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Dysmorphism-cleft palate-loose skin syndrome is a rare, genetic developmental defect during embryogenesis characterized by severe psychomotor delay, intellectual disability, congenital, symmetrical circumferential skin creases of arms and legs, cleft palate, and facial dysmorphism (incl. elongated face, high forehead, blepharophimosis, short palpebral fissures, microphthalmia, microcornea, epicanthic folds, telecanthus, microtia, posteriorly angulated ears, broad nasal bridge, microstomia and micrognathia). Additional features reported include short stature, microcephaly, hypotonia, pectus excavatum, severe scoliosis, hypoplastic scrotum, and mixed hearing 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Dysmorphism-cleft palate-loose skin syndrome	None	29,000	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1779	2021-01-23T17:41:22	{"gard": ["2009"]}
A number sign (#) is used with this entry because of evidence that the disorder is caused by heterozygous mutation in the gene that encodes factor V (F5; 612309) on chromosome 1q24. Description Thrombophilia due to activated protein C resistance is due to a mutation in the F5 gene that renders factor V resistant to cleavage and inactivation by activated protein C (PROC; 612283) and results in a tendency to thrombosis. See also factor V deficiency (227400), an allelic disorder resulting in a hemorrhagic diathesis due to lack of factor V. The most common mutation that causes this disorder is referred to as factor V Leiden (R506Q; 612309.0001), named after the town in the Netherlands where Bertina et al. (1994) discovered the defect. Homozygosity increases the risk of thrombotic complications to a greater extent than heterozygosity. However, heterozygous presence of the mutation may be combined with defects in other genes in the clotting pathway to contribute to the disorder. Expressivity is variable and influenced by environment. Clinical Features Dahlback et al. (1993) reported a family in which 5 individuals spanning 3 generations had adult-onset thromboembolic disease, most often deep venous thrombosis of the legs, inherited in an autosomal dominant pattern. Laboratory studies of patients' plasma demonstrated a poor anticoagulant response upon the addition of activated protein C (APC; 612283), as measured by the lack of prolongation of clotting time in an activated partial thromboplastin time (aPTT) assay. In addition, 14 of 19 tested family members showed a similar defect in this assay. Known coagulation defects and serum autoantibodies or inhibitors to APC were excluded. Two additional unrelated patients with thrombophilia and inherited poor response to APC were identified using this novel assay. The thromboembolic events occurred during pregnancy or in the postpartum period in the 2 additional families. Dahlback et al. (1993) concluded that these individuals were lacking a previously unrecognized cofactor for APC that was responsible for the subnormal APC effects in the degradation of factors Va and VIIIa (300841). Greengard et al. (1994) reported variability of thrombosis in a family in which 4 sibs were homozygous for the R560Q mutation. The oldest son, who was homozygous, developed deep vein thrombosis (DVT) of the leg after an injury to that extremity at age 18 years. Two weeks later, during treatment with warfarin, he developed a DVT of the other leg. A clip was placed on the inferior vena cava and warfarin therapy was continued for 2 years. He later developed severe bilateral postphlebitic syndrome with chronic leg ulcers. Another son, who was heterozygous, developed a spontaneous DVT of the leg at age 23 years. The youngest son, who was homozygous, had a spontaneous pulmonary embolus confirmed by pulmonary angiography at the age of 16 years. This recurred 1 year later after the discontinuation of warfarin treatment. At the age of 24, he had a DVT of the right leg when he was not receiving warfarin; he was treated for 6 months. Four months after the discontinuation of treatment, he had a recurrent DVT in the right leg. The heterozygous mother developed a DVT of the left leg during her most recent pregnancy at the age of 37. Two daughters, aged 28 and 33 years, who were homozygous for the mutation, and the father, who was heterozygous, had not developed thrombosis. Greengard et al. (1994) noted that the daughters had not been exposed to risk factors, such as major surgical procedures, the use of oral contraceptives, or pregnancy. Zoller and Dahlback (1994) studied a large kindred in which familial thrombophilia and APC resistance was inherited as an autosomal dominant trait, and all affected individuals had the R506Q mutation. Among 47 Swedish families with APC resistance and the R506Q mutation, Zoller et al. (1994) observed that by age 33 years, 8% of normals, 20% of heterozygotes, and 40% of homozygotes had had manifestations of venous thrombosis. In a majority of both heterozygous and homozygous individuals, thrombosis was associated with risk factors, most commonly pregnancy, oral contraceptives, trauma, and surgery. Pipe et al. (1996) reported a patient with neonatal purpura fulminans associated with heterozygosity for the R506Q mutation. At 8 hours of age, the neonate had progressive purpuric skin lesions and later had evidence of microvascular hemorrhagic thrombosis in the brain. The infant was treated with fresh frozen plasma infusions and had complete resolution of the skin lesions and no apparent long-term complications. Simioni et al. (1997) found heterozygosity for factor V Leiden in 41 (16.3%) of 251 unselected patients with a first episode of symptomatic deep vein thrombosis diagnosed by venography. The cumulative incidence of recurrent venous thromboembolism after follow-up of up to 8 years was 39.7% among carriers of the mutation, as compared with 18.3% among patients without the mutation. Jackson and Luplow (1998) described 2 adults with purpura fulminans related to sepsis who were found to be heterozygous for the factor V Leiden mutation. Each patient survived disseminated intravascular coagulation, shock, and digital necrosis, but eventually required digit amputations. The first patient was a 42-year-old man with Streptococcus pneumoniae. Acrocyanosis progressed to dry gangrene of all the fingers and toes; however, the skin of the forehead, ears, and nose recovered without scarring. The second patient was a 40-year-old woman with septicemia due to Bacteroides fragilis and Fusobacterium species. In a male neonate with inferior vena cava thrombosis, complicated by bilateral adrenal hemorrhage and left renal vein thrombosis Gorbe et al. (1999) identified a homozygous factor V Leiden mutation. The infant improved with intravenous administration of dopamine-dobutamine and low doses of heparin. An associated persistent ductus arteriosus detected by echocardiography was ligated during hospitalization. In a population-based cohort study of 9,253 Danish adults, Juul et al. (2004) found that heterozygotes and homozygotes for factor V Leiden had 2.7 and 18 times higher risk for venous thromboembolism, respectively, than noncarriers. Absolute 10-year risks for thromboembolism among heterozygote and homozygote nonsmokers younger than age 40 years who were not overweight were 0.7% and 3%, respectively. The 10-year risks in heterozygotes and homozygotes older than age 60 years who smoked and were overweight were 10% and 51%, respectively. Other Features ### Role in Pregnancy Complications Brenner et al. (1996) observed 2 patients with the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) who were heterozygous for the R506Q mutation. The HELLP syndrome is a severe presentation of preeclampsia (see 189800). The finding of the R506Q mutation suggested that the pathogenesis of HELLP syndrome may be associated with a thrombotic process. Among 122 pregnant women with preeclampsia or intrauterine growth retardation, Lindqvist et al. (1998) found a significantly reduced risk of intrapartum bleeding complications in the APC-resistant subgroup compared to non-APC-resistant subgroup, as indicated by reduced intrapartum blood loss and pre- and postpartum hemoglobin measurements. However, there was no difference between the 2 groups regarding preeclampsia or intrauterine growth retardation. Lindqvist et al. (1998) speculated that the remarkably high prevalence of a potentially harmful factor V gene mutation in the general population may be the result of an evolutionary selection mechanism conferring such survival advantages as reduction in the risk of intrapartum bleeding. Kupferminc et al. (1999) identified the factor V R506Q mutation in 22 of 110 women with obstetrical complications, including severe preeclampsia, abruptio placentae, fetal growth retardation, and stillbirth, and in 7 of 110 women with normal pregnancies (p = 0.003). In 24 of the women with complications, as compared with 9 women without complications, homozygosity for the 677C-T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR; 607093.0003) was also found. Overall, 57 women with obstetrical complications had a thrombophilic mutation, as compared with 19 women with normal pregnancies (p less than 0.001). Anticardiolipin antibodies or deficiency of protein S, protein C, or antithrombin III were detected in an additional 14 women with complications, as compared with 1 woman with a normal pregnancy (p less than 0.001). Kupferminc et al. (1999) recommended that women with such obstetrical complications should be tested for genetic and acquired markers of thrombophilia because these complications tend to recur in subsequent pregnancies. Faisel et al. (2004) analyzed the allele and genotype frequencies of 2 F5 polymorphisms, M385T, R485K, and the R506Q Leiden mutation in 133 Finnish women with preeclampsia (189800) and 112 controls. There were statistically significant differences in R485K allele (p = 0.003) and genotype (p = 0.03) frequencies between patients and controls. The A allele of R485K was overrepresented among the patients (12%) compared to the controls (4%), with an odds ratio of 2.8 (95% CI, 1.2-6.2) for combined A genotypes. Faisel et al. (2004) concluded that genetic variations in the factor V gene other than the Leiden mutation may play a role in disease susceptibility. ### Role in Other Diseases Heresbach et al. (1997) added small bowel infarctions to the many thrombotic states in which the factor V Leiden mutation plays a role. They observed the R506Q mutation in 2 cases of arterial and 2 cases of venous small bowel infarction. Two patients were heterozygous and 2 were homozygous. Three of the patients were in their mid-thirties and the fourth was a 45-year-old man. Mahmoud et al. (1997) reported the incidence of the factor V Leiden mutation in Budd-Chiari syndrome (600880) and portal vein thrombosis. The R506Q mutation was seen in 7 (23%) of 30 patients with Budd-Chiari syndrome (6 heterozygotes and 1 homozygote), 3 of whom had coexistent myeloproliferative disease. Only 1 (3%) of 32 patients with portal vein thrombosis was found to have the R506Q mutation. The mutation was found in 3 (6%) of the 54 controls, who had liver disease but no history of thrombophilia. Mahmoud et al. (1997) concluded that the R506Q mutation may be an important factor in the pathogenesis of Budd-Chiari syndrome but not of portal vein thrombosis. Leebeek et al. (1998) described a 27-year-old female homozygous for factor V Leiden with Budd-Chiari syndrome caused by hepatic vein thrombosis in association with portal and mesenteric vein thrombosis. She was treated by transjugular intrahepatic portosystemic stent placement followed by local thrombolytic therapy. Venous outflow from the liver was established and the thrombi in the portal and mesenteric veins were lysed completely. Gurakan et al. (1999) described a child with Budd-Chiari syndrome who was homozygous for the factor V Leiden mutation. The authors noted that Budd-Chiari syndrome is rare in children. De Bruijn et al. (1998) studied risk factors in cerebral venous sinus thrombosis in women. They found a clear and significant excess of both hereditary prothrombotic conditions, including factor V Leiden, and oral contraceptive use in 40 prospectively ascertained patients compared to 2,248 randomly sampled controls. The authors concluded that the presence of prothrombotic conditions like the factor V Leiden mutation and the use of oral contraceptives increase the risk of this rare condition in a multiplicative fashion. Chung et al. (2006) described Budd-Chiari syndrome in a 46-year-old woman who developed rapidly increasing abdominal girth over a period of several days with accumulation of ascites. The disorder was found to be associated with a mutation in JAK2 (V617F; 147796.0001) and the factor V Leiden mutation. As many as 50% of patients with Budd-Chiari syndrome have a myeloproliferative disorder, either preexisting or diagnosed at the time of the syndrome. However, some patients with the Budd-Chiari syndrome may have a latent myeloproliferative disorder without elevated blood counts. The V617F mutation of the JAK2 gene has been detected in a high proportion of patients with the Budd-Chiari syndrome, providing evidence that these patients have a latent myeloproliferative disorder (Patel et al., 2006). Debus et al. (1998) found that 6 of 24 children with porencephaly (175780) were heterozygous for the factor V Leiden mutation. Two of these also had familial raised Lp(a) levels (152200) and 1 child also had protein S deficiency (612336). An additional 10 children had protein C deficiency, protein S deficiency, or familial raised Lp(a) levels. Five of the 24 children had a positive family history of thrombosis. Debus et al. (1998) suggested that hereditary thrombophilic states may predispose to perinatal cerebroarterial occlusion and porencephaly. The authors commented that other interacting prenatal factors, such as infection, placental dysfunction, or fetal cardiac arrhythmias, should also be considered as causative factors. Debus et al. (2004) found a higher prevalence of the R506Q mutation among 76 patients with porencephaly compared to controls. Eighteen patients were heterozygous and 1 infant was homozygous; 4 controls carried the mutation. The authors suggested that patients with porencephaly have certain prothrombotic risk factors which may contribute to the development of the disorder. Kerlin et al. (2003) found that 4.1% of 65 patients with sepsis were heterozygous carriers of the factor V Leiden mutation. The 28-day mortality was lower in heterozygous carriers (13.9%) compared to those without the mutation (27.9%, p = 0.013). The mortality benefit of recombinant human activated protein C treatment was similar in both groups. Kerlin et al. (2003) suggested that F5 Leiden constitutes a rare example of a balanced gene polymorphism that maintains the F5 Leiden mutation in the general gene pool due to a survival advantage of heterozygotes in severe sepsis. In a comprehensive metaanalysis of 26 case-control studies including 4,588 white adult patients, Casas et al. (2004) found a statistically significant association between ischemic stroke (601367) and the R506Q substitution (odds ratio of 1.33). Diagnosis Meyer et al. (1999) described a method for simultaneously genotyping for factor V Leiden and the prothrombin 20210G-A variant (176930.0009) by a multiplex PCR-SSCP assay on whole blood. Greer (2000) stated that there is no evidence to support general screening of pregnant women for thrombophilia; however, all pregnant women with a personal or family history of venous thromboembolism should be screened. Drug prophylaxis against venous thromboembolism is warranted for pregnant women with thrombophilia who have had a previous thromboembolic event. Women with thrombophilia who have not had venous thromboembolism require individualized assessment of the defect and of additional risk factors. Screening should be extended to women with a history of second-trimester pregnancy loss (see 614389), severe or recurrent preeclampsia, or intrauterine growth restriction, although whether antithrombotic therapy will prevent these complications in women with congenital thrombophilia was not known. Krawczak et al. (2001) described a strategy called 'cascade genetic screening' whereby screening for genetic variants is targeted at the relatives of previously identified carriers rather than being performed at the general population level. They estimated that some 80% of all carriers of the factor V Leiden mutation would be detected if screening were to be targeted specifically at first- to third-degree relatives of patients with venous thrombosis. Segal et al. (2009) provided a metaanalysis of the predictive value of factor V Leiden for the development of venous thromboembolism using a literature review of 13 relevant articles. Heterozygosity and homozygosity for the mutation in probands were predictive of recurrent venous thromboembolism (OR of 1.56 and 2.65, respectively) compared to individuals without the mutation. In relatives of probands, heterozygosity and homozygosity also predicted venous thromboembolism (OR of 3.5 and 18.0, respectively) compared to family members without the mutation. It remained unknown whether testing for the mutation improved clinical outcome. Clinical Management Sarasin and Bounameaux (1998) used a Markov decision analysis model that incorporated all current data concerning recurrent venous thromboembolism and long-term anticoagulation. The model suggested that the benefits of prolonged oral anticoagulant treatment in factor V Leiden heterozygotes after a first episode of deep vein thrombosis were usually overwhelmed by its risks. Sarasin and Bounameaux (1998) concluded that any decision to promote widespread screening programs to detect factor V Leiden heterozygotes should be questioned in the absence of a clinical benefit provided by extended use of oral anticoagulants. Heterogeneity Zoller et al. (1994) identified the R506Q mutation in 47 of 50 Swedish families with inherited APC resistance. There was perfect cosegregation between a low APC ratio and the presence of the mutation in 40 families. However, the cosegregation was not perfect in 7 families, as 12 of 57 APC-resistant family members did not have the mutation. Moreover, in 3 families with APC resistance, the specific R506Q mutation was not found, suggesting another still unidentified cause of inherited APC resistance. Pathogenesis Dahlback and Hildebrand (1994) discovered that the APC cofactor deficient in this disorder was identical to factor V. An affinity-purified factor V corrected the poor anticoagulant response to APC of APC-resistant plasma in a dose-dependent manner. Because the APC-resistant plasma contained normal levels of factor V procoagulant activity, the results indicated that APC resistance was due to a selective defect in the anticoagulant function of factor V. The findings suggested that factor V not only has procoagulant properties after its activation by thrombin, but may also play an important role in the anticoagulant system as cofactor to activated protein C. Dahlback and Hildebrand (1994) commented on this appropriate, unique, and ingenious means of regulating blood coagulation. Sun et al. (1994) stated that APC resistance was 'currently the most common laboratory finding among venous thrombophilic patients.' They presented findings indicating that APC resistance is due to abnormality in factor V and not abnormality in factor VIII, which is also inactivated by APC, and that half of the patients' factor Va is resistant to APC, consistent with dominant inheritance. Molecular Genetics In affected members of a family with thrombophilia due to APC resistance, Bertina et al. (1994) identified a heterozygous R506Q mutation in the F5 gene. Of note, this family came to attention because of symptomatic protein C deficiency. The authors identified the mutation in 56 of 64 patients with APC-resistant thrombosis from a larger cohort of 301 consecutive patients with a first episode of deep vein thrombosis. The mutation was homozygous in 6 patients. Voorberg et al. (1994) found the R506Q mutation in 10 of 27 consecutive patients with recurrent thromboembolism. In a patient with thrombophilia due to APC resistance, Williamson et al. (1998) identified a heterozygous R306T mutation in the F5 gene (612309.0003). The mutation was also present in a first-degree relative with APC resistance. In 2 Caucasian brothers with thrombophilia due to APC resistance, Mumford et al. (2003) identified compound heterozygosity for 2 mutations in the F5 gene: a missense mutation (I359T; 612309.0013) and a nonsense mutation (E119X; 612309.0014). Both brothers developed spontaneous venous thromboses in the second decade of life. One presented at the age of 14 years with thrombosis of the right femoral vein and inferior vena cava; an older brother suffered recurrent episodes of femoral vein thrombosis from the age of 18 years and was managed with long-term warfarin therapy. Heterozygous family members were asymptomatic. The I359T allele was predicted to create an additional consensus site for N-linked glycosylation in factor V, which may have resulted in abnormal N-linked glycosylation within the factor V A2 domain and and reduced susceptibility of factor Va to proteolysis. Mumford et al. (2003) suggested that the E119X mutation resulted in an mRNA that was recognized and degraded by the cell via a process termed nonsense-mediated decay. Thus, the authors concluded that hemizygosity for the I359T variant was the cause of severe early-onset thrombophilia in these sibs. ### Pseudohomozygosity for Factor V Leiden Castaman et al. (1997) and Castoldi et al. (1998) described patients with thrombosis who were compound heterozygous for factor V Leiden and a factor V deficiency allele. The patients are referred to as having 'pseudohomozygosity' for factor V Leiden, since they present with venous thromboembolic events. Those with factor V null mutations show only factor V Leiden molecules, and those with deficiency mutations show decreased levels of factor V that are insufficient to protect against thrombosis. Zehnder et al. (1999) identified a man with thrombophilia who was compound heterozygous for factor V Leiden and a null allele of the F5 gene (612309.0005). The patient had 50% of normal levels of F5, all of which was of the Leiden type; hence he was pseudohomozygous for factor V Leiden. Castaman et al. (1999) referred to pseudohomozygosity for activated protein C resistance due to the association of heterozygous factor V Leiden mutation and factor V deficiency. Among 7 families with 11 pseudohomozygotes and 45 relatives, 16 relatives were heterozygous factor V Leiden carriers, 9 showed partial factor V deficiency, and 20 had no abnormalities. Deep vein thrombosis occurred in 4 (36.3%) of 11 pseudohomozygous patients versus 6 (37.4%) of 16 factor V Leiden carriers and 1 (5%) of 20 normal relatives. ### Modifier Genes Kemkes-Matthes et al. (2005) found that the presence of a heterozygous or homozygous arg225-to-his (R225H) substitution in exon 8 of the protein Z gene (PROZ; 176895) was associated with a higher frequency of thromboembolic complications in patients carrying the factor V Leiden mutation, although plasma levels of protein Z were not different between those with or without the R225H substitution. In a study of 134 carriers of factor V Leiden, the R225H mutation was found in 11 (14.4%) of 76 patients with thromboembolic events and in only 3 (5.1%) of 58 patients who did not have thromboembolic events. Genotype/Phenotype Correlations Koeleman et al. (1994) found that heterozygous carriers of both the factor V Leiden mutation and a mutation in the protein C gene were at higher risk of thrombosis compared to patients with either defect alone. Gandrille et al. (1995) detected the R506Q mutation in 15 (14%) of 113 patients with protein C deficiency and in 1 (1%) of 113 healthy controls. There was a significant difference in the allele frequency of the R506Q mutation between heterozygous protein C-deficient patients and protein C-deficient patients with no identified mutation in the PROC gene. The results demonstrated that a significant subset of thrombophilic patients have multiple genetic risk factors, although additional secondary genetic risk factors remained to be identified in a majority of symptomatic protein C-deficient patients. Talmon et al. (1997) described retinal arterial occlusion in a child heterozygous for the factor V R506Q mutation and homozygous for the thermolabile variant of methylene tetrahydrofolate reductase (607093.0003). Thus, the coexistence of 2 mild hereditary thrombophilic states can result in severe thrombotic manifestations in young people. Although factor V Leiden had been associated clearly with venous thrombosis, most studies had failed to demonstrate an association between isolated factor V Leiden and arterial thrombosis. De Stefano et al. (1999) examined the relative risk of recurrent deep venous thrombosis using a proportional-hazards model. The authors found that whereas patients who were heterozygous for factor V Leiden alone had a risk of recurrent deep venous thrombosis that was similar to that among patients who had neither mutation, patients who were heterozygous for both factor V Leiden and prothrombin 20210G-A (176930.0009) had a 2.6-fold higher risk of recurrent thrombosis than did carriers of factor V Leiden alone. Meinardi et al. (1999) described double homozygosity for factor V Leiden and prothrombin 20210G-A in a 34-year-old man with idiopathic venous thrombosis. Among 119 women with a history of venous thromboembolism during pregnancy, Gerhardt et al. (2000) found a prevalence of 43.7% for factor V Leiden, as compared with 7.7% among controls (relative risk of venous thromboembolism was 9.3). The prevalence of the 20210G-A prothrombin mutation (176930.0009) was 16.9% in the thromboembolism group as compared with 1.3% in the control group. The frequency of both factor V Leiden and the 20210G-A prothrombin mutation was 9.3% in the thromboembolism group as compared with 