newborns identified through other state newborn screening programs have had more positive outcomes [Orsini, personal observation]. Wright et al [2017] reported a 15-year study of outcomes for 18 individuals presumed to have a form of infantile-onset Krabbe disease who underwent HSCT in the first seven weeks of life. Following early HSCT, the long-term outcome of motor function reflected the severity of corticospinal tract involvement at birth. Peripheral nerve disease progressed with time, causing severe muscular atrophy and scoliosis. Compared to children not treated as babies, those treated early with HSCT can live relatively normal lives with variable motor disabilities until the teen years when the disease may progress. Mortality was 25%, slightly less than general mortality for non-malignant diseases. Outcomes following HSCT vary widely: some individuals live completely normal lives, whereas others are disabled (ranging from reliance on walkers for mobility to quadriplegia). The outcomes depend on how early disease is detected, the severity of disease, and progression of the disease prior to treatment. Asymptomatic newborns with infantile-onset Krabbe disease. Consensus guidelines recommend that asymptomatic newborns identified by either prenatal/neonatal evaluation because of a positive family history of Krabbe disease (see Evaluation of Relatives at Risk) or an abnormal newborn screening result undergo additional testing to identify those with infantile-onset Krabbe disease (see Establishing the Diagnosis, Scenario 2). Those with laboratory findings consistent with infantile-onset Krabbe disease are thus candidates for HSCT before age 14 days [Kwon et al 2018]. Asymptomatic newborns with abnormal newborn screening results presumed to be at risk for later-onset Krabbe disease. No guidelines have been published for monitoring these at-risk individuals and to date there are no validated markers that can predict later disease onset [Wasserstein et al 2016]. Symptomatic individuals with later-onset Krabbe disease. The manifestations of Krabbe disease progress more slowly; thus, individuals with later-onset Krabbe disease diagnosed early enough in the disease course may benefit from HSCT. In a single report by Laule et al [2018] treatment was found to arrest demyelination and axonal loss. ### Prevention of Secondary Complications Symptomatic individuals with Krabbe disease * Physical therapy can improve strength, mobility, flexibility, and function. * Erythromycin may be useful as a prophylactic antibiotic and may also improve gastrointestinal motility. * Annual influenza vaccination is recommended [Anderson et al 2014], although other routine vaccinations are typically avoided (see Agents/Circumstances to Avoid). ### Surveillance Symptomatic individuals with Krabbe disease Monitor for development of: * Hydrocephalus and need for VP shunt * Scoliosis, hip subluxation, and osteopenia (via DEXA scan) * Decreased vision and corneal ulcerations * Swallowing difficulties and chronic microaspiration (via modified barium swallow) ### Agents/Circumstances to Avoid Symptomatic individuals with Krabbe disease * Atypical antipsychotics and multiple medications for seizures [Author, personal experience], which can: overly sedate patients, further affecting cognition; affect respiratory drive; and accelerate the neurodegenerative cascade * Routine childhood vaccinations, including live virus vaccines, as the resulting immune response may accelerate disease progression [Escolar et al 2016] * Prolonged indwelling catheters for urinary retention due to the high risk of infection ### Evaluation of Relatives at Risk Couples who have had one child with molecularly confirmed infantile-onset Krabbe disease may choose prenatal molecular genetic testing in subsequent pregnancies so that newborns with biallelic GALC pathogenic variants can be promptly tested (see Establishing the Diagnosis, Scenario 2) and – if appropriate – referred for HSCT (see Prevention of Primary Manifestations). Note that because of intrafamilial variability, sibs of an individual with later-onset Krabbe disease may develop the disease at a much earlier age. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Studies are being conducted using well-characterized animal models to investigate other treatment options including enzyme replacement therapy, neural stem cell transplantation, substrate reduction therapy, and chemical chaperone therapy. To date experimental "combination therapies" (HSCT together with gene therapy) in the GALC-deficient murine model have demonstrated the potential to further advance treatment of GALC deficiency by synergistically increasing the life span of the treated mice [Reddy et al 2013, Rafi et al 2015, Ungari et al 2015]. 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	Krabbe Disease	c0023521	26,876	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1238/	2021-01-18T21:15:40	{"mesh": ["D007965"], "synonyms": ["Galactocerebrosidase Deficiency", "GALC Deficiency", "Globoid Cell Leukodystrophy"]}
Ochoa syndrome is characterized by the association of severe voiding dysfunction and a characteristic facial expression. ## Epidemiology Over 100 patients have been described so far. ## Clinical description Patients with Ochoa syndrome present with incontinence, urinary tract infection and hydronephrosis. Voiding dysfunction is the result of an obstructive uropathy. About two-thirds of the patients have moderate to severe constipation. Cryptorchidism has also been reported. The peculiar facial dysmorphism is related to an unusual inversion of facial expression that occurs when the child smiles or cries. ## Etiology A potential gene has been mapped to chromosome 10q23-q24. ## Diagnostic methods Diagnosis may be suspected following recognition of the peculiar facial expression during infancy. Ultrasonography, renal scan, voiding cystourethrogram and urodynamics can be used to evaluate the lower urinary tract dysfunction. ## Genetic counseling The syndrome is inherited as an autosomal recessive trait. ## Management and treatment Treatment is symptomatic and involves bladder re-education, antibiotic prophylaxis, anticholinergic therapy and alpha-blockers. Intermittent catheterization may be needed. Constipation should be treated. Early diagnosis and treatment are essential in order to prevent upper urinary tract deterioration and renal failure. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Ochoa syndrome	c0403555	26,877	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2704	2021-01-23T18:27:43	{"gard": ["104"], "mesh": ["C536480"], "omim": ["236730", "615112"], "umls": ["C0403555"], "icd-10": ["N31.8"], "synonyms": ["Hydronephrosis-inverted smile syndrome", "Inverted smile-neurogenic bladder syndrome", "Partial facial palsy with urinary abnormalities", "Urofacial syndrome"]}
Alleged condition of hair suddenly turning white This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article needs attention from an expert on the subject. Please add a reason or a talk parameter to this template to explain the issue with the article. When placing this tag, consider associating this request with a WikiProject. (July 2009) 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: "Marie Antoinette syndrome" – news · newspapers · books · scholar · JSTOR (December 2017) 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: "Marie Antoinette syndrome" – news · newspapers · books · scholar · JSTOR (December 2017) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Marie Antoinette syndrome is an alleged condition of hair suddenly turning white.[1] The name comes from folklore about the hair of Queen Marie Antoinette of France turning stark white after her capture following the ill-fated flight to Varennes during the French Revolution. According to the Federation of American Societies for Experimental Biology (FASEB), witnesses claimed that Antoinette's hair rapidly turned white on three occasions.[2][clarification needed][unreliable source?] It has been found that some hairs can become colored again when stress is reduced.[3][4] ## Causes[edit] The syndrome has been hypothesized to be a variant of alopecia areata diffusa or autoimmune non-scarring hair loss that selectively affects all pigmented hairs, leaving only the white hair behind. Marie Antoinette syndrome is caused by high levels of emotional stress, which, in turn, causes less pigmentation of the hair.[5][full citation needed] These form the basis of most uses of the idea in fictional works. One study[6] (which requires scientific replication and verification) experimented with the phenomenon in mice found that stress caused white hair even if the immune system was suppressed (ruling out auto-immune response) and if the glands producing cortisol were removed. The study concluded that over-activation of the sympathetic nervous system was causing stem cells to stop producing pigment cells in hair follicles.[7] ## History[edit] The earliest surviving recorded claim of sudden whitening of the hair is represented in the Talmud, by a story of a Jewish scholar who, at the age of 17 years, developed white hair locks due to overwork.[citation needed] Now and again, contemporary cases of accelerated (though not sudden) hair-whitening have been documented, as with bombing victims in the Second World War,[citation needed] and in a case covered in the medical journal Archives of Dermatology in 2009.[8] ## References[edit] 1. ^ Trüeb, Ralph M. (2013). Female Alopecia: Guide to Successful Management. Springer Science & Business Media. p. 132. ISBN 9783642355035. 2. ^ Weissmann, G. (30 September 2009). "Post-traumatic Stress Disorder: Obama, Palin and Marie-Antoinette". The FASEB Journal. Federation of American Societies for Experimental Biology. 23 (10): 3253–3256. doi:10.1096/fj.09-1001. PMID 19797298. S2CID 31870444. 3. ^ Alice Klein (June 6, 2020). "Grey hairs sometimes regain their colour when we feel less stressed". New Scientist. 4. ^ Ayelet Rosenberg; et al. (May 19, 2020). "Human Hair Graying is Naturally Reversible and Linked to Stress". bioRxiv. doi:10.1101/2020.05.18.101964. S2CID 218764733. 5. ^ Landois. 1866: Bubbles in the Hair Shaft 6. ^ Zhang, B., Ma, S., Rachmin, I. et al. Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells. Nature (2020). [1] 7. ^ How Stress Turns Hair White: Harvard Study Points To 'Fight-Or-Flight' Response 8. ^ Navarini, A. A.; Nobbe, S.; Trüeb, R. M. (June 2009). "Marie-Antoinette Syndrome" (PDF). Archives of Dermatology. 145 (6): 656. doi:10.1001/archdermatol.2009.51. PMID 19528420. * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Marie Antoinette syndrome	None	26,878	wikipedia	https://en.wikipedia.org/wiki/Marie_Antoinette_syndrome	2021-01-18T18:42:22	{"wikidata": ["Q6762748"]}
## Summary ### Clinical characteristics. RRM2B-related mitochondrial disease can be grouped by disease pathogenesis, phenotype, and mode of inheritance into two major types: mitochondrial DNA (mtDNA) depletion and multiple mtDNA deletions. * Mitochondrial DNA depletion usually manifests as severe multisystem disease (encephalomyopathy with proximal renal tubulopathy) and is often fatal in early life. Inheritance is autosomal recessive. * Multiple mtDNA deletions cause tissue-specific cytochrome c oxidase (COX) deficiency. Inheritance can be either autosomal recessive (with progressive external ophthalmoplegia [PEO] and multisystem involvement manifesting during early childhood/adulthood) or autosomal dominant (with less severe, often tissue-specific manifestations [e.g., chronic PEO] developing in later adulthood). Other rarer phenotypes are Kearns-Sayre syndrome (KSS) and mitochondrial neurogastrointestinal encephalopathy (MNGIE). ### Diagnosis/testing. The presence of biallelic RRM2B pathogenic variants confirms the diagnosis of an autosomal recessive RRM2B-related mitochondrial disease. The presence of a heterozygous RRM2B pathogenic variant confirms the diagnosis of an autosomal dominant RRM2B-related mitochondrial disease in those suspected of having a late-onset disorder of mtDNA maintenance. ### Management. Treatment of manifestations: No cures and few effective treatments exist for any form of mitochondrial disease, including this one. Treatment, which focuses on symptomatic management and supportive care, is best provided by a multidisciplinary team. Management issues for those with systemic involvement may include: nutritional support (gastrointestinal involvement), care by a pediatric nephrologist (renal tubulopathy), care by a pediatric pulmonologist (impaired respiratory function), physical therapy (to maintain strength and mobility and to prevent contractures), care by a pediatric neurologist (seizures), and care by hearing loss specialists (to determine the best habilitation options for sensorineural hearing loss). Management issues for those with PEO may include: ptosis surgery for cosmetic effect and/or symptomatic relief; ECG to screen for significant cardiac conduction defects. For both clinical presentations: aggressive management of fever and infection. Surveillance: No clinical guidelines specific to RRM2B-related mitochondrial disease are available; however, for those with systemic involvement the following should be considered: regular evaluation of: neurodevelopment, speech, and language; presence/severity of encephalopathy and/or seizures/subclinical status epilepticus; renal function; nutritional status, growth, and body mass index (BMI); and pulmonary function. For those with PEO the following biannual evaluations should be considered: neurologic status; occupational and physical therapy assessments; CBC, electrolytes, liver function (albumin, coagulation factors), liver enzymes (AST, ALT, GGT), blood glucose, and HBA1C; and nutritional status, weight, and body mass index (BMI). Agents/circumstances to avoid: Specifically: Valproic acid (theoretic risk of precipitating/exacerbating organ failure due to mitochondrial toxicity); metformin (theoretic risk of exacerbating metabolic acidosis); prolonged use of linezolid (reported association with optic and peripheral neuropathy and lactic acidosis due to mitochondrial toxicity); and zidovudine (reported risk of inducing mitochondrial disease by interfering with mtDNA replication). In general: dehydration and prolonged fasting to prevent clinical deterioration. Evaluation of relatives at risk: If the pathogenic variant(s) have been identified in an affected family member, it is appropriate to clarify the genetic status of at-risk relatives so that those who harbor the pathogenic variant(s) can (1) undergo timely routine surveillance for disease complications and (2) avoid possible precipitating factors. ### Genetic counseling. RRM2B-related mitochondrial disease can be inherited in either an autosomal recessive (AR) or an autosomal dominant (AD) manner. * AR inheritance. The parents of an affected child are obligate heterozygotes (carriers) and are asymptomatic. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. * AD inheritance. Most affected individuals likely have an affected parent; the proportion caused by de novo pathogenic variants is unknown. The offspring of an affected individual has a 50% chance of inheriting the pathogenic variant and, thus, being symptomatic. If the pathogenic variant(s) have been identified in an affected family member, prenatal testing for pregnancies at increased risk is possible. ## Diagnosis RRM2B-related mitochondrial disease can, for the most part, be characterized by disease pathogenesis, phenotype, and mode of inheritance: * Mitochondrial DNA (mtDNA) depletion, which usually manifests as severe multisystem disease (encephalomyopathy with proximal renal tubulopathy) and is often fatal in early life. Inheritance is autosomal recessive [Bourdon et al 2007, Bornstein et al 2008, Acham-Roschitz et al 2009, Kollberg et al 2009, Shaibani et al 2009, Spinazzola et al 2009] * Accumulation of clonally expanded (multiple) mtDNA deletions causing tissue-specific cytochrome c oxidase (COX) deficiency. Inheritance can be autosomal recessive (AR) or autosomal dominant (AD) [Tyynismaa et al 2009, Fratter et al 2011, Pitceathly et al 2011, Takata et al 2011, Pitceathly et al 2012]: * AR. Disease generally manifests during early childhood/adulthood with marked multisystem involvement (chronic progressive external ophthalmoplegia [PEO] and KSS). * AD. Disease typically develops in later adulthood, is usually less severe, and is often tissue-specific, such as chronic PEO. RRM2B-related mitochondrial disease should be suspected in the following * Children with: * Myopathy manifesting as muscle hypotonia and weakness, often associated with respiratory insufficiency * Gastrointestinal disturbance manifesting as dysmotility * Proximal renal tubulopathy with nephrocalcinosis * CNS findings including seizures, developmental delay, microcephaly, and hearing loss * Lactic acidosis * Skeletal muscle tissue showing severe mtDNA depletion and mitochondrial respiratory chain defects * Adults with: * Progressive external ophthalmoplegia (PEO) * Ptosis of variable severity * Proximal muscle weakness and/or fatigue * Bulbar dysfunction * Absent or minimal CNS findings, including ataxia, cognitive dysfunction, and mood disturbance * Sensorineural hearing loss (SNHL) * Sensory axonal peripheral neuropathy * Gastrointestinal problems, including irritable bowel syndrome-like symptoms and low body mass index (BMI) * Endocrinopathy (including hypothyroidism, hypoparathyroidism, diabetes mellitus, and hypogonadism) * Individuals with Kearns-Sayre syndrome when inheritance appears to follow a Mendelian pattern and/or examination of muscle tissue reveals evidence of multiple mtDNA deletions. * Individuals with mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease when plasma thymidine concentration is <3 µmol/L, plasma deoxyuridine concentration <5 µmol/L, thymidine phosphorylase enzyme activity in leukocytes is >10% of the control mean, and molecular genetic testing does not identify biallelic pathogenic variants in TYMP (the gene encoding thymidine phosphorylase). One strategy for establishing the molecular diagnosis of RRM2B-related mitochondrial disease in a proband is to perform a skeletal muscle biopsy to evaluate for characteristic histopathologic changes that are only apparent in muscle tissue: cytochrome c oxidase (COX)-deficient fibers and subsarcolemmal mitochondrial accumulation (classic "ragged-red" fibers). If the muscle tissue shows evidence of mitochondrial disease, perform (in skeletal muscle) the following: * Quantitative studies of mtDNA copy number for evidence of mtDNA depletion (typically <30% of age- and tissue-matched control samples) * Qualitative studies for evidence of clonally expanded multiple mtDNA deletions (deletion/duplication analysis, Table 1) If a skeletal muscle biopsy cannot be obtained, perform (on DNA extracted from leukocytes) sequence analysis of the entire RRM2B coding region, including intron/exon boundaries (Table 1). * The presence of biallelic (i.e., compound heterozygous or homozygous) RRM2B pathogenic variants confirms the diagnosis of autosomal recessive RRM2B-related mitochondrial disease. Note: If sequence analysis does not identify biallelic RRM2B pathogenic variants and autosomal recessive inheritance is suspected, deletion/duplication analysis should be considered. * The presence of a heterozygous RRM2B pathogenic variant confirms the diagnosis of autosomal dominant RRM2B-related mitochondrial disease. A different strategy for establishing the molecular diagnosis of RRM2B-related mitochondrial disease in a proband is the use of a multigene panel comprising a number of genes known to disturb mtDNA maintenance (see Differential Diagnosis for a discussion of some of these disorders). ### Table 1. Molecular Genetic Testing Used in RRM2B-Related Mitochondrial Disease View in own window Gene 1Test MethodProportion of Probands with a Pathogenic Variant Detectable by this Method RRM2BSequence analysis 2>95% 3 Deletion/duplication analysis 4Unknown 5 1\. See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants. 2\. 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. 3\. Because of the difficulty of detecting small deletions by conventional sequencing strategies, pathogenic variant frequency is reported to be <100%. 