0 in the control group (estimated odds ratio, 107). Assuming an overall risk of 1 in 1,500 pregnancies, the risk of thrombosis among carriers of factor V Leiden was 0.2%, among carriers of the 20210G-A prothrombin mutation, 0.5%, and among carriers of both defects, 4.6%, as calculated in a multivariate analysis. Thus, the risk among women with both mutations was disproportionately higher than that among women with only 1 mutation. Martinelli et al. (2000) found that both factor V Leiden and the 20210G-A prothrombin mutation were associated with an approximate tripling of the risk of late fetal loss. Population Genetics Koster et al. (1993) detected a poor anticoagulant response to activated protein C in 64 (21%) of 301 unselected consecutive patients younger than 70 years with a first episode of deep vein thrombosis unassociated with malignant disease. The frequency of the defect was 5% among 301 healthy controls. An autosomal dominant mode of transmission of the abnormality was confirmed in families of the probands with the defect. Both parents of a probable homozygote, with an extremely poor response to activated protein C, were found to have the abnormality. In a study of 104 consecutive patients with venous thrombosis and 211 members of 34 families of affected probands, Svensson and Dahlback (1994) determined that the prevalence of APC resistance was as much as 40% in patients with thrombosis. The anticoagulant response to APC was measured with a modified version of the aPTT test and the results were expressed as APC ratios. Thirty-three percent of patients showed an APC ratio below the 5th percentile of the control values. Thrombosis-free survival of APC-resistant family members was significantly less than that of non-APC-resistant family members. Majerus (1994) quoted estimates that 2 to 4% of the Dutch population and 7% of the Swedish population carried the factor V Leiden mutation. The high frequency of a single factor V mutation in diverse groups of people raised the question of whether positive selection pressure was involved in maintaining it in the population. Majerus (1994) suggested that a slight thrombotic tendency may confer some advantage in fetal implantation. Greengard et al. (1994) identified a heterozygous R506Q mutation in 8 patients with APC resistance; 2 were Ashkenazi Jews, 5 were Europeans of varying origins, and 1 was African American. Beauchamp et al. (1994) identified the R506Q mutation in all affected members of 2 families with inherited APC resistance associated with thrombosis studied in England. The molecular studies confirmed suspected homozygosity in 2 individuals. The mutation in heterozygous form was also found in approximately 3.5% of the normal population. Among 14,916 apparently healthy men in the Physicians' Health Study, including 121 with deep venous thrombosis, Ridker et al. (1995) found that the R506Q mutation of the F5 gene was present in 25.8% of men over the age of 60 in whom primary venous thrombosis developed. There was no increased risk for secondary venous thrombosis. The presence of the mutation was not associated with an increased risk of myocardial infarction or stroke. In a follow-up study, of 77 study participants who had a first idiopathic venous thromboembolism, Ridker et al. (1995) found that factor V Leiden was associated with a 4- to 5-fold increased risk of recurrent thrombosis. The data raised the possibility that patients with idiopathic venous thromboembolism and factor V Leiden may require more prolonged anticoagulation to prevent recurrent disease compared to those without the mutation. In a population study in southern Germany, Braun et al. (1996) found that 7.8% of 180 unrelated individuals were heterozygous for the factor V Leiden mutation. In a multiethnic survey of 602 Americans, Gregg et al. (1997) found that Hispanic Americans had the highest frequency of the Leiden mutant allele, 1.65%, while African Americans had a somewhat lower frequency, 0.87%. No instances of the Leiden mutation were found in 191 Asian Americans or 54 Native Americans tested. These results indicated that the Leiden mutation segregates in populations with significant Caucasian admixture and is rare in genetically distant non-European groups. The factor V Leiden mutation (612309.0001) and the 20210G-A mutation in the prothrombin gene (176930.0009) are the most frequent abnormalities associated with venous thromboembolism. Martinelli et al. (2000) compared the prevalence and incidence rate of venous thromboembolism in relatives with either of these 2 mutations or both. The study population included 1,076 relatives of probands with the prothrombin gene mutation, factor V Leiden, or both, who underwent screening for inherited thrombophilia and were found to be carriers of single mutations or double mutations or who were noncarriers. The prevalence of venous thromboembolism was 5.7% in relatives with the prothrombin gene mutation, 7.8% in those with factor V Leiden, 17.1% in those with both mutations, and 2.5% in noncarriers. Annual incidences of thrombosis were 0.13%, 0.19%, 0.42%, and 0.066%, respectively. The relative risk of thrombosis was 2 times higher in carriers of the prothrombin gene mutation, 3 times higher in those with factor V Leiden, and 6 times higher in double carriers than in noncarriers. The incidence of venous thromboembolism in carriers of the prothrombin gene mutation was slightly lower than that observed in carriers of factor V Leiden, whereas in carriers of both mutations it was 2 or 3 times higher. From these findings, Martinelli et al. (2000) concluded that lifelong primary anticoagulant prophylaxis of venous thromboembolism is not needed in asymptomatic carriers of single or double mutations. Anticoagulant prophylaxis seems to be indicated only when transient risk factors for thrombosis coexist with mutations. Zivelin et al. (2006) estimated the age of the factor V Leiden mutation to be 21,340 years. Like the prothrombin 20210G-A mutation, factor V Leiden occurred in whites toward the end of the last glaciation and their wide distribution in whites suggested selective evolutionary advantages. A selective disadvantage, i.e., thrombosis, was unlikely because until recent centuries humans did not live long enough to manifest a meaningful incidence of thrombosis. On the other hand, augmented hemostasis conceivably conferred a selective advantage by reducing mortality from postpartum hemorrhage, hemorrhagia associated with severe iron deficiency anemia, and posttraumatic bleeding. For example, Lindqvist et al. (1998) found that the amount of blood lost during labor was significantly smaller in heterozygotes with factor V Leiden than in women not carrying the mutation. Lindqvist et al. (2001) found that profuse menstrual bleeding was significantly less common in factor V heterozygotes. Nomenclature Greengard et al. (1994) proposed that thrombophilia associated with APC resistance caused by factor V mutations be designated 'thrombophilia V.' Animal Model Cui et al. (2000) generated mice carrying the R504Q mutation, homologous to human R506Q, inserted into the endogenous murine factor V gene. Adult heterozygous and homozygous mice were viable and fertile and exhibited normal survival. Compared with wildtype mice, adult homozygous mice demonstrated a marked increase in spontaneous tissue fibrin deposition. On a mixed genetic background, homozygous mice developed disseminated intravascular thrombosis in the perinatal period, resulting in significant mortality shortly after birth. Cui et al. (2000) suggested that these results may explain the high degree of conservation of the R504/R506 activated protein C cleavage site within factor V among mammalian species. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Vascular \- Venous thrombosis PRENATAL MANIFESTATIONS Maternal \- Increased risk for preeclampsia Delivery \- Increased fetal loss LABORATORY ABNORMALITIES \- Resistance to activated protein C \- Poor anticoagulant response to exogenous activated protein C as measured by the activated partial thromboplastin time (APTT) MISCELLANEOUS \- Most cases are caused by the factor V Leiden mutation (R506Q, 612309.0001 ) \- Onset of symptoms usually in adulthood \- Thrombosis triggered by pregnancy, oral contraceptives, trauma, surgery \- Homozygotes have more severe disease with earlier onset of thrombosis MOLECULAR BASIS \- Caused by mutation in the coagulation factor V gene (F5, 612309.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	THROMBOPHILIA DUE TO ACTIVATED PROTEIN C RESISTANCE	c1861171	29,001	omim	https://www.omim.org/entry/188055	2019-09-22T16:32:41	{"mesh": ["C566056"], "omim": ["188055"], "synonyms": ["Alternative titles", "ACTIVATED PROTEIN C RESISTANCE", "APC RESISTANCE", "THROMBOPHILIA DUE TO DEFICIENCY OF ACTIVATED PROTEIN C COFACTOR", "PROC COFACTOR DEFICIENCY", "PCCF DEFICIENCY", "THROMBOPHILIA V"], "genereviews": ["NBK1368"]}
Double inlet left ventricle Cyanotic neonate A double inlet left ventricle (DILV) or "single ventricle", is a congenital heart defect appearing in 5 in 100,000 newborns, where both the left atrium and the right atrium feed into the left ventricle. The right ventricle is hypoplastic or does not exist. Both atria communicate with the ventricle by a single atrio-ventricular valve. There is a big shunt left-right with a quickly evolutive pulmonary hypertension. Without life-prolonging interventions, the condition is fatal, but with intervention, the newborn may survive. Even if there is no foetal sickness, the diagnosis can be made in utero by foetal echocardiography. ## Contents * 1 Presentation * 2 Diagnosis * 3 Treatment * 4 Prognosis * 5 References * 6 External links ## Presentation[edit] Infants born with DILV cannot feed normally (breathlessness) and have difficulty gaining weight. The mixed blood in systemic circulation leads to hypoxia (lack of oxygen to the body and organs), so infants develop cyanosis and breathlessness early. ## Diagnosis[edit] This section is empty. You can help by adding to it. (October 2017) ## Treatment[edit] * In the first few days, if there is no pulmonary valve stenosis, a pulmonary valve banding is necessary to prevent pulmonary hypertension and the ductus must be kept open to allow blood-flow using medication containing prostaglandin. At same time, if necessary, the atrial and ventricular septum communications must be enlarged. * When possible Glenn procedure is done.[1] * Later, surgical options include the Damus–Kaye–Stansel procedure, the Fontan procedure, and the Norwood procedure. The goal of all of these is separating the pulmonary and the systemic circulation.[2] Usually, DILV is associated with other cardiac malformations. ## Prognosis[edit] Mortality is very high in the first 2 years, 85%, but after it decreases and between 2 and 15 years old the mortality is only around 9%. Few reach middle age.[3] Diagnosis must be made within few days or even hours to prevent death. ## References[edit] 1. ^ Glenn WWL. Circulatory by pass of the right side of the heart. Shunt between superior vena cava and distal right pulmonary artery report of a clinical application. N Engl J Med 259: 117, 1958 2. ^ Fontan F, Baudet E (1971). "Surgical repair of tricuspid atresia". Thorax. 26 (3): 240–8. doi:10.1136/thx.26.3.240. PMC 1019078. PMID 5089489. 3. ^ Éléments de prognostic du Ventricule Unique, M.Lurdes Cerol Leonardo, S. Godeau, S. Magnier, A. Casassoprana, P. Vernant 19th. Annual meeting of European Paediatric Cardiologists, Amsterdam, May 1982 ## External links[edit] Classification D External resources * MedlinePlus: 007327 * v * t * e Congenital heart defects Heart septal defect Aortopulmonary septal defect * Double outlet right ventricle * Taussig–Bing syndrome * Transposition of the great vessels * dextro * levo * Persistent truncus arteriosus * Aortopulmonary window Atrial septal defect * Sinus venosus atrial septal defect * Lutembacher's syndrome Ventricular septal defect * Tetralogy of Fallot Atrioventricular septal defect * Ostium primum Consequences * Cardiac shunt * Cyanotic heart disease * Eisenmenger syndrome Valvular heart disease Right * pulmonary valves * stenosis * insufficiency * absence * tricuspid valves * stenosis * atresia * Ebstein's anomaly Left * aortic valves * stenosis * insufficiency * bicuspid * mitral valves * stenosis * regurgitation Other * Underdeveloped heart chambers * right * left * Uhl anomaly * Dextrocardia * Levocardia * Cor triatriatum * Crisscross heart * Brugada syndrome * Coronary artery anomaly * Anomalous aortic origin of a coronary artery * Ventricular inversion [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Double inlet left ventricle	c3274516	29,002	wikipedia	https://en.wikipedia.org/wiki/Double_inlet_left_ventricle	2021-01-18T18:56:12	{"umls": ["C3274516", "C0344622"], "wikidata": ["Q361480"]}
Not to be confused with Sclerosis. Medical condition of the spine Scoliosis Pronunciation * /ˌskoʊliˈoʊsɪs/[1] SpecialtyOrthopedics SymptomsSideways curve in the back[2] Usual onset10–20 years old[2] CausesUsually unknown[3] Risk factorsFamily history, cerebral palsy, Marfan syndrome, tumors such as neurofibromatosis[2] Diagnostic methodX-ray[2] TreatmentWatchful waiting, bracing, exercises, surgery[2][4] Frequency3%[5] Scoliosis is a medical condition in which a person's spine has a sideways curve.[2] The curve is usually "S"- or "C"-shaped over three dimensions.[2][6] In some, the degree of curve is stable, while in others, it increases over time.[3] Mild scoliosis does not typically cause problems, but more severe cases can affect breathing and movement.[3][7] Pain is usually present in adults, and can worsen with age.[8] The cause of most cases is unknown, but it is believed to involve a combination of genetic and environmental factors.[3] Risk factors include other affected family members.[2] It can also occur due to another condition such as muscle spasms, cerebral palsy, Marfan syndrome, and tumors such as neurofibromatosis.[2] Diagnosis is confirmed with X-rays.[2] Scoliosis is typically classified as either structural in which the curve is fixed, or functional in which the underlying spine is normal.[2] Treatment depends on the degree of curve, location, and cause.[2] Minor curves may simply be watched periodically.[2] Treatments may include bracing, specific exercises, posture checking, and surgery.[2][4] The brace must be fitted to the person and used daily until growing stops.[2] Specific exercises may be used to try to decrease the risk of worsening.[4] They may be done alone or along with other treatments such as bracing.[9][10] Evidence that chiropractic manipulation, dietary supplements, or exercises can prevent the condition from worsening is weak.[2][11] However, exercise is still recommended due to its other health benefits.[2] Scoliosis occurs in about 3% of people.[5] It most commonly develops between the ages of 10 and 20.[2] Females typically are more severely affected than males.[2][3] The term is from Ancient Greek: σκολίωσις, romanized: skoliosis which means "a bending".[12] ## Contents * 1 Signs and symptoms * 1.1 Course * 2 Causes * 2.1 Resulting from other conditions * 3 Diagnosis * 3.1 Definition * 4 Management * 4.1 Bracing * 4.2 Surgery * 5 Prognosis * 6 Epidemiology * 7 History * 7.1 Surgery * 7.2 Evolution * 8 Society and culture * 9 Research * 10 See also * 11 References * 12 External links ## Signs and symptoms[edit] A 20th-century illustration of a severe case of a "S" shaped scoliosis Symptoms associated with scoliosis can include: * Pain in the back, shoulders, neck and buttock pain nearest the bottom of the back * Respiratory or cardiac problems in severe cases * Constipation due to curvature causing "tightening" of stomach, intestines, etc. * Limited mobility secondary to pain or functional limitation in adults The signs of scoliosis can include: * Uneven musculature on one side of the spine * Rib prominence or a prominent shoulder blade, caused by rotation of the rib cage in thoracic scoliosis * Uneven hips, arms, or leg lengths * Slow nerve action * Heart and lung problems in severe cases * Calcium deposits in the cartilage endplate and sometimes in the disc itself[13] ### Course[edit] People who have reached skeletal maturity are less likely to have a worsening case.[14] Some severe cases of scoliosis can lead to diminishing lung capacity, pressure exerted on the heart, and restricted physical activities.[15] Recent longitudinal studies reveal that the most common form of the condition, late-onset idiopathic scoliosis, causes little physical impairment other than back pain and cosmetic concerns, even when untreated, with mortality rates similar to the general population.[16][17] Older beliefs that untreated idiopathic scoliosis necessarily progresses into severe (cardiopulmonary) disability by old age have been refuted by later studies.[18] ## Causes[edit] The many causes of scoliosis include neuromuscular problems and inherited diseases or conditions caused by the environment. An estimated 65% of scoliosis cases are idiopathic, about 15% are congenital, and about 10% are secondary to a neuromuscular disease.[19] About 38% of variance in scoliosis risk is due to genetic factors, and 62% is due to the environment.[20] The genetics are likely complex, however, given the inconsistent inheritance and discordance among monozygotic twins.[20] The specific genes that contribute to development of scoliosis have not been conclusively identified. At least one gene, CHD7, has been associated with the idiopathic form of scoliosis.[21] Several candidate gene studies have found associations between idiopathic scoliosis and genes mediating bone formation, bone metabolism, and connective tissue structure.[20] Several genome-wide studies have identified a number of loci as significantly linked to idiopathic scoliosis.[20] In 2006, idiopathic scoliosis was linked with three microsatellite polymorphisms in the MATN1 gene (encoding for matrilin 1, cartilage matrix protein).[22] Fifty-three single nucleotide polymorphism markers in the DNA that are significantly associated with adolescent idiopathic scoliosis were identified through a genome-wide association study.[23] Adolescent idiopathic scoliosis has no clear causal agent, and is generally believed to be multifactorial.[21][24] The prevalence of scoliosis is 1% to 2% among adolescents, but the likelihood of progression among adolescents with a Cobb angle less than 20° is about 10% to 20%.[25] Congenital scoliosis can be attributed to a malformation of the spine during weeks three to six in utero due to a failure of formation, a failure of segmentation, or a combination of stimuli.[26] Incomplete and abnormal segmentation results in an abnormally shaped vertebra, at times fused to a normal vertebra or unilaterally fused vertebrae, leading to the abnormal lateral curvature of the spine.[27] ### Resulting from other conditions[edit] Secondary scoliosis due to neuropathic and myopathic conditions can lead to a loss of muscular support for the spinal column so that the spinal column is pulled in abnormal directions. Some conditions which may cause secondary scoliosis include muscular dystrophy, spinal muscular atrophy, poliomyelitis, cerebral palsy, spinal cord trauma, and myotonia.[28][29] Scoliosis often presents itself, or worsens, during an adolescent's growth spurt and is more often diagnosed in females than males.[25] Scoliosis associated with known syndromes is often subclassified as "syndromic scoliosis".[citation needed] Scoliosis can be associated with amniotic band syndrome, Arnold–Chiari malformation, Charcot–Marie–Tooth disease, cerebral palsy, congenital diaphragmatic hernia, connective tissue disorders, muscular dystrophy, familial dysautonomia, CHARGE syndrome, Ehlers–Danlos syndrome (hyperflexibility, "floppy baby" syndrome, and other variants of the condition), fragile X syndrome,[30][31] Friedreich's ataxia, hemihypertrophy, Loeys–Dietz syndrome, Marfan syndrome, nail–patella syndrome, neurofibromatosis, osteogenesis imperfecta, Prader–Willi syndrome, proteus syndrome, spina bifida, spinal muscular atrophy, syringomyelia, and pectus carinatum.[citation needed] Another form of secondary scoliosis is degenerative scoliosis, also known as de novo scoliosis, which develops later in life secondary to degenerative (may or may not be associated with aging) changes. This is a type of deformity that starts and progresses because of the collapse of the vertebral column in an asymmetrical manner. As bones start to become weaker and the ligaments and discs located in the spine become worn as a result of age-related changes, the spine begins to curve. The word 'de novo' is associated with this form of scoliosis as it means 'new', referring to the occurrence of the condition during later life.[citation needed] ## Diagnosis[edit] Cobb angle measurement of a scoliosis People who initially present with scoliosis undergo physical examination to determine whether the deformity has an underlying cause and to exclude the possibility of the underlying condition more serious than simple scoliosis.[citation needed] The person's gait is assessed, with an exam for signs of other abnormalities (e.g., spina bifida as evidenced by a dimple, hairy patch, lipoma, or hemangioma). A thorough neurological examination is also performed, the skin for café au lait spots, indicative of neurofibromatosis, the feet for cavovarus deformity, abdominal reflexes and muscle tone for spasticity.[citation needed] When a person can cooperate, he or she is asked to bend forward as far as possible. This is known as the Adams forward bend test[32] and is often performed on school students. If a prominence is noted, then scoliosis is a possibility and an X-ray may be done to confirm the diagnosis. As an alternative, a scoliometer may be used to diagnose the condition.[33] When scoliosis is suspected, weight-bearing, full-spine AP/coronal (front-back view) and lateral/sagittal (side view) X-rays are usually taken to assess the scoliosis curves and the kyphosis and lordosis, as these can also be affected in individuals with scoliosis. Full-length standing spine X-rays are the standard method for evaluating the severity and progression of the scoliosis, and whether it is congenital or idiopathic in nature. In growing individuals, serial radiographs are obtained at 3- to 12-month intervals to follow curve progression, and, in some instances, MRI investigation is warranted to look at the spinal cord.[34] The standard method for assessing the curvature quantitatively is measuring the Cobb angle, which is the angle between two lines, drawn perpendicular to the upper endplate of the uppermost vertebra involved and the lower endplate of the lowest vertebra involved. For people with two curves, Cobb angles are followed for both curves. In some people, lateral-bending X-rays are obtained to assess the flexibility of the curves or the primary and compensatory curves.[citation needed] Congenital and idiopathic scoliosis that develops before the age of 10 is referred to as early-onset scoliosis.[35] Scoliosis that develops after 10 is referred to as adolescent idiopathic scoliosis.[3] Screening adolescents without symptoms for scoliosis is of unclear benefit.[36] ### Definition[edit] Scoliosis is defined as a three-dimensional deviation in the axis of a person's spine.[25][6] Most instances, including The Scoliosis Research Society, define scoliosis as a Cobb angle of more than 10° to the right or left as the examiner faces the person, i.e. in the coronal plane.[37] Scoliosis has been described as a biomechanical deformity, the progression of which depends on asymmetric forces otherwise known as the Hueter-Volkmann Law.[23] ## Management[edit] Main article: Management of scoliosis The traditional medical management of scoliosis is complex and is determined by the severity of the curvature and skeletal maturity, which together help predict the likelihood of progression. The conventional options for children and adolescents are:[38] 1. Observation 2. Bracing 3. Surgery For adults, treatment usually focuses on relieving any pain:[39][40] 1. Pain medication 2. Posture checking 3. Bracing 4. Surgery[41] Treatment for idiopathic scoliosis also depends upon the severity of the curvature, the spine's potential for further growth, and the risk that the curvature will progress. Mild scoliosis (less than 30° deviation) and moderate scoliosis (30–45°) can typically be treated conservatively with bracing in conjunction with scoliosis-specific exercises.[4] Severe curvatures that rapidly progress may require surgery with spinal rod placement and spinal fusion. In all cases, early intervention offers the best results.[citation needed] A specific type of physical therapy may be useful.[42][4] Evidence to support their use however is weak.[2][11] Low quality evidence suggests scoliosis-specific exercises (SSE) may be more effective than electrostimulation.[43] Evidence for the Schroth method is insufficient to support its use.[44] ### Bracing[edit] A Chêneau brace achieving correction from 56° to 27° Cobb angle Bracing is normally done when the person has bone growth remaining and is, in general, implemented to hold the curve and prevent it from progressing to the point where surgery is recommended. In some cases with juveniles, bracing has reduced curves significantly, going from a 40° (of the curve, mentioned in length above) out of the brace to 18°. Braces are sometimes prescribed for adults to relieve pain related to scoliosis. Bracing involves fitting the person with a device that covers the torso; in some cases, it extends to the neck.[citation needed] The most commonly used brace is a TLSO, such as a Boston brace, a corset-like appliance that fits from armpits to hips and is custom-made from fiberglass or plastic. It is sometimes worn 22–23 hours a day, depending on the doctor's prescription, and applies pressure on the curves in the spine. The effectiveness of the brace depends on not only brace design and orthotist skill, but also people's compliance and amount of wear per day. The typical use of braces is for idiopathic curves that are not grave enough to warrant surgery, but they may also be used to prevent the progression of more severe curves in young children, to buy the child time to grow before performing surgery, which would prevent further growth in the part of the spine affected.[citation needed] Indications for bracing: people who are still growing who present with Cobb angles less than 20° should be closely monitored. People who are still growing who present with Cobb angles of 20 to 29° should be braced according to the risk of progression by considering age, Cobb angle increase over a six-month period, Risser sign, and clinical presentation. People who are still growing who present with Cobb angles greater than 30° should be braced. However, these are guidelines and not every person will fit into this table. For example, a person who is still growing with a 17° Cobb angle and significant thoracic rotation or flatback could be considered for nighttime bracing. On the opposite end of the growth spectrum, a 29° Cobb angle and a Risser sign three or four might not need to be braced because the potential for progression is reduced.[45] The Scoliosis Research Society's recommendations for bracing include curves progressing to larger than 25°, curves presenting between 30 and 45°, Risser sign 0, 1, or 2 (an X-ray measurement of a pelvic growth area), and less than six months from the onset of menses in girls.[46] Scoliosis braces are usually comfortable, especially when well designed and well fitted, also after the 7- to 10-day break-in period. A well fitted and functioning scoliosis brace provides comfort when it is supporting the deformity and redirecting the body into a more corrected and normal physiological position.[47] Evidence supports that bracing prevents worsening of disease, but whether it changes quality of life, appearance, or back pain is unclear.[48] ### Surgery[edit] Preoperative (left) and postoperative (right) X-ray of a person with thoracic dextroscoliosis and lumbar levoscoliosis: The X-ray is usually projected such that the right side of the subject is on the right side of the image; i.e., the subject is viewed from the rear (see left image; the right image is seen from the front). This projection is typically used by spine surgeons, as it is how surgeons see their patients when they are on the operating table (in the prone position). This is the opposite of conventional chest X-ray, where the image is projected as if looking at the patient from the front. The surgery was a fusion with instrumentation.[citation needed] Surgery is usually recommended by orthopedists for curves with a high likelihood of progression (i.e., greater than 45 to 50° of magnitude), curves that would be cosmetically unacceptable as an adult, curves in people with spina bifida and cerebral palsy that interfere with sitting and care, and curves that affect physiological functions such as breathing.[49] Surgery is indicated by the Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT) at 45 to 50°[4] and by the Scoliosis Research Society (SRS) at a Cobb angle of 45°.[50] SOSORT uses the 45 to 50° threshold as a result of the well-documented, plus or minus 5° measurement error that can occur while measuring Cobb angles.[citation needed] Surgeons who are specialized in spine surgery perform surgery for scoliosis. To completely straighten a scoliotic spine is usually impossible, but for the most part, significant corrections are achieved.[51] The two main types of surgery are:[citation needed] * Anterior fusion: This surgical approach is through an incision at the side of the chest wall. * Posterior fusion: This surgical approach is through an incision on the back and involves the use of metal instrumentation to correct the curve. One or both of these surgical procedures may be needed. The surgery may be done in one or two stages and, on average, takes four to eight hours. ## Prognosis[edit] A 50-year follow-up study published in the Journal of the American Medical Association (2003) asserted the lifelong physical health, including cardiopulmonary and neurological functions, and mental health of people with idiopathic scoliosis are comparable to those of the general population. Scoliosis that interferes with normal systemic functions is "exceptional"[52] and "rare", and "untreated [scoliosis] people had similar death rates and were just as functional and likely to lead productive lives 50 years after diagnosis as people with normal spines".[16][53] In an earlier University of Iowa follow-up study, 91 percent of people with idiopathic scoliosis displayed normal pulmonary function, and their life expectancy was 2% less than that of the general population.[17] Generally, the prognosis of scoliosis depends on the likelihood of progression. The general rules of progression are larger curves carry a higher risk of progression than smaller curves, and thoracic and double primary curves carry a higher risk of progression than single lumbar or thoracolumbar curves. In addition, people not having yet reached skeletal maturity have a higher likelihood of progression (i.e., if the person has not yet completed the adolescent growth spurt).[54] ## Epidemiology[edit] Scoliosis affects 2–3% of the United States population, which is equivalent to about 5 to 9 million cases.[4] A scoliosis spinal column curve of 10° or less affects 1.5% to 3% of individuals.[46] The age of onset is usually between 10 years and 15 years (can occur at a younger age) in children and adolescents, making up to 85% of those diagnosed. This is seen to be due to rapid growth spurts occurring at puberty when spinal development is most relenting to genetic and environmental influences.[55] Because female adolescents undergo growth spurts before postural musculoskeletal maturity, scoliosis is more prevalent among females.[56] Although fewer cases are present today using Cobb angle analysis for diagnosis, scoliosis remains a prevailing condition, appearing in otherwise healthy children. Despite the fact that scoliosis is a disfigurement of the spine, it has been shown to influence the pneumonic function, balance while standing and stride execution of kids with scoliosis. The impacts of backpack carriage on these three side effects have been broadly researched.[57] Incidence of idiopathic scoliosis (IS) stops after puberty when skeletal maturity is reached, however, further curvature may proceed during late adulthood due to vertebral osteoporosis and weakened musculature.[4] ## History[edit] Female with lateral curvature of the spine Ever since the condition was discovered by the Greek physician Hippocrates, the search for a cure has been sought. Treatments such as bracing and the insertion of rods into the spine were employed during the 1900s. In the mid-20th century, new treatments and improved screening methods have been developed to reduce the progression of scoliosis in patients and alleviate the associated pain they suffer. School children were during this period believed to suffer from poor posture as a result of working at their desks, and many were diagnosed with scoliosis. It was also considered to be caused by tuberculosis or poliomyelitis, diseases that were successfully managed using vaccines and antibiotics.[citation needed] The American orthopaedic surgeon Alfred Shands Jr. discovered that two percent of patients had non-disease related scoliosis, later termed idiopathic scoliosis, or the "cancer of orthopaedic surgery". These patients were treated with questionable remedies.[58] A theory at the time—now discredited—was that the condition needed to be detected early to halt its progression, and so some schools made screening for scoliosis mandatory. Measurements of shoulder height, leg length and spinal curvature were made, and the ability to bend forwards, along with body posture, was tested, but students were sometimes misdiagnosed because of their poor posture.[citation needed] An early treatment was the Milwaukee brace, a rigid contraption of metal rods attached to a plastic or leather girdle, designed to straighten the spine. Because of the constant pressure applied to the spine, the brace was uncomfortable. It caused jaw and muscle pain, skin irritation, as well as low self-esteem.[citation needed] ### Surgery[edit] In 1962, the American orthopaedic surgeon Paul Harrington introduced a metal spinal system of instrumentation that assisted with straightening the spine, as well as holding it rigid while fusion took place. The now obsolete Harrington rod operated on a ratchet system, attached by hooks to the spine at the top and bottom of the curvature that when cranked would distract—or straighten—the curve. The Harrington rod obviates the need for prolonged casting, allowing patients greater mobility in the postoperative period and significantly reducing the quality of life burden of fusion surgery. The Harrington rod was the precursor to most modern spinal instrumentation systems. A major shortcoming was that it failed to produce a posture wherein the skull would be in proper alignment with the pelvis, and it did not address rotational deformity. As the person aged, there would be increased wear and tear, early onset arthritis, disc degeneration, muscular stiffness, and acute pain. "Flatback" became the medical name for a related complication, especially for those who had lumbar scoliosis.[59] In the 1960s, the gold standard for idiopathic scoliosis was a posterior approach using a single Harrington rod. Post-operative recovery involved bed rest, casts, and braces. Poor results became apparent over time.[60] In the 1970s, an improved technique was developed using two rods and wires attached at each level of the spine. This segmented instrumentation system allowed patients to become mobile soon after surgery.[60] In the 1980s, Cotrel-Dubousset instrumentation improved fixation and addressed sagittal imbalance and rotational defects unresolved by the Harrington rod system. This technique used multiple hooks with rods to give stronger fixation in three dimensions, usually eliminating the need for postoperative bracing.[60] ### Evolution[edit] A 14–15th century woman who had severe scoliosis, and died at about 35 years, Limburgs Museum Venlo There are links between human spinal morphology, bipedality, and scoliosis which suggest an evolutionary basis for the condition. Scoliosis has not been found in chimpanzees or gorillas.[61] Thus, it has been hypothesized that scoliosis may actually be related to humans' morphological differences from these apes.[61] Other apes have a shorter and less mobile lower spine than humans. Some of the lumbar vertebrae in Pan are "captured", meaning that they are held fast between the ilium bones of the pelvis. Compared to humans, Old World monkeys have far larger erector spinae muscles, which are the muscles which hold the spine steady.[61] These factors make the lumbar spine of most primates less flexible and far less likely to deviate than those of humans. While this may explicitly relate only to lumbar scolioses, small imbalances in the lumbar spine could precipitate thoracic problems as well.[61] Scoliosis may be a byproduct of strong selection for bipedalism. For a bipedal stance, a highly mobile, elongated lower spine is very beneficial.[61] For instance, the human spine takes on an S-shaped curve with lumbar lordosis, which allows for better balance and support of an upright trunk.[62] Selection for bipedality was likely strong enough to justify the maintenance of such a disorder. Bipedality is hypothesized to have emerged for a variety of different reasons, many of which would have certainly conferred fitness advantages. It may increase viewing distance, which can be beneficial in hunting and foraging as well as protection from predators or other humans; it makes long-distance travel more efficient for foraging or hunting; and it facilitates terrestrial feeding from grasses, trees, and bushes.[63] Given the many benefits of bipedality which depends on a particularly formed spine, it is likely that selection for bipedalism played a large role in the development of the spine as we see it today, in spite of the potential for "scoliotic deviations".[61] According to the fossil record, scoliosis may have been more prevalent among earlier hominids such as Australopithecus and Homo erectus, when bipedality was first emerging. Their fossils indicate that there may have been selected over time for a slight reduction in lumbar length to what we see today, favouring a spine that could efficiently support bipedality with a lower risk of scoliosis.[61] ## Society and culture[edit] The cost of scoliosis involves both monetary losses and lifestyle limitations that increase with severity. Respiratory deficiencies may also arise from thoracic deformities and cause abnormal breathing.[64] This directly affects exercise and work capacity, decreasing the overall quality of life.[4] In the health care system of the United States, the average hospital cost for cases involving surgical procedures was $30,000 to $60,000 per person in 2010.[65] As of 2006, the cost of bracing has been published as up to $5,000 during rapid growth periods, when braces must be consistently replaced across multiple follow-ups.[4] ## Research[edit] Genetic testing for AIS, which became available in 2009 and is still under investigation, attempts to gauge the likelihood of curve progression.[66] ## See also[edit] * Back brace * Kyphosis * Lordosis * Neuromechanics of idiopathic scoliosis * Pott disease * Scheuermann's disease * Schooliosis * Scoliosis Research Society ## References[edit] 1. ^ "scoliosis". Merriam Webster. Archived from the original on 11 August 2016. 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Archived from the original on 2 January 2014. Retrieved 1 January 2014. ## External links[edit] Wikimedia Commons has media related to Scoliosis. * Scoliosis at Curlie * Early Onset Scoliosis is the abnormal, side-to-side curve of the spine in children under five years old, often including children with congenital scoliosis (present at birth, with spine abnormalities) and infantile scoliosis (birth to 3 years). * Questions and Answers about Scoliosis in Children and Adolescents – US National Institute of Arthritis and Musculoskeletal and Skin Diseases Classification D * ICD-10: M41 * ICD-9-CM: 737 * MeSH: D012600 * DiseasesDB: 26545 External resources * MedlinePlus: 001241 * v * t * e Spinal disease Deforming Spinal curvature * Kyphosis * Lordosis * Scoliosis Other * Scheuermann's disease * Torticollis Spondylopathy inflammatory * Spondylitis * Ankylosing spondylitis * Sacroiliitis * Discitis * Spondylodiscitis * Pott disease non inflammatory * Spondylosis * Spondylolysis * Spondylolisthesis * Retrolisthesis * Spinal stenosis * Facet syndrome Back pain * Neck pain * Upper back pain * Low back pain * Coccydynia * Sciatica * Radiculopathy Intervertebral disc disorder * Schmorl's nodes * Degenerative disc disease * Spinal disc herniation * Facet joint arthrosis * 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 Authority control * BNF: cb11944282c (data) * GND: 4055267-6 * LCCN: sh85118750 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Scoliosis	c0036439	29,003	wikipedia	https://en.wikipedia.org/wiki/Scoliosis	2021-01-18T18:30:43	{"mesh": ["D012600"], "umls": ["C0036439"], "wikidata": ["Q174857"]}
A number sign (#) is used with this entry because tuberous sclerosis-2 (TSC2) is caused by heterozygous mutation in the TSC2 gene (191092) on chromosome 16p13. The TSC2 gene product is known as 'tuberin.' Description Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by hamartomas in multiple organ systems, including the brain, skin, heart, kidneys, and lung. These changes can result in epilepsy, learning difficulties, behavioral problems, and renal failure, among other complications (reviews by Crino et al., 2006 and Curatolo et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of tuberous sclerosis, see tuberous sclerosis-1 (191100), caused by mutation in the TSC1 gene (605284) on chromosome 9q34. Approximately 10 to 30% of cases of tuberous sclerosis are due to mutations in the TSC1 gene: the frequency of cases due to mutations in the TSC2 gene is consistently higher. TSC2 mutations are associated with more severe disease (Crino et al., 2006) (see GENOTYPE/PHENOTYPE CORRELATIONS section). Clinical Features Kumar et al. (1995) reported a 2-year-old Caucasian female with tuberous sclerosis-2. At birth, she had a hypopigmented patch on her left ankle and multiple hypopigmented patches on her back and trunk. She later developed facial plaques on her forehead but no facial angiofibromas or ungual fibromata. Onset of generalized seizures occurred at 7 months of age. CT scan of the brain demonstrated cerebral cortical tubers and subependymal nodules. Renal ultrasound showed multiple cysts in both kidneys. The parents were clinically normal. Vrtel et al. (1996) reported a father and his son with tuberous sclerosis-2. The family was ascertained through a discovery of fetal bradycardia and arrhythmia in the proband at 20 weeks' gestation. At 24 weeks' gestation, an intracardiac mass suspected of being a rhabdomyosarcoma was detected by fetal ultrasound and the diagnosis of tuberous sclerosis was suggested. A boy, weighing 2,500 g, was delivered at 39 weeks. Postnatal ECG showed intermittent second and third degree atrioventricular block. Echography of the brain, liver, and kidneys showed no abnormalities, and the studies of the retina were also normal. At 3 months of age a hypomelanotic macule, 25 x 15 mm, was noted on the buttock using Woods light. The 30-year-old father showed no abnormalities on study of the brain, heart, skin, and retina, and the most questionable changes in the kidneys. All tooth surfaces showed pit-shaped enamel defects, corresponding to the dental pits described in patients with tuberous sclerosis. In addition, 2 gingival fibromas were found. Khare et al. (2001) reported a 4-generation family with mild physical features of tuberous sclerosis-2, but in which there was significant clustering of neuropsychiatric disorders including mood disorder, anxiety disorder, and autism among affected individuals. A second family also had mild physical features of tuberous sclerosis, but no neuropsychiatric assessment had been performed. Martin et al. (2003) reported a pair of twin boys discordant for tuberous sclerosis-2 in whom marker studies supported a probability of monozygosity greater than 99.9%. The twins had similar CNS features, as both were severely mentally retarded with motor delay. Obvious differences were seen in the skin, heart, and kidneys. Whereas twin T had a shagreen patch of the skin and a heart rhabdomyoma, twin M had none. Twin M was diagnosed early (at the age of 3 years) with renal lesions, namely, angiomyolipomas and cystic alterations. At 6 years of age, twin T also started to have the same types of renal lesions as twin M. Martin et al. (2003) suggested that the Knudson hypothesis (Knudson, 1971) explained the difference, assuming that many of the features such as the skin, cardiac, and renal alterations present a 2-hit phenomenon, the second hit depending on a random somatic event. Genetic analysis identified a germline mutation in the TSC2 gene (191092.0012) in both boys. Jansen et al. (2006) reported a large 5-generation French Canadian family with a mild form of tuberous sclerosis-2 due to a heterozygous mutation in the TSC2 gene (R905Q; 191092.0013). The proband was a 25-year-old man who started having seizures at age 8 years. Family studies showed that 25 individuals carried the mutation, but only 5 had definite TSC according to diagnostic criteria and 11 did not meet any diagnostic criteria. Examination of mutation carriers showed hypomelanotic macules in 92%, epilepsy in 60%, learning difficulties or mild cognitive impairment in 52%, and brain imaging abnormalities (white matter lesions, subependymal nodule, or subependymal giant cell astrocytoma) in 24%. None had cortical tubers. Renal lesions were found in 8% and retinal abnormalities in 4%. Five additional families with the same mutation were found, and all had a similarly mild phenotype, although cortical tubers were present in some. In a retrospective review, McMaster et al. (2011) identified 10 cases of chordoma associated with tuberous sclerosis complex, although only 3 patients had documented mutations: 2 in the TSC1 gene and 1 in the TSC2 gene. The median age at onset in TSC-associated chordoma was 6.2 months (range 0 to 16 years), with only 1 patient diagnosed with chordoma after age 5. Chordomas were skull-based in 50% and sacral-based in 40%; the 16-year-old had a spinal-based tumor. The 5-year survival was 83%. Molecular and immunohistochemical studies of the chordomas from 2 patients with identified mutations in the TSC1 and TSC2 genes, respectively, demonstrated that 1 tumor had loss of heterozygosity (LOH) for the wildtype TSC1 allele, while the other tumor had LOH for the wildtype TSC2 allele, suggesting a pathogenetic role for the TSC1/TSC2 genes in these chordomas. Comparison with 65 cases of non-TSC-associated pediatric chordoma (215400) showed important clinical differences. The latter patients had onset between ages 0 and 18 years (median age at diagnosis was 12 years). Most (64.1%) were intracranial, 26.6% were spinal, and 9.4% were sacral. Chordomas were exclusively skull-based in the youngest age tertile, while sacral chordomas were confined to patients in the oldest tertile. Survival was poorer, at 68.2% at 5 years and 53.1% at 20 years. The findings suggested that TSC-associated chordoma has an unusually early onset and/or rapid growth, and that chordoma can be a rare pediatric manifestation of TSC. Diagnosis The tuberous sclerosis complex consensus conference (Roach et al., 1998) proposed major and minor diagnostic criteria. Since no single feature is diagnostic, an evaluation that includes consideration of all clinical features is necessary to make a correct diagnosis. The clinical manifestations of TSC appear at distinct developmental points, which may further complicate the clinical diagnosis. Major criteria include retinal hamartomas, renal angiomyolipomas, facial angiofibromas, and cortical tubers, among other features. Minor criteria include dental pits, bone cysts, and cerebral white-matter radial migration lines, among other features. Brackley et al. (1999) reported detection by ultrasound of cranial abnormalities at 14 weeks' gestation in a fetus subsequently confirmed as having tuberous sclerosis using DNA linkage analysis within the affected family. The presence of asymmetric ventricular enlargement persisted antenatally. MRI at 26 weeks indicated the possibility of poor gyral formation consistent with a neuronal migration disorder. Cardiac rhabdomyomata were not visualized on ultrasound scan until 30 weeks' gestation. Postnatal cranial ultrasound confirmed the significant neuropathology that was manifested by severe developmental delay and intractable fits in the child. The right fundus of the patient showed multiple peripheral pigmented areas and a persistent pupillary membrane also consistent with TSC. Pathogenesis Liang et al. (2014) generated a mosaic Tsc1-knockout mouse model in which mutant mice developed renal mesenchymal lesions that recapitulated perivascular epithelioid cell tumors (PEComas) found in patients with TSC. The authors found that YAP (YAP1; 606608) was upregulated by MTOR (601231) in mouse and human PEComas. Genetic or pharmacologic inhibition of Yap blunted abnormal proliferation and induced apoptosis of mouse Tsc1/Tsc2-deficient cells in culture and in mosaic Tsc1-knockout mice. Yap accumulated in cells lacking Tsc1/Tsc2 due to impaired degradation of Yap by autophagy in an Mtor-dependent manner. Liang et al. (2014) proposed that YAP is a potential therapeutic target for TSC and other disease with dysregulated MTOR activity. Inheritance Most patients with tuberous sclerosis-2 have de novo heterozygous mutations in the TSC2 gene. Patients with tuberous sclerosis-2 generally have more severe disease than patients with tuberous sclerosis-1, thus reducing the chance of these patients having a family (Curatolo et al., 2008). ### Mosaicism Verhoef et al. (1995) reported somatic mosaicism in the father of a 2-year-old boy with tuberous sclerosis 2: the father had subclinical signs of TSC and an apparently low proportion of cells with the TSC2 mutation. Verhoef et al. (1999) identified 6 families with mosaicism in a series of 62 unrelated families with a mutation in either the TSC1 or the TSC2 gene. In 5 families, somatic mosaicism was present in the mildly affected parent of an index patient. In 1 family with clinically unaffected parents, gonadal mosaicism was detected after tuberous sclerosis was found in 3 children. The detection of mosaicism has obvious consequences for genetic counseling. Clinical investigation of the parents of patients with seemingly sporadic mutations is essential to determine their residual chance of gonadal and/or somatic mosaicism, unless a mosaic pattern is detected in the index patient, proving a de novo event. In the data set of Verhoef et al. (1999), the exclusion of signs of tuberous sclerosis in the parents of a patient with tuberous sclerosis reduced the chance of one of the parents to be a mosaic mutation carrier from 10% to 2%. In the 5 families with somatic mosaicism, the parent was given the diagnosis after the diagnosis was made in the child. During TSC2 mutational analysis, Roberts et al. (2002) identified 10 single-nucleotide polymorphisms (SNPs) that occur within or close to exon boundaries at minor allele frequencies greater than 5%. The authors determined the haplotypes for 6 of these SNPs and the microsatellite marker kg8 in the 3-prime region of TSC2 in a set of 40 parent-child trios. The most common haplotypes accounted for 53%, 11%, 6%, and 5% of chromosomes. Thirty-eight TSC2 mutation-bearing haplotypes had a similar distribution, indicating that there was no haplotype that predisposed to mutation in this region in TSC2. Family analysis was possible