4\. Testing that identifies exon or whole-gene deletions/duplications not detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Methods used may include quantitative PCR, long RRM2B -range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment. 5\. No RRM2B deletions have been reported to date. ## Clinical Characteristics ### Clinical Description Pathogenic variants in RRM2B are associated predominantly with either: * Mitochondrial DNA depletion syndrome (encephalomyopathic form with renal tubulopathy), which usually presents as a childhood-onset severe multisystem disease; OR * Chronic progressive external ophthalmoplegia with multiple mtDNA deletions, which is usually adult-onset, milder, and often tissue-specific. However, other phenotypes include Kearns-Sayre syndrome and mitochondrial neurogastrointestinal encephalopathy (MNGIE). RRM2B-related mitochondrial diseases are emerging as an important cause of both pediatric and adult-onset mitochondrial disease. To date, 73 individuals from 42 families with molecularly confirmed RRM2B-related mitochondrial disease have been reported [Bourdon et al 2007, Bornstein et al 2008, Acham-Roschitz et al 2009, Kollberg et al 2009, Shaibani et al 2009, Spinazzola et al 2009, Tyynismaa et al 2009, Fratter et al 2011, Takata et al 2011, Pitceathly et al 2011, Pitceathly et al 2012]. Mitochondrial DNA depletion syndrome (encephalomyopathic form with renal tubulopathy), the most severe form of the disease, is a multisystem disorder associated with severe mtDNA depletion; it has been reported in 15 individuals [Bourdon et al 2007, Bornstein et al 2008, Acham-Roschitz et al 2009, Kollberg et al 2009, Spinazzola et al 2009]. Onset typically occurs in the first six months of life; affected children succumb in early childhood. Disease characteristics include myopathy manifest as muscle hypotonia (in all 15 affected individuals), weakness associated with respiratory insufficiency (in 10), lactic acidosis (13), failure to thrive and gastrointestinal dysmotility (9), and proximal renal tubulopathy with nephrocalcinosis (9) [Bourdon et al 2007, Bornstein et al 2008]. Central nervous system (CNS) features can include seizures (5 affected individuals), sensorineural hearing loss of varying severity (3), microcephaly (2), cerebral atrophy (1), and generalized central hypomyelination (1). Chronic progressive external ophthalmoplegia (PEO) with multiple mtDNA deletions. In 31 adults with chronic PEO and multiple mtDNA deletions in muscle in whom mutation of all other genes known to cause this phenotype (i.e., POLG, POLG2, SLC25A4, and TWNK) had been excluded, Pitceathly et al [2012], identified an autosomal dominant RRM2B-related disorder in 24 individuals and an autosomal recessive RRM2B\- related disorder in seven. Ptosis and PEO were universal. Extra-ocular neurologic complications were common in adults with genetically confirmed RRM2B-related mitochondrial disease. Also prominent were myopathy (followed by bulbar dysfunction) and fatigue. Sensorineural hearing loss of varying severity and gastrointestinal dysmotility (including irritable bowel syndrome-like symptoms and low body mass index) were also common. Endocrinopathies including diabetes mellitus, hypothyroidism, hypoparathyroidism, and hypogonadism were important additional clinical features. * Autosomal dominant inheritance * The first individuals reported were from two large, unrelated families with autosomal dominant PEO caused by a heterozygous nonsense pathogenic variant in exon 9 (c.979C >T) predicting p.Arg327Ter) that resulted in truncation of the translated p53R2 (see Molecular Genetics, Normal gene product) protein [Tyynismaa et al 2009]. In these families the earliest onset was in the third decade (average age 46 years). The cardinal features were PEO and ptosis as well as ataxia, cognitive dysfunction, exercise intolerance, sensorineural hearing loss, mood disturbance, and peripheral neuropathy. * More recently, heterozygous RRM2B pathogenic variants have been shown to be frequent in familial PEO with muscle-restricted multiple mtDNA deletions [Fratter et al 2011, Pitceathly et al 2012]. The phenotype is a milder myopathy with proximal muscle weakness, bulbar dysfunction, and fatigue. Mean age of disease onset is 46 years. * Autosomal recessive inheritance * In children with compound heterozygous RRM2B pathogenic variants, disease onset was at a mean age of seven years. The predominantly myopathic phenotype of PEO, ptosis, proximal muscle weakness, and bulbar dysfunction was more severe than the multisystem disorder observed in individuals with a heterozygous RRM2B pathogenic variant [Pitceathly et al 2012]. * Additionally, a homozygous missense pathogenic variant in RRM2B has been described in a 43-year-old man who presented at age 16 years with progressive hearing loss followed by the insidious onset of PEO, muscle weakness, retinopathy, and a major depressive disorder, findings that further extend the phenotype [Takata et al 2011]. Mitochondrial neurogastrointestinal encephalopathy (MNGIE) has been reported in a woman age 42 years with RRM2B biallelic missense pathogenic variants and mtDNA depletion in clinically relevant tissues [Shaibani et al 2009]. For more information about this phenotype, see MNGIE. Kearns-Sayre syndrome (KSS). RRM2B pathogenic variants have been identified in one individual with onset before age 20 years of PEO-plus / Kearns-Sayre syndrome (PEO, pigmentary retinopathy, sensorineural hearing loss, and increased CSF protein), which is similar to single mtDNA deletion disorders [Pitceathly et al 2011]. ### Genotype-Phenotype Correlations Genotype-phenotype correlations cannot be clearly defined in RRM2B-related mitochondrial disease. RRM2B pathogenic variants have been associated with both simplex (i.e., a single occurrence in a family) and familial mitochondrial disease characterized by either autosomal recessive mtDNA depletion syndrome (which is associated with a quantitative loss of mtDNA copies) or autosomal recessive and autosomal dominant pathogenic variants (which cause the accumulation of multiple mtDNA deletions in post-mitotic tissues). The same RRM2B pathogenic variants are associated with varied phenotypic severity depending on whether they are biallelic or heterozygous. Mitochondrial DNA depletion is commonly seen in children with clinically severe biallelic pathogenic variants in genes encoding proteins essential to mtDNA maintenance [Bourdon et al 2007, Bornstein et al 2008, Acham-Roschitz et al 2009, Kollberg et al 2009, Shaibani et al 2009, Spinazzola et al 2009]; however, it has also been observed in one adult with biallelic RRM2B pathogenic variants [Shaibani et al 2009, Takata et al 2011]. Thus, RRM2B-related mtDNA depletion can potentially cause a relatively mild clinical phenotype. ### Penetrance The clinical manifestations of RRM2B-related disorders are similar in males and females. ### Prevalence The prevalence of RRM2B-related mitochondrial disorders is unknown. Pathogenic variants in RRM2B are now increasingly recognized as an important cause of familial mitochondrial disease in both adults and children and represent the third most common cause of multiple mtDNA deletions in adults, following pathogenic variants in POLG (encoding pol γ) and TWNK (encoding the Twinkle helicase) [Pitceathly et al 2012]. ## Differential Diagnosis The first reported human diseases attributed to mutation of RRM2B were associated with a quantitative loss of mtDNA copies – the so-called mtDNA depletion syndromes. To date, mutation of the following nine nuclear genes has been associated with mtDNA depletion syndromes: DGUOK, MPV17, TWNK, POLG, SUCLA2, SUCLG1, TK2, TYMP, and RRM2B. Clinical characteristics (and the associated gene) can be summarized as [Suomalainen & Isohanni 2010]: * Myopathic (TK2) * Hepatocerebral (DGUOK, MPV17, POLG, and TWNK) * Encephalomyopathic (SUCLA2, SUCLG1, TYMP, and RRM2B) See Mitochondrial DNA depletion syndrome: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM. Comparison of RRM2B-related mitochondrial disorders with other mtDNA depletion and mtDNA deletion syndromes In children. Hypotonia, lactic acidosis, and proximal renal tubulopathy in association with mitochondrial respiratory chain defects and severe mtDNA depletion in skeletal muscle should prompt testing of RRM2B before other nuclear-encoded genes (in which muscle weakness is the predominant clinical feature). In children with biallelic RRM2B pathogenic variants gastrointestinal disturbance is often severe, but CNS involvement is less common than in other syndromic mitochondrial disorders [Fratter et al 2011, Pitceathly et al 2012]. In adults. Progressive external ophthalmoplegia (PEO), ptosis, and proximal muscle weakness are the predominant clinical characteristics seen with mutation of POLG and TWNK (encoding twinkle), the two most common causes of multiple mtDNA deletions. In contrast, bulbar dysfunction, sensorineural hearing loss, and gastrointestinal problems (including irritable bowel syndrome-like symptoms and low body mass index) appear to occur more often in adults with mutation of RRM2B than mutation of POLG or TWNK. Thus, in adults the presence of PEO, multiple mtDNA deletions in skeletal muscle, bulbar dysfunction, sensorineural hearing loss, and gastrointestinal problems in the absence of overt CNS features supports testing of RRM2B before POLG and TWNK. Kearns-Sayre syndrome (KSS). RRM2B testing should be considered when the pattern of inheritance appears to be Mendelian and/or evidence of multiple mtDNA deletions is observed on muscle biopsy. Mitochondrial neurogastrointestinal encephalopathy (MNGIE). RRM2B testing should be considered in individuals with MNGIE if deoxyuridine and thymidine levels in both blood and urine are negative, thymidine phosphorylase activity is normal in white cells and platelets, and molecular genetic testing does not identify causative pathogenic variants in TYMP. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with RRM2B-related mitochondrial disease, the following evaluations are recommended: * Comprehensive clinical examination and neurology consultation that includes measures of functional neurologic status * Formal developmental evaluation (particularly in a child with the encephalomyopathic form with renal tubulopathy) * Formal assessment of vision and hearing * Brain MRI and electroencephalogram (EEG) in individuals with encephalopathy and/or seizures. Note: these may be normal with certain RRM2B-related mitochondrial disease phenotypes. * Nutritional assessment * Speech and language assessment * Physical therapy assessment * Occupational therapy assessment * Pulmonary function testing * For those with Kearns-Sayre syndrome, cardiac evaluation to include electrocardiogram (ECG) and/or echocardiogram * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Detailed evaluations are outlined in Wellcome Trust Centre for Mitochondrial Research Clinical Guidelines. To date, there are no known cures and few effective treatments for any forms of mitochondrial disease, including RRM2B-related mitochondrial disease. Treatment modalities currently focus on symptomatic management and supportive care, and are best implemented by a multidisciplinary team. General management guidelines for those with systemic involvement: * Nutritional support (e.g., nasogastric tube, gastrostomy) as needed for significant gastrointestinal involvement * Early referral to a pediatric renal specialist for those with proximal renal tubulopathy * Early referral to a pediatric pulmonologist for children with evidence of reduced respiratory function. Management may include consideration of tracheostomy and artificial ventilation. * Physical therapy to maintain muscle strength and mobility and to prevent contractures * Referral to a pediatric neurologist for seizure management. Of note, seizures may be refractory to treatment. * Referral to hearing loss specialists to determine the best habilitation options for sensorineural hearing loss (see Hereditary Hearing Loss and Deafness for discussion of management issues) General management guidelines for those with progressive external ophthalmoplegia (PEO): * Ptosis surgery for cosmesis and/or symptomatic relief in those with good residual orbicularis oculi muscle strength * ECG in all individuals with PEO to screen for significant cardiac conduction defects which may warrant placement of a pacemaker, particularly in those with the Kearns-Sayre syndrome phenotype General management guidelines for both those with systemic involvement and those with PEO: * Aggressive management of fever and infection ### Surveillance No clinical guidelines specific to RRM2B-related mitochondrial disease are available; however, detailed evaluations are outlined in Wellcome Trust Centre for Mitochondrial Research Clinical Guidelines. The following evaluations should be considered: RRM2B-related mitochondrial DNA depletion syndrome (encephalo-myopathic form with renal tubulopathy) * Regular assessments of neurodevelopment, speech, and language * Regular evaluations by a pediatric neurologist to evaluate for the presence and/or severity of encephalopathy, with consideration of EEG and video EEG monitoring to determine presence of seizures and/or subclinical status epilepticus * Regular evaluation by a pediatric renal specialist, including assessment of renal function (electrolytes in blood and urine and urine analysis) * Routine assessment of nutritional status, growth, and body mass index (BMI) * Regular pulmonary function testing including monitoring of blood gases for early detection of respiratory compromise RRM2B-related mitochondrial DNA depletion syndrome and mitochondrial neurogastrointestinal encephalopathy * Biannual: * Comprehensive neurology consultation and clinical examination to include measures of functional neurologic status * Occupational therapy and physical therapy assessments * CBC, electrolytes, liver function (albumin, coagulation factors), liver enzymes (AST, ALT, GGT), blood glucose, and HBA1C * Annual pulmonary function testing including assessment of blood gases to monitor for early respiratory compromise * Routine assessment of nutritional status, weight gain, and BMI, including regular review with speech and language therapist with consideration of gastrostomy as needed for nutritional support * Imaging and diagnostic procedures including EEG, ECG, and brain MRI as indicated by clinical findings and rate of disease progression RRM2B-related multiple mtDNA deletions with external ophthalmoplegia Care will be directed by clinical findings. The following general evaluations are recommended: * Biannual: * Comprehensive neurology consultation and clinical examination to include measures of functional neurologic status * Occupational therapy and physical therapy assessments * CBC, electrolytes, liver function (albumin, coagulation factors), liver enzymes (AST, ALT, GGT), blood glucose, and HBA1C * Annual pulmonary function testing including assessment of blood gases to monitor for early respiratory compromise * Routine assessment of nutritional status, weight gain and BMI, biannually * Imaging and diagnostic procedures to include EEG, ECG, and MRI brain- as indicated by clinical findings and rate of disease progression * ECG advised biannually (KSS phenotype) ### Agents/Circumstances to Avoid Avoid the following: * Valproic acid (commonly used for seizures and known to interfere with beta-oxidation) because it is considered to be a mitochondrial toxin with a theoretic risk of precipitating/exacerbating organ failure * Metformin (used to treat diabetes mellitus) because of the theoretic risk of exacerbating metabolic acidosis * Prolonged use of linezolid (an antibiotic used to treat S. aureus infections) because of the reported association with optic and peripheral neuropathy and lactic acidosis due to mitochondrial toxicity * Zidovudine (an antiretroviral nucleoside analog reverse transcriptase used to treat HIV) because of the reported risk of inducing mitochondrial disease by interfering with mtDNA replication * Dehydration and prolonged fasting, which can lead to clinical deterioration ### Evaluation of Relatives at Risk If the pathogenic variant(s) have been identified in an affected family member, it is appropriate to clarify the genetic status of at-risk relatives so that those who harbor the pathogenic variant(s) can (1) undergo timely routine surveillance for disease complications and (2) avoid possible precipitating factors. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for 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	RRM2B-Related Mitochondrial Disease	None	26,879	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK195854/	2021-01-18T21:00:18	{"synonyms": []}
A rare, genetic, benign disorder of cobalamin transport, due to variable degrees of transcobalamin I deficiency, characterized by mildly low to almost undetectable plasma transcobalamin I levels and slighly low to absent serum cobalamin levels. Normal methylmalonic acid and homocysteine serum values and absence of megaloblastic anemia are reported. No specific clinical manifestations are associated and patients are typically asymptomatic. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Transcobalamin I deficiency	c0342700	26,880	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2967	2021-01-23T18:30:52	{"gard": ["4522"], "mesh": ["C562798"], "omim": ["193090"], "umls": ["C0342700"], "icd-10": ["E53.8"], "synonyms": ["Haptocorrin deficiency", "TCI deficiency", "Transcobalamin-1 deficiency"]}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article relies largely or entirely on a single source. Relevant discussion may be found on the talk page. Please help improve this article by introducing citations to additional sources. Find sources: "Equine exertional rhabdomyolysis" – news · newspapers · books · scholar · JSTOR (October 2010) 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. (May 2013) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Equine exertional rhabdomyolysis (ER, also known as tying up, azoturia, or Monday morning disease) is a syndrome that damages the muscle tissue in horses. It is usually due to overfeeding a horse carbohydrates and appears to have a genetic link. ## Contents * 1 Causes and process of ER * 2 Symptoms * 3 Treatment * 3.1 Mild or moderate cases * 3.2 Severe cases * 3.3 Returning the animal to work * 4 Prognosis * 5 Prevention * 5.1 Diet * 5.2 Exercise * 5.3 Supplements and drugs * 6 References ## Causes and process of ER[edit] Beyond a highly probable hereditary factor, there does not seem to be a single cause that triggers ER in horses. Exercise is seen in every case, but exercise is always accompanied by another factor. It is likely that several factors must act together in order to cause an ER attack. Other possible factors include: * The overfeeding of non-structural carbohydrates (grain and pellets, for example) * Poor conditioning or fitness, sudden increase of workload * The work of a horse after a period of rest, if the concentrate ration was not reduced * Electrolyte or mineral imbalances, especially seen with potassium * A deficiency in selenium or vitamin E * Imbalance of hormones, including the reproductive hormones in nervous fillies and mares and thyroid hormones in horses with hypothyroidism * Wet, cold, or windy weather conditions The more factors that are present, the greater the likelihood that the horse will develop ER. However, the most common cause of ER is an imbalance between the animal's diet and his workload, especially when he has a high-grain diet. ER occurs when there is an inadequate flow of blood to the muscles of an exercising horse. The muscle cells, lacking in oxygen, begin to function anaerobically to produce the needed ATP. The anaerobic work creates a buildup of waste products, acid, and heat. This subsequently alters the cell by preventing the cell's enzymes from functioning and the myofilaments from efficiently contracting. The cell membranes may then be damaged if the horse is forced to continue work, which allows muscle enzymes and myoglobin to leak into the bloodstream. The body builds up a store of glycogen from converted carbohydrates in muscle cells. Glycogen, a fuel used by muscles for energy, is depleted during work and restocked when a horse rests. Oxygen-carrying blood metabolizes glycogen, but the blood can not flow fast enough to metabolise the excess stored glycogen. The glycogen that is not metabolized aerobically (by the oxygenated blood) must then be metabolized anaerobically, which then creates the cell waste products and heat, and ER has begun. A horse on a high-grain diet with little work collects more glycogen in its muscles than it can use efficiently when exercise begins, which is why horses on a high-grain diet are more likely to develop ER. Proper conditioning can help prevent ER, as it promotes the growth of capillaries in muscles and the number of enzymes used for energy production in muscle cells. However, improvement in these areas can take several weeks. Thus, ER is more common in horses that are only worked sporadically or lightly, and in horses just beginning an exercise regimen. A common misconception is that ER is caused by the buildup of lactic acid. Lactate is not a waste product for a cell, but a fuel, used when the cell's oxygen supply is insufficient. Lactate does not damage a cell, but is rather a byproduct of the true cause of cell damage: inadequate blood supply and altered cell function. Lactate naturally builds up in an exercising horse without harming the muscle cells, and is metabolized within an hour afterwards. The pain is caused by the inadequate blood flow to the muscle tissue, the inflammation from the resulting cell damage, and the release of cell contents. Muscle spasms, caused by the lack of blood to the muscle tissue, are also painful. ## Symptoms[edit] A horse developing ER will usually begin showing signs right after the beginning of exercise, although for mild cases, signs may not be seen until after the horse is cooled out. Signs include reluctance to move, stiffness or shortened gait when the animal is forced to move, and muscle spasms or cramps, with hard, painful muscles (especially the hindquarters) when palpated. If an observer is unfamiliar with ER, initial symptoms may appear to be tiredness or perhaps lameness but the condition is far more complex. Signs of a severe bout of ER may include: reluctance to move, sweating, elevated heart and respiratory rates as a result of the pain, anxious expression, shifting of weight from side to side, standing hunched and tense, passing reddish-brown urine, dehydration, shock, and inability to rise. Usually there is a correlation between how long it takes the signs to be seen and how severe the bout of ER is, with the more severe bouts of ER displaying signs right after work has begun. If signs of ER are seen, the horse should not be moved. Movement can cause further muscle damage. If the animal is far from the barn, it is best to trailer him back rather than move him. After a bout of ER, blood levels of CPK and AST rise. ## Treatment[edit] ### Mild or moderate cases[edit] The horse should receive several days of NSAIDs, rest, and grain or pellets should be withheld. To improve blood flow to the muscles and help to with muscle spasms, heat therapy and Equine Massage may be beneficial, as well as hand-walking if the horse is comfortable walking. Turn-out in a pasture or paddock will encourage movement. A horse should be moving normally within 12–36 hours after the attack. ### Severe cases[edit] A horse may need fluids, especially if its urine is colored, the horse is receiving NSAIDs, or if he is dehydrated. Fluids will increase the production of urine that will in turn help flush out the excess, and potentially damaging, myoglobin from the kidneys and will reduce NSAID-produced kidney damage. Fluids should be administered until the urine is clear, which usually takes from a few hours to a few days. Vasodilators, such as acepromazine, can help improve blood flow to the muscles. However, the owner should only give acepromazine if it is prescribed by the horse's veterinarian, as it can lower the animal's blood pressure and can cause collapse in a severely dehydrated horse. The human drug dantrolene is sometimes given to alleviate the muscle spasms and prevent further degeneration of muscle tissue. Vitamin E is an anti-oxidant, and so may help prevent further cell degeneration in the affected muscles. However, vitamin E products must be used with caution if they also contain selenium. Bicarbonate will not help offset any lactic acid in the bloodstream, as lactic acid generally only accumulates in the affected muscles. Except to get a horse to his stall, a horse showing signs of severe ER should not be moved until he is comfortable enough to do so eagerly. This may take several days. After this point, it is important to either hand-walk the horse a few times each day, or provide him with a few hours of turnout in a pasture or paddock. ### Returning the animal to work[edit] A horse may be returned to work after it is no longer showing signs of ER, and is no longer on NSAIDs—which can hide signs of another bout of ER. If NSAIDs are needed to keep the horse comfortable, or if the horse is reluctant to continue work, the animal is not yet ready for a return to his regular training program. Blood tests should reveal that the horse's CPK concentration and AST levels are normal before the horse is returned to work. To begin bringing the horse back, he should be exercised at the walk and trot for 10–15 minutes at least once every day. This regimen will gradually be increased as the horse becomes more willing. For a moderate or severe bout of ER, it may take 4–6 weeks to return to the regular program. It is important not to push the horse more than he is ready or a relapse may occur. A second bout of ER is usually more severe than the first, not only taking the horse out of training for a longer time, but possibly causing permanent muscle damage. Grain is gradually reintroduced as exercise resumes, but grain can contribute to the development of ER. ## Prognosis[edit] For mild to moderate cases of ER, the prognosis is excellent, with the horse successfully returning to its former level of competition. However, if the vet's recommendations for preventing ER are not followed, ER may likely recur. Horses who experience a severe case of ER (the muscle degeneration is significant) are less likely to return to their previous level of competition, as fibrosis may have occurred, which would result in loss of muscle function. The prognosis is guarded for these horses. ## Prevention[edit] ### Diet[edit] Reducing any extra energy in a horse's diet is essential to maintaining a horse that has experienced ER. Decreasing carbohydrates and increasing the daily intake of hay or pasture can usually accomplish this. Grain may need to be cut out altogether and replaced by a substitute, such as vegetable oil, to meet the individual energy needs of the horse. Grain should be reduced or removed from a horse's ration on days when he cannot be worked. ### Exercise[edit] Proper conditioning is very important in preventing ER. Beginning with a base of long, slow distance work will ensure that the horse has a foundation before proceeding on to more strenuous work. The horse should always have a 10-minute warm-up at the walk and trot before more strenuous work is begun, and should always have a proper cool down of 10 minutes. It is best that a horse receive exercise every day, or possibly twice a day, to prevent the recurrence of ER. If possible, avoid breaks in the horse's exercise schedule. Training, riding, driving, longeing, or turnout are all suitable. Daily pasture turnout is ideal for horses likely to suffer from ER, as it provides exercise and adds roughage to the animal's diet. ### Supplements and drugs[edit] As with any supplements and drugs, it is best to confer with a veterinarian as to the recommended dosages. Some drugs are not allowed in competition and may need to be withheld a few days before. Adding potassium and salt to the diet may be beneficial to horses that suffer from recurrent bouts of ER. Horses in hard training may need a vitamin E supplement, as their requirements are higher than horses in more moderate work. The horse may also be deficient in selenium, and need a feed in supplement. Selenium can be dangerous if overfed, so it is best to have a blood test to confirm that the horse is in need of supplemental selenium. Thyroid hormone supplementation is often beneficial for horses with low thyroid activity (only do so if the horse has been diagnosed with hypothyroidism). Other drugs that have been used with success include phenytoin, dantrolene, and dimethylglycine. Bicarbonate and NSAIDs are of no use in preventing ER. ## References[edit] * King, Christine & Mansmann, Richard, VMD, PhD. Equine Lameness. Copyright Equine Research (1997). Pages 357–368. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Equine exertional rhabdomyolysis	None	26,881	wikipedia	https://en.wikipedia.org/wiki/Equine_exertional_rhabdomyolysis	2021-01-18T18:32:55	{"wikidata": ["Q595708"]}
A number sign (#) is used with this entry because this form of common variable immunodeficiency (CVID), referred to here as CVID1, is caused by homozygous mutation in the ICOS gene (604558) on chromosome 2q33. Description Common variable immunodeficiency (CVID) is a clinically and genetically heterogeneous group of disorders characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections, and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B cells are usually in the normal range, but can be low. Most individuals with CVID have onset of infections after age 10 years. CVID represents the most common form of primary immunodeficiency disorders and is the most common form of primary antibody deficiency. Approximately 10 to 20% of patients with a diagnosis of CVID have a family history of the disorder (reviews by Chapel et al., 2008, Conley et al., 2009, and Yong et al., 2009). ### Genetic Heterogeneity of Common Variable Immunodeficiency Common variable immunodeficiency is a genetically heterogeneous disorder. See also CVID2 (240500), caused by mutation in the TACI gene (TNFRSF13B; 604907); CVID3 (613493), caused by mutation in the CD19 gene (107265); CVID4 (613494), caused by mutation in the BAFFR gene (TNFRSF13C; 606269); CVID5 (613495), caused by mutation in the CD20 gene (112210); CVID6 (613496), caused by mutation in the CD81 gene (186845); CVID7 (614699), caused by mutation in the CD21 gene (CR2; 120650); CVID8 (614700), caused by mutation in the LRBA gene (606453); CVID10 (615577), caused by mutation in the NFKB2 gene (164012); CVID11 (615767), caused by mutation in the IL21 gene (605384); CVID12 (616576), caused by mutation in the NFKB1 gene (164011); CVID13 (616873), caused by mutation in the IKZF1 gene (603023); and CVID14 (617765), caused by mutation in the IRF2BP2 gene (615332). The disorder formerly designated CVID9 has been found to be a form of autoimmune lymphoproliferative disorder; see ALPS3 (615559). Clinical Features In a comprehensive review of common variable immunodeficiency, Hammarstrom and Smith (1999) stated that patients have a marked reduction in serum levels of both IgG and IgA, and in half of the patients, IgM is also reduced. Patients usually present with clinical symptoms due to hypogammaglobulinemia, such as frequent bacterial respiratory and gastrointestinal tract infections. In addition to the B-cell defect, some patients may have variable degrees of T-cell dysfunction. The onset of infection can occur at any age, but there are 2 main peaks in the first and third decades (Hermaszewski and Webster, 1993), and the disorder is equally distributed between the 2 sexes. Cunningham-Rundles and Bodian (1999) described the clinical and immunologic status of 248 consecutively referred patients ranging in age from 3 to 79 years with a clinical diagnosis of CVID. The median age at the time of onset of symptoms and diagnosis was in the third decade for both males and females, although males showed an earlier age of both. In addition to reduced serum immunoglobulins, 40% of patients had subnormal lymphocyte proliferation responses to mitogens, indicating T-cell abnormalities. Associated conditions included autoimmune diseases and lymphoma. Survival 20 years after the diagnosis of CVID was 64% for males and 67% for females. Parameters associated with mortality in the 20-year period were lower levels of serum IgG, poorer T-cell responses to phytohemagglutinin, and particularly, a lower percentage of peripheral B cells. Chapel et al. (2008) followed 334 European patients diagnosed with CVID for more than 5 years (average length of follow-up, 25.6 years) and defined 5 distinct clinical phenotypes: no complications, autoimmunity, polyclonal lymphocytic infiltration, enteropathy, and lymphoid malignancy. The authors found that 83% of patients had only 1 of these phenotypes; 12.6% had criteria for 2 phenotypes. Analysis by clinical phenotypes showed that the highest mortality rates were associated with enteropathy or polyclonal lymphocytic infiltration (relative risks of 4.0 and 3.0, respectively; p less than 0.001 for both). The only clinical predictor was polyclonal lymphocytic infiltration, which was associated with a 5-fold increased risk of lymphoid malignancy. There was widespread variation in the levels of serum immunoglobulin isotypes as well as in the percentages and absolute numbers of B cells, confirming the heterogeneity of these conditions. Higher serum IgM and lower circulating CD8 T-cell (see 186910) levels were found to be predictive markers for polyclonal lymphocytic infiltration and autoimmunity, respectively. In a review of the clinical features of CVID, Yong et al. (2009) stated that the majority of patients are prone to recurrent respiratory and gastrointestinal infections. A subset of patients may develop other complications, including lymphoid proliferation, splenomegaly, granulomatous inflammation, autoimmune disorders, and malignancy. In addition to hypogammaglobulinemia and an inability to mount an antibody response to stimulation, some patients may have additional immunologic abnormalities of monocyte-derived cells and/or T cells. Relatives of patients with CVID have an increased frequency of selective IgA deficiency (see, e.g., IGAD1, 137100). ### Common Variable Immunodeficiency 1 Grimbacher et al. (2003) reported 4 patients between the ages of 19 and 28 years from 2 unrelated families with recurrent bacterial infections of the respiratory and digestive tracts characteristic of humoral immunodeficiency and consistent with a clinical diagnosis of CVID. They lacked other complicating features such as splenomegaly, autoimmune phenomena, or sarcoid-like granulomas, and did not present with clinical signs of overt T-cell immunodeficiency. One of the patients was female, suggesting autosomal recessive inheritance. Laboratory studies showed low peripheral blood B-cell counts ranging from 0.7 to 1.3% in 1 family and 2.8 to 3.3% in the other. Although there were no gross abnormalities in T-cell substrate development, there was a severe disturbance of T-cell-dependent B-cell maturation occurring in secondary lymphoid tissue. No ICOS-specific signal was detected on activated T cells, whereas normal amounts of ICOS were expressed in the activated T cells of the other CVID patients and in those of controls. Patient monocytes expressed normal amounts of ICOS ligand (ICOSLG; 605717). Nearly all B cells of ICOS-deficient individuals exhibited a naive IgD+/IgM+ phenotype. Correspondingly, the numbers of IgM memory and switched memory B cells were substantially reduced. CD80 (112203) expression was reduced on resting B cells of ICOS-deficient individuals, whereas equivalent CD86 (601020) expression was observed on both patient and control B cells. However, ICOSLG expression on the patients' B cells was elevated, an observation consistent with the notion that interaction of ICOS with its ligand downregulates the ligand (Witsch et al., 2002). Data on these 4 affected individuals revealed a profound disturbance of the memory B-cell compartment and decreased Ig production. Salzer et al. (2004) reported 5 patients from 2 additional CVID families with ICOS deficiency. The age at onset ranged from 18 months to 15 years, which was slightly earlier than that reported by Grimbacher et al. (2003). Infections included recurrent bronchitis, sinusitis, and pneumonia, as well as diarrhea. Additional variable features in some patients included splenomegaly, lymphadenopathy, herpes simplex eruptions, and chronic autoimmune neutropenia due to IgG anti-neutrophil antibodies. All patients had decreased switched memory B cells and decreased levels of serum IgG and IgA; IgM was low-normal or low. The T-cell compartment appeared normal. Treatment with intravenous Ig resulted in resolution in some cases. Population Genetics In a comprehensive review of common variable immunodeficiency, Hammarstrom and Smith (1999) estimated that the disorder affects approximately 1 in 10,000 to 100,000 individuals. Pathogenesis Kirkpatrick and Schimke (1967) focused on low IgM as a 'marker' in familial hypogammaglobulinemia. In patients with low serum gammaglobulin, Cooper et al. (1971) found normal numbers of B lymphocytes bearing membrane-bound immunoglobulins; germinal centers were normally formed in antigen-stimulated lymph nodes. They postulated that although the B lymphocytes in such patients have surface recognition antigens, they lack the mechanism for plasma cell differentiation. Farrington et al. (1994) found that 23 of 31 patients (74%) with CVID also had a T-cell defect, whereas the remaining 8 patients did not. Patients with T-cell dysfunction could be further subdivided into those with a broader defect (n = 11) resulting in depressed expression of gp39 (CD40LG; 300386) and variable lymphokine deficiency; others had a more selective defect of either CD40 ligand expression (n = 2) or deficiency of 1 particular lymphokine (n = 10). Thus, CVID may arise from a number of different molecular aberrations. Inefficient signaling via CD40 may be responsible, in part, for failure of B-cell differentiation in some patients with CVID. In a study of 8 patients, including 6 with CVID and 2 with slightly less severe hypogammaglobulinemia and recurrent infections, Levy et al. (1998) found that 2 CVID patients had a dramatic reduction in somatic hypermutation in the variable (V) region of Ig genes. Between 40 and 75% of IgG transcripts were totally devoid of somatic mutation in the circulating memory B-cell compartment. Since functional assays of the T-cell compartment were normal, the findings pointed to an intrinsic B-cell defect in the process of antibody affinity maturation in CVID. Holm et al. (2003) found that T cells from CVID patients activated by anti-CD3 (see 186740) and anti-CD28 (186760) secreted less IL10 (124092) than healthy controls, regardless of proportions of T-cell subsets. Furthermore, sensitivity to cAMP-dependent inhibition of protein kinase A type I (see 188830)-mediated T-cell activation was greater in CVID patients. Holm et al. (2003) proposed that impaired IL10 secretion by CVID patient T cells may be a link between T-cell deficiency and impaired B-cell function in CVID. Using flow cytometry to assess the immunologic profiles of 32 patients with CVID, Cunningham-Rundles et al. (2006) found that, in addition to reduced levels of CD27 (TNFRSF7; 186711)-positive memory B cells, CVID patients had unrelated, pronounced TLR9 (605474) defects. CpG oligonucleotides did not activate CVID B cells, even when costimulated by B-cell receptor, and they did not stimulate surface or intracytoplasmic expression of TLR9 or production of IL6 (147620) or IL10. In addition, CVID plasmacytoid dendritic cells, which expressed normal amounts of intracytoplasmic TLR9, produced only low amounts of IFNA (147660). No TLR9 mutations or polymorphisms were detected. Cunningham-Rundles et al. (2006) concluded that CVID patients have broad TLR9 activation defects that result in impaired CpG-initiated innate immunity. By flow cytometric analysis, Bossaller et al. (2006) found that ICOS-deficient patients, but not other CVID patients, had a severe reduction of CXCR5 (BLR1; 601613)-positive/CD4 (186940)-positive T cells and nearly complete absence of CD57 (see 151290)-positive/CXCR5-positive/CD4-positive T cells. Immunohistochemical analysis demonstrated disturbed germinal center formation in the lymph node of an ICOS-deficient patient. T-cell stimulation with anti-CD3 and anti-ICOS induced CXCR5 expression in normal individuals, but did so only poorly in ICOS-deficient patients. CD40L (300386)-deficient patients also had abrogated germinal center formation and a severe reduction of CXCR5-positive T cells. Molecular Genetics In ICOS-deficient individuals with CVID1, Grimbacher et al. (2003) identified a partial deletion of ICOS mRNA with fully absent protein. The 443-nucleotide deletion of mRNA was due to a deletion of 1,815 basepairs of the ICOS gene, comprising partial deletion of intron 1, a complete deletion of exon 2, intron 2, and exon 3, and a partial deletion of intron 3 (604558.0001). The DNA region deleted in the patients is normally flanked by and partially involves two 150-bp stretches of highly homologous DNA sequences, including a 13-bp (TCTTGTCAGAGTA) repeat. Grimbacher et al. (2003) proposed that the original deletion event occurred during meiotic recombination through homologous unequal recombination, eliminating 1 of the two 13-bp repeats and the entire intervening sequence. This deletion was found in all 4 affected patients from 2 families who were thought to be unrelated; however, identical SNPs were seen in the sequenced region, suggesting a common founder for all 4 patients. This deletion was not found in 100 healthy control alleles. In 5 affected individuals from 2 families with CVID due to ICOS deficiency, Salzer et al. (2004) identified the same homozygous deletion in the ICOS gene that was found by Grimbacher et al. (2003). All 4 families were from the same region along the Danube River in Austria and Germany, and haplotype analysis indicated a founder effect. History Wollheim (1961) described 2 females with 'acquired' hypogammaglobulinemia who came from different parts of Sweden but were remotely related. He suggested that a recessive genetic factor may be involved in 'acquired' hypogammaglobulinemia. Kamin et al. (1968) found that phytohemagglutinin-induced incorporation of labeled precursors into DNA and RNA by lymphocytes was significantly diminished in cells of adults with so-called 'acquired' agammaglobulinemia. The difference was independent of the characteristics of the culture-medium, indicating a cellular abnormality. Animal Model McAdam et al. (2001) found that Icos-deficient mice had similar basal levels of IgM, slightly elevated IgG3, and reduced IgG1, IgG2a, and IgE compared to wildtype mice. Immunized knockout and wildtype mice, except in the presence of the highly inflammatory complete Freund adjuvant, also had similar levels of IgM-specific antibody but reduced IgG1- and IgG2a-specific antibody and reduced germinal center formation. Class switching from IgM to IgG was restored in Icos -/- mice by stimulation of CD40 (109535). Bossaller et al. (2006) showed that Icos-deficient mice had reduced numbers of Cxcr5-positive/Cd4-positive T cells in blood, spleen, and lymph node. Immunohistologic analysis demonstrated a lack of full germinal centers and a reduction of Cd4-positive T cells in B-cell follicles of Icos-deficient mice. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Sinusitis, recurrent Ears \- Otitis media, recurrent Eyes \- Conjunctivitis RESPIRATORY Airways \- Bronchiectasis \- Bronchitis, recurrent Lung \- Pneumonia, recurrent ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly Gastrointestinal \- Enteritis, recurrent \- Diarrhea IMMUNOLOGY \- Recurrent bacterial infections \- Herpes infections \- Lymphadenopathy \- Hypogammaglobulinemia \- Normal or reduced numbers of B cells \- Defective antibody production \- Normal numbers of T cells \- Variable degree of T cell dysfunction \- Autoimmune neutropenia (less common) LABORATORY ABNORMALITIES \- Markedly reduced IgA levels \- Markedly reduced IgG levels \- Reduced IgM levels MISCELLANEOUS \- Variable age at onset, ranging from 18 months to 27 years MOLECULAR BASIS \- Caused by mutation in the inducible costimulator gene (ICOS, 605448.0001 ) ▲ 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, COMMON VARIABLE, 1	c0009447	26,882	omim	https://www.omim.org/entry/607594	2019-09-22T16:09:01	{"doid": ["12177"], "mesh": ["D017074"], "omim": ["607594"], "icd-9": ["279.06"], "icd-10": ["D83.9", "D83"], "orphanet": ["1572"], "synonyms": ["Alternative titles", "ANTIBODY DEFICIENCY DUE TO ICOS DEFECT"]}