in 12 sporadic cases, and indicated that the mother was the parent of origin in 7 cases (3 point mutations, 2 small deletions, 2 large deletions), while the father was the parent of origin in 5 cases (2 point mutations, 3 small deletions). Roberts et al. (2002) concluded that TSC2 mutations occur at substantial frequency on both the maternally and paternally derived TSC alleles, in contrast to many other genetic diseases. There was no major age effect for mutations of paternal origin. The observation was considered significant to genetic counseling of parents of a sporadic TSC case; each parent should be considered the potential parent of origin, and some alternative reproductive choices such as use of a sperm donor only or egg donor only are not guaranteed to prevent recurrence. Mapping Using tuberous sclerosis families in which linkage to the TSC1 locus on chromosome 9 had been excluded, Kandt et al. (1992) demonstrated linkage with D16S283, the closest marker on the proximal side of the locus for polycystic kidney disease type 1 (173900), on chromosome 16p13. A lod score of 9.50 at theta = 0.02 was observed; 1 family independently presented a lod score of 4.44 at theta = 0.05. Kandt et al. (1992) estimated that about 40% of tuberous sclerosis families are linked to chromosome 9, and most of the rest, the majority, to chromosome 16. No clear evidence for a locus on other chromosomes was found. Confirmation of a tuberous sclerosis locus on chromosome 16 (TSC2) was provided by Pericak-Vance et al. (1992), Short et al. (1992) and Smith et al. (1992). Povey et al. (1994) did linkage studies in 32 families of tuberous sclerosis, using genetic markers on chromosomes 9, 11, 12, and 16. Approximately half the families appeared to be linked to TSC1 on chromosome 9 between ASS1 (603470) and D9S298 and half to TSC2 on chromosome 16 close to D16S291. Molecular Genetics Approximately 10 to 30% of tuberous sclerosis cases are due to TSC1 mutations, whereas the frequency of TSC2 mutations is consistently higher. TSC1 mutations account for 15 to 30% of familial cases and 10 to 15% of sporadic cases. The frequency of TSC2 mutations in sporadic cases ranges from 75 to 80%. About 15 to 20% of patients have no identifiable mutations, which may be due to mosaicism (Crino et al., 2006; Curatolo et al., 2008). In a patient with tuberous sclerosis-2, Kumar et al. (1995) identified a de novo 1-bp deletion in the TSC2 gene (191092.0001). In a father and son with tuberous sclerosis-2, Vrtel et al. (1996) identified a truncating mutation in the TSC2 gene (K12X; 191092.0003). The father had a milder phenotype, and was only diagnosed after his son was diagnosed. Flanking markers suggested that the mutated chromosome was of grandmaternal origin. The authors noted that it is possible that the mildly affected father was mosaic (although this was not detected), with the new mutation occurring by chance on the chromosome 16 he received from his mother. Vrtel et al. (1996) stated that the case illustrated the usefulness of mutation analysis in the diagnosis of families with an incomplete phenotype of tuberous sclerosis. In 2 unrelated families with tuberous sclerosis-2, Khare et al. (2001) identified a missense mutation in the TSC2 gene (Q1503P; 191092.0011). In 6 families with a mild form of tuberous sclerosis, Jansen et al. (2006) identified a heterozygous mutation in the TSC2 gene (R905Q; 191092.0013). The authors identified 2 additional mutations in the same codon, R905W (191092.0014) and R905G (191092.0015), in other families with a more severe phenotype, including cortical tubers, seizures, cognitive impairment, and severe skin lesions. Jansen et al. (2006) noted that the R905W and R905G substitutions resulted in the incorporation of nonpolar amino acids into the sequence, whereas the R905Q substitution introduced a polar amino acid with an amido functional group. Jansen et al. (2006) emphasized that patients with a mild form of tuberous sclerosis may not meet established diagnostic criteria, but can still have detrimental mutations in disease-associated genes. ### Modifier of TSC2 Renal Angiomyolipomas Because interferon-gamma (IFNG; 147570) is a useful mediator of tumor regression in animal models of kidney tumors and because there is a polymorphism within intron 1 of the IFNG gene for which 1 common allele (allele 2, with 12 CA repeats; 147570.0001) is associated with a higher expression of interferon-gamma in humans, Dabora et al. (2002) examined the relationship between the IFNG genotype and the severity of renal disease in patients with tuberous sclerosis who had TSC2 mutations. Patients were genotyped for the IFNG microsatellite polymorphism, allele 2, and its association with the development of kidney angiomyolipomas (which the authors called KAMLs) was examined. Both chi square analysis and the transmission/disequilibrium test (TDT) suggested an association between allele 2 and the absence of KAMLs in patients with known TSC2 mutations. Among the 127 patients who were more than 5 years old, KAMLs were present in 95 (75%) and absent in 32 (25%). In the group with KAMLs, the frequency of allele 2 was 56%; in the group without KAMLs, the frequency of allele 2 was significantly higher, at 78%. Family-based TDT analysis gave similar results. Subgroup analyses showed that both age and gender may influence the impact of this association. This study suggested that modifier genes play a role in the variable expression of tuberous sclerosis and also suggested a potential therapy for KAMLs in patients with tuberous sclerosis. Genotype/Phenotype Correlations Lewis et al. (2004) used validated tools measuring intellectual function, depression, anxiety, and autistic and behavioral disorders to study the relationships between genotype, seizures, mental retardation, and behaviors in a cohort of 92 patients with mutations in the TSC1 or TSC2 genes. TSC2 but not TSC1 mutations were associated with autistic disorder (p = 0.001), infantile spasms (p = 0.001), and higher risk of low IQ (p = 0.0004) even after adjustment for a history of infantile spasms using logistical regression (OR, 3.50; 95% CI, 1.03-11.95). Previously unrecognized anxiety was frequently diagnosed in patients with mutations in either gene. Au et al. (2007) performed mutation analyses on 325 individuals with definite tuberous sclerosis complex diagnostic status. The authors identified mutations in 72% (199 of 257) of de novo and 77% (53 of 68) of familial cases, with 17% of mutations in the TSC1 gene and 50% in the TSC2 gene. There were 4% unclassified variants and 29% with no mutation identified. Genotype/phenotype analyses of all observed tuberous sclerosis complex findings in probands were performed, including several clinical features not analyzed in 2 previous large studies. Au et al. (2007) showed that patients with TSC2 mutations have significantly more hypomelanotic macules and learning disability in contrast to those with TSC1 mutations, findings not noted in previous studies. The authors also observed results consistent with 2 similar studies suggesting that individuals with mutations in TSC2 have more severe symptoms. On performing metaanalyses of their data and the other 2 large studies in the literature (Dabora et al., 2001; Sancak et al., 2005), Au et al. (2007) found significant correlations for several features that individual studies did not have sufficient power to conclude. Male patients showed more frequent neurologic and eye symptoms, renal cysts, and ungual fibromas. Jansen et al. (2008) compared the clinical features of 17 TS patients with mutations in the TSC1 gene and 31 patients with mutations in the TSC2 gene. Patients with TSC2 mutations tended to have an earlier onset of seizures, a higher incidence of infantile spasms, and lower cognition scores compared to those with TSC1 mutations. Patients with TSC2 mutations had more tubers and more tubers per brain proportion than those with TSC1 mutations, but the ranges overlapped. Patients with a mutation deleting or inactivating the GTPase-activating protein domain had more tubers than those with intact GTPase-activating domains. Despite some of these small differences, Jansen et al. (2008) concluded that there was considerable overlap between the groups and that prediction of the phenotype in patients with tuberous sclerosis should not be based on their particular TSC1 or TSC2 mutation. Some patients with tuberous sclerosis develop pulmonary lymphangioleiomyomatosis (LAM; 606690), also known as pulmonary lymphangiomyomatosis, which has been reported in 34 to 39% of asymptomatic women and in some men with tuberous sclerosis. In a retrospective review of the chest CT scans of 45 female and 20 male patients with tuberous sclerosis, Muzykewicz et al. (2009) found cysts consistent with LAM in 22 (49%) women and 2 (10%) men. Among the women, changes consistent with LAM were observed in 6 (40%) of 15 with TSC1 mutations, 11 (48%) of 23 with TSC2 mutations, and 5 (71%) of 7 with no mutation identified. While the predominant size of cysts did not differ across these 3 groups, LAM women with TSC2 mutations had a significantly greater number of cysts than did women with TSC1 mutations. Some of the same mutations were identified in patients with LAM and in those without LAM. These findings suggested a higher rate of LAM in patients with TSC1 than previously recognized, as well as a fundamental difference in CT presentation between individuals with TSC1 and TSC2. In a retrospective chart review of brain MRI scans of 173 patients with TSC, Chu-Shore et al. (2009) found that 46% of patients had at least 1 cyst-like cortical tuber. The tubers are called cyst-like because they presumably lack the inner endothelial lining seen in true cysts. Patients with TSC2 mutations were more likely to have a cyst-like tuber than patients with TSC1 mutation (p = 0.002) or patients with no mutation identified (p = 0.039). Patients with at least 1 cyst-like cortical tuber were more likely to have a history of infantile spasms (p = 0.00005; relative risk, 2.18), epilepsy (p = 0.0038; relative risk, 1.22), and refractory epilepsy (p = 0.0007; relative risk, 1.47) than patients without a cyst-like cortical tuber. Chu-Shore et al. (2009) concluded that cyst-like cortical tubers are strongly associated with TSC2 gene mutations and a more aggressive seizure phenotype in patients with tuberous sclerosis complex. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Achromatic retinal patches \- Retinal astrocytoma \- Optic gliomas Mouth \- Pitted dental enamel \- Gingival fibroma CARDIOVASCULAR Heart \- Wolf-Parkinson-White syndrome \- Cardiac rhabdomyoma RESPIRATORY Lung \- Lymphangiomyomatosis, rare GENITOURINARY Kidneys \- Renal cysts \- Tumors of the kidney (may progress to malignancy in less than 2%) SKELETAL \- Cystic areas of bone rarefaction, esp. phalanges SKIN, NAILS, & HAIR Skin \- Facial angiofibroma (adenoma sebaceum) \- White ash leaf-shaped macules \- Shagreen patch \- Subcutaneous nodules \- Cafe-au-lait spots \- Subungual fibromata NEUROLOGIC Central Nervous System \- Hamartomatous lesions of the brain \- Subependymal nodules \- Cortical tubers \- Infantile spasms \- Seizures \- Mental retardation (30%) \- Learning difficulties \- Intracranial calcification by x-ray or CT Behavioral Psychiatric Manifestations \- Attention deficit disorder \- Hyperactivity \- Autism ENDOCRINE FEATURES \- Precocious puberty \- Hypothyroidism NEOPLASIA \- Myocardial rhabdomyoma \- Multiple bilateral renal angiomyolipoma \- Ependymoma \- Renal carcinoma \- Giant cell astrocytoma \- Chordoma \- Benign tumors of the eye, heart, and lungs LABORATORY ABNORMALITIES \- Increased frequency of premature centromere disjunction (PCD) in cultured fibroblasts, esp. chromosome 3 \- Allelic loss on 16p13.3 in angiomyolipoma, cardiac rhabdomyoma, cortical tuber, and giant cell astrocytoma MISCELLANEOUS \- Genetic heterogeneity (see 191100 ) \- Many studies have reported that the phenotype of tuberous sclerosis-2 (TSC2) is more severe than that of tuberous sclerosis-1 (e.g., lower IQ, more seizures, more macules, cust-like cortical tubers) \- Highly variable phenotype \- One-third of cases are familial \- Majority of cases are sporadic \- Prevalence of 1 in 6,000 to 1 in 10,000 \- Frequent new mutations (~60%) and/or gonadal mosaicism in TSC2 MOLECULAR BASIS \- Caused by mutation in the tuberin gene (TSC2, 191092.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	TUBEROUS SCLEROSIS 2	c0041341	29,004	omim	https://www.omim.org/entry/613254	2019-09-22T15:59:09	{"doid": ["0080325"], "mesh": ["D014402"], "omim": ["613254"], "orphanet": ["805"], "genereviews": ["NBK1220"]}
Erythema multiforme majus Other namesErythema multiforme majus[1] Micrograph of confluent epidermal necrosis. H&E stain. SpecialtyDermatology Erythema multiforme major is a form of rash with skin loss or epidermal detachment. The term "erythema multiforme majus" is sometimes used to imply a bullous (blistering) presentation.[2] According to some sources, there are two conditions included on a spectrum of this same disease process: * Stevens–Johnson syndrome (SJS) * Toxic epidermal necrolysis (TEN) which described by Alan Lyell and previously called Lyell syndrome[5]. In this view, EM major, SJS and TEN are considered a single condition, distinguished by degree of epidermal detachment.[3][4] However, a consensus classification separates erythema multiforme minor, erythema multiforme major, and SJS/TEN as three separate entities.[3] ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ Daniel J. Trozak; Dan J. Tennenhouse (1 October 2005). Dermatology skills for primary care: an illustrated guide. Humana Press. pp. 161–. ISBN 978-1-58829-489-0. Archived from the original on 21 June 2013. Retrieved 5 June 2010. 3. ^ a b "Erythema Multiforme: eMedicine Emergency Medicine". 2019-02-02. Archived from the original on 2010-08-06. Cite journal requires `\|journal=` (help) 4. ^ Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC (January 1993). "Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme". Arch Dermatol. 129 (1): 92–6. doi:10.1001/archderm.129.1.92. PMID 8420497.[permanent dead link] 5\. Orphanet Journal of Rare Diseases 2010, 5:39 doi:10.1186/1750-1172-5-39 ## External links[edit] Classification D * ICD-9-CM: 695.12 * v * t * e Urticaria and erythema Urticaria (acute/chronic) Allergic urticaria * Urticarial allergic eruption Physical urticaria * Cold urticaria * Familial * Primary cold contact urticaria * Secondary cold contact urticaria * Reflex cold urticaria * Heat urticaria * Localized heat contact urticaria * Solar urticaria * Dermatographic urticaria * Vibratory angioedema * Pressure urticaria * Cholinergic urticaria * Aquagenic urticaria Other urticaria * Acquired C1 esterase inhibitor deficiency * Adrenergic urticaria * Exercise urticaria * Galvanic urticaria * Schnitzler syndrome * Urticaria-like follicular mucinosis Angioedema * Episodic angioedema with eosinophilia * Hereditary angioedema Erythema Erythema multiforme/ drug eruption * Erythema multiforme minor * Erythema multiforme major * Stevens–Johnson syndrome, Toxic epidermal necrolysis * panniculitis (Erythema nodosum) * Acute generalized exanthematous pustulosis Figurate erythema * Erythema annulare centrifugum * Erythema marginatum * Erythema migrans * Erythema gyratum repens Other erythema * Necrolytic migratory erythema * Erythema toxicum * Erythroderma * Palmar erythema * Generalized erythema This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Erythema multiforme major	c3241919	29,005	wikipedia	https://en.wikipedia.org/wiki/Erythema_multiforme_major	2021-01-18T18:43:24	{"umls": ["C3241919"], "icd-9": ["695.12"], "wikidata": ["Q5396392"]}
Biliary dyskinesia SpecialtyGeneral surgery Biliary dyskinesia is a disorder of some component of biliary part of the digestive system in which bile physically can not move normally in the proper direction through the tubular biliary tract. It most commonly involves abnormal biliary tract peristalsis muscular coordination within the gallbladder in response to dietary stimulation of that organ to squirt the liquid bile through the common bile duct into the duodenum. Ineffective peristaltic contraction of that structure produces postprandial (after meals) right upper abdominal pain (cholecystodynia) and almost no other problem. When the dyskinesia is localized at the biliary outlet into the duodenum just as increased tonus of that outlet sphincter of Oddi, the backed-up bile can cause pancreatic injury with abdominal pain more toward the upper left side. In general, biliary dyskinesia is the disturbance in the coordination of peristaltic contraction of the biliary ducts, and/or reduction in the speed of emptying of the biliary tree into the duodenum. ## Contents * 1 Mechanism * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Mechanism[edit] Normally, the downstream gallbladder stores and concentrates the bile which originates in liver hepatocyte cells and is released into the microscopic component of the biliary system by the liver. Through aggregating tubules of increasing diameter, the bile leaves the liver and reaches the upstream (proximal) component of the common bile duct. Apparently, the common bile duct beyond (distal to) the gallbladder tends to normally have a greater tone so that the bile backs up into the gallbladder. When bile enters the duodenum (the first part of the small intestine), it aids in digesting the fat within food leaving the stomach. When the bile can not be properly propelled from the not-mechanically-obstructed gallbladder or can not flow out of the end of the common bile duct properly, there is a state of biliary dyskinesia. So, biliary dyskinesia is a dynamically (functional...not fixed mechanical) obstructive, pain-producing disorder. Obstruction by a stone or tumor is a static, mechanical obstruction and tends to produce a more intense pain known as biliary colic. Failure of the biliary sphincter of Oddi can be distinguished from failure of the pancreatic sphincter.[1] ## Diagnosis[edit] Diagnosis may or may not be determined by an ultrasound, but most likely the disease and other biliary diseases of the liver, gallbladder, and bile duct are found by what is most commonly referred to as a hepatobiliary or HIDA scan. This type of imaging is known as cholescintigraphy. Cholescintigraphy or hepatobiliary scintigraphy is scintigraphy of the hepatobiliary tract, including the gallbladder and bile ducts. The image produced by this type of medical imaging, called a cholescintigram, is also known by other names depending on which radiotracer is used, such as HIDA scan, PIPIDA scan, DISIDA scan, or BrIDA scan. Cholescintigraphic scanning is a nuclear medicine procedure to evaluate the health and function of the gallbladder and biliary system. A radioactive tracer is injected through any accessible vein and then allowed to circulate to the liver and starts accumulating in the gall bladder which can take up to an hour. A standard fatty meal (usually a high fat milk shake) is then given and more imaging is performed for another hour so that the response to the fatty meal by the gall bladder can be shown. The gall bladder should respond and begin emptying into the duodenum, the amount of bile ejected can then be calculated as an ejection fraction (EF). An EF < 35% is considered to be diagnostic of biliary dyskinesia and suitable for cholecystectomy to be considered. ## Treatment[edit] Laparoscopic cholecystectomy has been used to treat the condition when due to dyskinesia of the gallbladder.[2] Symptoms may persist after cholecystectomy,[3] and have been linked to the use of proton pump inhibitors.[4] ## References[edit] 1. ^ Toouli J (August 2002). "Biliary Dyskinesia". Curr Treat Options Gastroenterol. 5 (4): 285–291. doi:10.1007/s11938-002-0051-9. PMID 12095476. 2. ^ Haricharan RN, Proklova LV, Aprahamian CJ, et al. (June 2008). "Laparoscopic cholecystectomy for biliary dyskinesia in children provides durable symptom relief". J. Pediatr. Surg. 43 (6): 1060–1064. doi:10.1016/j.jpedsurg.2008.02.032. PMID 18558183. 3. ^ Geiger TM (May 2008). "Prognostic indicators of quality of life after cholecystectomy for biliary dyskinesia". Am Surg. 74 (5): 1364–1367. PMID 18481495. 4. ^ Cahan MA (Sep 2006). "Proton pump inhibitors reduce gallbladder function". Surg. Endosc. 20 (9): 1364–1367. doi:10.1007/s00464-005-0247-x. PMID 16858534. ## External links[edit] Classification D * ICD-10: K82.8 * ICD-9-CM: 575.8 * MeSH: D001657 * DiseasesDB: 12297 External resources * eMedicine: med/347 * 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Biliary dyskinesia	c0005416	29,006	wikipedia	https://en.wikipedia.org/wiki/Biliary_dyskinesia	2021-01-18T19:03:44	{"mesh": ["D001657"], "umls": ["C0005416"], "wikidata": ["Q2028354"]}
## Summary ### Clinical characteristics. 3q29 recurrent deletion is characterized by global developmental delay and/or intellectual disability, and commonly, speech delay, and increased risk for neuropsychiatric disorders (including autism spectrum disorder, anxiety disorder, psychosis, and/or schizophrenia). Other common findings are failure to thrive and feeding problems in infancy that persist into childhood, heart defects (especially patent ductus arteriosus), gastrointestinal disorders (including gastroesophageal reflux disease), and dental abnormalities. To date findings in fewer than 50 affected individuals have been reported. ### Diagnosis/testing. The diagnosis of the 3q29 recurrent deletion is established by detection of the 1.6-Mb heterozygous deletion by chromosomal microarray at the approximate position of chr3:195998129-197623129 in the reference genome (NCBI Build 38). ### Management. Treatment of manifestations: Early speech and language therapy to address speech delays; physical therapy as needed to address fine and gross motor delays; individualized education program (IEP) for school-age children; care by a child psychiatrist/psychologist as needed for neuropsychiatric disorders; feeding therapy and consideration of gastrostomy tube as needed; routine management of dental caries, congenital heart defects, recurrent ear infections. Surveillance: Continued assessment of feeding and nutrition, developmental milestones, cognitive development, and possible neuropsychiatric manifestations. Evaluation of relatives at risk: Parents and older and younger sibs of a proband should be tested for the 3q29 recurrent deletion to encourage close assessment/monitoring of developmental milestones (in children) and monitoring for neuropsychiatric manifestations (in children and adults). ### Genetic counseling. The 3q29 recurrent deletion is inherited in an autosomal dominant manner. Although most deletions are de novo, inherited deletions have been reported. If the 3q29 recurrent deletion identified in the proband is not identified in one of the parents, the risk to sibs is low (<1%) but greater than that of the general population because of the possibility of parental germline mosaicism for the deletion. Once the 3q29 recurrent deletion has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis 3q29 recurrent deletion is characterized by the (almost universally present) clinical features of developmental delay and/or intellectual disability; however, no single clinical feature distinguishes this condition from other similar conditions. ### Suggestive Findings The 3q29 recurrent deletion should be considered in individuals with the following clinical findings [Glassford et al 2016]: * Global developmental delay or intellectual disability, including speech delay * Autism spectrum disorder (ASD) * Slight facial dysmorphology, including a long, narrow face; short philtrum; high nasal bridge; and large ears [Ballif et al 2008] * Failure to thrive, failure to gain weight, and/or feeding problems in infancy that persist into childhood * Heart defects, especially patent ductus arteriosus * Gastrointestinal disorders, including gastroesophageal reflux disease (GERD) * Dental abnormalities Of note, most individuals with the 3q29 recurrent deletion are identified by chromosomal microarray (CMA) analysis performed in the context of evaluation for global developmental delay, intellectual disability, and/or ASD. ### Establishing the Diagnosis The diagnosis of the 3q29 recurrent deletion is established by detection of the 1.6-Mb heterozygous deletion at chromosome 3q29, typically by chromosomal microarray (CMA). For this GeneReview, the 3q29 recurrent deletion is defined as the presence of a recurrent 1.6-Mb deletion at the approximate position of chr3:195998129-197623129 in the reference genome (NCBI Build 38). This is a recurrent deletion, mediated by nonallelic homologous recombination (NAHR) between segmental duplications (or low-copy repeats) flanking the deletion region. Note: The phenotype of significantly larger or smaller deletions within this region may be clinically distinct from the 3q29 recurrent deletion (see Genetically Related Disorders). Although several genes of interest (e.g., DLG1, FBXO45, PAK2, RNF168) are within the 1.6-Mb recurrent deletion, no single gene in which pathogenic variants are causative has been identified (see Molecular Genetics for genes of interest in the deleted region). Genomic testing methods that determine the copy number of sequences can include chromosomal microarray (CMA) or targeted deletion analysis. Note: The 3q29 recurrent deletion cannot be identified by routine analysis of G-banded chromosomes or other conventional cytogenetic banding techniques. * Chromosomal microarray (CMA) using oligonucleotide arrays or SNP arrays can detect the recurrent deletion in a proband. The ability to size the deletion depends on the type of microarray used and the density of probes in the chr3:195998129-197623129 region. Note: (1) Most individuals with a 3q29 recurrent deletion are identified by CMA performed in the context of evaluation for developmental delay, intellectual disability, or autism spectrum disorder. (2) Prior to 2005 many CMA platforms did not include coverage for this region and thus may not have detected this deletion. This recurrent deletion was detected by early BAC arrays; at least 14 individuals with 3q29 deletion were identified with this technology [Ballif et al 2008]. * Targeted deletion analysis. FISH analysis, quantitative PCR (qPCR), multiplex ligation-dependent probe amplification (MLPA), or other targeted quantitative methods may be used to test relatives of a proband known to have the 3q29 recurrent deletion. Note: (1) Targeted deletion testing is not appropriate for an individual in whom the 3q29 recurrent deletion was not detected by CMA designed to target chr3:195998129-197623129. (2) It is not possible to size the deletion routinely by use of targeted methods. ### Table 1. Genomic Testing Used in the 3q29 Recurrent Deletion View in own window Deletion 1ClinGen ID 2Region Location 3, 4MethodSensitivity ProbandAt-risk family members 1.6-Mb heterozygous deletion at 3q29ISCA-37443GRCh37/hg19 chr3:195,756,054-197,344,665CMA 5100%100% Targeted deletion analysis 6See footnote 7100% 8 1\. See Molecular Genetics for details of the deletion. 