Mathematical anxiety, also known as math phobia, is anxiety about one's ability to do mathematics. It is a phenomenon that is often considered when examining students' problems in mathematics. ## Contents * 1 Math anxiety * 2 Performance * 3 Anxiety rating scale * 4 Math and culture * 5 Math and gender * 6 Math pedagogy * 7 Common beliefs * 8 In schools * 8.1 Causes * 8.2 Solutions * 9 See also * 10 References * 11 External links ## Math anxiety[edit] Mark H. Ashcraft defines math anxiety as "a feeling of tension, apprehension, or fear that interferes with math performance" (2002, p. 1).[1] The academic study of math anxiety originates as early as the 1950s, where Mary Fides Gough introduced the term mathemaphobia to describe the phobia-like feelings of many towards mathematics.[2] The first math anxiety measurement scale was developed by Richardson and Suinn in 1972.[citation needed] Since this development, several researchers have examined math anxiety in empirical studies.[1] Hembree[3] (1990) conducted a meta-analysis of 151 studies concerning math anxiety. It determined that math anxiety is related to poor math performance on math achievement tests and that math anxiety is related to negative attitudes concerning math. Hembree also suggests that math anxiety is directly connected with math avoidance. Ashcraft[1] (2002) suggests that highly anxious math students will avoid situations in which they have to perform mathematical calculations. Unfortunately, math avoidance results in less competency, exposure and math practice, leaving students more anxious and mathematically unprepared to achieve. In college and university, anxious math students take fewer math courses and tend to feel negative towards math. In fact, Ashcraft found that the correlation between math anxiety and variables such as confidence and motivation are strongly negative. According to Schar,[4] because math anxiety can cause math avoidance, an empirical dilemma arises. For instance, when a highly math-anxious student performs disappointingly on a math question, it could be due to math anxiety, or the lack of competency in math because of math avoidance. Ashcraft determined that by administering a test that becomes increasingly more mathematically challenging, he noticed that even highly math-anxious individuals do well on the first portion of the test measuring performance. However, on the latter and more difficult portion of the test, there was a stronger negative relationship between accuracy and math anxiety. According to the research found at the University of Chicago by Sian Beilock and her group, math anxiety is not simply about being bad at math. After using brain scans, scholars confirmed that the anticipation or the thought of solving math actually causes math anxiety. The brain scans showed that the area of the brain that is triggered when someone has math anxiety overlaps the same area of the brain where bodily harm is registered.[5] And Trezise and Reeve[6][7] show that students' math anxiety can fluctuate throughout the duration of a math class. ## Performance[edit] The impact of mathematics anxiety on mathematics performance has been studied in much recent literature. An individual with math anxiety does not necessarily lack ability in mathematics, rather, they cannot perform to their full potential due to the interfering symptoms of their anxiety.[8] Math anxiety manifests itself in a variety of ways, including physical, psychological, and behavioral symptoms, that can all disrupt a student's mathematical performance.[9] The strong negative correlation between high math anxiety and low achievement is often thought to be due to the impact of math anxiety on working memory. Working memory has a limited capacity, and when solving mathematical problems, a large portion of this capacity is dedicated to problem solving. However, in individuals with math anxiety, much of this space is taken up by anxious thoughts, thus compromising the individual's ability to perform.[10] In addition, a frequent reliance in schools on high-stakes and timed testing, where students tend to feel the most anxiety, can lead to lower achievement for math anxious individuals.[11] Programme for International Student Assessment (PISA) results demonstrate that students experiencing high math anxiety demonstrate mathematics scores that are 34 points lower than students who do not have math anxiety, equivalent to one full year of school.[12] These findings demonstrate the clear link between math anxiety and reduced levels of achievement, suggesting that alleviating math anxiety may lead to a marked improvement in student achievement. ## Anxiety rating scale[edit] A rating scale for mathematics anxiety was written about in 1972 by Richardson and Suinn.[13] Richardson and Suinn defined mathematical anxiety as "feelings of apprehension and tension concerning manipulation of numbers and completion of mathematical problems in various contexts".[14] Richardson and Suinn introduced the MARS (Mathematics Anxiety Rating Scale) in 1972. Elevated scores on the MARS test translate to high math anxiety. The authors presented the normative data, including a mean score of 215.38 with a standard deviation of 65.29, collected from 397 students that replied to an advertisement for behavior therapy treatment for math anxiety.[15] For test-retest reliability, the Pearson product-moment coefficient was used and a score of 0.85 was calculated, which was favorable and comparable to scores found on other anxiety tests. Richardson and Suinn validated the construct of this test by sharing previous results from three other studies that were very similar to the results achieved in this study. They also administered the Differential Aptitude Test, a 10-minute math test including simple to complex problems. Calculation of the Pearson product-moment correlation coefficient between the MARS test and Differential Aptitude Test scores was −0.64 (p < .01), indicating that higher MARS scores relate to lower math test scores and "since high anxiety interferes with performance, and poor performance produces anxiety, this result provides evidence that the MARS does measure mathematics anxiety".[16] This test was intended for use in diagnosing math anxiety, testing efficacy of different math anxiety treatment approaches and possibly designing an anxiety hierarchy to be used in desensitization treatments.[15] The MARS test is of interest to those in counseling psychology[17] and the test is used profusely in math anxiety research. It is available in several versions of varying length[18] and is considered psychometrically sound.[19] Other tests are often given to measure different dimensionalities of math anxiety, such as Elizabeth Fennema and Julia Sherman's Fennema-Sherman Mathematics Attitudes Scales (FSMAS). The FSMAS evaluates nine specific domains using Likert-type scales: attitude toward success, mathematics as a male domain, mother's attitude, father's attitude, teacher's attitude, confidence in learning mathematics, mathematics anxiety, affectance motivation and mathematics usefulness.[20] Despite the introduction of newer instrumentation, the use of the MARS test appears to be the educational standard for measuring math anxiety due to its specificity and prolific use.[21] ## Math and culture[edit] While there are overarching similarities concerning the acquisition of math skills, researchers have shown that children's mathematical abilities differ across countries. In Canada, students score substantially lower in math problem-solving and operations than students in Korea, India and Singapore. Researchers[who?] have conducted thorough comparisons between countries, and have determined that in countries such as Taiwan and Japan, parents place more emphasis on effort rather than one's innate intellectual ability in school success. By parents placing a higher emphasis on effort rather than one's innate intellectual ability they are helping their child develop a growth mindset.[22] People who develop a growth mindset believe that everyone has the ability to grow their intellectual ability, learn from their mistakes and become more resilient learners. Moreover, parents in these countries tend to set higher expectations and standards for their children. In turn, students spend more time on homework and value homework more than American children.[23] ## Math and gender[edit] Another difference in mathematic abilities often explored in research concerns gender disparities. There has been research examining gender difference in performance on standardized tests across various countries. Beller and Gafni's have shown that children at approximately nine years of age do not show consistent gender difference in relation to math skills. However, in 17 out of the 20 countries examined in this study, 13-year-old boys tended to score higher than girls. Moreover, mathematics is often labeled as a masculine ability; as a result, girls often have low confidence in their math capabilities.[24] These gender stereotypes can reinforce low confidence in girls and can cause math anxiety as research has shown that performance on standardized math tests is affected by one's confidence.[25] As a result, educators have been trying to abolish this stereotype by fostering confidence in math in all students in order to avoid math anxiety.[26] ## Math pedagogy[edit] The principles of mathematics are generally understood at an early age; preschoolers can comprehend the majority of principles underlying counting. By kindergarten, it is common for children to use counting in a more sophisticated manner by adding and subtracting numbers. While kindergarteners tend to use their fingers to count, this habit is soon abandoned and replaced with a more refined and efficient strategy; children begin to perform addition and subtraction mentally at approximately six years of age. When children reach approximately eight years of age, they can retrieve answers to mathematical equations from memory. With proper instruction, normally functioning children acquire these basic mathematical skills and are able to solve more complex mathematical problems with more sophisticated training.[26] (Kail & Zolner, 2005). High risk teaching styles are often explored to gain a better understanding of math anxiety. Goulding, Rowland, and Barber[27] (2002) suggest that there are linkages between a teacher's lack of subject knowledge and ability to plan teaching material effectively. These findings suggest that teachers that do not have a sufficient background in mathematics may struggle with the development of comprehensive lesson plans for their students. Similarly, Laturner's research[28] (2002) shows that teachers with certification in math are more likely to be passionate and committed about teaching math than those without certification. However, those without certification vary in their commitment to the profession depending on coursework preparation. Moreover, a study conducted by Kawakami, Steele, Cifa, Phills, and Dovidio[29] (2008) examined attitudes towards math and behavior during math examinations. The study examined the effect of extensive training in teaching women to approach math. The results showed that women who were trained to approach rather than avoid math showed a positive implicit attitude towards math. These findings were only consistent with women low in initial identification with math. This study was replicated with women who were either encouraged to approach math or who received neutral training. Results were consistent and demonstrated that women taught to approach math had an implicit positive attitude and completed more math problems than women taught to approach math in a neutral manner. Johns, Schmader, and Martens[30] (2005) conducted a study in which they examined the effect of teaching stereotype threat as a means of improving women's math performance. The researchers concluded that women tended to perform worse than men when problems were described as math equations. However, women did not differ from men when the test sequence was described as problem solving or in a condition in which they learned about stereotype threats. This research has practical implications. The results suggested that teaching students about stereotype threat could offer a practical means of reducing its detrimental effects and lead to an improvement in a girl's performance and mathematical ability. Concluding that educating female teachers about stereotype threat can reduce its negative effects in the classroom. ## Common beliefs[edit] A view associated with Francis Galton author of Hereditary Genius (1869)[31] suggests that "when asked to explain why some children do better in math than others, Asian children, their teachers, and their parents point to hard work, their American counterparts to ability."[32] According to Margaret Murray, female mathematicians in the United States have almost always been a minority. Although the exact difference fluctuates with the times, as she has explored in her book Women Becoming Mathematicians: Creating a Professional Identity in Post-World War II America, "Since 1980, women have earned over 17 percent of the mathematics doctorates.... [In The United States]".[33] The trends in gender are by no means clear, but perhaps parity is still a way to go. Since 1995, studies have shown that the gender gap favored males in most mathematical standardized testing as boys outperformed girls in 15 out of 28 countries. However, as of 2015 the gender gap has almost been reversed, showing an increase in female presence. This is being caused by women's steadily increasing their performance on math and science testing and enrollment, but also from males' losing ground at the same time. This role reversal can largely be associated with the gender normative stereotypes that are found in the Science, technology, engineering, and mathematics (STEM) field, deeming "who math is for" and "who STEM careers are for". These stereotypes can fuel mathematical anxiety that is already present among young female populations.[34] Thus parity will take more work to overcome mathematical anxiety and this is one reason why women in mathematics are role models for younger women. ## In schools[edit] This section has been nominated to be checked for its neutrality. Discussion of this nomination can be found on the talk page. (September 2013) (Learn how and when to remove this template message) ### Causes[edit] Students often develop mathematical anxiety in schools, often as a result of learning from teachers who are themselves anxious about their mathematical abilities in certain areas. Typical examples of areas where mathematics teachers are often incompetent or semi-competent include fractions, (long) division, algebra, geometry "with proofs", calculus, and topology. In many countries, would-be math teachers are required only to obtain passing grades of 51% in mathematics exams, so that a math student who has failed to understand 49% of the math syllabus throughout his or her education can, and often does, become a math teacher. His or her fears and lack of understanding then pass naturally to his or her students. According to John Taylor Gatto, as expounded in several lengthy books,[35][page needed] modern Western schools were deliberately[dubious – discuss] designed during the late 19th century to create an environment which is ideal for fostering fear and anxiety, and for preventing or delaying learning. Many who are sympathetic to Gatto's thesis regard his position as unnecessarily extreme.[36] Diane Ravitch, former assistant secretary of education during the George H.W. Bush administration, agrees with Gatto up to a point, conceding that there is an element of social engineering (i.e. manufacture of compliant citizenry) in the construction of the American education system,[36] which prioritizes conformance over learning. The role of attachment has been suggested as having an impact in the development of the anxiety.[37] Children with an insecure attachment style were more likely to demonstrate the anxiety. Math is usually taught as a right and wrong subject and as if getting the right answer were paramount. In contrast to most subjects, mathematics problems almost always have a right answer. Additionally, the subject is often taught as if there were a right way to solve the problem and any other approaches would be wrong, even if students got the right answer. When learning, understanding the concepts should be paramount, but with a right/wrong approach to teaching math, students are encouraged not to try, not to experiment, not to find algorithms that work for them, and not to take risks. "Teachers benefit children most when they encourage them to share their thinking process and justify their answers out loud or in writing as they perform math operations. ... With less of an emphasis on right or wrong and more of an emphasis on process, teachers can help alleviate students' anxiety about math".[38] While teaching of many subjects has changed from rote memorization to the current Constructivist approach, math is frequently taught with a rote learning behaviorist approach. That is, * A problem set is introduced * A solution technique is introduced * Practice problems are repeated until mastery is achieved Constructivist theory says the learning and knowledge is the student's creation, yet rote learning and a right/wrong approach to teaching math ensures that it is external to the student. ### Solutions[edit] There have been many studies that show parent involvement in developing a child's educational processes is essential. A student's success in school is increased if their parents are involved in their education both at home and school (Henderson & Map, 2002).[39] As a result, one of the easiest ways to reduce math anxiety is for the parent to be more involved in their child's education. In addition, research has shown that a parent's perception on mathematics influences their child's perception and achievement in mathematics (Yee & Eccles, 1988).[40] This means that if a parent makes it apparent that they do not enjoy mathematics or that they are not good at mathematics, this can influence the way in which their child views mathematics. Furthermore, studies by Herbert P. Ginsburg, Columbia University, show the influence of parents' and teachers' attitudes on "'the child's expectations in that area of learning.'... It is less the actual teaching and more the attitude and expectations of the teacher or parents that count". This is further supported by a survey of Montgomery County, Maryland students who "pointed to their parents as the primary force behind the interest in mathematics".[41] Claudia Zaslavsky[41] contends that math has two components. The first component, commonly focused on in many schools, is to calculate the answer. This component also has two subcomponents, namely the answer and the process or method used to determine the answer. Focusing more on the process or method enables students to make mistakes, but not 'fail at math'. The second component is to understand the mathematical concepts that underlay the problem being studied. "... and in this respect studying mathematics is much more like studying, say, music or painting than it is like studying history or biology." Amongst others supporting this viewpoint is the work of Dr. Eugene Geist, Associate Professor at Ohio University – Athens, Ohio and an early childhood education specialist.[42] Dr. Geist's recommendations include focusing on the concepts rather than the right answer and letting students work on their own and discuss their solutions before the answer is given. Emphasis is given that young people hate to be wrong and hate situations where they can be embarrassed by being wrong. National Council of Teachers of Mathematics (NCTM) (1989, 1995b) suggestions for teachers seeking to prevent math anxiety include: > * Accommodating for different learning styles > * Creating a variety of testing environments > * Designing positive experiences in math classes > * Refraining from tying self-esteem to success with math > * Emphasizing that everyone makes mistakes in mathematics > * Making math relevant > * Letting students have some input into their own evaluations > * Allowing for different social approaches to learning mathematics > * Emphasizing the importance of original, quality thinking rather than rote manipulation of formulas > Hackworth (1992)[43] suggests that the following activities can help in reducing and mitigating mathematical anxiety: > * Discuss and write about math feelings; > * Become acquainted with good math instruction, as well as study techniques; > * Recognize what type of information needs to be learned; > * Be an active learner, and create problem-solving techniques; > * Evaluate your own learning; > * Develop calming/positive ways to deal with fear of math, including visualization, positive messages, relaxation techniques, frustration breaks; > * Use gradual, repeated success to build math confidence in students > Math (and Statistics) Therapy is a combination of coaching and counseling, provided for adults by people with credentials in both counseling and math education. In Math Therapy the reasons for anxiety are addressed, as well as the mathematical skills which are lacking. New coping skills are introduced and practiced, so that fear, distaste or other negative emotions do not block math (or statistics) learning. There are several anxiety reducing techniques that teachers can teach their children and practice periodically throughout the year. Teachers will need to learn these techniques and encourage the students to practice them at home and to use them prior to testing or when feeling anxious during math class. Several studies have shown that relaxation techniques can be used to help alleviate anxiety related to mathematics. In her workbook Conquering Math Anxiety, Cynthia Arem offers specific strategies to reduce math avoidance and anxiety. One strategy she advocates for is relaxation exercises and indicates that by practicing relaxation techniques on a regular basis for 10–20 minutes students can significantly reduce their anxiety.[44] Dr. Edmundo Jacobson's Progressive Muscle Relaxation taken from the book Mental Toughness Training for Sports, Loehr (1986) can be used in a modified form to reduce anxiety as posted on the website HypnoGenesis.[45] Visualization has also been used effectively to help reduce math anxiety. Arem has a chapter that deals with reducing test anxiety and advocates the use of visualization. In her chapter titled Conquer Test Anxiety (Chapter 9) she has specific exercises devoted to visualization techniques to help the student feel calm and confident during testing.[46] Studies have shown students learn best when they are active rather than passive learners.[47] The theory of multiple intelligences suggests that there is a need for addressing different learning styles. Math lessons can be tailored for visual/spatial, logical/mathematics, musical, auditory, body/kinesthetic, interpersonal and intrapersonal and verbal/linguistic learning styles. This theory of learning styles has never been demonstrated to be true in controlled trials. Studies show no evidence to support tailoring lessons to an individual students learning style to be beneficial.[48] New concepts can be taught through play acting, cooperative groups, visual aids, hands on activities or information technology.[49] To help with learning statistics, there are many applets found on the Internet that help students learn about many things from probability distributions to linear regression. These applets are commonly used in introductory statistics classes, as many students benefit from using them.[original research?][who?] Active learners ask critical questions, such as: Why do we do it this way, and not that way? Some teachers may find these questions annoying or difficult to answer, and indeed may have been trained to respond to such questions with hostility and contempt, designed to instill fear. Better teachers respond eagerly to these questions, and use them to help the students deepen their understanding by examining alternative methods so the students can choose for themselves which method they prefer. This process can result in meaningful class discussions. Talking is the way in which students increase their understanding and command of math.[50] Teachers can emphasize the importance of original thinking rather than rote manipulation of formulas. This can be done through class conversations. Teachers can give students insight as to why they learn certain content by asking students questions such as "what purpose is served by solving this problem?" and "why are we being asked to learn this?"[51] Reflective journals help students develop metacognitive skills by having them think about their understanding. According to Pugalee,[52] writing helps students organize their thinking which helps them better understand mathematics. Moreover, writing in mathematics classes helps students problem solve and improve mathematical reasoning. When students know how to use mathematical reasoning, they are less anxious about solving problems. However, there is still a large part of school math teaching which consists of "mass-produced" memorization, repetition, and mechanically performed operations. Times tables are one example, wherein rote learning is essential to mathematics performance. When a student fails to learn the times tables at a young age, they can experience math anxiety later, when all the students' classmates can remember the tables but they cannot. Children learn best when math is taught in a way that is relevant to their everyday lives. Children enjoy experimenting. To learn mathematics in any depth, students should be engaged in exploring, conjecturing, and thinking, as well as in rote learning of rules and procedures.[53] ## See also[edit] * Cognitive science of mathematics * Dyscalculia, a specific developmental disorder * Educational psychology * Foreign language anxiety * Learning theory * Primary education * Pygmalion effect, the phenomenon whereby higher expectations lead to an increase in performance * Stage fright * Test anxiety ## References[edit] 1. ^ a b c Ashcraft, M.H. 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New York, New York: Cambridge University Press. pp. 163–189. 51. ^ Franklin, Margaret (2006). Add-ventures for girls: building math confidence, Junior High teacher's guide. Newton, Massachusetts: WEEA Publishing Center. 52. ^ Pugalee, D. (2004). "A Comparison of Verbal and Written Descriptions of Students' Problem Solving Processes". Educational Studies in Mathematics. 55 (3): 27–47. doi:10.1023/b:educ.0000017666.11367.c7. S2CID 122937513. 53. ^ http://www.marilyncurtainphillips.com ## External links[edit] * Online information about and demonstration of a short mathematics anxiety test * Defence Mechanisms against Mathematics [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Mathematical anxiety	None	26,883	wikipedia	https://en.wikipedia.org/wiki/Mathematical_anxiety	2021-01-18T18:47:01	{"wikidata": ["Q845527"]}
Pheochromocytomas are tumors of the adrenal glands. These glands are located right above the kidneys. Pheochromocytomas cause the adrenal glands to make too many stress hormones called epinephrines and norepinephrines. This can lead to high blood pressure and cause symptoms such as severe headaches, irritability, sweating, rapid heart rate, nausea, vomiting, weight loss, weakness, chest pain, and anxiety. Rarely, this kind of tumor occurs outside the adrenal gland, usually somewhere in the abdomen. These are called extra-adrenal pheochromocytomas or paragangliomas. The cause of most pheochromocytomas is unknown. In some cases, there is a genetic cause. This type of tumor can occur in certain familial genetic syndromes, including multiple endocrine neoplasia, type 2 (MEN2), neurofibromatosis type 1, Von Hippel-Lindau disease, hereditary paraganglioma-pheochromocytoma syndrome, Carney triad, and Carney-Stratakis dyad. There are also several genes that have been associated with pheochromocytoma when it does not occur as part of a 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	Pheochromocytoma	c0031511	26,884	gard	https://rarediseases.info.nih.gov/diseases/7385/pheochromocytoma	2021-01-18T17:58:20	{"mesh": ["D010673"], "synonyms": ["Adrenal Gland Chromaffin Paraganglioma", "Adrenal Gland Chromaffinoma", "Adrenal Gland Paraganglioma", "Intraadrenal Paraganglioma", "Chromaffin Paraganglioma of the Adrenal Gland", "Adrenal Gland Pheochromocytoma"]}
Renal oncocytoma Micrograph of a renal oncocytoma. A renal oncocytoma is a tumour of the kidney made up of oncocytes, epithelial cells with an excess amount of mitochondria.[1][2] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 2.1 Histologic appearance * 3 Diagnosis * 3.1 Immunohistochemical profile * 4 Treatment * 5 Prognosis * 6 Additional images * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] Renal oncocytoma of the right kidney at CT. Renal oncocytomas are often asymptomatic and are frequently discovered by chance on a CT or ultrasound of the abdomen. Possible signs and symptoms of a renal oncocytoma include blood in the urine, flank pain, and an abdominal mass. ## Pathophysiology[edit] Renal oncocytoma is thought to arise from the intercalated cells of collecting ducts of the kidney. It represent 5% to 15% of surgically resected renal neoplasms. Ultrastructurally, the eosinophilic cells have numerous mitochondria. ### Histologic appearance[edit] This section needs expansion. You can help by adding to it. (January 2011) An oncocytoma is an epithelial tumor composed of oncocytes, large eosinophilic cells having small, round, benign-appearing nuclei with large nucleoli and excessive amounts of mitochondria. ## Diagnosis[edit] Gross appearance of a renal oncocytoma (left of image) and a slice of a normal kidney (right of image). Note the rounded contour, the mahogany colour and the central scar. In gross appearance, the tumors are tan or mahogany brown, well circumscribed and contain a central scar. They may achieve a large size (up to 12 cm in diameter). The main differential diagnosis of renal oncocytoma is chromophobe renal cell carcinoma oncocytic variant, which like the renal oncocytoma has eosinophilic cytoplasm, but has perinuclear clearing and, typically, some degree of nuclear atypia. ### Immunohistochemical profile[edit] * Cytokeratin AE1/AE3 + * Vimentin - * EMA + * CD10+/- * CK7 +/- parcellaire * CK20 - * CK19 - * AMACR (Racemase) - * S100 + * c-kit (CD117) + * Cadherin-E + * TFE3 - * CAM5.2 + [3] ## Treatment[edit] Renal oncocytoma is considered benign, cured by nephrectomy. There are some familial cases in which these tumors are multicentric rather than solitary.[4] However, they may be resected to exclude a malignant tumor, e.g. renal cell carcinoma. ## Prognosis[edit] Histopathologic types of kidney tumor, with relative incidences and prognoses. Oncocytoma is seen at right in the pie chart. The overall five-year survival rate has been estimate to be 63%, with most individuals dying from cardiovascular diseases or other cancers.[5] ## Additional images[edit] * Micrograph of a renal oncocytoma. H&E stain. * Micrograph of a renal oncocytoma. H&E stain. * Micrograph of a renal oncocytoma. H&E stain. * Micrograph of a renal oncocytoma. H&E stain. * Micrograph of a renal oncocytoma. H&E stain. * Micrograph of chromophobe RCC oncocytic variant, the main differential diagnosis of renal oncocytoma. ## See also[edit] * Kidney * Renal cell carcinoma ## References[edit] 1. ^ Coburn V, Radfar A, Snook D, Mahalingam M (2007). "Cutaneous oncocytoma - a report of three cases and review of the literature". J. Cutan. Pathol. 34 (4): 355–9. doi:10.1111/j.1600-0560.2006.00620.x. PMID 17381809. 2. ^ "Atlas of Genetics and Cytogenetics in Oncology and Haematology - Thyroid:oncocytic tumors". Retrieved 2009-02-01. 3. ^ [Renal Neoplasms: An Update on Immunohistochemical and Histochemical Features http://www.dako.com/08066_12may10_webchapter26.pdf] 4. ^ Robbins pathology, page 1015[full citation needed] 5. ^ Gudbjartsson, Tomas; Hardarson, Sverrir; Petursdottir, Vigdis; Thoroddsen, Asgeir; Magnusson, Jonas; Einarsson, Gudmundur V. (2005). "Renal oncocytoma: a clinicopathological analysis of 45 consecutive cases". BJU International. 96 (9): 1275–1279. doi:10.1111/j.1464-410X.2005.05827.x. ISSN 1464-4096. ## External links[edit] Classification D * ICD-O: M8290/0 * MeSH: C537750 C537750, C537750 * DiseasesDB: 31956 * v * t * e Glandular and epithelial cancer Epithelium Papilloma/carcinoma * Small-cell carcinoma * Combined small-cell carcinoma * Verrucous carcinoma * Squamous cell carcinoma * Basal-cell carcinoma * Transitional cell carcinoma * Inverted papilloma Complex epithelial * Warthin's tumor * Thymoma * Bartholin gland carcinoma Glands Adenomas/ adenocarcinomas Gastrointestinal * tract: Linitis plastica * Familial adenomatous polyposis * pancreas * Insulinoma * Glucagonoma * Gastrinoma * VIPoma * Somatostatinoma * Cholangiocarcinoma * Klatskin tumor * Hepatocellular adenoma/Hepatocellular carcinoma Urogenital * Renal cell carcinoma * Endometrioid tumor * Renal oncocytoma Endocrine * Prolactinoma * Multiple endocrine neoplasia * Adrenocortical adenoma/Adrenocortical carcinoma * Hürthle cell Other/multiple * Neuroendocrine tumor * Carcinoid * Adenoid cystic carcinoma * Oncocytoma * Clear-cell adenocarcinoma * Apudoma * Cylindroma * Papillary hidradenoma Adnexal and skin appendage * sweat gland * Hidrocystoma * Syringoma * Syringocystadenoma papilliferum Cystic, mucinous, and serous Cystic general * Cystadenoma/Cystadenocarcinoma Mucinous * Signet ring cell carcinoma * Krukenberg tumor * Mucinous cystadenoma / Mucinous cystadenocarcinoma * Pseudomyxoma peritonei * Mucoepidermoid carcinoma Serous * Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma Ductal, lobular, and medullary Ductal carcinoma * Mammary ductal carcinoma * Pancreatic ductal carcinoma * Comedocarcinoma * Paget's disease of the breast / Extramammary Paget's disease Lobular carcinoma * Lobular carcinoma in situ * Invasive lobular carcinoma Medullary carcinoma * Medullary carcinoma of the breast * Medullary thyroid cancer Acinar cell * Acinic cell carcinoma * v * t * e Tumors of the urinary and genital systems Kidney Glandular and epithelial neoplasm * Renal cell carcinoma * Renal oncocytoma Mixed tumor * Wilms' tumor * Mesoblastic nephroma * Clear-cell sarcoma of the kidney * Angiomyolipoma * Cystic nephroma * Metanephric adenoma by location * Renal medullary carcinoma * Juxtaglomerular cell tumor * Renal medullary fibroma Ureter * Ureteral neoplasm Bladder * Transitional cell carcinoma * Squamous-cell carcinoma * Inverted papilloma Urethra * Transitional cell carcinoma * Squamous-cell carcinoma * Adenocarcinoma * Melanoma Other * Malignant fibrous histiocytoma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Renal oncocytoma	c0346255	26,885	wikipedia	https://en.wikipedia.org/wiki/Renal_oncocytoma	2021-01-18T18:43:12	{"gard": ["8477"], "mesh": ["C537750"], "umls": ["C0346255"], "wikidata": ["Q3882418"]}
Lewis lung carcinoma is a tumor that spontaneously developed as an epidermoid carcinoma in the lung of a C57BL mouse. It was discovered in 1951 by Dr. Margaret Lewis of the Wistar Institute and became one of the first transplantable tumors.[1] ## Contents * 1 Models * 1.1 Syngeneic * 1.2 Orthotopic * 2 Characterization * 3 Research * 4 References ## Models[edit] ### Syngeneic[edit] According to a 2015 review article, Lewis lung carcinoma is the only reproducible syngeneic lung cancer model, meaning that it is the only reproducible lung cancer model that utilizes a transplant that is immunologically compatible. Syngeneic models have proven to be useful in predicting clinical benefit of therapy in preclinical experiments. However, there has been criticism directed towards syngeneic model usage when attempting to translate therapies from another species to humans. For example, cancer therapies that exhibited promising results in mouse models can and have failed in clinical trials due to physiological differences in the activity of the targeted gene product. The activity of the mouse product did not translate to the activity of the human counterpart. [2] ### Orthotopic[edit] Lewis lung carcinoma can also be utilized as an orthotopic model.[2] Orthotopic models focus upon correctly modeling the tumor microenvironment by injecting or implanting tumors into the corresponding organ that they originated from (i.e. implanting a Lewis lung carcinoma into the lung of another C57BL mouse). Because of this fidelity to mimicking the tumor microenvironment, orthotopic models are considered to be more physiologically relevant in representing human tumorigenesis. However, the creation of such models is a typically more involved and technically challenging process. They also require more complex imaging modalities for data collection.[3] ## Characterization[edit] Generally, Lewis lung carcinoma is highly metastatic in immunocompetent mice.[4] If subcutaneously injected into mice, it is known to avidly metastasize to the lung. In fact, a 1996 study found that the carcinoma predominantly metastasized into the lungs after tail vein injections.[5] Lewis lung carcinoma has the appearance of a semi-firm homogeneous mass that is not grossly hemorrhagic.[6] Tumor progression was observed after subcutaneous injection into the dorsal subcutis for 107 wild type, 129/Black Swiss mice. These mice were selected for their genetic background proximity to C57BL/6J mice. They observed the progression as being characterized by skin ulceration followed by ulcer hemorrhaging. Not only that, there was also basal hemorrhaging and/or edema.[4] The cells were anaplastic, varying in size and shape; and they appeared to have little cytoplasm. The nuclei of the cells were highly distorted and prominent.[4] The tumors were highly vascularized and metastasized to different sites, including the lungs, lymph nodes, liver, pleural cavity, diaphragm, pericardium, cardiac muscle, pancreas, adipose tissue, and esophagus. In cases of lung metastasis, large tumor masses underwent necrosis, with some of them hemorrhaging and even fewer exhibiting acute inflammation. Smaller metastases positioned themselves to be eccentric or concentric to vessels. In large tumor nodules, the cells grew, without patterning, into confluent sheets. The nodules had capillaries predominantly forming and supplying blood to the surface. The capillaries were fine and thin-walled. The nodules did exhibit expansion, interfering with and invading the space of surrounding tissues. This caused tissue degeneration.[4] ## Research[edit] The Lewis lung carcinoma tumor model’s role in cancer has been its use for research into tumor metastasis and angiogenesis properties. The model is also useful for chemotherapeutic testing in vivo. Navelbine and carboplatin, two chemotherapeutics currently on the market, were tested in C57BL mice with Lewis lung carcinoma tumors in their hind flank. Tumor regression reached 72.7% in the navelbine trials, with the carboplatin trials showing that 30-50 percent of the population had a prolonged tumor survival after treatment with carboplatin and paclitaxel.[2] Melittin, a polypeptide found in bee venom, on tumor-associated macrophages has been examined in a Lewis lung carcinoma model. Melittin has a background in research as a possible cancer drug due to its activity against malignant cells. Tumor-associated macrophages facilitate tumor progression through the promotion of angiogenesis and immunosuppression. In the in vivo tests, melittin inhibited rapid tumor growth and was correlated with decreased angiogenesis marker levels, VEGF and CD31.[7] Toll-like receptor 4 mediates cancer-induced muscle wasting in a Lewis lung carcinoma model. It does so by directly activating muscle catabolism and stimulating an innate immune response in the mice.[8] Targeting of CD169+ macrophages in order to inhibit tumor Lewis lung carcinoma growth also caused depletion of bone and bone marrow in mice. This depletion disrupted bone homeostasis and caused bone weight loss and a bone density decrease in mice. Not only that, erythropoietic activity was severely impaired. Therefore, the use of CD169+ macrophage targeting cancer therapies requires careful consideration of pitfalls.[9] Cannabinoids suppress Lewis lung carcinoma cell growth. The mechanism of this action was shown to be inhibition of DNA synthesis[10] Cannabinoids increase the life span of mice carrying Lewis lung tumors and decrease primary tumor size.[11] There are multiple modes of action.[12] ## References[edit] 1. ^ Rashidi B, Yang M, Jiang P, Baranov E, An Z, Wang X, Moossa AR, Hoffman RM (2000-01-01). "A highly metastatic Lewis lung carcinoma orthotopic green fluorescent protein model". Clinical & Experimental Metastasis. 18 (1): 57–60. doi:10.1023/A:1026596131504. PMID 11206839. 2. ^ a b c Kellar A, Egan C, Morris D (2015). "Preclinical Murine Models for Lung Cancer: Clinical Trial Applications". BioMed Research International. 2015: 621324. doi:10.1155/2015/621324. PMC 4433653. PMID 26064932. 3. ^ Qiu W, Su GH (2013). "Development of orthotopic pancreatic tumor mouse models". Methods in Molecular Biology. 980: 215–23. doi:10.1007/978-1-62703-287-2_11. PMC 4049460. PMID 23359156. 4. ^ a b c d Bugge TH, Kombrinck KW, Xiao Q, Holmbäck K, Daugherty CC, Witte DP, Degen JL (December 1997). "Growth and dissemination of Lewis lung carcinoma in plasminogen-deficient mice". Blood. 90 (11): 4522–31. PMID 9373263. 5. ^ Anderson IC, Shipp MA, Docherty AJ, Teicher BA (February 1996). "Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine Lewis lung carcinoma". Cancer Research. 56 (4): 715–8. PMID 8631001. 6. ^ Mayo JG (November 1972). "Biologic characterization of the subcutaneously implanted Lewis lung tumor". Cancer Chemotherapy Reports. Part 2. 3 (1): 325–30. PMID 4660735. 7. ^ Lee C, Bae SS, Joo H, Bae H (August 2017). "Melittin suppresses tumor progression by regulating tumor-associated macrophages in a Lewis lung carcinoma mouse model". Oncotarget. 8 (33): 54951–54965. doi:10.18632/oncotarget.18627. PMC 5589633. PMID 28903394. 8. ^ Zhang G, Liu Z, Ding H, Miao H, Garcia JM, Li YP (May 2017). "Toll-like receptor 4 mediates Lewis lung carcinoma-induced muscle wasting via coordinate activation of protein degradation pathways". Scientific Reports. 7 (1): 2273. doi:10.1038/s41598-017-02347-2. PMC 5442131. PMID 28536426. 9. ^ Jing W, Zhang L, Qin F, Li X, Guo X, Li Y, Qiu C, Zhao Y. "Targeting macrophages for cancer therapy disrupts bone homeostasis and impairs bone marrow erythropoiesis in mice bearing Lewis lung carcinoma tumors". Cellular Immunology. doi:10.1016/j.cellimm.2017.09.006. 10. ^ Friedman MA (1977). "In vivo effects of cannabinoids on macromolecular biosynthesis in Lewis lung carcinomas". Cancer Biochemistry Biophysics. 2 (2): 51–4. PMID 616322. 11. ^ Kogan NM (October 2005). "Cannabinoids and cancer". Mini Reviews in Medicinal Chemistry. 5 (10): 941–52. doi:10.2174/138955705774329555. PMID 16250836. 12. ^ Portella G, Laezza C, Laccetti P, De Petrocellis L, Di Marzo V, Bifulco M (September 2003). "Inhibitory effects of cannabinoid CB1 receptor stimulation on tumor growth and metastatic spreading: actions on signals involved in angiogenesis and metastasis". FASEB Journal. 17 (12): 1771–3. doi:10.1096/fj.02-1129fje. PMID 12958205. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Lewis lung carcinoma	c0243038	26,886	wikipedia	https://en.wikipedia.org/wiki/Lewis_lung_carcinoma	2021-01-18T18:37:44	{"mesh": ["D018827"], "wikidata": ["Q6537255"]}