2\. Standardized clinical annotation and interpretation for genomic variants from the Clinical Genome Resource (ClinGen) project (formerly the International Standards for Cytogenomic Arrays (ISCA) Consortium) 3\. Genomic coordinates represent the minimum deletion size associated with the 3q29 recurrent deletion as designated by ClinGen. Deletion coordinates may vary slightly based on array design used by the testing laboratory. Note that the size of the deletion as calculated from these genomic positions may differ from the expected deletion size due to the presence of segmental duplications near breakpoints. The phenotype of significantly larger or smaller deletions within this region may be clinically distinct from the 3q29 recurrent deletion (see Genetically Related Disorders). 4\. See Molecular Genetics for genes of interest included in this region. 5\. Chromosomal microarray analysis (CMA) using oligonucleotide arrays or SNP arrays. CMA designs in current clinical use target the 3q29 region. Note: The 3q29 recurrent deletion may not have been detectable by older oligonucleotide or BAC platforms. 6\. Targeted deletion analysis methods can include FISH, quantitative PCR (qPCR), and multiplex ligation-dependent probe amplification (MLPA) as well as other targeted quantitative methods. 7\. Not applicable. Targeted deletion analysis is not appropriate for an individual in whom the 3q29 recurrent deletion was not detected by CMA designed to target this region. 8\. Targeted deletion analysis may be used to test at-risk relatives of a proband known to have the 3q29 recurrent deletion. Evaluating at-risk relatives. FISH, qPCR, or other quantitative methods of targeted deletion analysis can be used to identify the 3q29 recurrent deletion in at-risk relatives of the proband. Testing parental samples is important in determining recurrence risk (see Genetic Counseling). ## Clinical Characteristics ### Clinical Description Global developmental delay and/or intellectual disability (ID) are common to almost all individuals with the 3q29 recurrent deletion. Aside from this, clinical presentation can vary. Although some facial dysmorphology has been noted – including a long narrow face, short philtrum, high nasal bridge, and large ears [Ballif et al 2008] – the facial phenotype is subtle and not specific. The summary below is based on the comprehensive review of all reported cases in Cox & Butler [2015] and the self-reported findings in 44 individuals from the 3q29 deletion registry [Glassford et al 2016]. The following clinical manifestations have been reported in more than one individual with the recurrent deletion. In the first year of life * Feeding problems (64%) and failure to gain weight (39%) * Jaundice (34%) * Hypotonia (34%) and hyporeflexia (7%) * Respiratory distress (25%) (although this may have to do with normal respiratory disease due to RSV, parainfluenza, influenza, or rhinovirus, and may not be related to the deletion) * Congenital heart defects including patent ductus arteriosus (12%), ventricular septal defect (5%), pulmonary valvar stenosis (5%) Developmental delay. Specific data on developmental issues are limited. On average achievement of developmental milestones is delayed between six to twelve months (depending on the milestone). For example, walking is usually achieved at age 20 months (vs 12 months) and speaking single words at age 23 months (vs 12 months). Over time, children with the 3q29 deletion show a range of intellectual disability, with most having mild to moderate ID. Fewer than 5% have severe ID. Likewise, only one of 44 individuals reported to have the 3q29 deletion is completely nonverbal. Learning problems * Speech delay (60%) * Receptive language delay (33%) * Verbal apraxia (a motor speech disorder) (19%) * Short-term memory problems (17%) * Visual processing deficits (12%) * Dysphasia/aphasia (10%) * Auditory processing disorder (7%) Neuropsychiatric disorders (see Note) * Autism spectrum disorder (26%) * Anxiety disorder (19%) * Panic attacks (10%) * Schizophrenia (5%-40%) * Depression (at least 5%) * Bipolar disorder (5%) Individuals with the 3q29 deletion may exhibit more than one neuropsychiatric disorder. For example, roughly 50% of individuals with 3q29 deletion and ASD also report an anxiety disorder. At least two case reports suggest that the age at onset for psychosis can be younger than the typical age at onset in the general population; Sagar et al reported psychosis in a boy age five years with 3q29 deletion [Sagar et al 2013] and Quintero-Rivera reported psychosis in a girl age ten years with 3q29 deletion [Quintero-Rivera et al 2010]. The average age of onset for schizophrenia and psychosis in the general population is 20-25 years. Note: Data from neuropsychiatric phenotypes were obtained from 44 children, many of whom had not yet reached the age of risk for psychiatric phenotypes. Research in adults has established that the risk for schizophrenia is 40-fold increased [Mulle 2015, Mulle et al 2010]; the risk for bipolar disorder is also increased [Clayton-Smith et al 2010]. Recurrent ear infections (32%) Gastrointestinal * Feeding problems in childhood (42%) sometimes necessitating feeding by gastrostomy tube * Gastroesophageal reflux disease (39%) * Chronic constipation (22%) * Dysphagia (12%) * Hiatal hernia (5%) * Chronic diarrhea (5%) Dental * Dental caries (24%), weak or soft tooth enamel (19%), enamel hypoplasia (10%) * Abnormal dental spacing: crowded teeth (24%); widely spaced teeth (17%), large gap between central incisors (12%) * Abnormal tooth size: large (10%), small (7%) * Missing teeth (5%) ### Genotype-Phenotype Correlations No genotype-phenotype correlations for the 3q29 recurrent deletion are known. ### Penetrance Penetrance for the 3q29 recurrent deletion is not known. Reports of the deletion having been inherited from an unaffected parent suggest that while penetrance is high, it is likely not 100%. It is unknown if penetrance differs in males and females. ### Nomenclature The 3q29 recurrent deletion may also be referred to as the “3q29 microdeletion syndrome” or the “3q29 deletion syndrome.” ### Prevalence The approximate prevalence is 1:30,000-1:40,000, based on a large population-based study in Iceland in which three of 101,655 individuals tested had the 3q29 recurrent deletion [Stefansson et al 2014]. Prevalence in other populations is not known. ## Differential Diagnosis The differential diagnosis of the 3q29 recurrent deletion is broad due to the variable spectrum and presence of relatively common abnormal phenotypes that occur in affected individuals including developmental delay, learning problems, and neuropsychiatric disorders. All manifestations of the 3q29 recurrent deletion can also be seen in individuals with other genomic disorders. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with the 3q29 recurrent deletion, the following evaluations should be considered: * Comprehensive developmental assessment including evaluation of cognitive, speech and language, motor, and social skills * Psychiatric evaluation in individuals with evidence of neuropsychiatric manifestations including autism spectrum disorder (ASD) * Assessment for feeding problems and nutrition; consultation with pediatric feeding specialists as needed * Early consultation with a pediatric dentist * Evaluation in infancy for evidence of congenital heart disease * Consultation with a pediatric otolaryngologist as needed for recurrent otitis media * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations The following measures are appropriate: * Early speech and language therapy to address speech delays * Physical therapy as necessary to address fine and gross motor delays * Individualized education program (IEP) for school-age children * Care by a child psychiatrist for anxiety disorder and/or other neuropsychiatric manifestations * Applied behavioral analysis or other treatment for manifestations of ASD * Feeding therapy (including nutrition assessment) with a pediatric feeding specialist or behavioral pediatric psychologist; consideration of gastronomy tube for severe feeding problems and continued failure to thrive * Routine management of dental caries, congenital heart defects, and recurrent ear infections ### Surveillance Continued assessment of: * Feeding and nutrition * Developmental milestones * Cognitive development * Possible psychiatric manifestations ### Evaluation of Relatives at Risk Parents and older and younger at-risk sibs of a proband should be tested for the 3q29 recurrent deletion. Parents or sibs may have the deletion, but with only mild or nonexistent developmental delay or intellectual disability. The average age at onset for schizophrenia is 20-25 years; thus, mildly affected individuals remain at risk for neuropsychiatric manifestations and would benefit from monitoring and clinical evaluation. 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	3q29 Recurrent Deletion	c2674949	29,007	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK385289/	2021-01-18T21:46:19	{"mesh": ["C567184"], "synonyms": ["3q29 Deletion Syndrome", "3q29 Microdeletion Syndrome"]}
For the Hungarian government agency (Nemzeti Közlekedési Hatóság), see National Transport Authority (Hungary). Glycine encephalopathy (non-ketotic hyperglycinemia) Other namesNon-ketotic hyperglycinemia or NKH Glycine SpecialtyNeurology, medical genetics, endocrinology Glycine encephalopathy is a rare autosomal recessive disorder of glycine metabolism. After phenylketonuria, glycine encephalopathy is the second most common disorder of amino acid metabolism. The disease is caused by defects in the glycine cleavage system, an enzyme responsible for glycine catabolism. There are several forms of the disease, with varying severity of symptoms and time of onset. The symptoms are exclusively neurological in nature, and clinically this disorder is characterized by abnormally high levels of the amino acid glycine in bodily fluids and tissues, especially the cerebrospinal fluid. Glycine encephalopathy is sometimes referred to as "nonketotic hyperglycinemia" (NKH), as a reference to the biochemical findings seen in patients with the disorder, and to distinguish it from the disorders that cause "ketotic hyperglycinemia" (seen in propionic acidemia and several other inherited metabolic disorders). To avoid confusion, the term "glycine encephalopathy" is often used, as this term more accurately describes the clinical symptoms of the disorder. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Pathophysiology * 3.1 Glycine metabolism * 4 Diagnosis * 4.1 Classification * 5 Treatment * 6 Prognosis * 7 Research * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] It typically presents as a severe encephalopathy with myoclonic seizures, is rapidly progressive and eventually results in respiratory arrest. Standard evaluation for inborn errors of metabolism and other causes of this presentation does not reveal any abnormality (no acidosis, no hypoglycaemia, or hyperammonaemia and no other organ affected). Pronounced and sustained hiccups in an encephalopathic infant have been described as a typical observation in non-ketotic hyperglycinaemia.[citation needed] ## Genetics[edit] Glycine Encephalopathy (Nonketotic Hyperglycinemia) has an autosomal recessive pattern of inheritance. Glycine encephalopathy has an estimated incidence of 1 in 60,000, making it the second most common disorder of amino acid metabolism, after phenylketonuria. It is caused by a defect in the glycine cleavage system (GCS), which is made up of four protein subunits. Each of these four subunits is encoded by a separate gene. Defects in three of these four genes have been linked to glycine encephalopathy.[1]:790 Gene Name Percent GLDC encodes the "glycine dehydrogenase" subunit, also called "glycine decarboxylase" About 70-75% of cases of glycine encephalopathy result from mutations in the GLDC gene. GCST or AMT encoding the "aminomethyltransferase" subunit About 20% of cases are caused by mutations in the AMT gene. GCSH encoding the subunit "glycine cleavage system protein H" Mutations in the GCSH gene account for less than 1% of cases. There is a fourth unit in the complex, dihydrolipoamide dehydrogenase or GCSL. However, to date there have been no mutations in GCSL found to be associated with glycine encephalopathy. A small percentage of affected individuals do not have detectable mutations in any of the three genes (listed above) that are typically associated with the disease. However, they still show defective glycine-cleavage enzymatic activity. It is thought that these patients may have mutations in the genes encoding one of the cofactors associated with the GCS complex.[citation needed] Defects in the GCS proteins can prevent the complex from functioning properly or can prevent the GCS complex from forming entirely. When the complex is unable to metabolize glycine properly, this causes excess glycine to build up to toxic levels in the body's organs and tissues. Damage caused by elevated levels of glycine in the brain and cerebrospinal fluid is responsible for the characteristic seizures, breathing difficulties, movement disorders, and intellectual disability.[citation needed] This disorder is inherited in an autosomal recessive pattern. The term "autosomal" signifies that the gene associated with the disorder is located on an autosome. In an autosomal recessive inheritance pattern, two defective copies of the gene (one inherited from each parent) are required in order for a child to be born with the disorder. Therefore, each parent of an individual with an autosomal recessive disorder has at least one defective copy of the gene. With autosomal recessive disorders, individuals with only one copy of a defective gene (heterozygotes) are considered "carriers" for the disorder. Carriers usually do not show signs or symptoms of the disorder.[2] ## Pathophysiology[edit] Glycine is the simplest amino acid, having no stereoisomers. It can act as a neurotransmitter in the brain, act as an inhibitor in the spinal cord and brain stem, while having excitatory effects in the cortex of the brain. Glycine is metabolized to final end products of ammonia and carbon dioxide through the glycine cleavage system (GCS), an enzyme complex made up of four protein subunits. Defects in these subunits can cause glycine encephalopathy, although some causes of the disease are still unknown. Normally, GCS shows its highest enzymatic activity in liver, brain and placental tissue. One of its main functions is to maintain normal glycine levels in the brain. Defects in GCS cause an increase of glycine concentration in blood plasma and cerebrospinal fluid.[1] The exact pathophysiology of the disorder is not known, but it is considered likely that buildup of glycine in the brain is responsible for the symptoms.[3] All forms of glycine encephalopathy show elevated levels of glycine in the plasma, as well as in cerebral spinal fluid (CSF).[1]:793 Glycine concentrations in the CSF of affected patients are typically more markedly elevated than in plasma, leading to a corresponding elevation in the ratio of glycine concentrations in the cerebral spinal fluid to that in the plasma. This ratio can also be slightly elevated in patients receiving valproic acid.[1]:811 Glycine encephalopathy (nonketotic hyperglycinemia, or NKH) should not be confused with other metabolic disorders that can produce elevated glycine levels. For example, certain inherited 'organic acidurias' (aka 'organic acidemias') can produce elevated glycine in plasma and urine, although these disorders are not caused by defects in the glycine cleavage system, and they are not typically accompanied by corresponding elevations of glycine in cerebrospinal fluid (CSF).[4] Glycine encephalopathy is unique in the fact that levels of glycine are disproportionately elevated in CSF (in addition to elevations in blood and urine), whereas CSF glycine levels are normal or near-normal in patients with inherited organic acidurias.[citation needed] ### Glycine metabolism[edit] Glycine is metabolized in the body's cells to end products of carbon dioxide and ammonia. The glycine cleavage system, which is responsible for glycine metabolism in the mitochondria is made up of four protein subunits, the P-protein, H-protein, T-protein and L-protein.[1]:793 ## Diagnosis[edit] ### Classification[edit] There are several different forms of glycine encephalopathy, which can be distinguished by the age of onset, as well as the types and severity of symptoms. All forms of glycine encephalopathy present with only neurological symptoms, including intellectual disability (IQ scores below 20 are common[5]), hypotonia, apneic seizures, and brain malformations.[1]:811 With the classical, or neonatal presentation of glycine encephalopathy, the infant is born after an unremarkable pregnancy, but presents with lethargy, hypotonia, apneic seizures and myoclonic jerks, which can progress to apnea requiring artificial ventilation, and often death. Apneic patients can regain spontaneous respiration in their second to third week of life. After recovery from the initial episode, patients have intractable seizures and profound intellectual disability, remaining developmentally delayed. Some mothers comment retrospectively that they noticed fetal rhythmic "hiccuping" episodes during pregnancy, most likely reflecting seizure episodes in utero.[3] Patients with the infantile form of glycine encephalopathy do not show lethargy and coma in the neonatal period, but often have a history of hypotonia. They often have seizures, which can range in severity and responsiveness to treatment, and they are typically developmentally delayed.[6] Glycine encephalopathy can also present as a milder form with episodic seizures, ataxia, movement disorders, and gaze palsy during febrile illness. These patients are also developmentally delayed, to varying degrees. In the later onset form, patients typically have normal intellectual function, but present with spastic diplegia and optic atrophy.[6] The mild form of the disorder corresponds to greatly reduced but not fully absent GCS activity.[7] Transient neonatal hyperglycinemia has been described in a very small number of cases. Initially, these patients present with the same symptoms and laboratory results that are seen in the classical presentation. However, levels of glycine in plasma and cerebrospinal fluid typically normalize within eight weeks, and in five of six cases there were no neurological issues detected at follow-up times up to thirteen years. A single patient was severely retarded at nine months. The suspected cause of transient neonatal hyperglicinemia is attributed to low activity of the glycine cleavage system in the immature brain and liver of the neonate.[3] ## Treatment[edit] A treatment of sodium benzoate, which binds to glycine and forms hippurate, and dextromethorphan, which weakly inhibits the N-methyl-D-aspartate receptors that glycine acts on has been shown to improve outcomes in select cases where the disorder is present in attenuated form.[7] ## Prognosis[edit] The prognosis is very poor. Two studies reported typical age of deaths in infancy or early childhood, with the first reporting a median age of death of 2.6 for boys and less than 1 month for girls.[8][5] ## Research[edit] Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).[9] ## See also[edit] * List of amino acid metabolism disorders * inborn errors of metabolism ## References[edit] 1. ^ a b c d e f Sarafoglou, Kyriakie; Hoffmann, Georg F.; Roth, Karl S. (eds.). Pediatric Endocrinology and Inborn Errors of Metabolism. New York: McGraw Hill Medical. p. 811. 2. ^ "Autosomal recessive: MedlinePlus Medical Encyclopedia". 3. ^ a b c "Nonketotic hyperglycinemia". McGraw Hill. Retrieved 2011-09-22. 4. ^ "The Organic Acidemias: An Overview -- GeneReviews -- NCBI Bookshelf". Archived from the original on 2010-05-27. 5. ^ a b Hennermann, Julia B.; Berger, Jeanne-Marie; Grieben, Ulrike; Scharer, Gunter; Hove, Johan L. K. Van (2011-10-15). "Prediction of long-term outcome in glycine encephalopathy: a clinical survey". Journal of Inherited Metabolic Disease. 35 (2): 253–261. doi:10.1007/s10545-011-9398-1. ISSN 0141-8955. PMID 22002442. S2CID 25206831. 6. ^ a b "Glycine Encephalopathy". National Center for Biotechnology Information, U.S. National Library of Medicine. 1993. Retrieved 2011-09-22. 7. ^ a b Bjoraker, Kendra J.; Swanson, Michael A.; Coughlin, Curtis R.; Christodoulou, John; Tan, Ee S.; Fergeson, Mark; Dyack, Sarah; Ahmad, Ayesha; Friederich, Marisa W.; Spector, Elaine B.; Creadon-Swindell, Geralyn; Hodge, M. Antoinette; Gaughan, Sommer; Burns, Casey; Van Hove, Johan L.K. (2016). "Neurodevelopmental Outcome and Treatment Efficacy of Benzoate and Dextromethorphan in Siblings with Attenuated Nonketotic Hyperglycinemia". The Journal of Pediatrics. 170: 234–239. doi:10.1016/j.jpeds.2015.12.027. PMID 26749113. 8. ^ Hoover-Fong, J. E.; Shah, S.; Van Hove, J. L. K.; Applegarth, D.; Toone, J.; Hamosh, A. (2004-11-23). "Natural history of nonketotic hyperglycinemia in 65 patients". Neurology. 63 (10): 1847–1853. doi:10.1212/01.wnl.0000144270.83080.29. ISSN 1526-632X. PMID 15557500. S2CID 23783707. 9. ^ "Patient registry". ## External links[edit] Classification D * OMIM: 605899 * MeSH: D020158 * v * t * e Inborn error of amino acid metabolism K→acetyl-CoA Lysine/straight chain * Glutaric acidemia type 1 * type 2 * Hyperlysinemia * Pipecolic acidemia * Saccharopinuria Leucine * 3-hydroxy-3-methylglutaryl-CoA lyase deficiency * 3-Methylcrotonyl-CoA carboxylase deficiency * 3-Methylglutaconic aciduria 1 * Isovaleric acidemia * Maple syrup urine disease Tryptophan * Hypertryptophanemia G G→pyruvate→citrate Glycine * D-Glyceric acidemia * Glutathione synthetase deficiency * Sarcosinemia * Glycine→Creatine: GAMT deficiency * Glycine encephalopathy G→glutamate→ α-ketoglutarate Histidine * Carnosinemia * Histidinemia * Urocanic aciduria Proline * Hyperprolinemia * Prolidase deficiency Glutamate/glutamine * SSADHD G→propionyl-CoA→ succinyl-CoA Valine * Hypervalinemia * Isobutyryl-CoA dehydrogenase deficiency * Maple syrup urine disease Isoleucine * 2-Methylbutyryl-CoA dehydrogenase deficiency * Beta-ketothiolase deficiency * Maple syrup urine disease Methionine * Cystathioninuria * Homocystinuria * Hypermethioninemia General BC/OA * Methylmalonic acidemia * Methylmalonyl-CoA mutase deficiency * Propionic acidemia G→fumarate Phenylalanine/tyrosine Phenylketonuria * 6-Pyruvoyltetrahydropterin synthase deficiency * Tetrahydrobiopterin deficiency Tyrosinemia * Alkaptonuria/Ochronosis * Tyrosinemia type I * Tyrosinemia type II * Tyrosinemia type III/Hawkinsinuria Tyrosine→Melanin * Albinism: Ocular albinism (1) * Oculocutaneous albinism (Hermansky–Pudlak syndrome) * Waardenburg syndrome Tyrosine→Norepinephrine * Dopamine beta hydroxylase deficiency * reverse: Brunner syndrome G→oxaloacetate Urea cycle/Hyperammonemia (arginine * aspartate) * Argininemia * Argininosuccinic aciduria * Carbamoyl phosphate synthetase I deficiency * Citrullinemia * N-Acetylglutamate synthase deficiency * Ornithine transcarbamylase deficiency/translocase deficiency Transport/ IE of RTT * Solute carrier family: Cystinuria * Hartnup disease * Iminoglycinuria * Lysinuric protein intolerance * Fanconi syndrome: Oculocerebrorenal syndrome * Cystinosis Other * 2-Hydroxyglutaric aciduria * Aminoacylase 1 deficiency * Ethylmalonic encephalopathy * Fumarase deficiency * Trimethylaminuria [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Glycine encephalopathy	c0268560	29,008	wikipedia	https://en.wikipedia.org/wiki/Glycine_encephalopathy	2021-01-18T18:36:55	{"gard": ["7219"], "mesh": ["D020158", "C562672"], "umls": ["C0268560"], "orphanet": ["407"], "wikidata": ["Q3053945"]}