Melnick-Needles syndrome (MNS) belongs to the otopalatodigital syndrome spectrum disorder and is associated with a short stature, facial dysmorphism, osseous abnormalities involving the majority of the axial and appendicular skeleton resulting in impaired speech and masticatory problems. ## Epidemiology To date, less than 70 cases with MNS have been documented. MNS is a disorder essentially limited to females as it is lethal in males. Survivorship in males is possible due to mosaicism. ## Clinical description MNS is a congenital disorder characterized by a short stature, facial dysmorphism (small facies with prominent forehead, full cheeks, retrognathia, marked micrognathia), impaired speech, masticatory problems, and bowing of the arms and lower legs. Eye and ear abnormalities include bilateral exophthalmus, strabismus, blue sclera, conductive deafness and large pinna. Kyphoscoliosis is common. Mitral and tricuspid valve prolapse, bowel malrotation, hydronephrosis, and joint subluxation may be observed. Severe mandibular hypoplasia can cause upper airway restriction, obstructive sleep apnea syndrome and pneumonia and occasionally respiratory failure. Complete atrioventricular canal, prune belly syndrome and omphalocele have been reported in lethally affected males. Intelligence is normal. In females, the syndrome presents with bone dysplasia and facial dysmorphism. Males born to affected mothers show a lethal course of the disease in the embryonic or perinatal period. ## Etiology MNS is caused by gain of function mutations in the gene FLNA (Xq28) that encodes the actin-binding cytoskeletal protein filamin A. Several lines of evidence suggest that filamin participates in the remodeling of the cytoskeleton during development by integrating cell signaling events with subsequent alterations in cellular shape and motility. MNS is allelic with 4 other skeletal dysplasias (otopalatodigital syndrome type 1 and 2 (OPD1 and OPD2, respectively), terminal osseous dysplasia - pigmentary defects (TOD) and frontometaphyseal dysplasia (FMD). ## Genetic counseling MNS is inherited in an X-linked dominant manner. Male-to-male transmission has not been reported. The risk of transmitting the mutation in each pregnancy is 50%; males inheriting the mutation will be affected while females who inherit the mutation are less severely affected. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Melnick-Needles syndrome	c0025237	26,887	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2484	2021-01-23T17:44:28	{"gard": ["7011"], "mesh": ["D010009"], "omim": ["309350"], "umls": ["C0025237"], "icd-10": ["Q77.8"], "synonyms": ["Melnick-Needles osteodysplasty"]}
Seckel syndrome is a genetic disorder characterized by growth retardation, very small head (microcephaly( with intellectual disability , and unique facial features such as large eyes, beak-like nose, narrow face, and receding lower jaw. About less than 25% of the patients also have blood abnormalities. Seckel syndrome is inherited in an autosomal recessive fashion. The condition may be divided in 8 different subtypes, according to the specific gene alteration (mutation ). Treatment is supportive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Seckel syndrome	c0265202	26,888	gard	https://rarediseases.info.nih.gov/diseases/8562/seckel-syndrome	2021-01-18T17:57:47	{"omim": ["210600", "606744", "608664"], "umls": ["C0265202"], "orphanet": ["808"], "synonyms": ["SCKL", "Nanocephalic dwarfism", "Seckel-type dwarfism", "Bird-headed dwarfism"]}
Respiratory compromise SpecialtyPulmonology Respiratory compromise describes a deterioration in respiratory function with a high likelihood of rapid progression to respiratory failure and death.[1] Respiratory failure occurs when inadequate gas exchange by the respiratory system occurs, with a low oxygen level or a high carbon dioxide level. ## Contents * 1 Causes * 1.1 Risk factors * 2 Diagnosis * 2.1 Recognition and intervention * 3 Prevention * 4 Treatment * 5 References ## Causes[edit] Patients in acute care hospitals, particularly those with respiratory conditions, are at risk for developing respiratory compromise. Respiratory failure requiring emergency mechanical ventilation occurs in over 40,000 patients per year in the United States.[2] In postoperative patients in the United States, the National Surgical Quality Improvement Program reports that 1.03% of all surgical patients require an unplanned intubation postoperatively.[3] Although respiratory compromise may develop de novo during hospitalization in patients without preexisting lung disease, in other patients, it develops as a complication of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD). Although respiratory failure is caused by a heterogeneous group of processes, there are subsets of patients who manifest similar physiologic patterns of deterioration[4] * Impaired control of breathing – e.g. opioid overdose * Impaired airway protection – e.g. cerebrovascular accident (CVA) * Parenchymal lung disease – e.g. Acute Respiratory Distress Syndrome (ARDS) * Increased airway resistance – e.g. COPD exacerbation * Hydrostatic pulmonary edema – e.g. left ventricular heart failure * Right ventricular failure – e.g. acute pulmonary embolism ### Risk factors[edit] The term respiratory compromise is used to describe various intensities of respiratory dysfunction that can range from a chronic state of respiratory insufficiency to conditions that require emergency resuscitation and a breathing machine.[citation needed] Risk factors include a variety of substances, conditions, and environments:[5] * Acute respiratory distress syndrome * Age * Asthma * Care setting * COPD * COVID-19 * General anesthesia, opioids, and neuromuscular blocking agents * Obesity * Pneumonia and other respiratory infections * Pulmonary fibrosis * Sleep apnea In addition to the lung deterioration observed for the various etiologies and mechanisms of respiratory compromise, severe respiratory compromise can have a concomitant impact on non-pulmonary systems of the body.[6] ## Diagnosis[edit] Central to implementing therapies to reverse or mitigate a state of respiratory compromise is an accurate diagnosis of the condition. Correctly diagnosing respiratory compromise requires a screening to determine the amount of gas in the patient's bloodstream. Two different tests are available for clinical diagnosis.[citation needed] Testing and monitoring blood gas levels requires one of the following diagnostic procedures: * Pulse oximetry For this test, a small sensor is attached to the patient's finger or ear. The sensor uses light to estimate how much oxygen is in the blood. A pulse oximeter works by beaming red and infrared light through capillaries. The amount of red and infrared light transmitted provides an approximate measure of oxygen in the blood. The oximeter reading is based on the color of the blood: oxygenated blood is a brighter red than deoxygenated blood, which appears as bluish purple. * Arterial blood gas test (ABG) This test measures the precise levels of oxygen and carbon dioxide in the blood. A blood sample is drawn from an artery, typically in the wrist. A laboratory then processes the blood sample to determine oxygen and carbon dioxide levels. Assessing and monitoring blood gas levels is the most accurate means to identify a state of respiratory compromise in patients. ABG testing does however require an arterial blood sample, which is more invasive and uncomfortable for patients than a pulse oximetry reading that uses a reading based on light and color.[7] ### Recognition and intervention[edit] The importance of diagnosing respiratory compromise is that with earlier diagnosis and treatment progression to respiratory failure may be prevented. Enhanced monitoring techniques and specific therapies may prevent progression of respiratory compromise to respiratory failure and possible death. ## Prevention[edit] Classifying acutely ill respiratory patients into one or more of these categories may help in determining appropriate screening and monitoring strategies that are most effective for the patient's particular pathophysiology. Although specific diagnostic and therapeutic interventions must be individualized, standardized screening and monitoring practices for patients with similar mechanisms of deterioration may enhance the ability to predict respiratory failure early and prevent its occurrence.[citation needed] ## Treatment[edit] Therapy interventions for respiratory compromise target secondary effects of the condition, which manifest as pulmonary pathologies or aggravate existing pulmonary conditions. Appropriately administered antibiotic therapy can reduce the risk of mortality in patients with moderate to severe pneumonia, and timely ventilation therapy can reduce mortality in patients with a diagnosis of COPD.[8] ## References[edit] 1. ^ Morris, T. A; Gay, P. C; MacIntyre, N. R; Hess, D. R; Hanneman, S. K; Lamberti, J. P; Doherty, D. E; Chang, L; Seckel, M. A (2017). "Respiratory Compromise as a New Paradigm for the Care of Vulnerable Hospitalized Patients". Respiratory Care. 62 (4): 497–512. doi:10.4187/respcare.05021. PMID 28341777. 2. ^ Andersen, L. W; Berg, K. M; Chase, M; Cocchi, M. N; Massaro, J; Donnino, M. W; American Heart Association's Get With The Guidelines(®)-Resuscitation Investigators (2016). "Acute respiratory compromise on inpatient wards in the United States: Incidence, outcomes, and factors associated with in-hospital mortality". Resuscitation. 105: 123–9. doi:10.1016/j.resuscitation.2016.05.014. PMID 27255952. 3. ^ Alvarez, M. P; Samayoa-Mendez, A. X; Naglak, M. C; Yuschak, J. V; Murayama, K. M (2015). "Risk factors for postoperative unplanned intubation: analysis of a national database". The American Surgeon. 81 (8): 820–5. PMID 26215247. 4. ^ "Patient Monitoring: Preventing Respiratory Compromise". 5. ^ "Respiratory Compromise: Recognition and Management in Clinical Settings". 6. ^ "Respiratory Compromise Institute Highlights Dangers and Growing Incidence of Respiratory Compromise" (PDF). 7. ^ Simpson, H (2004). "Interpretation of arterial blood gases: a clinical guide for nurses". British Journal of Nursing. 13 (9): 522–8. doi:10.12968/bjon.2004.13.9.12962. PMID 15215728. 8. ^ "Respiratory Compromise as a New Paradigm for the Care of Vulnerable Hospitalized Patients" (PDF). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Respiratory compromise	None	26,889	wikipedia	https://en.wikipedia.org/wiki/Respiratory_compromise	2021-01-18T19:04:30	{"umls": ["CL976588"], "wikidata": ["Q55631475"]}
## Summary ### Clinical characteristics. Individuals with hereditary distal renal tubular acidosis (dRTA) typically present in infancy with failure to thrive, although later presentations can occur, especially in individuals with autosomal dominant SLC4A1-dRTA. Initial clinical manifestations can also include emesis, polyuria, polydipsia, constipation, diarrhea, decreased appetite, and episodes of dehydration. Electrolyte manifestations include hyperchloremic non-anion gap metabolic acidosis and hypokalemia. Renal complications of dRTA include nephrocalcinosis, nephrolithiasis, medullary cysts, and impaired renal function. Additional manifestations include bone demineralization (rickets, osteomalacia), growth deficiency, sensorineural hearing loss (in ATP6V0A4-, ATP6V1B1-, and FOXI1-dRTA), and hereditary hemolytic anemia (in some individuals with SLC4A1-dRTA). ### Diagnosis/testing. The diagnosis of hereditary dRTA is established in a proband with dRTA and biallelic pathogenic variants in ATP6V0A4, ATP6V1B1, FOXI1, or WDR72, or a heterozygous or biallelic pathogenic variants in SLC4A1, identified by molecular genetic testing. ### Management. Treatment of manifestations: Oral alkaline therapy to correct metabolic acidosis and hypokalemia with additional potassium chloride as needed; standard treatments for sensorineural hearing loss. Surveillance: Fasting venous blood gas or total CO2 prior to alkali dose in rapidly growing infants and children at least every 3-4 months, and at least every 6 months in older individuals. Serum creatinine, urea, sodium, potassium, chloride, calcium, phosphate, alkaline phosphatase, and albumin in rapidly growing infants and children at least every 3-4 months, and at least every 6 months in older individuals. Urinalysis, urine creatinine, sodium, potassium, calcium, and citrate annually and more frequently when adjusting treatment. Annual renal ultrasound to evaluate for nephrocalcinosis, urolithiasis, and cysts in asymptomatic individuals. Audiometry annually in at-risk individuals. Bone densitometry as needed. Growth assessment with calculation of body mass index in infants at least every 3 months, and in older children at least every 6 months until achievement of final height. Agents/circumstances to avoid: Potassium-sparing diuretics should be used with caution or avoided. Pregnancy management: Women with hereditary dRTA may develop severe metabolic acidosis and hypokalemia during pregnancy, especially when complicated by hyperemesis gravidarum. Close monitoring of women with hereditary dRTA during pregnancy is necessary. ### Genetic counseling. Hereditary dRTA caused by pathogenic variants in ATP6V0A4, ATP6V1B1, FOXI1, or WDR72 is inherited in an autosomal recessive manner. Hereditary dRTA caused by pathogenic variants in SLC4A1 is inherited in an autosomal dominant or autosomal recessive manner. Autosomal recessive inheritance: At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Autosomal dominant inheritance: Each child of an individual with autosomal dominant dRTA has a 50% chance of inheriting the pathogenic variant. Molecular genetic prenatal testing is possible for pregnancies at increased risk in families in which the pathogenic variant(s) have been identified. ## Diagnosis Formal diagnostic criteria for hereditary distal renal tubular acidosis (dRTA) have not been established. ### Suggestive Findings Hereditary dRTA should be suspected in individuals with the following clinical, laboratory, and radiographic features. Clinical features * Failure to thrive in childhood * Sensorineural hearing loss * Symptoms of hypokalemia, including muscle weakness and muscle cramps * Bone manifestations (10%-23%): osteomalacia in adults, rickets in children, fractures, bone pain * Exclusion of secondary causes of dRTA (e.g., autoimmune, drug induced) Laboratory features * Hyperchloremic non-anion gap metabolic acidosis in the absence of GI losses * Hypokalemia (blood potassium level <3.5 mEq/L) * Hypobicarbonatemia (blood bicarbonate levels below 20 mEq/L in infants and 22 mEq/L in older children), but with normal fractional excretion of bicarbonate * Inappropriately elevated urine pH (>5.3) in the absence of gastrointestinal bicarbonate losses * Absence of a negative urine anion gap (UAG) in an individual with metabolic acidosis. Calculation of the UAG (UAG=[Na+]U+[K+]U\- [Cl-]U) can help to distinguish between primary forms of proximal and dRTA. * Elevated urine calcium * Decreased urine citrate * Failure to acidify the urine (urine pH always >5.3): * After an ammonium chloride challenge (100 mg/kg) [Wrong & Davies 1959]; OR * When increased distal delivery of sodium is induced, via the co-administration of a mineralocorticoid (e.g., fludrocortisone 0.02 mg/kg) and furosemide (0.5 mg/kg) [Walsh et al 2007, Shavit et al 2016]; OR * In an individual who presents with spontaneous acidosis Imaging features * Renal ultrasound. Nephrocalcinosis is almost universal; nephrolithiasis is less common, but does occur. Medullary cysts may be detected, typically in later childhood or in adults [Igarashi et al 1991, Besouw et al 2017]. * Plain radiographs of the bones may show rachitic changes. * Bone densitometry examination may show decreased bone density in children and adults [Besouw et al 2017]. * CT examination of the inner ear may demonstrate dilation of the vestibular aqueduct in individuals with hereditary dRTA associated with hearing loss [Palazzo et al 2017]. ### Establishing the Diagnosis The diagnosis of hereditary dRTA is established in a proband with dRTA and biallelic pathogenic variants in ATP6V0A4, ATP6V1B1, FOXI1, or WDR72, or a heterozygous or biallelic pathogenic variants in SLC4A1, identified by molecular genetic testing. SLC4A1-dRTA has been associated with autosomal dominant and autosomal recessive inheritance. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved. Because the phenotype of hereditary dRTA is relatively broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of hereditary dRTA has not been considered are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 When the phenotypic and laboratory findings suggest the diagnosis of hereditary dRTA, molecular genetic testing approaches can include use of a multigene panel. A multigene panel that includes the genes listed in Table 1 and other genes of interest (see Differential Diagnosis) may identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. Note: Hereditary dRTA caused by pathogenic variants in a specific gene can be associated with specific clinical features and inheritance patterns, which may or may not be recognizable at the time of clinical presentation. * ATPV0A4 and ATPV1B1 are the most common causes of autosomal recessive dRTA. * ATP6V0A4- and ATP6V1B1-dRTA commonly occur in the presence of sensorineural hearing loss, although onset of hearing loss varies from early childhood to adulthood. Typically, hearing loss occurs in infancy with ATPV1B1-dRTA and later in childhood with ATP6V0A4-dRTA. Pathogenic variants in FOXI1 are usually associated with early-onset hearing loss. * For adolescent/adult presentation, autosomal dominant inheritance, or dRTA associated with an inherited hemolytic anemia, SLC4A1-dRTA is most likely. #### Option 2 When the diagnosis of hereditary dRTA is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is the most commonly used genomic testing method; genome sequencing is also possible. If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. 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 Hereditary Distal Renal Tubular Acidosis View in own window Gene 1, 2Proportion of Hereditary dRTA Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Detectable by Method Sequence analysis 4Gene-targeted deletion/duplication analysis 5 ATP6V0A440% 6, 7~98% 6, 7~2% 8 ATP6V1B130% 6, 7100%Unknown 9 FOXI12 families 10100%Unknown 9 SLC4A115% 6>95% 11, 12See footnote 12 WDR722 families 13100%Unknown 9 Unknown15% 6NA 1\. Genes are listed alphabetically. 2\. See Table A. Genes and Databases for chromosome locus and protein. 3\. See Molecular Genetics for information on allelic variants detected in this gene. 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Vargas-Poussou et al [2006], Gómez et al [2016], Besouw et al [2017], Palazzo et al [2017], Alonso-Varela et al [2018] 7\. Stover et al [2002] 8\. Miura et al [2013], Escobar et al [2016], Palazzo et al [2017] 9\. No data on detection rate of gene-targeted deletion/duplication analysis are available. 10\. Enerbäck et al [2018] 11\. Bruce et al [1997], Chu et al [2010], Khositseth et al [2012] 12\. Intra-exon deletions of 27-170 base pairs have been reported [Hooman et al 2015]. Depending on assay design, these deletions may be detectable by sequencing or gene-targeted deletion/duplication assays. 