Kyrle disease Other namesHyperkeratosis follicularis et parafollicularis in cutem penetrans SpecialtyDermatology Kyrle disease is identified as a form of an acquired perforating disease. Other major perforating diseases are elastosis perforans serpiginosa and reactive perforating collagenosis. Recently, however, there is a controversy on categorizing Kyrle disease with perforating dermatosis or a subtype of acquired perforating collagenosis.[1] Kyrle disease was first described by Josef Kyrle in 1916 when a diabetic woman presented generalized hyperkeratotic nodules.[2] The disease is distinguished by large papules with central keratin plug on the skin, usually on the legs of the patient and is often in conjunction with liver, kidney or diabetic disorders. It can affect both females and males with a 6:1 ratio. The papules usually show up on the patient with an average age of 30 years.[1][3] Kyrle disease is a rare disease unless there is a high count of patients with chronic kidney failure. The disease seems to be more prevalent in African Americans, which can be correlated to the high incidence of diabetes mellitus and kidney failure in the population.[4] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Mechanism * 4 Diagnosis * 5 Treatment * 5.1 Medical care * 5.2 Radiation therapy * 5.3 Surgical care * 6 Prognosis * 7 Recent research * 8 References * 9 External links ## Signs and symptoms[edit] Kyrle disease symptoms are chronic and have an onset during adulthood between the ages of 30 and 50 years of age. However, there were reported cases of early onset as early as 5 years of age and late onset as late as 75 years of age. The main symptom is the development of small papules into painless lesions that are surrounded by silvery scales. The lesions are painless, however, there is a chance that the patient may experience extreme urges to itch them. In time, these lesions grow up to a radius of 0.75 inch and develop into red-brown nodules with a central plug of keratin. As more lesions develop, they can come together and form larger keratotic plaques. These lesions are usually observed on the lower extremities, however, can also develop on the upper extremities, such as, the arms, the head and the neck. The only parts of the body that Kyrle disease do not form are the palms, soles, and mucous membranes. Lesions may heal spontaneously without treatment, however, new ones will develop in its place.[1] Other symptoms that may be observed:[5] * Hyperkeratotic cone-shaped papular plugs * Hyperkeratotic verrucous plaques * Diabetes mellitus * Hepatic insufficiency * Presence of albumin in the urine * Excess sugar in the urine ## Causes[edit] The causes of Kyrle disease are unclear and can be idiopathic. The only correlation that has shown light is the frequent association with an underlying disorder, such as, diabetes mellitus, chronic kidney disease, hyperlipoproteinemia, liver abnormalities, and congestive heart failure. However, there had been cases where Kyrle disease was seen without any conjunction with the previous mentioned disorders.[3] Due to the causes of Kyrle disease is unknown, the best way to prevent the disease is to prevent the disorders that are usually reported in conjunction with it. ## Mechanism[edit] The pathophysiology of Kyrle disease is unclear. Some scientists believe that it may be a variation of prurigo nodularis. The theory that most scientists agree upon is that Kyrle disease is an elimination of keratin and other cellular material across the epidermis. Keratinization in Kyrle disease form at the basilar layer that is lower than the normal proliferation region in the epidermis. This causes an inflammatory response which results with the keratin, along with other cellular material and connective tissue, to be forced out the epidermis.[6][7][8] Another reason for an inflammatory response may be due to an alteration of the dermal connective tissue. This is theorized because this step is a main reason for inflammatory responses in other skin diseases, such as, elastosis perforans serpiginosa and perforating collagenosis.[9] ## Diagnosis[edit] Since many other skin disorders can be characterized by abnormal papules or nodules, a dermatologist will determine if a patient has Kyrle disease by the depth of penetrating keratotic plugs, localized distribution of the plugs, size of plugs, and the age of onset. A physician will also have to test for disorders, such as, diabetes, hepatic, and renal disease to help bolster the diagnosis of Kyrle disease.[1] Other underlying diseases that Kyrle disease is observed with are tuberculosis, pulmonary aspergillosis, scabies, atopic dermatitis, AIDS, neurodermatitis, and endocrinological disorders.[10] The inheritance of Kyrle disease is unknown as reported cases point to both autosomal dominance and autosomal recessiveness.[3] ## Treatment[edit] The best treatment for Kyrle's disease is to treat the underlying disease if present as life expectancy is also determined by the underlying disease. However, if there are no other diseases associated with Kyrle disease, treatment of the lesions is the course of action. There is a chance of the lesions healing without treatment but new ones will develop. ### Medical care[edit] Isotretinoin, high doses of vitamin A and tretinoin cream can be utilized.[1] Also, emollients, oral antihistamines, and antipruritic creams that contain menthol and camphor may be helpful because the lesions can become very itchy.[4] ### Radiation therapy[edit] UV irradiation can be utilized after curetting the hyperkeratosis with a combination medication treatment of oral retinoids, psoralen and Ultraviolet A radiation.[1] ### Surgical care[edit] Surgical options are considered the final option for treating Kyrle disease. The use of a carbon dioxide laser, electrocautery, or cryosurgery to rid of limited lesions can be implemented. Patients with darker skin must take extra precaution as these options can lead to dyspigmentation. In addition, performing on patients that had Kyrle disease due to diabetes mellitus or have poor circulation can lead to poor healing.[4] ## Prognosis[edit] Morbidity and mortality range from both extremes as the significance correlate with the underlying systemic disease.[4] ## Recent research[edit] There seems to be beneficial responses to clindamycin therapy as the lesions regress. This leads to the hypothesis that microorganisms may be playing a role in the initial stages of Kyrle disease.[2] A family with Kyrle disease were examined which their skin lesions were benign. However, when three of the young adult members were closely examined, they had posterior subcapsular cataracts and two of those three developed multiple tiny yellow-brown anterior stromal corneal opacities. In order to determine if there is any correlation between Kyrle disease and the ocular observations, more cases of Kyrle disease are to be analyzed.[11] All in all, since Kyrle disease is relatively rare, more cases need to be studied and analyzed in order to understand the underlying pathogenesis and to improve the management of the disease. ## References[edit] 1. ^ a b c d e f "Kyrle disease. DermNet NZ". dermnetnz.org. Retrieved 2015-12-11. 2. ^ a b Akçalı C, Baba M, Seçkin D, Kayaselçuk F, Güleç T (2007). "Kyrle's Disease: A Case Report". Journal of the Turkish Academy of Dermatology. 3. ^ a b c Bhambri S, Del Rosso JQ, Mobini N, Janda P (2008). "Kyrle's Disease". Cosmetic Dermatology. 4. ^ a b c d "Kyrle Disease: Background, Pathophysiology, Epidemiology". 2018-08-14. Cite journal requires `\|journal=` (help) 5. ^ "Symptoms of Kyrle disease - RightDiagnosis.com". www.rightdiagnosis.com. Retrieved 2015-12-11. 6. ^ Carter VH, Constantine VS (June 1968). "Kyrle's disease. I. Clinical findings in five cases and review of literature". Arch Dermatol. 97 (6): 624–32. doi:10.1001/archderm.1968.01610120014002. ISSN 0003-987X. PMID 5652970. 7. ^ Constantine VS, Carter VH (June 1968). "Kyrle's disease. II. Histopathologic findings in five cases and review of the literature". Arch Dermatol. 97 (6): 633–9. doi:10.1001/archderm.1968.01610120023003. PMID 4172447. 8. ^ Rapini RP, Herbert AA, Drucker CR (August 1989). "Acquired perforating dermatosis. Evidence for combined transepidermal elimination of both collagen and elastic fibers". Arch Dermatol. 125 (8): 1074–8. doi:10.1001/archderm.1989.01670200050007. PMID 2757403. 9. ^ "Kyrle Disease: Background, Pathophysiology, Epidemiology". 2018-08-14. Cite journal requires `\|journal=` (help) 10. ^ Saray, Y.; Seçkin, D.; Bilezikçi, B. (2006-07-01). "Acquired perforating dermatosis: clinicopathological features in twenty-two cases". Journal of the European Academy of Dermatology and Venereology: JEADV. 20 (6): 679–688. doi:10.1111/j.1468-3083.2006.01571.x. ISSN 0926-9959. PMID 16836495. 11. ^ Tessler HH, Apple DJ, Goldberg MF (October 1973). "Ocular findings in a kindred with Kyrle disease. Hyperkeratosis follicularis et parafollicularis in cutem penetrans". Arch. Ophthalmol. 90 (4): 278–80. doi:10.1001/archopht.1973.01000050280005. ISSN 0003-9950. PMID 4746641. ## External links[edit] Classification D * ICD-10: L87.0 (ILDS L87.000) * MeSH: C538130 * DiseasesDB: 32593 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Kyrle disease	c0263382	29,009	wikipedia	https://en.wikipedia.org/wiki/Kyrle_disease	2021-01-18T18:59:27	{"gard": ["9738"], "mesh": ["C538130"], "umls": ["C0263382"], "icd-10": ["L87.0"], "wikidata": ["Q6452559"]}
Baraitser et al. (1982) described a 5-year-old girl with craniosynostosis, mental retardation, seizures, choroidal coloboma, dysplastic kidneys, bat ears, cleft lip and palate, and beaked nose. The same disorder was detected in a later pregnancy by fetoscopy, which demonstrated cleft lip. The electively aborted male fetus showed also palatal cleft, choroidal coloboma, and small posterior fontanel. GU \- Dysplastic kidneys Neuro \- Mental retardation \- Seizures Inheritance \- Autosomal recessive Skel \- Slightly shortened forearms and legs Skin \- Dry HEENT \- Craniosynostosis \- Bat ears \- Cleft lip/palate \- Beaked nose \- Choroidal coloboma \- Microcephaly \- Flattened occiput \- Broad forehead ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CRANIOSYNOSTOSIS-MENTAL RETARDATION-CLEFTING SYNDROME	c1857472	29,010	omim	https://www.omim.org/entry/218650	2019-09-22T16:29:15	{"mesh": ["C565663"], "omim": ["218650"]}
The superficial corneal dystrophies refer to a group of rare genetically determined corneal dystrophies (CDs) characterized by lesions affecting the corneal epithelium and its basement membrane and the superficial corneal stroma, and variable effects on vision depending on the type of dystrophy. ## Epidemiology Prevalence of this group of corneal dystrophies is unknown, but all are rare and found mainly in populations carrying the responsible mutated genes. ## Clinical description Age of onset is variable, between early childhood and the second decade of life. Eight subtypes of superficial corneal dystrophy have been identified: Grayson-Willbrandt CD, Epithelial recurrent erosion dystrophy, Subepithelial mucinous CD, Meesmann CD, Lisch epithelial CD, Gelatinous drop-like CD, Reis-Bücklers CD, and Thiel-Behnke CD (see these terms). ## Etiology Genetic heterogeneity has been reported but all superficial corneal dystrophies appear to be genetically determined, and are usually inherited as Mendelian traits. Mutations in four genes:KRT3 (12q13.13), KRT12 (17q11-q12), TGFBI (5q31), and TACSTD2 (1p32), are currently known to cause inherited diseases that are apparently limited to the superficial cornea. ## Genetic counseling Transmission is autosomal dominant, autosomal recessive, or X-linked recessive depending on 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Superficial corneal dystrophy	c2315777	29,011	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98625	2021-01-23T17:29:49	{"umls": ["C2315777"], "icd-10": ["H18.5"], "synonyms": ["Anterior corneal dystrophy"]}
Micrograph showing a colorectal carcinoma metastasis to the cerebellum. HPS stain. A brain metastasis is a cancer that has metastasized (spread) to the brain from another location in the body and is therefore considered a secondary brain tumor.[1] The metastasis typically shares a cancer cell type with the original site of the cancer.[2] Metastasis is the most common cause of brain cancer, with primary tumors that originate in the brain being less common.[3] The most common sites of primary cancer which metastasize to the brain are lung, breast, colon, kidney, and skin cancer. Brain metastases can occur in patients months or even years after their original cancer is treated. Brain metastases have a poor prognosis for cure, but modern treatments are allowing patients to live months and sometimes years after the diagnosis.[4] ## Contents * 1 Symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 4.1 Symptomatic care * 4.2 Radiotherapy * 4.3 Surgery * 4.4 Chemotherapy * 4.5 Immunotherapy * 5 Prognosis * 6 Epidemiology * 7 See also * 8 References ## Symptoms[edit] Brain metastasis in the right cerebral hemisphere from lung cancer shown on T1-weighted magnetic resonance imaging with intravenous contrast. Because different parts of the brain are responsible for different functions, symptoms vary depending on the site of metastasis within the brain. However, brain metastases should be considered in any cancer patient who presents with neurological or behavioral changes.[5] Brain metastases can cause a wide variety of symptoms which can also be present in minor, more common conditions. Neurological symptoms are often caused by increased intracranial pressure,[6] with severe cases resulting in coma.[7] The most common neurological symptoms include: * New onset headaches: headaches occur in roughly half of brain metastasis patients, especially in those with many tumors.[5] * Paresthesias: patients often present with (hemiparesis), or weakness on only one side of the body, which is often a result of damage to neighboring brain tissue.[6] * Ataxia: when metastasis occurs to the cerebellum, patients will experience various difficulties with spatial awareness and coordination.[8] * Seizures: when present, often indicates disease involvement of the cerebral cortex.[9] ## Causes[edit] The most common sources of brain metastases in a case series of 2,700 patients undergoing treatment at the Memorial Sloan–Kettering Cancer Center were:[10] * Lung cancer, 48% * Breast cancer, 15% * Genitourinary tract cancers, 11% * Osteosarcoma, 10% * Melanoma, 9% * Head and neck cancer, 6% * Neuroblastoma, 5% * Gastrointestinal cancers, especially colorectal and pancreatic carcinoma, 3% * Lymphoma, 1% Lung cancer and melanoma are most likely to present with multiple metastasis, whereas breast, colon, and renal cancers are more likely to present with a single metastasis.[2] ## Diagnosis[edit] Brain imaging (neuroimaging such as CT or MRI) is needed to determine the presence of brain metastases.[5] In particular, contrast-enhanced MRI is the best method of diagnosing brain metastases, though detection is primarily done by CT.[9] Biopsy is often recommended to confirm diagnosis.[5] The diagnosis of brain metastases typically follows a diagnosis of a systemic cancer.[9] Occasionally, brain metastases will be diagnosed concurrently with a primary tumor or before the primary tumor is found. In brain metastasis due to malignant melanoma, MRI imaging showed high T1 and low T2 intensity due to the deposition of melanin in the brain. In susceptibility weighted imaging (SWI), it usually shows abnormal SWI hypointensity in larger proportion than brain metastasis caused by breast carcinoma.[11] ## Treatment[edit] Treatment for brain metastases is primarily palliative, with the goals of therapy being reduction of symptoms and prolongation of life. However, in some patients, particularly younger, healthier patients, aggressive therapy consisting of open craniotomy with maximal excision, chemotherapy, and radiosurgical intervention (Gamma Knife therapy) may be attempted. ### Symptomatic care[edit] Symptomatic care should be given to all patients with brain metastases, as they often cause severe, debilitating symptoms. Treatment consists mainly of: * Corticosteroids – Corticosteroid therapy is essential for all patients with brain metastases, as it prevents development of cerebral edema, as well as treating other neurological symptoms such as headaches, cognitive dysfunction, and emesis. Dexamethasone is the corticosteroid of choice.[9] Although neurological symptoms may improve within 24 to 72 hours of starting corticosteroids, cerebral edema may not improve for up to a week.[12] In addition, patients may experience adverse side effects from these drugs, such as myopathy and opportunistic infections, which can be alleviated by decreasing the dose.[12] * Anticonvulsants – Anticonvulsants should be used for patients with brain metastases who experience seizures, as there is a risk of status epilepticus and death.[13] Newer generation anticonvulsants including Lamotrigine and Topiramate are recommended due to their relatively limited side effects.[13] It is not recommended to prophylactically give anti-seizure medications when a seizure has not yet been experienced by a patient with brain metastasis.[13] ### Radiotherapy[edit] Radiotherapy plays a critical role in the treatment of brain metastases, and includes whole-brain irradiation, fractionated radiotherapy, and radiosurgery.[5] Whole-brain irradiation is used as a primary treatment method in patients with multiple lesions and is also used alongside surgical resection when patients have single and accessible tumors.[5] However, it often causes severe side effects, including radiation necrosis, dementia, toxic leukoencephalopathy, partial to complete hair loss, nausea, headaches, and otitis media.[14] In children this treatment may cause mental retardation, psychiatric disturbances, and other neuropsychiatric effects.[15] ### Surgery[edit] Brain metastases are often managed surgically if they are accessible. Surgical resection followed by stereotactic radiosurgery or whole-brain irradiation deliver superior survival compared to whole brain irradiation alone.[5] Therefore, in patients with only one metastatic brain lesion and controlled or limited systemic disease, a life expectancy of at least 3 months and a good performance status might be expected.[16] ### Chemotherapy[edit] Chemotherapy is rarely used for the treatment of brain metastases, as chemotherapeutic agents penetrate the blood brain barrier poorly.[1] However, some cancers such as lymphomas, small cell lung carcinomas (SCLC) and breast cancer may be highly chemosensitive and chemotherapy may be used to treat extracranial sites of metastatic disease in these cancers.[1] The effectiveness and safety of using chemotherapy to treat a brain metastasis that came from a SCLC is not clear.[17] An experimental treatment for brain metastases is intrathecal chemotherapy, a technique in which a chemotherapeutic drug is delivered via intralumbar injection into the cerebrospinal fluid.[18] Current research on the treatment of brain metastases includes creating new drug molecules to effectively target the blood-brain barrier and studying the relationship between tumors and various genes.[19] In 2015, the United States FDA approved Alecensa (alectinib) for use in patients with a specific type of non-small cell lung cancer (NSCLC; ALK-positive), a type of cancer which often metastasizes to the brain, whose condition worsened after use or were unable to take another medication, Xalkori (crizotinib).[20] ### Immunotherapy[edit] Immunotherapy, for instance Anti-PD-1 alone or in combination with anti-CTLA-4, appears to be effective in some patients with brain metastases especially when these are asymptomatic, stable and not previously treated [21] ## Prognosis[edit] The prognosis for brain metastases is variable; it depends on the type of primary cancer, the age of the patient, the absence or presence of extracranial metastases, and the number of metastatic sites in the brain.[5] For patients who do not undergo treatment the average survival is between one and two months.[5] However, in some patients, such as those with no extracranial metastases, those who are younger than 65, and those with a single site of metastasis in the brain only, prognosis is much better, with median survival rates of up to 13.5 months.[1] Because brain metastasis can originate from various different primary cancers, the Karnofsky performance score is used for a more specific prognosis.[5] ## Epidemiology[edit] It is estimated that the worldwide incidence rate for brain metastases lies around 9% to 17%, based on the region of diagnosis.[22][23] However, the baseline incidence rate of brain metastases were found to increase with improvements to brain imaging technology.[24] Approximately 5 - 11% of brain metastasis were found to be deadly at 30 days, and 14 - 23% were found to be deadly at three months.[25] More cases of brain metastases were found in adults, compared to children.[26] 67% to 80% of all cancer patients were found to develop brain metastases, as of 2012. Lung cancer, breast cancer and melanoma patients were found to be at the highest risk of developing brain metastases.[27][28][29][30][31] However, recent trends in brain metastasis epidemiology have shown an increase in incidence for patients with renal, colorectal or ovarian cancers.[32] Brain metastases are most commonly diagnosed within multiple intracranial areas within the context of extracranial diseases. Both population studies and autopsy studies have historically been used to calculate the incidence of brain metastases. However, many researchers have stated that population studies may express inaccurate data for brain metastases, given that surgeons have, in the past, been hesitant to take in patients with the condition. As a result, population studies regarding brain metastases have historically been inaccurate and incomplete.[33][34] Recent advances in systemic treatments of brain metastases, such as radiosurgery, whole-brain radiotherapy and surgical resection has led to an increase in median survival rate of brain metastases patients.[35] ## See also[edit] * Neoplasm * Metastasis * Cancer * Brain tumor ## References[edit] 1. ^ a b c d Tse V (10 November 2009). "Brain Metastasis". Medscape. Retrieved 13 January 2010. 2. ^ a b "Metastatic Brain Tumors" (PDF). Archived from the original (PDF) on 29 August 2017. Retrieved 13 August 2017. 3. ^ "Tumor Types - National Brain Tumor Society". National Brain Tumor Society. Retrieved 1 August 2017. 4. ^ "Archived copy". Archived from the original on 2010-04-06. Retrieved 2010-03-17.CS1 maint: archived copy as title (link) 5. ^ a b c d e f g h i j Loeffler JS. Wen PY, Eichler AF (eds.). "Epidemiology, clinical manifestations, and diagnosis of brain metastases". UpToDate. Retrieved 2 August 2017. 6. ^ a b Sawaya R (September 2001). "Considerations in the diagnosis and management of brain metastases". Oncology. Williston Park, N.Y. 15 (9): 1144–54, 1157–8, discussion 1158, 1163–5. PMID 11589063. 7. ^ "Metastatic Brain Tumors". American Association of Neurological Surgeons. Retrieved 3 August 2017. 8. ^ "Metastatic Brain Tumors". Memorial Sloan Kettering Cancer Center. Retrieved 3 August 2017. 9. ^ a b c d Wen PY, Loeffler JS (July 1999). "Management of brain metastases". Oncology. Williston Park, N.Y. 13 (7): 941–54, 957–61, discussion 961–2, 9. PMID 10442342. 10. ^ Ts V (10 November 2009). "Brain Metastasis - Morbidity/Mortality". Medscape. Retrieved 13 January 2010. 11. ^ Pope WB (2018). "Brain metastases: neuroimaging". Handbook of Clinical Neurology. Elsevier. 149: 89–112. doi:10.1016/b978-0-12-811161-1.00007-4. ISBN 978-0-12-811161-1. PMC 6118134. PMID 29307364. 12. ^ a b Drappatz J. Wen PY, Eichler AF (eds.). "Management of Vasogenic Edema in Patients with Primary and Metastatic Brain Tumors". UpToDate. Retrieved 2 August 2017. 13. ^ a b c Drappatz J. Avila EK, Schachter SC, Wen PY, Dashe JF (eds.). "Seizures in Patients with Primary and Metastatic Brain Tumors". UpToDate. Retrieved 2 August 2017. 14. ^ Loeffler JS. Wen PY, Eichler AF (eds.). "Overview of the Treatment of Brain Metastases". UpToDate. Retrieved 2 August 2017. 15. ^ "Archived copy" (PDF). Archived from the original (PDF) on 2010-06-13. Retrieved 2010-03-17.CS1 maint: archived copy as title (link) 16. ^ "Archived copy". Archived from the original on 2010-01-29. Retrieved 2010-01-16.CS1 maint: archived copy as title (link) 17. ^ Reveiz L, Rueda JR, Cardona AF (June 2012). "Chemotherapy for brain metastases from small cell lung cancer". The Cochrane Database of Systematic Reviews (6): CD007464. doi:10.1002/14651858.CD007464.pub2. PMID 22696370. 18. ^ "Definition of intrathecal chemotherapy". 2011-02-02. Retrieved 2017-08-13. 19. ^ El-Habashy SE, Nazief AM, Adkins CE, Wen MM, El-Kamel AH, Hamdan AM, Hanafy AS, Terrell TO, Mohammad AS, Lockman PR, Nounou MI (May 2014). "Novel treatment strategies for brain tumors and metastases". Pharmaceutical Patent Analyst. 3 (3): 279–96. doi:10.4155/ppa.14.19. PMC 4465202. PMID 24998288. 20. ^ "FDA approves new oral therapy to treat ALK-positive lung cancer". FDA. 11 December 2015. Retrieved 4 August 2017. 21. ^ Caponnetto S, Draghi A, Borch TH, Nuti M, Cortesi E, Svane IM, Donia M (May 2018). "Cancer immunotherapy in patients with brain metastases". Cancer Immunology, Immunotherapy. 67 (5): 703–711. doi:10.1007/s00262-018-2146-8. hdl:11573/1298742. PMID 29520474. 22. ^ Park DM, Posner JB, "Management of Intracranial Metastases: History", Intracranial Metastases, Blackwell Publishing, Inc., pp. 1–19, ISBN 9780470753064 23. ^ Kintomo T (1982). Metastatic tumors of the central nervous system. Igaku-Shoin. ISBN 978-0896400672. OCLC 805657369. 24. ^ Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE (July 2004). "Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System". Journal of Clinical Oncology. 22 (14): 2865–72. doi:10.1200/jco.2004.12.149. PMID 15254054. 25. ^ Stelzer KJ (2013-05-02). "Epidemiology and prognosis of brain metastases". Surgical Neurology International. 4 (Suppl 4): S192-202. doi:10.4103/2152-7806.111296. PMC 3656565. PMID 23717790. 26. ^ Bouffet E, Doumi N, Thiesse P, Mottolese C, Jouvet A, Lacroze M, Carrie C, Frappaz D, Brunat-Mentigny M (January 1997). "Brain metastases in children with solid tumors". Cancer. 79 (2): 403–10. doi:10.1002/(SICI)1097-0142(19970115)79:2<403::AID-CNCR25>3.0.CO;2-3. PMID 9010115. 27. ^ Counsell CE, Collie DA, Grant R (August 1996). "Incidence of intracranial tumours in the Lothian region of Scotland, 1989-90". Journal of Neurology, Neurosurgery, and Psychiatry. 61 (2): 143–50. doi:10.1136/jnnp.61.2.143. PMC 1073987. PMID 8708681. 28. ^ Fabi A, Felici A, Metro G, Mirri A, Bria E, Telera S, Moscetti L, Russillo M, Lanzetta G, Mansueto G, Pace A, Maschio M, Vidiri A, Sperduti I, Cognetti F, Carapella CM (January 2011). "Brain metastases from solid tumors: disease outcome according to type of treatment and therapeutic resources of the treating center". Journal of Experimental & Clinical Cancer Research. 30: 10. doi:10.1186/1756-9966-30-10. PMC 3033846. PMID 21244695. 29. ^ Stark AM, Stöhring C, Hedderich J, Held-Feindt J, Mehdorn HM (January 2011). "Surgical treatment for brain metastases: Prognostic factors and survival in 309 patients with regard to patient age". Journal of Clinical Neuroscience. 18 (1): 34–8. doi:10.1016/j.jocn.2010.03.046. PMID 20851611. 30. ^ Lagerwaard FJ, Levendag PC, Nowak PJ, Eijkenboom WM, Hanssens PE, Schmitz PI (March 1999). "Identification of prognostic factors in patients with brain metastases: a review of 1292 patients". International Journal of Radiation Oncology, Biology, Physics. 43 (4): 795–803. doi:10.1016/S0360-3016(98)00442-8. PMID 10098435. 31. ^ Graf AH, Buchberger W, Langmayr H, Schmid KW (1988). "Site preference of metastatic tumours of the brain". Virchows Archiv. A, Pathological Anatomy and Histopathology. 412 (5): 493–8. doi:10.1007/BF00750584. PMID 3128919. 32. ^ Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE (July 2004). "Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System". Journal of Clinical Oncology. 22 (14): 2865–72. doi:10.1200/JCO.2004.12.149. PMID 15254054. 33. ^ Percy AK, Elveback LR, Okazaki H, Kurland LT (January 1972). "Neoplasms of the central nervous system. Epidemiologic considerations". Neurology. 22 (1): 40–8. doi:10.1212/WNL.22.1.40. PMID 5061838. 34. ^ Walker AE, Robins M, Weinfeld FD (February 1985). "Epidemiology of brain tumors: the national survey of intracranial neoplasms". Neurology. 35 (2): 219–26. doi:10.1212/WNL.35.2.219. PMID 3969210. 35. ^ Tabouret E, Metellus P, Gonçalves A, Esterni B, Charaffe-Jauffret E, Viens P, Tallet A (March 2014). "Assessment of prognostic scores in brain metastases from breast cancer". Neuro-Oncology. 16 (3): 421–8. doi:10.1093/neuonc/not200. PMC 3922513. PMID 24311640. Authority control * GND: 4262900-7 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Brain metastasis	c0220650	29,012	wikipedia	https://en.wikipedia.org/wiki/Brain_metastasis	2021-01-18T18:36:37	{"wikidata": ["Q1620196"]}
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-35 (EIEE35) is caused by homozygous mutation in the ITPA gene (147520) on chromosome 20p13. Description Early infantile epileptic encephalopathy-35 is an autosomal recessive neurodegenerative disorder characterized by onset of seizures in the first months of life associated with essentially no normal development. Brain imaging shows a characteristic pattern consistent with lack of myelination of early structures, including the posterior limb of the internal capsule, brainstem tracts, and tracts to the primary visual and motor cortices. Many patients die in early childhood (summary by Kevelam et al., 2015) For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see 308350. Clinical Features Kevelam et al. (2015) reported 7 patients from 4 unrelated families with severe early-onset epileptic encephalopathy associated with a distinctive pattern of MRI abnormalities on brain imaging. Two of the families were consanguineous. Between 2 and 4 months of age, the patients showed T2 signal abnormalities and diffusion restriction in the posterior limb of the internal capsule. The optic radiation, brainstem tract, and cerebellar white matter regions were often affected. Imaging also showed delayed myelination and progressive brain atrophy. The patients presented shortly after birth with microcephaly, seizures, and failure to achieve developmental milestones; there was virtually no cognitive or motor development after disease onset, and all showed hypotonia with poor feeding. Additional features included cardiomyopathy (1 patient), electrocardiographic abnormalities (3 patients), and cataracts (3 sibs born of consanguineous parents). Six patients died between 10 months and 2.5 years; 1 was alive but severely disabled at age 3 years. Extensive metabolic screening showed no abnormalities. Kevelam et al. (2015) noted that the brain imaging pattern was consistent with a neuronal degenerative disease process particularly affecting early myelinating structures. Inheritance The transmission pattern of EIEE35 in the families reported by Kevelam et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In 7 patients from 4 unrelated families with EIEE35, Kevelam et al. (2015) identified 4 different homozygous mutations in the ITPA gene (147520.0003-147520.0006). In 3 families, the mutations were found by homozygosity mapping and/or whole-exome sequencing. The erythrocytes of 1 proband showed severely reduced ITPase activity and accumulation of ITP, whereas fibroblasts of the other 3 probands showed severely reduced ITPase activity and no accumulation of ITP. Kevelam et al. (2015) postulated that the abnormal accumulation of ITP could be toxic to neurons and other cells if it is incorporated into DNA and RNA instead of the canonical nucleotides. ITP may also interfere with normal ATP- and GTP-related signal transduction within the cell. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation \- Poor overall growth HEAD & NECK Head \- Microcephaly (up to -6 SD) Eyes \- Cataracts (1 family) \- Minimal eye contact CARDIOVASCULAR Heart \- Cardiomyopathy (1 patient) \- Electrocardiogram abnormalities (in some patients) ABDOMEN Gastrointestinal \- Feeding difficulties MUSCLE, SOFT TISSUES \- Hypotonia, severe NEUROLOGIC Central Nervous System \- Encephalopathy \- Lack of psychomotor development \- Seizures \- Cerebral atrophy \- Delayed myelination \- Abnormal T2-weighted signals and diffusion restriction in the posterior limb of the internal capsule \- Abnormal T2-weighted signals in the optic radiations \- Abnormal T2-weighted signals in the midbrain brainstem tracts \- Abnormal T2-weighted signals in the cerebellar white matter MISCELLANEOUS \- Onset soon after birth \- Death in early childhood may occur MOLECULAR BASIS \- Caused by mutation in the inosine triphosphatase gene (ITPA, 147520.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 35	c4225256	29,013	omim	https://www.omim.org/entry/616647	2019-09-22T15:48:21	{"doid": ["0080458"], "omim": ["616647"], "orphanet": ["457375"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that congenital myasthenic syndrome-11 (CMS11) associated with acetylcholine receptor (AChR) deficiency is caused by homozygous or compound heterozygous mutation in the RAPSN gene (601592), which plays an essential role in the clustering of AChR at the endplate, on chromosome 11p11. Description Congenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) clinically characterized by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Treatment with cholinesterase inhibitors or amifampridine may be helpful (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). Clinical Features Ohno et al. (2002) reported 4 unrelated patients with CMS and AChR deficiency. All patients had a similar disease course with weak fetal movements in utero, hypotonia with poor suck and cry, and ptosis at birth. They all learned to walk at ages 15 to 18 months but had frequent falls, and most could never walk fast or run. Other features included easy fatigability, positive Gowers sign, and high-arched palate. On several occasions, respiratory infections or other intercurrent illnesses precipitated generalized weakness, often requiring assisted ventilation. One patient was born with multiple joint contractures, although her mother was unaware of decreased fetal movement in utero. All patients had type 1 fiber predominance on muscle biopsy and markedly attenuated numbers of AChR. Burke et al. (2003) reported 16 patients with CMS11. Thirteen patients had an early onset, with arthrogryposis multiplex congenita, hypotonia, bulbar and/or respiratory difficulties at birth, and episodic crises and/or apnea. Most patients improved later in life. Three patients had a later onset, at 13, 21, and 48 years, with proximal and ankle dorsiflexion weakness and mild ptosis in 2. All 3 late-onset patients were initially diagnosed with seronegative myasthenia gravis (see 254200). Both early- and late-onset patients responded well to anticholinesterase therapy. Das et al. (2014) reported a male infant with severe CMS11 who presented at birth with weak cry, hypotonia, joint contractures, limited spontaneous movement, and severe respiratory insufficiency. He also had prominent occiput, low-set ears, hypertelorism with small palpebral fissures, micrognathia, broad nasal bridge, and high-arched palate. Skeletal muscle biopsy showed mild myofiber atrophy consistent with denervation. The child remained hypotonic with decreased muscle bulk, but cognitive function progressed normally. Treatment with pyridostigmine at age 16 months resulted in dramatically improved motor strength and movement. ### Clinical Variability In 14 Jewish patients from 10 families of either Iraqi or Iranian origin, Goldhammer et al. (1990) described congenital myasthenia associated with facial malformations, which included an elongated face, mandibular prognathism with class III malocclusion, and a high-arched palate. Muscle weakness was restricted predominantly to ptosis, weakness of facial and masticatory muscles, and fatigable speech. The course was mild and nonprogressive. Patients showed satisfactory response to cholinesterase inhibitors. Laboratory studies showed absence of antibodies to AChR and decremental response on repetitive stimulation at 3 Hz, but there was no repetitive compound muscle action potential (CMAP) in response to a single nerve stimulus. Goldhammer et al. (1990) suggested that the facial abnormalities observed in these patients could be secondary to the neuromuscular defects. Despite the early onset associated with this phenotype, half of the patients had been diagnosed between the ages of 18 and 42 years. Mapping Menold et al. (1998) studied DNA from 5 consanguineous families of Iranian Jewish origin in which several members had CMS beginning in infancy. The disease followed a nonprogressive course with muscle weakness confined mainly to the facial and masticatory muscles. Linkage studies excluded regions of chromosomes 2 and 17 where CMS had previously been mapped. Affected members of these families were later found to have mutations in the RAPSN gene on 11p (Ohno et al., 2003). Molecular Genetics In 4 patients with CMS and AChR deficiency, Ohno et al. (2002) identified homozygous or compound heterozygous mutations in the RAPSN gene (601592.0001-601592.0003). Burke et al. (2003) reported 16 patients with CMS caused by the RAPSN N88K mutation (601592.0001): 7 were homozygous and 9 were compound heterozygous. Gaudon et al. (2010) found that 3 (15%) of 20 unrelated patients with CMS due to RAPSN mutations were compound heterozygous for the common N88K mutation and an intragenic multiexonic deletion in the RAPSN gene. The 3 different deletions, which encompassed the first, middle, and last exons, respectively, were detected by SNP analysis and gene dosage studies. Two of the deletions occurred between repeated sequences within the RAPSN gene, and Gaudon et al. (2010) suggested that RAPSN may be particularly prone to genomic recombination because it contains numerous repeated sequences. In a patient with severe CMS11, Das et al. (2014) identified compound heterozygous mutations in the RAPSN gene: the common N88K mutation and a 2-bp duplication (c.1083_1084dupCT; 601592.0015). The mutations were found by whole-exome sequencing and segregated with the disorder in the family. Functional studies of the variants were not performed. Population Genetics In 6 Iraqi/Iranian patients with CMS and AChR deficiency associated with facial dysmorphism originally reported by Goldhammer et al. (1990), Ohno et al. (2003) identified a homozygous mutation in the promoter region of the RAPSN gene (601592.0006). Haplotype analysis showed a founder effect for the mutation. Zlotogora (1995) reviewed hereditary disorders among Jewish individuals originating from Iran and Iraq. Dunne and Maselli (2004) stated that all previously reported patients with postsynaptic CMS carried the N88K mutation in the RAPSN gene. The authors used 7 intragenic SNPs spanning 8 kb to characterize the haplotype associated with N88K. In 3 affected N88K homozygous individuals, they identified a common haplotype present in all heterozygous carriers of N88K. Of note, in 2 asymptomatic N88K homozygous individuals, a second haplotype was present that differed at 3 SNP sites downstream from the N88K mutation. The finding of a common haplotype associated with N88K supported a founder effect. The discordant haplotype in homozygous individuals suggested that recombination events may have occurred within the RAPSN gene, which could have implications for the phenotypic expression of the disease. By haplotype analysis of 21 CMS patients of European and Indian origin with the RAPSN N88K mutation, Muller et al. (2004) identified a core founder haplotype of 10 SNPs encompassing a region of 0.36 Mb flanking the mutation. The authors concluded that N88K derived from a single founder event in an ancient Indo-European population. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Long face \- Ptosis Mouth \- High-arched palate RESPIRATORY \- Respiratory insufficiency, episodic ABDOMEN Gastrointestinal \- Poor feeding SKELETAL \- Joint contractures \- Arthrogryposis (in some patients) MUSCLE, SOFT TISSUES \- Hypotonia, neonatal \- Muscle weakness, mainly proximal \- Gower sign \- Easy fatigability \- Decremental compound muscle action potential (CMAP) in response to repetitive nerve stimulation \- Decreased AChR at the endplate NEUROLOGIC Central Nervous System \- Delayed motor development due to muscle weakness PRENATAL MANIFESTATIONS Movement \- Decreased fetal movements MISCELLANEOUS \- Onset at birth \- Favorable response to treatment with cholinesterase inhibitors or amifampridine MOLECULAR BASIS \- Caused by mutation in the receptor-associated protein of the synapse, 43-kD gene (RAPSN, 601592.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MYASTHENIC SYNDROME, CONGENITAL, 11, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY	c0751882	29,014	omim	https://www.omim.org/entry/616326	2019-09-22T15:49:12	{"doid": ["0110675"], "mesh": ["D020294"], "omim": ["616326"], "orphanet": ["98913", "590"], "synonyms": ["Alternative titles", "MYASTHENIC SYNDROME, CONGENITAL, Ie, FORMERLY", "CMS Ie, FORMERLY"], "genereviews": ["NBK1168"]}
A rare, genetic, hematologic disorder characterized by bone marrow failure which manifests with aplastic anemia and/or myelodysplasia, associated with hearing/ear abnormalities (such as deafness, labyrinthitis), inherited in an autosomal dominant manner. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autosomal dominant aplasia and myelodysplasia	c3808553	29,015	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314399	2021-01-23T17:08:04	{"mesh": ["C536572"], "omim": ["614675"], "icd-10": ["D61.0"], "synonyms": ["Autosomal dominant aplastic anemia and myelodysplasia"]}
Spinal muscular atrophy type 2 (SMA2) is a genetic neuromuscular disorder that affects the nerve cells that control voluntary muscles (motor neurons). Without treatment, progressive muscle weakness develops in babies with SMA2 between ages 6 and 12 months. Babies with SMA2 can sit without support, however, they cannot stand or walk independently. Feeding and breathing problems also develop. SMA2 is caused by changes (pathogenic variants also called mutations) in the SMN1 gene and is inherited in an autosomal recessive manner. Diagnosis of SMA2 is suspected by symptoms and confirmed by genetic testing. SMA has been added to the list of recommended newborn screening tests in the United States, so that it can be detected prior to symptoms developing. This occurred because treatments are being developed that are changing the course of the disease. In December 2016, nusinersen (Spinraza) became the first FDA approved treatment for SMA2. Continued treatment with nusinersen is allowing many babies and children with SMA2 to reach and maintain age appropriate developmental milestones, including sitting, crawling, and walking. Breathing problems, nutrition problems, and hospital admissions also decrease in general. However, response to treatment does vary. Some children with SMA2 may not respond to the nusinersen at all or may have medical complications that prevent use of the treatment. Other treatments remain supportive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Spinal muscular atrophy type 2	c0393538	29,016	gard	https://rarediseases.info.nih.gov/diseases/4945/spinal-muscular-atrophy-type-2	2021-01-18T17:57:37	{"mesh": ["D014897"], "omim": ["253550"], "orphanet": ["83418"], "synonyms": ["SMA2", "Muscular atrophy, spinal, intermediate type", "Muscular atrophy, spinal, infantile chronic form", "Spinal muscular atrophy type II", "SMA II", "Dubowitz disease"]}
This article is about the disease in humans. For the disease in equines, see Hyperkalemic periodic paralysis (equine). Hyperkalemic periodic paralysis Other namesGamstorp episodic adynamy SpecialtyNeurology Hyperkalemic periodic paralysis (HYPP, HyperKPP) is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is characterized by muscle hyperexcitability or weakness which, exacerbated by potassium, heat or cold, can lead to uncontrolled shaking followed by paralysis. Onset usually occurs in early childhood, but it still occurs with adults. The mutation which causes this disorder is dominant on SCN4A with linkage to the sodium channel expressed in muscle. The mutation causes single amino acid changes in parts of the channel which are important for inactivation. These mutations impair "ball and chain" fast inactivation of SCN4A following an action potential. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Treatment * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (April 2017) (Learn how and when to remove this template message) Hyperkalemic periodic paralysis causes episodes of extreme muscle weakness, with attacks often beginning in childhood.[1] Depending on the type and severity of the HyperKPP, it can increase or stabilize until the fourth or fifth decade where attacks may cease, decline, or, depending on the type, continue on into old age. Factors that can trigger attacks include rest after exercise, potassium-rich foods, stress, fatigue, weather changes, certain pollutants (e.g., cigarette smoke) and fasting. Muscle strength often improves between attacks, although many affected people may have increasing bouts of muscle weakness as the disorder progresses (abortive attacks). Sometimes with HyperKPP those affected may experience degrees of muscle stiffness and spasms (myotonia) in the affected muscles. This can be caused by the same things that trigger the paralysis, dependent on the type of myotonia. Some people with hyperkalemic periodic paralysis have increased levels of potassium in their blood (hyperkalemia) during attacks. In other cases, attacks are associated with normal blood potassium levels (normokalemia). Ingesting potassium can trigger attacks in affected individuals, even if blood potassium levels do not rise in response. In contrast to HyperKPP, hypokalemic periodic paralysis (noted in humans) refers to loss-of-function mutations in channels that prevent muscle depolarisation and therefore are aggravated by low potassium ion concentrations. ## Genetics[edit] In humans, the most common underlying genetic cause is one of several possible point mutations in the gene SCN4A.[2] This gene codes for a voltage-gated sodium channel Nav1.4 found at the neuromuscular junction. This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause it. Action potentials from the central nervous system cause end-plate potentials at the NMJ which causes sodium ions to enter by Nav1.4 and depolarise the muscle cells. This depolarisation triggers the entry of calcium from the sarcoplasmic reticulum to cause contraction (tensing) of the muscle. To prevent the muscle from being perpetually contracted, the channel contains a fast inactivation gate that plugs the sodium pore very quickly after it opens. This prevents further entry of sodium. In time, potassium ions will leave the muscle cells, repolarising the cells and causing the pumping of calcium away from the contractile apparatus to relax the muscle.[citation needed] Mutations altering the usual structure and function of this sodium channel therefore disrupt regulation of muscle contraction, leading to episodes of severe muscle weakness or paralysis. Mutations have been identified in residues between transmembrane domains III and IV which make up the fast inactivation gate of Nav1.4. Mutations have been found on the cytoplasmic loops between the S4 and S5 helices of domains II, III and IV, which are the binding sites of the inactivation gate.[3][4] The pathological mechanism of SCN4A mutations in hyperkalemic periodic paralysis is complex, but explains the autosomal dominant and hyperkalemia-related aspects of the disease.[5] In patients with mutations in SCN4A, not all copies of the channel inactivate following the action potential. This results in a sodium leak and failure to return to the original resting membrane potential. In the presence of hyperkalemia, which causes an additional chronic depolarization of the membrane potential, this sodium leak raises the membrane potential to the point that all sodium channels, including channels produced from the wild-type allele and mutant channels that did inactivate, fail to be release from inactivation (enter depolarization block). Since the motor end plate is depolarised, further signals to contract have no effect (paralysis).[6][7] ## Treatment[edit] * Glucose or other carbohydrates can be given during an attack and may reduce the severity.[1] * Intravenous calcium decreases activity of sodium channels. It may stop sudden attacks.[1] * Diuretics such as furosemide may be needed to stop sudden attacks;[1] acetazolamide and thiazide diuretics such as chlorothiazide are also effective.[1] * Intravenous glucose and insulin stimulates potassium uptake into the cell by the Na-K ATPase and may reduce weakness without a loss of total body potassium.[1] * A high-carbohydrate diet may be recommended.[1] * Avoidance of other known attack triggers.[8] ## See also[edit] * Hyperkalemic periodic paralysis (equine) ## References[edit] 1. ^ a b c d e f g MedlinePlus: Hyperkalemic periodic paralysis Update Date: 7/25/2006. Updated by: David M. Charytan, M.D., M.Sc., Department of Medicine, Division of Nephrology, Brigham and Women's Hospital, Boston, MA. 2. ^ Online Mendelian Inheritance in Man (OMIM): Hyperkalemic Periodic Paralysis; HYPP - 17050 3. ^ Rojas CV, Wang JZ, Schwartz LS, Hoffman EP, Powell BR, Brown RH (December 1991). "A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis". Nature. 354 (6352): 387–9. Bibcode:1991Natur.354..387R. doi:10.1038/354387a0. PMID 1659668. S2CID 4372717. 4. ^ Bendahhou S, Cummins TR, Kula RW, Fu YH, Ptácek LJ (April 2002). "Impairment of slow inactivation as a common mechanism for periodic paralysis in DIIS4-S5". Neurology. 58 (8): 1266–72. doi:10.1212/wnl.58.8.1266. PMID 11971097. S2CID 10412539. 5. ^ Cannon, Stephen C. (2018). "Sodium Channelopathies of Skeletal Muscle". Voltage-gated Sodium Channels: Structure, Function and Channelopathies. Handbook of Experimental Pharmacology. Springer International Publishing. 246: 309–330. doi:10.1007/164_2017_52. ISBN 978-3-319-90283-8. PMC 5866235. PMID 28939973. 6. ^ Rüdel R, Lehmann-Horn F, Ricker K, Küther G (February 1984). "Hypokalemic periodic paralysis: in vitro investigation of muscle fiber membrane parameters". Muscle Nerve. 7 (2): 110–20. doi:10.1002/mus.880070205. PMID 6325904. 7. ^ Jurkat-Rott K, Lehmann-Horn F (August 2005). "Muscle channelopathies and critical points in functional and genetic studies". J. Clin. Invest. 115 (8): 2000–9. doi:10.1172/JCI25525. PMC 1180551. PMID 16075040. 8. ^ Lee, GM; Kim, JB (June 2011). "Hyperkalemic periodic paralysis and paramyotonia congenita caused by a de novo mutation in the SCN4A gene". Neurology Asia. 16 (2): 163–6. * National Library of Medicine. Hyperkalemic periodic paralysis ## External links[edit] * GeneReview/NIH/UW entry on Hyperkalemic Periodic Paralysis Type 1 Classification D * ICD-10: G72.3 * ICD-9-CM: 359.3 * OMIM: 170500 * MeSH: D020513 * DiseasesDB: 6252 * SNOMED CT: 278513006 External resources * MedlinePlus: 000316 * eMedicine: article/1171678 * GeneReviews: Hyperkalemic Periodic Paralysis Type 1 * Orphanet: 682 * v * t * e Diseases of muscle, neuromuscular junction, and neuromuscular disease Neuromuscular- junction disease * autoimmune * Myasthenia gravis * Lambert–Eaton myasthenic syndrome * Neuromyotonia Myopathy Muscular dystrophy (DAPC) AD * Limb-girdle muscular dystrophy 1 * Oculopharyngeal * Facioscapulohumeral * Myotonic * Distal (most) AR * Calpainopathy * Limb-girdle muscular dystrophy 2 * Congenital * Fukuyama * Ullrich * Walker–Warburg XR * dystrophin * Becker's * Duchenne * Emery–Dreifuss Other structural * collagen disease * Bethlem myopathy * PTP disease * X-linked MTM * adaptor protein disease * BIN1-linked centronuclear myopathy * cytoskeleton disease * Nemaline myopathy * Zaspopathy Channelopathy Myotonia * Myotonia congenita * Thomsen disease * Neuromyotonia/Isaacs syndrome * Paramyotonia congenita Periodic paralysis * Hypokalemic * Thyrotoxic * Hyperkalemic Other * Central core disease Mitochondrial myopathy * MELAS * MERRF * KSS * PEO General * Inflammatory myopathy * Congenital myopathy * v * t * e Diseases of ion channels Calcium channel Voltage-gated * CACNA1A * Familial hemiplegic migraine 1 * Episodic ataxia 2 * Spinocerebellar ataxia type-6 * CACNA1C * Timothy syndrome * Brugada syndrome 3 * Long QT syndrome 8 * CACNA1F * Ocular albinism 2 * CSNB2A * CACNA1S * Hypokalemic periodic paralysis 1 * Thyrotoxic periodic paralysis 1 * CACNB2 * Brugada syndrome 4 Ligand gated * RYR1 * Malignant hyperthermia * Central core disease * RYR2 * CPVT1 * ARVD2 Sodium channel Voltage-gated * SCN1A * Familial hemiplegic migraine 3 * GEFS+ 2 * Febrile seizure 3A * SCN1B * Brugada syndrome 6 * GEFS+ 1 * SCN4A * Hypokalemic periodic paralysis 2 * Hyperkalemic periodic paralysis * Paramyotonia congenita * Potassium-aggravated myotonia * SCN4B * Long QT syndrome 10 * SCN5A * Brugada syndrome 1 * Long QT syndrome 3 * SCN9A * Erythromelalgia * Febrile seizure 3B * Paroxysmal extreme pain disorder * Congenital insensitivity to pain Constitutively active * SCNN1B/SCNN1G * Liddle's syndrome * SCNN1A/SCNN1B/SCNN1G * Pseudohypoaldosteronism 1AR Potassium channel Voltage-gated * KCNA1 * Episodic ataxia 1 * KCNA5 * Familial atrial fibrillation 7 * KCNC3 * Spinocerebellar ataxia type-13 * KCNE1 * Jervell and Lange-Nielsen syndrome * Long QT syndrome 5 * KCNE2 * Long QT syndrome 6 * KCNE3 * Brugada syndrome 5 * KCNH2 * Short QT syndrome * KCNQ1 * Jervell and Lange-Nielsen syndrome * Romano–Ward syndrome * Short QT syndrome * Long QT syndrome 1 * Familial atrial fibrillation 3 * KCNQ2 * BFNS1 Inward-rectifier * KCNJ1 * Bartter syndrome 2 * KCNJ2 * Andersen–Tawil syndrome * Long QT syndrome 7 * Short QT syndrome * KCNJ11 * TNDM3 * KCNJ18 * Thyrotoxic periodic paralysis 2 Chloride channel * CFTR * Cystic fibrosis * Congenital absence of the vas deferens * CLCN1 * Thomsen disease * Myotonia congenita * CLCN5 * Dent's disease * CLCN7 * Osteopetrosis A2, B4 * BEST1 * Vitelliform macular dystrophy * CLCNKB * Bartter syndrome 3 TRP channel * TRPC6 * FSGS2 * TRPML1 * Mucolipidosis type IV Connexin * GJA1 * Oculodentodigital dysplasia * Hallermann–Streiff syndrome * Hypoplastic left heart syndrome * GJB1 * Charcot–Marie–Tooth disease X1 * GJB2 * Keratitis–ichthyosis–deafness syndrome * Ichthyosis hystrix * Bart–Pumphrey syndrome * Vohwinkel syndrome) * GJB3/GJB4 * Erythrokeratodermia variabilis * Progressive symmetric erythrokeratodermia * GJB6 * Clouston's hidrotic ectodermal dysplasia Porin * AQP2 * Nephrogenic diabetes insipidus 2 See also: ion channels [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hyperkalemic periodic paralysis	c0238357	29,017	wikipedia	https://en.wikipedia.org/wiki/Hyperkalemic_periodic_paralysis	2021-01-18T18:30:36	{"gard": ["195"], "mesh": ["D020513"], "umls": ["C0238357"], "icd-9": ["359.3"], "orphanet": ["682"], "wikidata": ["Q3269843"]}