13\. Rungroj et al [2018] ## Clinical Characteristics ### Clinical Description Individuals with hereditary distal renal tubular acidosis (dRTA) typically present in infancy with failure to thrive, although later presentations can occur, especially in individuals with autosomal dominant SLC4A1-dRTA. Initial clinical manifestations may also include emesis, polyuria, polydipsia, constipation, diarrhea, decreased appetite, and episodes of dehydration [Besouw et al 2017, Palazzo et al 2017]. Electrolyte manifestations include hypokalemia and hyperchloremic non-anion gap metabolic acidosis with inappropriately elevated urine pH (which may lead to secondary tachypnea if severe [Besouw et al 2017, Palazzo et al 2017]). Some individuals may present with evidence of proximal tubular dysfunction (e.g., amino aciduria, decreased reabsorption of phosphate, and low molecular weight proteinuria); however, this resolves with correction of the acidosis [Besouw et al 2017]. Renal complications in dRTA include nephrocalcinosis, nephrolithiasis, medullary cysts, and impaired renal function, which may occur in childhood [Igarashi et al 1991, Besouw et al 2017]. Nephrocalcinosis, typically bilateral, results from calcium deposition in the renal parenchyma. Reports on the frequency vary in the literature, ranging from approximately 25% [Chang & Lin 2002] to 100% of children with dRTA [Pirojsakul et al 2011, Besouw et al 2017, Enerbäck et al 2018]. In a large mostly European cohort of 340 individuals with dRTA, more than 90% of individuals with molecularly confirmed hereditary dRTA had nephrocalcinosis [Lopez-Garcia et al 2019]. The occurrence appears to increase with age and with later onset of alkalinizing therapy [Caldas et al 1992]. Medullary cysts develop in many individuals during childhood or in adulthood, likely secondary to hypokalemia [Igarashi et al 1991, Besouw et al 2017]. A mild-to-moderate decrease in glomerular filtration rate can occur and increase in prevalence with age but may be present in childhood [Besouw et al 2017, Palazzo et al 2017]. Hypokalemia (blood potassium level <3.5 mEq/L) is found in the majority of individuals with dRTA [Caldas et al 1992, Domrongkitchaiporn et al 2001, Pirojsakul et al 2011]. Individuals with ATP6V1B1- or ATP6V0A4-dRTA tend to have more severe hypokalemia than individuals with autosomal dominant SLC4A1-dRTA [Karet 2002, Alonso-Varela et al 2018]. Symptoms of hypokalemia include muscle weakness and muscle cramps [Nilwarangkur et al 1990, Domrongkitchaiporn et al 2001, Pirojsakul et al 2011]. Paralysis and respiratory depression due to muscle weakness may occur with severe hypokalemia [Caldas et al 1992, Domrongkitchaiporn et al 2002a]. Renal cysts are likely related to hypokalemia. Skeletal manifestations. The metabolic acidosis in dRTA results in the release of bicarbonate and phosphate – which are complexed with calcium – from bone. These salts act as alkalizing buffers to promote restoration of physiologic blood pH [Bushinsky & Frick 2000, Chan et al 2001, Domrongkitchaiporn et al 2001, Bushinsky et al 2003, Fry & Karet 2007]. Bone demineralization can cause rickets in children and osteomalacia in adults [Escobar et al 2013]. These conditions increase the risk of fractures and may cause bone pain. The frequency and severity of bone findings reported in the literature vary significantly. Rickets can cause bone deformities; ambulation may be impaired due to leg deformities [Bushinsky & Frick 2000, Domrongkitchaiporn et al 2001, Bushinsky et al 2003]. In a European cohort, rickets was present in 25% of children with dRTA [Caldas et al 1992]; however, others failed to identify any radiographic evidence of rickets in their cohort [Brenner et al 1982]. The reported prevalence of osteomalacia ranges from 10% to 23% [Nilwarangkur et al 1990, Jha et al 2011]. Low bone mass has been commonly reported in individuals of Thai descent with dRTA [Domrongkitchaiporn et al 2001]. Alkali treatment has been shown to improve bone mineral density in these individuals [Domrongkitchaiporn et al 2002b]. Growth. dRTA is often diagnosed during the evaluation of infants or young children with failure to thrive (principally manifesting as poor linear growth with normal weight for height) [Besouw et al 2017]. The majority of children with dRTA have short stature prior to adequate alkali therapy [Besouw et al 2017].The height deficit at diagnosis can be severe [Domrongkitchaiporn et al 2001, Bajpai et al 2005]. Children treated with adequate alkali therapy have improved growth velocity and catch-up growth is common, frequently allowing achievement of a normal height [Besouw et al 2017, Lopez-Garcia et al 2019]. Sensorineural hearing loss occurs in individuals with pathogenic variants in ATP6V1B1 or ATP6V0A4. Both early-childhood onset and later-adult onset can occur; the hearing loss can be profound [Karet et al 1999, Vargas-Poussou et al 2006, Enerbäck et al 2018]. Increased severity and earlier-onset hearing loss is more common in individuals with ATP6V1B1-dRTA. Progression or appearance of hypoacusia is not prevented by medical treatment. Hearing impairment is treated with hearing aids or cochlear implants when necessary. Hematologic manifestations. A small number of individuals with SLC4A1-dRTA will also have hereditary hemolytic anemia. Pathogenic variants causing both dRTA and hemolytic anemia most commonly occur in Southeast Asia and have also been reported in families in the Middle East and India. The combination of dRTA and hemolytic anemia usually presents in infants and children [Fawaz et al 2012, Khositseth et al 2012]. In one series including 78 affected individuals, hemoglobin values ranged from 4.4 to 15.7 g/dL [Khositseth et al 2012]. Biallelic SLC4A1 pathogenic variants can result in morphologic changes in erythrocytes. These altered erythrocytes are vulnerable to hemolysis under conditions of metabolic acidosis. Alkali therapy is associated with correction of anemia and reticulocytosis [Khositseth et al 2008]. Affected individuals also respond to transfusion and iron therapy [Khositseth et al 2012]. Heterozygotes for pathogenic variants in genes typically associated with autosomal recessive complete dRTA. Heterozygous ATP6V1B1 pathogenic variants have been identified in a few individuals with mild renal acidification defects that do not result in altered blood pH; these individuals are said to have incomplete dRTA [Zhang et al 2014, Dhayat et al 2016]. The diagnosis can be made with an ammonium chloride or fludrocortisone/furosemide challenge, as these individuals also fail to adequately acidify their urine. These individuals also commonly have hypercalciuria and kidney stones. ### Phenotype Correlations by Gene ATP6V0A4 may be associated with a more severe metabolic acidosis and later onset of deafness [Karet et al 1999, Stover et al 2002, Vargas-Poussou et al 2006, Besouw et al 2017]. ATP6V1B1 is associated with symptom onset in infancy or childhood, and deafness typically with onset in infancy. FOXI1 is associated with autosomal recessive dRTA and early-onset deafness [Enerbäck et al 2018]. SLC4A1 is typically associated with a milder form of dRTA; affected individuals may have a compensated hyperchloremic metabolic acidosis (low serum bicarbonate, but normal pH) [Besouw et al 2017]. Symptom onset occurs in childhood or later, with less impact on growth than in the autosomal recessive forms. ### Genotype-Phenotype Correlations No genotype-phenotype correlations for hereditary dRTA have been identified. ### Nomenclature Hereditary dRTA includes both "complete RTA" and "incomplete RTA." Complete RTA refers to a failure to excrete acid leading to metabolic acidosis. Incomplete RTA refers to a failure to excrete acid in the absence of frank metabolic acidosis and is a mild renal acidification defect. Hereditary dRTA may also be referred to as "secretory-defect dRTA." ### Prevalence The prevalence of hereditary dRTA is unclear; although it is certainly rare and quite low (~350 individuals have been reported in the literature). ## Differential Diagnosis ### Table 3. Disorder to Consider in the Differential Diagnosis of Hereditary Distal Renal Tubular Acidosis View in own window DisorderGeneMOIClinical Features of Differential Diagnosis Disorder Overlapping w/dRTADistinguishing from dRTA Osteopetrosis with renal tubular acidosisCA2ARdRTA * Proximal RTA * Osteopetrosis * ID * Visual impairment from optic nerve compression AR = autosomal recessive; dRTA = distal renal tubular acidosis; ID = intellectual disability; MOI = mode of inheritance; RTA = renal tubular acidosis ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with hereditary distal renal tubular acidosis (dRTA), the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Hereditary Distal Renal Tubular Acidosis View in own window System/ ConcernEvaluationComment RenalVenous blood gas or total plasma CO2 * Evaluation of acid-base equilibrium * Sample to be drawn in fasting conditions & immediately before scheduled dose of alkali to assess effectiveness of therapy Serum creatinine, urea, sodium, potassium, chlorideEvaluate glomerular filtration rate; assess hypokalemia, hydration status. Serum calcium, phosphate, alkaline phosphatase, magnesiumAssess for hypocalcemia, biochemical evidence of rickets, hypophosphatemia. Uric acid, albuminAssess for associated tubular dysfunction. UrinalysisDetection of proteinuria, hematuria, & leukocyturia Isolated urine sample for creatinine, sodium, potassium, calcium, & citrate. Note: Sample should be taken simultaneously w/serum/plasma samples enabling calculation of renal tubular handling of these electrolytes. * Excretion of sodium & potassium can be estimated by calculation of appropriate indices (mL/dL glomerular filtrate, fractional excretions of sodium & potassium) to monitor renal function & therapy. * Detection of hypercalciuria by calcium/creatinine ratio. Hypercalciuria may indicate inadequate correction of acidosis. * Detection of hypocitraturia may imply inadequate treatment. UltrasoundEvaluation for nephrocalcinosis, urolithiasis, & medullary cysts ENTAudiometryEvaluation for sensorineural hearing loss ConstitutionalMeasurement of length/height & weightUse for calculation of body mass index to assess nutritional status; baseline values to assess response to therapy (correction of height deficit expected if short stature is present) & to adjust alkali dosage ### Treatment of Manifestations Renal tubular acidosis. The goal of treatment is to correct the metabolic acidosis and hypokalemia [Karet 2002, Rodríguez Soriano 2002, Both et al 2014]. Maintaining bicarbonate and potassium in the normal range decreases the likelihood of acute symptoms and decreases the severity of long-term complications (e.g., poor growth, nephrocalcinosis, osteomalacia, decreased GFR). Standard of care in dRTA is oral alkaline therapy, usually in the form of a bicarbonate and/or citrate salt [Chan et al 2001, Karet 2002, Rodríguez Soriano 2002, Both et al 2014]. As these salts have a short half-life, they should be taken repeatedly throughout the day and night to maintain normal blood pH. The alkali salt is usually potassium given that hypokalemia is commonly associated, although some individuals may receive some sodium alkali preparations. Other individuals require potassium chloride as an additional source of potassium. The alkali requirement is highest in infants (>8 mEq/kg/day of alkali in some individuals) but decreases to approximately 1 mEq/kg/day in adults. Dosing is ideally every six hours, although practical considerations may lead clinicians and affected individuals to adapt dosing to accommodate sleep, work, and school schedules. Sodium salts should be avoided due to their contribution to worsening hypercalciuria. Note: (1) Compensated metabolic acidosis (normal pH but low bicarbonate) is not sufficient to facilitate growth. (2) Alkali and citrate supplementation prevent the progression of nephrocalcinosis, but do not reverse it. (3) Treatment decreases the risk of developing urolithiasis. Growth retardation is corrected with appropriate alkali treatment. In most cohort studies, growth with treatment is within normal range, but still below average. Skeletal manifestations. Alkali treatment has been shown to improve bone mineral density in individuals of Thai descent [Domrongkitchaiporn et al 2002b]. Sensorineural hearing loss. Correction of metabolic acidosis does not correct hypoacusia, which should be treated according to standard procedures. ### Surveillance No surveillance guidelines have been published. ### Table 5. Recommended Surveillance for Individuals with Hereditary Distal Renal Tubular Acidosis View in own window System/ ConcernEvaluationComment RenalVenous blood gas * In rapidly growing individuals (infants & young children): at least every 3-4 mos once blood pH is normalized w/out evidence of respiratory compensation; in older children & adults: at least every 6 mos * Sample to be drawn in fasting conditions & immediately before scheduled dose of alkali Serum creatinine, urea, sodium, potassium, chloride, calcium, phosphate, alkaline phosphatase, albumin * In rapidly growing individuals (infants & young children), at least every 3-4 mos once adequate control is achieved * In older children & adults, at least every 6 mos Urinalysis, urine creatinine, sodium, potassium, calcium, citrateAnnually; more frequently when adjusting treatment Renal ultrasoundAnnual evaluation for nephrocalcinosis, urolithiasis, & cysts in asymptomatic individuals ENTAudiometryAnnual evaluation for hearing loss SkeletalBone densitometryThere is no consensus on the benefit of follow-up bone densitometry. ConstitutionalMeasurement of length/height, weight; calculation of body mass indexIn infants, at least every 3 mos; in older children, at least every 6 mos until achievement of final height ### Agents/Circumstances to Avoid Potassium-sparing diuretics should be used with caution or avoided altogether. ### Evaluation of Relatives at Risk It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures. Evaluations can include: * Molecular genetic testing if the pathogenic variant(s) in the family are known; * Venous blood gas or total CO2 and plasma electrolytes if the pathogenic variant(s) in the family are not known. Newborns should undergo assessment of acid-base status and serum electrolytes: specifically, blood gas analysis and plasma electrolytes to identify a normal anion gap metabolic acidosis and hypokalemia while results of molecular genetic testing are completed. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Women with hereditary dRTA may develop severe metabolic acidosis and hypokalemia during pregnancy, especially when complicated by hyperemesis gravidarum. Close monitoring of women with hereditary dRTA during pregnancy is necessary [Seeger et al 2017]. See MotherToBaby for further information on medication use during pregnancy. ### Therapies Under Investigation One therapy for dRTA is under investigation in Europe and North America. ADV7103 is a combination of controlled-release granules of potassium bicarbonate and potassium citrate designed to provide 24-hour control of metabolic acidosis and hypokalemia in individuals with dRTA with twice-a-day dosing. A Phase III trial has been completed in Europe, with an extension ongoing, and a second trial is ongoing in the US (ClinicalTrials.gov identifier: NCT03644706) for individuals with primary dRTA. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hereditary Distal Renal Tubular Acidosis	None	26,890	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK547595/	2021-01-18T21:21:12	{"synonyms": ["Classic Renal Tubular Acidosis", "Type 1 RTA"]}
Caprine arthritis encephalitis (CAE) is a viral disease of goats caused by a lentivirus called caprine arthritis encephalitis virus. The disease is found worldwide.[1] Two syndromes of CAE occur. Adult goats develop a chronic progressive arthritis, whereas young goats develop a neurological syndrome, with signs of paresis or paralysis.[1] Less commonly, mastitis or pneumonia may occur.[1] Infection is life-long, and it may be years before signs of the disease occur.[2] The reason for the long (and variable) period of dormancy of the virus is not known.[3] In goats which develop arthritis, the joints become inflamed and swollen, and the goats will slowly lose condition.[4] In some cases the goat will not be able to stand. In goats which develop the neurological form of the disease, the onset of signs is gradual over several weeks. The hind legs are most often affected. The goat will be uncoordinated, and unable to place its feet properly, so that it "knuckles", that is, it stands with the front of its fetlock on the ground, rather than its hoof. The goat has increased difficulty standing and eventually is unable to stand.[3] The disease is spread to goat kids when they drink colostrum or milk from infected goats.[4] Separating goat kids from infected goats, and feeding the kids with cow's milk, or pasteurized goat milk, will prevent infection.[1] The disease can be spread from goat to goat via direct contact and body fluids, such as saliva.[5] Blood testing goats for CAE virus before moving them into a new herd will prevent the spread of the disease.[5] There is no known cure. To prevent spread of the disease, infected animals are separated from non-infected goats, or culled.[5] ## References[edit] 1. ^ a b c d Maclachlan, NJ; Dubovi, EJ, eds. (2010). "Caprine arthritis encephalitis virus". Fenner's Veterinary Virology (5th ed.). Academic Press. pp. 294–295. ISBN 9780128011706. 2. ^ Stonos, N; Wootton, SK; Karrow, N (22 August 2014). "Immunogenetics of small ruminant lentiviral infections". Viruses. 6 (8): 3311–33. doi:10.3390/v6083311. PMC 4147697. PMID 25153344. 3. ^ a b Smith, MC; Sherman, DM, eds. (2011). "Caprine arthritis encephalitis (CAE) and Maedi Visna (MV)". Goat medicine (2nd ed.). John Wiley & Sons. ISBN 9781119949527. 4. ^ a b Peacock, Christie (1996). "Caprine arthritis encephalitis". Improving goat production in the tropics : a manual for development workers. Oxford: Oxfam. p. 208. ISBN 9780855982690. 5. ^ a b c Matthews, JG (2016). "Caprine arthritis encephalitis". Diseases of the goat (4th ed.). John Wiley & Sons. pp. 98–102. ISBN 9781119073529. This veterinary medicine–related 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	Caprine arthritis encephalitis	None	26,891	wikipedia	https://en.wikipedia.org/wiki/Caprine_arthritis_encephalitis	2021-01-18T18:54:35	{"wikidata": ["Q1034947"]}
A number sign (#) is used with this entry because of evidence that Galloway-Mowat syndrome-7 (GAMOS7) is caused by homozygous or compound heterozygous mutation in the NUP107 gene (607617) on chromosome 12q15. Biallelic mutation in the NUP107 gene can also cause nephrotic syndrome type 11 (NPHS11; 616730). Description Galloway-Mowat syndrome-7 (GAMOS7) is an autosomal recessive disorder characterized by developmental delay, microcephaly, and early-onset nephrotic syndrome (summary by Rosti et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300). Clinical Features Rosti et al. (2017) reported 5 patients from 2 unrelated consanguineous families, one of which was of Turkish descent, with a nephrotic syndrome similar to Galloway-Mowat syndrome. The patients had microcephaly (-5 to -9 SD), poor overall growth with short stature, and mildly delayed intellectual development with speech delay, although most could attend special schools. Two sibs from 1 family (MIC-670) developed progressive nephrotic syndrome in the first decade, manifest as proteinuria, hypoalbuminemia, edema, and hypercholesterolemia. Renal biopsy showed focal segmental glomerulosclerosis. One patient underwent renal transplantation at age 16 years after developing renal failure. The 2 younger sibs in this family did not have proteinuria at ages 7 years and 20 months, respectively, but were being closely monitored. The single patient in the second family (MIC-5233) developed proteinuria at age 12 years, and renal biopsy showed IgA nephropathy. All patients had similar dysmorphic features, including sloping forehead, bitemporal narrowing, smooth philtrum, and micrognathia. Some patients had skeletal anomalies, including clinodactyly, bifid thumb, cubitus valgus, hallux valgus, pectus excavatum, and kyphoscoliosis. Brain imaging showed simplified gyri and sulci, and reduced frontal cortex volume. All patients carried the same NUP107 mutation (607617.0006). Bierzynska et al. (2017) reported 3 sibs (patients 45, 46, and 47), and an unrelated patient (patient 48), all born of consanguineous Pakistani parents, with GAMOS7. Clinical details were limited, but all had neurologic involvement, including developmental delay, learning difficulties, and microcephaly. Two of the sibs had eczema. Patients developed renal disease in the first or second decade; 1 patient was diagnosed and in end-stage renal failure at age 14 years. Renal biopsy, when available, showed focal segmental glomerulosclerosis. One patient underwent successful renal transplantation with no disease recurrence. Braun et al. (2018) reported 5 unrelated consanguineous families in which multiple individuals had onset in the first or second decade of steroid-resistant nephrotic syndrome that was associated with extrarenal manifestations, namely short stature, microcephaly, and intellectual disability. One patient had a ventricular septal defect, and 2 had arachnodactyly and high-arched palate. All affected individuals carried the c.303G-A mutation, which was demonstrated to be a South Asian founder allele. Two families were of Pakistani descent, and the others were Turkish, Indian, and Arabic, respectively. A patient from a family (A1830) of European descent who was compound heterozygous for a frameshift and an in-frame 3-bp deletion in the NUP107 gene also had nephrotic syndrome with microcephaly, intellectual disability, and dilated cardiomyopathy. Renal findings in these patients included focal segmental glomerulosclerosis, effacement of podocyte foot processes, tubular atrophy, interstitial fibrosis, proteinuria, and end-stage renal disease. Inheritance The transmission pattern of GAMOS7 in the families reported by Braun et al. (2018) was consistent with autosomal recessive inheritance. Molecular Genetics In 5 patients from 2 unrelated consanguineous Turkish families with GAMOS7, Rosti et al. (2017) identified a homozygous c.303G-A transition in the last coding base of exon 4, predicted to result in a splicing defect or a met101-to-ile (M101I) substitution (607617.0006). The mutation, which was found by homozygosity mapping followed by direct gene sequencing, segregated with the disorder in both families. Analysis of patient fibroblasts showed that the mutation resulted in the skipping of exon 4, which would result in a frameshift and nonsense-mediated mRNA decay. Patient cells showed about a 90% reduction in NUP107 protein levels compared to controls, as well as a reduction in NUP133 levels, consistent with a loss of function. High-resolution microscopy of patient fibroblasts showed a 40% decrease in density of nuclear pores. Rosti et al. (2017) noted that this homozygous variant had been reported by Alazami et al. (2015) in a patient (11DG0417) with developmental delay and early-onset focal segmental glomerulosclerosis who also had microcephaly (-5.7 SD) and intellectual disability, suggesting an allele-specific phenotype. Bierzynska et al. (2017) identified the homozygous c.303G-A mutation in the NUP107 gene in 3 sibs, born of consanguineous Pakistani parents, with GAMOS7. An unrelated patient, born of consanguineous Pakistani parents, carried a homozygous missense mutation in the NUP107 gene (C442Y; 607617.0008). The mutations were found by whole-exome sequencing of a large cohort of patients. Functional studies of the variants and studies of patient cells were not performed. Braun et al. (2018) identified a homozygous c.303G-A mutation in the NUP107 gene in affected members of 5 consanguineous families with GAMOS7. One of the families was a large multigenerational Pakistani family (PN-1), whereas the others were of Pakistani, Turkish, Indian, and Arabic descent, respectively. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. It was found in heterozygous state in 1 of 245,544 alleles in the gnomAD database. The mutation represents a South Asian founder allele. Patient lymphoblastoid cells with the M101I mutation showed reduced or absent levels of NUP107, NUP160, NUP133, and NUP37 compared to controls. In vitro functional expression studies showed that the NUP107 mutations were unable to rescue abnormal kidney morphology in nup107-null Xenopus embryos, consistent with a loss of function. CRISPR/Cas9-mediated knockout of NUP107 in human podocytes increased the formation of filopodia and was associated with increased CDC42 (116952) activity, suggesting alteration of actin and cytoskeletal dynamics. CRISPR/Cas9-mediated knockout of the nup107 gene in zebrafish embryos resulted in developmental abnormalities, including small eyes, body axis curvature, and edema, as well as early lethality. The patients were part of a large study in which various nucleopore (NUP) genes were found to be mutated in NPHS, suggesting a common pathogenic pathway. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature (in some patients) Other \- Poor overall growth HEAD & NECK Head \- Microcephaly (-5 to -8 SD) Face \- Dysmorphic facial features (in some patients) \- Sloping forehead \- Bitemporal narrowing \- Smooth philtrum \- Micrognathia Mouth \- Cleft lip \- Cleft palate \- High-arched palate CARDIOVASCULAR Heart \- Dilated cardiomyopathy (1 patient) \- Ventricular septal defect (1 patient) CHEST External Features \- Pectus excavatum GENITOURINARY Kidneys \- Nephrotic syndrome \- Focal segmental glomerulosclerosis \- Minimal change disease \- End-stage renal disease \- Diffuse mesangial sclerosis \- Effacement of podocyte foot processes \- Tubular atrophy \- Interstitial fibrosis \- IgA nephropathy (1 patient) SKELETAL \- Skeletal anomalies (in some patients) Spine \- Kyphoscoliosis Limbs \- Cubitus valgus Hands \- Clinodactyly \- Bifid thumb \- Arachnodactyly Feet \- Hallux valgus MUSCLE, SOFT TISSUES \- Edema NEUROLOGIC Central Nervous System \- Impaired intellectual development (in some patients) \- Developmental delay \- Speech delay \- Learning disabilities LABORATORY ABNORMALITIES \- Proteinuria \- Decreased serum albumin \- Hypercholesterolemia MISCELLANEOUS \- Onset of renal disease in first decade \- Progressive disorder \- Variable severity \- Not responsive to steroid treatment \- Most patients require renal transplantation \- No recurrence of nephrotic syndrome after transplantation MOLECULAR BASIS \- Caused by mutation in the 107-kD nucleoporin gene (NUP107, 607617.0006 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	GALLOWAY-MOWAT SYNDROME 7	c0795949	26,892	omim	https://www.omim.org/entry/618348	2019-09-22T15:42:25	{"mesh": ["C537548"], "omim": ["618348"], "orphanet": ["2065"]}
A number sign (#) is used with this entry because of evidence that lipoid congenital adrenal hyperplasia (LCAH) is caused by homozygous or compound heterozygous mutation in the gene encoding steroidogenic acute regulatory protein (STAR; 600617) on chromosome 8p11. Description Lipoid congenital adrenal hyperplasia, the most severe disorder of steroid hormone biosynthesis, is caused by a defect in the conversion of cholesterol to pregnenolone, the first step in adrenal and gonadal steroidogenesis. All affected individuals are phenotypic females with a severe salt-losing syndrome that is fatal if not treated in early infancy (summary by Lin et al., 1991 and Bose et al., 1996). Clinical Features Affected individuals may have a severe deficiency of adrenal or gonadal steroids. All affected individuals are phenotypic females irrespective of gonadal sex, and frequently die in infancy if mineralocorticoid and glucocorticoid replacement are not instituted. Only 11 of the first 32 patients described survived infancy (Hauffa et al., 1985), although some treated patients have survived to adulthood (Hauffa et al., 1985; Kirkland et al., 1973). In the series of 15 patients reported by Bose et al. (1996), 3 were XX females but all had phenotypically normal female genitalia at birth. All patients had normal birth weight and gestational ages. Their plasma corticotropin and renin values were high; serum cortisol and testosterone values varied substantially but responded poorly to corticotropin and chorionic gonadotropin. There were substantial variations in the degree of hyponatremia and hyperkalemia and in the age of onset of symptoms, with 1 child surviving for 6 months without hormonal replacement. At least 5 neonates had hyperglycemia, and at least 5 had respiratory disorders. Bose et al. (1996) noted that both of these features could be caused by glucocorticoid deficiency. At least 12 patients had hyperpigmentation at birth, indicating intrauterine glucocorticoid deficiency, which caused excessive corticotropin secretion. Fujieda et al. (1997) reported clinical, endocrinologic, and molecular analyses of 2 unrelated Japanese kindreds with 46,XX subjects affected with lipoid CAH who manifested spontaneous puberty. Phenotypic female infants with 46,XX karyotypes were identified as having lipoid CAH as newborns based on a clinical history of failure to thrive, hyperpigmentation, hyponatremia, hyperkalemia, and low basal values of serum cortisol and urinary 17-hydroxycorticosteroid and 17-ketosteroid. These patients responded to treatment with glucocorticoid and 9-alpha-fludrocortisone. Spontaneous thelarche (breast development) occurred in association with increased serum estradiol levels at the age of 10 and 11 years, respectively. Pubic hair developed at the age of 12 years in one subject, and menarche occurred at the age of 12 years in both cases. Both subjects reported periodic menstrual bleeding and subsequently developed polycystic ovaries. These findings demonstrated that ovarian steroidogenesis can be spared to some extent through puberty when the STAR gene product is inactive. This is in marked contrast to the early onset of severe defects in testicular and adrenocortical steroidogenesis that characterize lipoid CAH. Pathogenesis Bose et al. (1996) concluded that the congenital lipoid adrenal hyperplasia phenotype is the result of 2 separate events: the primary defect is genetic loss of steroidogenesis that is dependent on STAR protein; there is a subsequent loss of steroidogenesis that is independent of STAR due to cellular damage from accumulated cholesterol esters. Deficient fetal testicular steroidogenesis in patients with a 46,XY karyotype results in phenotypically normal female genitalia. The adrenal cortex becomes engorged with cholesterol and cholesterol esters; consequent deficient adrenal steroidogenesis leads to salt wasting, hyponatremia, hypovolemia, hyperkalemia, acidosis, and death in infancy, although patients can survive to adulthood with appropriate mineralocorticoid- and glucocorticoid-replacement therapy. Inheritance The first clue to the genetic basis of this syndrome was the observation of consanguinity in the parents of cases (Prader and Siebenmann, 1957). Population Genetics Lipoid congenital adrenal hyperplasia is common among the Japanese, Korean, and Palestinian Arab populations, but is rare elsewhere (Bose et al., 2000). Molecular Genetics Because studies had shown that LCAH was caused by an inability to convert cholesterol to pregnenolone, the disorder was initially mislabeled '20,22 desmolase deficiency,' and was thought to involve the cholesterol side-chain cleavage enzyme P450scc (CYP11A1; 118485); see HISTORY. In a newborn Korean infant with XY karyotype and characteristics of lipoid congenital adrenal hyperplasia and in a Japanese patient previously described by Matteson et al. (1986), Lin et al. (1991) found by Southern blotting patterns that the CYP11A1 gene was grossly intact. Furthermore, sequencing of the gene demonstrated no abnormalities in either the gene or in gonadal RNA. Northern blots of gonadal RNA from the Korean patient contained normal-sized mRNAs for P450scc and also for adrenodoxin reductase, adrenodoxin, sterol carrier protein-2, endozepine, and GRP-78 (the precursor of steroidogenesis activator peptide). Thus, the lesion responsible for lipoid CAH did not reside in the P450SCC gene in these patients. In 3 unrelated patients with LCAH, 2 of whom were previously studied by Lin et al. (1991), Lin et al. (1995) demonstrated homozygous mutations in the STAR gene (600617.0002; 600617.0014). Tee et al. (1995) described an unusual intronic mutation in the STAR gene (600617.0001) that resulted in an mRNA splicing error and caused lipoid CAH. All patients with this disorder studied up to the time of report had mutations in STAR, suggesting to the authors that they are the sole cause of this disorder. Bose et al. (1996) sequenced the gene for STAR in 15 patients with this disorder from 10 countries. Among 14 patients, 15 different mutations in the STAR gene were found: gln258 to ter (Q258X; 600617.0002) was found in 80% of affected alleles from Japanese and Korean patients, whereas arg182 to leu (R182L; 600617.0003) was found in 78% of affected alleles from Palestinian patients. The investigators found that 13 of the 15 identified mutations were in exons 5, 6, or 7. Fujieda et al. (1997) found homozygosity for the Q258X mutation (600617.0002) in exon 7 in one patient; a second patient was a genetic compound for the Q258X mutation and a frameshift mutation in the other allele that rendered the STAR protein nonfunctional. Their clinical findings demonstrated that ovarian steroidogenesis can be spared to some extent through puberty when the STAR gene product is inactive. This is in marked contrast to the early onset of severe defects in testicular and adrenocortical steroidogenesis that characterize lipoid CAH. Baker et al. (2006) studied the gene encoding STAR in 3 children from 2 families who presented with primary adrenal insufficiency at 2 to 4 years of age; the males had normal genital development. DNA sequencing identified homozygous STAR mutations val187 to met (600617.0011) and arg188 to cys (600617.0012) in these 2 families. Functional studies of StAR activity in cells and in vitro and cholesterol-binding assays showed these mutants retained approximately 20% of wildtype activity. The authors referred to these patients as cases of nonclassic lipoid congenital adrenal hyperplasia, and stated that they represented a new cause of nonautoimmune Addison disease (primary adrenal failure). History In steroidogenic tissues such as adrenal cortex, testis, ovary, and placenta, the initial and rate-limiting step in the pathway leading from cholesterol to steroid hormones is the cleavage of the side chain of cholesterol to yield pregnenolone. This reaction, known as cholesterol side-chain cleavage, is catalyzed by a specific form of cytochrome P-450 called P450scc or P45011A (118485), which is localized to the inner mitochondrial membrane. The conversion of cholesterol to pregnenolone entails 3 steps, all mediated by P450scc (EC 1.14.15.67). The 3 steps are: 20-hydroxylation, 22-hydroxylation, and cleavage of the C20-C22 bond to produce pregnenolone and isocaproic acid. Degenhart et al. (1972) had the opportunity to study postmortem adrenal gland from a patient with congenital lipoid adrenal hyperplasia. They proposed deficiency of 20-alpha-cholesterol hydroxylase. The earliest step in the conversion of cholesterol to hormonal steroids is hydroxylation at carbon 20, with subsequent cleavage of the 20-22 side chain (a desmolase reaction) to form pregnenolone. This process is essential to the formation of all adrenal and gonadal steroids. GU \- Hypospadias \- Phenotypic female Inheritance \- Autosomal recessive Lab \- 20, 22 desmolase deficiency Endo \- Adrenogenital syndrome \- Lipoid adrenal hyperplasia Metabolic \- Salt-wasting ▲ 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	LIPOID CONGENITAL ADRENAL HYPERPLASIA	c0001627	26,893	omim	https://www.omim.org/entry/201710	2019-09-22T16:31:28	{"doid": ["0050811"], "mesh": ["D000312"], "omim": ["201710"], "orphanet": ["418", "90790"], "synonyms": ["Alternative titles", "ADRENAL HYPERPLASIA I", "LIPOID HYPERPLASIA, CONGENITAL, OF ADRENAL CORTEX WITH MALE PSEUDOHERMAPHRODITISM"]}
This disorder consists of malformation of the retina and persistence of the primary vitreous. Absence of the definitive vitreous is not surprising since its formation is dependent on the retina. The abnormality may simulate Norrie disease (310600). It is the characteristic eye change in trisomy 13 (the Bartholin-Patau syndrome), which is characterized by delay in the development of several proteins, such as adult hemoglobin and red cell catalase (Lee et al., 1966). Multiple visceral manifestations and others such as polydactyly were known to be associated (Harris and Thomson, 1937; Reese and Blodi, 1950; Reese and Straatsma, 1958; Yudkin, 1928) long before the chromosomal basis was elucidated. Aside from the importance in the differential diagnosis of microphthalmos, anophthalmos, and Norrie disease, the main reason for including mention here of Reese retinal dysplasia is that Reese and Straatsma (1958) observed 2 sibships with multiple affected members--2 out of 3 in one and 3 out of 4 in a second. In reporting the case of a 10-year-old boy, Matthes and Stenzel (1968) described minor changes in the mother and 2 sibs. Karyotype was normal in the proband. Eyes \- Retinal malformation \- Persistent primary vitreous Inheritance \- Autosomal recessive ▲ 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	REESE RETINAL DYSPLASIA	c1849450	26,894	omim	https://www.omim.org/entry/266400	2019-09-22T16:22:48	{"mesh": ["C564854"], "omim": ["266400"]}
A histological variant of medulloblastoma, an embryonic malignancy, associated with extremely low survival rates and a high risk of metastatic disease and manifesting with symptoms of increased intracranial pressure such as vomiting, headache, listlessness, papilledema and diplopia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Anaplastic/large cell medulloblastoma	None	26,895	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251855	2021-01-23T17:39:01	{"icd-10": ["C71.6"]}
Juberg-Hayward syndrome Other namesCleft lip/palate with abnormal thumbs and microcephaly[1] Juberg-Hayward syndrome is a rare genetic syndrome characterised by cleft lip and cleft palate, microcephaly, ptosis, short stature, hypoplasia or aplasia of thumbs, dislocation of radial head and fusion of humerus and radius. The abnormalities in the arm lead to restriction of movement in the elbow. ## Contents * 1 Presentation * 2 Genetics * 3 History * 4 References * 5 External links ## Presentation[edit] These include[2] * Growth retardation * Microcephaly * Cleft lip and palate * Minor vertebral and rib anomalies * Horseshoe kidneys * Thumb anomalies * Triphalangeal thumb * Radial ray anomalies ## Genetics[edit] This syndrome is caused by mutations in the establishment of cohesion 1 homolog 2 (ESCO2) gene.[3] This gene is located on the short arm of chromosome 8 (8p21.1). Mutations in this gene also cause Roberts/SC phocomelia syndrome.[citation needed] Juberg-Hayward syndrome is inherited in both an autosomal recessive and autosomal dominant fashion.[citation needed] ## History[edit] This condition was first described in 1969 by Juberg and Hayward.[4] ## References[edit] 1. ^ "Juberg-Hayward syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 20 July 2020. 2. ^ Verloes A, Le Merrer M , Davin J-C Briard ML, et al (1992) The orocraniodigital syndrome of Juberg and Hayward. J Med Gen 29(4):262-265 3. ^ Kantaputra PN, Dejkhamron P, Intachai W, Ngamphiw C, Kawasaki K, Ohazama A, Krisanaprakornkit S, Olsen B, Tongsima S, Ketudat Cairns JR (2020) Juberg-Hayward syndrome is a cohesinopathy, caused by mutation in ESCO2. Eur J Orthod 4. ^ Juberg RC, Hayward JR (1969) A new familial syndrome of oral, cranial, and digital anomalies. J Pediat 74: 755-762 ## External links[edit] Classification D * OMIM: 216100 * MeSH: C537690 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Juberg-Hayward syndrome	c0796099	26,896	wikipedia	https://en.wikipedia.org/wiki/Juberg-Hayward_syndrome	2021-01-18T18:38:41	{"gard": ["3060"], "mesh": ["C537690"], "umls": ["C0796099"], "orphanet": ["2319"], "wikidata": ["Q18021495"]}
Chromosome 9q deletion is a chromosome abnormality that occurs when there is a missing (deleted) copy of genetic material on the long arm (q) of chromosome 9. The severity of the condition and the signs and symptoms depend on the size and location of the deletion and which genes are involved. Features that often occur in people with chromosome 9q deletion include developmental delay, intellectual disability, behavioral problems and distinctive facial features. Chromosome testing of both parents can provide more information on whether or not the deletion was inherited. In most cases, parents do not have any chromosomal anomaly. However, sometimes one parent is found to have a balanced translocation, where a piece of a chromosome has broken off and attached to another one with no gain or loss of genetic material. The balanced translocation normally does not cause any signs or symptoms, but it increases the risk for having an affected child with a chromosomal anomaly like a deletion. Treatment is based on the signs and symptoms present in each person. This page is meant to provide general information about 9q deletions. You can contact GARD if you have questions about a specific deletion on chromosome 9. To learn more about chromosomal anomalies please visit our GARD webpage on FAQs about Chromosome Disorders. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Chromosome 9q deletion	None	26,897	gard	https://rarediseases.info.nih.gov/diseases/10844/chromosome-9q-deletion	2021-01-18T18:01:19	{"synonyms": ["Deletion 9q", "Monosomy 9q", "9q deletion", "9q monosomy", "Partial monosomy 9q"]}
A rare genetic primary lymphedema characterized by uniform, widespread lymphedema, often with systemic involvement such as intestinal and pulmonary lymphangiectasia, pleural and pericardial effusions, and chylothorax. There is a high incidence of non-immune hydrops fetalis, which may result in fetal demise or fully resolve after birth. Severe, recurrent facial cellulitis is observed in some patients. Presence of epicanthic folds or micrognathia has occasionally been reported, while intelligence is normal, and seizures are absent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis	c4225184	26,898	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=568062	2021-01-23T18:54:17	{"synonyms": ["Generalized lymphatic dysplasia of Fotiou", "PIEZO1-related LRHF/GLD", "PIEZO1-related generalized lymphatic dysplasia with systemic involvement", "PIEZO1-related lymphatic-related hydrops fetalis"]}
A rare multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, intellectual disability, growth retardation, hearing impairment, characteristic facial dysmorphology (including prominent supraorbital ridges, downslanting palpebral fissures, deep-set eyes, long face, sagging cheeks, anteverted nares, and pointed chin), generalized hypotonia, joint hypermobility, gluteal crease with sacral caudal remnant and sacral dimple, and variable neurological features. Various ophthalmic, cutaneous, musculoskeletal, gastrointestinal, and cardiovascular anomalies have also 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	X-linked intellectual disability-global development delay-facial dysmorphism-sacral caudal remnant syndrome	c4225418	26,899	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=480907	2021-01-23T19:11:35	{"omim": ["300966"]}

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