Contagious bacterial disease Contagious bovine pleuropneumonia (CBPP – also known as lung plague), is a contagious bacterial disease that afflicts the lungs of cattle, buffalo, zebu, and yaks. It is caused by the bacterium Mycoplasma mycoides, and the symptoms are pneumonia and inflammation of the lung membranes.[1] The incubation period is 20 to 123 days. It was particularly widespread in the United States in 1879, affecting herds from several states. The outbreak was so severe that it resulted in a trade embargo by the British government, blocking U.S. cattle exports to Britain and Canada. This prompted the United States to establish the Bureau of Animal Industry, set up in 1884 to eradicate the disease, which it succeeded in doing by 1892.[2] Louis Willems, a Belgian doctor, began pioneering work in the 1850s on animal inoculation against the disease.[3] The bacteria are widespread in Africa, the Middle East, Southern Europe, as well as parts of Asia. It is an airborne species, and can travel up to several kilometres in the right conditions. ## Contents * 1 In Australia * 2 See also * 3 References * 4 External links ## In Australia[edit] Contagious bovine pleuropneumonia came to Australia on a shipment of five head of cattle from England in 1858, imported by one of Melbourne's earliest settlers Mr Boadle. Three weeks later, a heifer named St Bees fell ill. Boadle called in a veterinarian who diagnosed it with the disease. The heifer died three weeks later. Whilst Boadle destroyed the herd, St Bees had already infected a bullock team grazing on a neighbouring property. Pleuropneumonia spread up the overland route to New South Wales, into Queensland and across northern Australia. It later arrived in Western Australia via a shipload of cattle. Only Tasmania was to remain free of the epidemic in Australia.[4] A national management strategy was implemented in 1959, inspired by the work of chief veterinary officer of the Northern Territory Colonel Lionel Rose. A National Committee for the Control and Eradication of Pleuropneumonia was established, under the Chief of the CSIRO Division of Animal Health and Production, D A Gill. It defined infected, protected and disease-free areas. Once these were established, there were restrictions on the movement of cattle between zones. The national programme was empowered to employ veterinary officers, stock inspectors and police across Australia. Pleuropneumonia was announced to be eradicated in Australia by 1973.[4] ## See also[edit] * Contagious caprine pleuropneumonia * Fog fever * Minimal genome project ## References[edit] 1. ^ "Contagious Bovine Pleuropneumonia". The Merck Veterinary Manual. 2006. Archived from the original on 2016-03-04. Retrieved 2007-06-14. 2. ^ Cima, Greg (1 March 2013). "LEGENDS: America's first DVM". Journal of the American Veterinary Medical Association – JAVMANews. Retrieved 14 October 2017. 3. ^ Bazin, Hervé (2011). "Louis Willems and bovine pleuropneumonia: 1852…". Vaccination a history from Lady Montagu to genetic engineering. Montrouge: John Libbey Eurotext. pp. 129–133. ISBN 9782742013449. 4. ^ a b "Contagious bovine pleuropneumonia eradication – CSIROpedia". CSIROpedia. CSIRO. 6 February 2011. Retrieved 24 June 2016. ## External links[edit] * Current status of Contagious bovine pleuropneumonia worldwide at OIE. WAHID Interface – OIE World Animal Health Information Database * Disease card [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Contagious bovine pleuropneumonia	c0276044	29,018	wikipedia	https://en.wikipedia.org/wiki/Contagious_bovine_pleuropneumonia	2021-01-18T19:00:07	{"wikidata": ["Q574005"]}
Unstable angina SpecialtyCardiology Unstable angina (UA), also called crescendo angina, is a type of angina pectoris[1] that is irregular.[2] It is also classified as a type of acute coronary syndrome (ACS).[3] It can be difficult to distinguish unstable angina from non-ST elevation (non-Q wave) myocardial infarction (NSTEMI).[4][5] They differ primarily in whether the ischemia is severe enough to cause sufficient damage to the heart's muscular cells to release detectable quantities of a marker of injury (typically troponin T or troponin I). Unstable angina is considered to be present in patients with ischemic symptoms suggestive of an ACS and no elevation in troponin, with or without ECG changes indicative of ischemia (e.g., ST segment depression or transient elevation or new T wave inversion). Since an elevation in troponin may not be detectable for up to 12 hours after presentation, UA and NSTEMI are frequently indistinguishable at initial evaluation. ## Contents * 1 Pathophysiology * 2 Diagnosis * 3 Management * 4 See also * 5 References * 6 External links ## Pathophysiology[edit] The pathophysiology of unstable angina is controversial. Until recently, unstable angina was assumed to be angina pectoris caused by disruption of an atherosclerotic plaque with partial thrombosis and possibly embolization or vasospasm leading to myocardial ischemia.[6][7] However, sensitive troponin assays reveal rise of cardiac troponin in the bloodstream with episodes of even mild myocardial ischemia. [8] Since unstable angina is assumed to occur in the setting of acute myocardial ischemia without troponin release, the concept of unstable angina is being questioned with some calling for retiring the term altogether.[9] ## Diagnosis[edit] Unstable angina is characterized by at least one of the following: 1. Occurs at rest or minimal exertion and usually lasts more than 20 minutes (if nitroglycerin is not administered) 2. Being severe (at least Canadian Cardiovascular Society Classification 3) and of new onset (i.e. within 1 month) 3. Occurs with a crescendo pattern (brought on by less activity, more severe, more prolonged or increased frequency than previously).[10][11] Fifty percent of people with unstable angina will have evidence of necrosis of the heart's muscular cells based on elevated cardiac serum markers such as creatine kinase isoenzyme (CK)-MB and troponin T or I, and thus have a diagnosis of non-ST elevation myocardial infarction.[11][12] ## Management[edit] Nitroglycerin can be used immediately to dilate the venous system and reduce the circulating blood volume, therefore reducing the work and oxygen demand of the heart.[13][14] In addition, nitroglycerin causes peripheral venous and artery dilation reducing cardiac preload and afterload. These reductions allow for decreased stress on the heart and therefore lower the oxygen demand of the heart's muscle cells.[15] Antiplatelet drugs such as aspirin and clopidogrel can help reduce the progression of atherosclerotic plaque formation, as well as combining these with an anticoagulant such as a low molecular weight heparin. ## See also[edit] * Variant angina ## References[edit] 1. ^ Yeghiazarians Y, Braunstein JB, Askari A, Stone PH (January 2000). "Unstable angina pectoris". N. Engl. J. Med. 342 (2): 101–14. doi:10.1056/NEJM200001133420207. PMID 10631280. 2. ^ "unstable angina" at Dorland's Medical Dictionary 3. ^ Wiviott, S. D.; Braunwald, E (2004). "Unstable Angina and Non–ST-Segment Elevation Myocardial Infarction: Part I. Initial Evaluation and Management, and Hospital Care". American Family Physician. 70 (3): 525–32. PMID 15317439. 4. ^ Roffi, M; et al. (2016). "2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)". European Heart Journal. 37 (3): 267–315. doi:10.1093/eurheartj/ehv320. PMID 26320110. 5. ^ Jneid, H; et al. (2012). "2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Journal of the American College of Cardiology. 60 (7): 645–81. doi:10.1016/j.jacc.2012.06.004. PMID 22809746. 6. ^ Robbins (2005). Pathologic Basis of Disease (7th ed.). 7. ^ Braunwald, E. (1998). "Unstable Angina: An Etiologic Approach to Management". Circulation. 98 (21): 2219–2222. doi:10.1161/01.CIR.98.21.2219. PMID 9826306. 8. ^ Sabatine, M. S.; Morrow, R. W.; de Lemos, J.A.; Jarolim, P.; Braunwald, E. (2009). "Detection of acute changes in circulating troponin in the setting of transient stress test-induced myocardial ischaemia using an ultrasensitive assay: results from TIMI 35". European Heart Journal. 30 (2): 162–169. doi:10.1093/eurheartj/ehn504. PMC 2721709. PMID 18997177. 9. ^ Braunwald, E.; Morrow, R. W. (2013). "Unstable Angina. Is It Time for a Requiem?". Circulation. 127 (24): 2452–2457. doi:10.1161/CIRCULATIONAHA.113.001258. PMID 23775194. 10. ^ Braunwald, E; et al. (2002). "ACC/AHA guideline update for the management of patients with unstable angina and non-ST segment elevation myocardial infarction-2002: Summary Article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina)". Circulation. 106 (14): 1893–1900. doi:10.1161/01.cir.0000037106.76139.53. PMID 12356647. 11. ^ a b Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine 12. ^ Markenvard, J; Dellborg, M; Jagenburg, R; Swedberg, K (1992). "The predictive value of CKMB mass concentration in unstable angina pectoris: preliminary report". Journal of Internal Medicine. 231 (4): 433–6. doi:10.1111/j.1365-2796.1992.tb00956.x. PMID 1588271. 13. ^ Murrell, William (1879). "Nitroglycerin as a remedy for angina pectoris". The Lancet. 1: 80–81, 113–115, 151–152, 225–227. doi:10.1016/s0140-6736(02)46032-1. 14. ^ Sneader, Walter (2005). Drug Discovery: A History. John Wiley and Sons. ISBN 978-0-471-89980-8. 15. ^ Sidhu, M.; Boden, W. E.; Padala, S. K.; Cabral, K.; Buschmann, . (2015). "Role of short-acting nitroglycerin in the management of ischemic heart disease". Drug Design, Development and Therapy. 9: 4793–805. doi:10.2147/DDDT.S79116. PMC 4548722. PMID 26316714.CS1 maint: numeric names: authors list (link) ## External links[edit] Classification D * ICD-10: I20.0 * ICD-9-CM: 411.1 * MeSH: D000789 * DiseasesDB: 13530 External resources * MedlinePlus: 000201 * 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Unstable angina	c0002965	29,019	wikipedia	https://en.wikipedia.org/wiki/Unstable_angina	2021-01-18T18:32:48	{"mesh": ["D000789"], "umls": ["C0002965"], "wikidata": ["Q2032041"]}
Malignant fibrous cytoma is a soft tissue sarcoma that usually occurs in the limbs, most commonly the legs, and may also occur in the abdomen. Also called malignant fibrous histiocytoma. ## References[edit] * Malignant fibrous cytoma entry in the public domain NCI Dictionary of Cancer Terms This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms". This oncology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Malignant fibrous cytoma	c0334463	29,020	wikipedia	https://en.wikipedia.org/wiki/Malignant_fibrous_cytoma	2021-01-18T18:58:58	{"mesh": ["D051677"], "umls": ["C0334463"], "wikidata": ["Q6743507"]}
A tumor that often causes a syndrome of diarrhea and electrolyte imbalance VIPoma SpecialtyOncology A VIPoma or vipoma (/vɪˈpoʊmə/) is a rare endocrine tumor[1] that overproduces vasoactive intestinal peptide (thus VIP \+ -oma). The incidence is about 1 per 10,000,000 per year. VIPomas usually (about 90%) originate from the non-β islet cells of the pancreas. They are sometimes associated with multiple endocrine neoplasia type 1. Roughly 50%-75% of VIPomas are malignant, but even when they are benign, they are problematic because they tend to cause a specific syndrome: the massive amounts of VIP cause a syndrome of profound and chronic watery diarrhea and resultant dehydration, hypokalemia, achlorhydria, acidosis, flushing and hypotension (from vasodilation), hypercalcemia, and hyperglycemia.[2][3] This syndrome is called Verner–Morrison syndrome (VMS), WDHA syndrome (from watery diarrhea–hypokalemia–achlorhydria), or pancreatic cholera syndrome (PCS). The eponym reflects the physicians who first described the syndrome.[4] ## Contents * 1 Symptoms and signs * 2 Diagnosis * 3 Treatment * 4 Prognosis * 5 References * 6 External links ## Symptoms and signs[edit] The major clinical features are prolonged watery diarrhea (fasting stool volume > 750 to 1000 mL/day) and symptoms of hypokalemia and dehydration. Half of the patients have relatively constant diarrhea while the rest have alternating periods of severe and moderate diarrhea. One third have diarrhea < 1yr before diagnosis, but in 25%, diarrhea is present for 5 yr or more before diagnosis. Lethargy, muscle weakness, nausea, vomiting and crampy abdominal pain are frequent symptoms. Hypokalemia and impaired glucose tolerance occur in < 50% of patients. Achlorhydria is also a feature. During attacks of diarrhea, flushing similar to the carcinoid syndrome occur rarely.[citation needed] ## Diagnosis[edit] Besides the clinical picture, fasting VIP plasma level may confirm the diagnosis, and CT scan and somatostatin receptor scintigraphy are used to localise the tumor, which is usually metastatic at presentation.[citation needed] Tests include: * Blood chemistry tests (basic or comprehensive metabolic panel) * CT scan of the abdomen * MRI of the abdomen * Stool examination for cause of diarrhea and electrolyte levels * Vasoactive intestinal peptide (VIP) level in the blood[citation needed] ## Treatment[edit] The first goal of treatment is to correct dehydration. Fluids are often given through a vein (intravenous fluids) to replace fluids lost in diarrhea. The next goal is to slow the diarrhea. Some medications can help control diarrhea. Octreotide, which is a human-made form of the natural hormone somatostatin, blocks the action of VIP.[citation needed] The best chance for a cure is surgery to remove the tumor. If the tumor has not spread to other organs, surgery can often cure the condition.[citation needed] For metastatic disease, peptide receptor radionuclide therapy (PRRT) can be highly effective. This treatment involves attaching a radionuclide (Lutetium-177 or Yttrium-90) to a somatostatin analogue (octreotate or octreotide). This is a novel way to deliver high doses of beta radiation to kill tumours.Some people seem to respond to a combination chemo called capecitabine and temozolomide but there is no report that it totally cured people from vipoma.[citation needed] ## Prognosis[edit] Surgery can usually cure VIPomas. However, in one-third to one-half of patients, the tumor has spread by the time of diagnosis and cannot be cured.[citation needed] ## References[edit] 1. ^ "VIPoma" at Dorland's Medical Dictionary 2. ^ Mansour JC, Chen H (Jul 2004). "Pancreatic endocrine tumors". J Surg Res. 120 (1): 139–61. doi:10.1016/j.jss.2003.12.007. PMID 15172200. 3. ^ "VIPoma \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17. 4. ^ Verner JV, Morrison AB (Sep 1958). "Islet cell tumor and a syndrome of refractory watery diarrhea and hypokalemia". Am J Med. 25 (3): 374–80. doi:10.1016/0002-9343(58)90075-5. PMID 13571250. * Jensen RT, Norton JA. Endocrine tumors of the pancreas and gastrointestinal tract. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease . 9th ed. Philadelphia, Pa: Saunders Elsevier; 2010:chap 32. * National Cancer Institute. Islet cell tumors (pancreatic) treatment PDQ. Updated October 31, 2008. ## External links[edit] Classification D * ICD-10: C25.4 or E16.8 * ICD-O: M8155/3 * MeSH: D003969 * DiseasesDB: 13877 * SNOMED CT: 447643008 External resources * MedlinePlus: 000228 * eMedicine: med/2379 med/2399 ped/2428 * Orphanet: 97282 * 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 Tumours of endocrine glands Pancreas * Pancreatic cancer * Pancreatic neuroendocrine tumor * α: Glucagonoma * β: Insulinoma * δ: Somatostatinoma * G: Gastrinoma * VIPoma Pituitary * Pituitary adenoma: Prolactinoma * ACTH-secreting pituitary adenoma * GH-secreting pituitary adenoma * Craniopharyngioma * Pituicytoma Thyroid * Thyroid cancer (malignant): epithelial-cell carcinoma * Papillary * Follicular/Hurthle cell * Parafollicular cell * Medullary * Anaplastic * Lymphoma * Squamous-cell carcinoma * Benign * Thyroid adenoma * Struma ovarii Adrenal tumor * Cortex * Adrenocortical adenoma * Adrenocortical carcinoma * Medulla * Pheochromocytoma * Neuroblastoma * Paraganglioma Parathyroid * Parathyroid neoplasm * Adenoma * Carcinoma Pineal gland * Pinealoma * Pinealoblastoma * Pineocytoma MEN * 1 * 2A * 2B [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	VIPoma	c0011993	29,021	wikipedia	https://en.wikipedia.org/wiki/VIPoma	2021-01-18T18:42:46	{"gard": ["5493"], "mesh": ["D003969"], "umls": ["C0011993"], "icd-10": ["E16.8", "C25.4"], "orphanet": ["97282"], "wikidata": ["Q1518637"]}
## Description Torus palatinus (TP) is a spindle-shaped bony elevation along the midline of the hard palate. Torus mandibularis (TM) is a bony elevation along the mandible generally just below the lower premolars. Both exostoses usually appear in the form of a series of swellings (summary by Suzuki and Sakai, 1960). Clinical Features Belsky et al. (2003) studied a possible correlation of bone density with torus palatinus. Subjects referred from community physicians had a visual examination of the open mouth to estimate the size of any torus palatinus (0 for none/trace to 5 for very large) before undergoing a bone density measurement by dual energy x-ray absortiometry. Bone density T and z scores were correlated with the size of each subject's torus palatinus. Regression correlations for torus size were modest, but significantly related to T and z scores of lumbar vertebrae and left hip (P less than 0.01 for each). Belsky et al. (2003) suggested that the study showed a small but significant positive relation for postmenopausal, Caucasian women between bone mineral density and torus size after controlling for several variables known to affect bone density were examined. Inheritance The study of Suzuki and Sakai (1960) suggested that TP and TM are equivalent, i.e., due to the same gene, and that the inheritance is autosomal dominant with reduced penetrance. A study by Johnson et al. (1965) supported dominant inheritance of torus mandibularis. They found that 85.7% and 89.7%, respectively, of children with TP or TM had at least 1 parent with one or the other anomaly. A sex predilection was noted, males having torus only 70% as often as females. Barbujani et al. (1986) studied the inheritance of torus palatinus in 99 sibships in 2 samples from Venezuela and Japan. They concluded that the trait is inherited as an autosomal dominant with variable expressivity and penetrance close to 85%, without significant heterogeneity between the populations studied. No evidence of sporadic cases was found. Gorsky et al. (1998) performed segregation analysis of the trait torus palatinus in 37 randomly selected Israeli Jewish families. Vertical transmission of TP was found in 19 families, suggesting autosomal dominant transmission, which was supported by the results of segregation analysis. A significantly higher number of affected offspring (60.3%) was observed compared to the expected figure (50%) for an autosomal dominant trait with full penetrance. This was thought to be explained by the high gene frequency of TP and a relatively high proportion of homozygous parents. Misc \- Female predilection Mouth \- Torus palatinus \- Torus mandibularis Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	TORUS PALATINUS AND TORUS MANDIBULARIS	c1861044	29,022	omim	https://www.omim.org/entry/189700	2019-09-22T16:32:27	{"mesh": ["C566043"], "omim": ["189700"]}
Unequal leg length A girl with a congenital, structural difference in leg lengths is walking in a clinic. SpecialtyRheumatology Unequal leg length (also termed leg length inequality, LLI or leg length discrepancy, LLD) is where the legs are either different lengths or appear to be different lengths because of misalignment. The condition has been estimated to affect between 40% and 70% of the population, with at least 0.1% having a difference greater than 20 mm.[1] ## Contents * 1 Classification * 2 Diagnosis and workup * 3 Treatment * 4 Measurement challenges * 5 References * 6 External links ## Classification[edit] There are two main types of leg length inequalities: * Structural differences are caused by the legs themselves being measurably different in length, usually due to differences in the length of the femur in the thigh or the tibia and fibula bones in the lower leg. This may be a birth defect or it may occur after a broken leg, serious infection, or local damage to one of the growth plates in a leg. * The other, more common, type is seen when the legs themselves are the same length, but due to neuromuscular injuries in the pelvis or upper leg, one leg or hip is held higher and tighter than the other (hypertonicity in the musculature of the pelvis or leg). These unequally tightened muscles cause the legs to seem to be different lengths, even though careful measurement would show equal lengths of the actual leg. This is called leg length alignment asymmetry (LLAA) and can be seen while lying down.[2] ## Diagnosis and workup[edit] X-rays for leg length measurement. Unequal leg length in children is frequently first suspected by parents noticing a limp that appears to be getting worse.[3] The standard workup in children is a thorough physical examination, including observing the child while walking and running.[3] Also, at least in United States, standard workup in children also includes X-rays to quantify actual length of the bones of the legs.[3] On X-rays, there is generally measurement of both the femur and the tibia, as well as both combined.[4] Various measuring points for these have been suggested, but a functional method is to measure the distances between joint surfaces:[4] * Femur length: The superior aspect of the femoral head and the distal portion of the medial femoral condyle. * Tibial length: The medial tibial plateau and the tibial plafond A leg length difference can result from a pelvic torsion. Abnormal (gravity drive) pronation will drive the innominate bones forward (anteriorly). The forward rotation of the innominate will shorten the leg (See Rothbart 2006). The more pronated foot will have the more forwardly rotated innominate bone. And will be the side with the functionally short leg. ## Treatment[edit] The most common treatment for discrepancies in leg length is the use of a simple heel lift, which can be placed within the shoe. In cases where the length discrepancy is moderate, an external build up to the shoe is usually more comfortable. In severe cases, surgery can be used to make the longer leg shorter (or impede its growth), and/or make the shorter leg longer via limb lengthening. ## Measurement challenges[edit] Although prone "functional leg length" is a widely used chiropractic tool in their Activator technique, it is not a recognized anthropometric technique, since legs are usually of unequal length, and measurements in the prone position are not entirely valid estimates of standing X-ray differences.[5] Measurements in the standing position are far more reliable.[6] Another confounding factor is that simply moving the two legs held together and leaning them imperceptibly to one side or the other produces different results.[7] Clinical measurement of leg length conventionally uses the distance from the anterior superior iliac spine to the medial malleolus.[8] Projectional radiographic measurements of leg length have two main variants:[9] * Teleroentgenogram, which projects the entirety of both legs at the same time. * Orthoroentgenogram, which takes separate images of the hip, knee and ankle. On X-rays, the length of the lower limb can be measured from the proximal end of femoral head to the center of the plafond of the distal tibia.[10] ## References[edit] 1. ^ Gurney, Burke (2002-04-01). "Leg length discrepancy". Gait & Posture. 15 (2): 195–206. doi:10.1016/S0966-6362(01)00148-5. ISSN 0966-6362. "LLD is a relatively common problem found in as many as 40 [1] to 70% [2] of the population. In a retrospective study, it was found that LLD of greater than 20 mm affects at least one in every 1000 people [3]." 2. ^ Knutson G. A. (2005). "Anatomic and functional leg-length inequality: A review and recommendation for clinical decision-making. Part II, the functional or unloaded leg-length asymmetry". Chiropractic & Osteopathy. 13 (12): 12. doi:10.1186/1746-1340-13-12. PMC 1198238. PMID 16080787. 3. ^ a b c "Leg Length Discrepancy (Pediatric)". Columbia University. Retrieved 2019-02-14. 4. ^ a b Sabharwal, Sanjeev; Kumar, Ajay (2008). "Methods for Assessing Leg Length Discrepancy". Clinical Orthopaedics and Related Research. 466 (12): 2910–2922. doi:10.1007/s11999-008-0524-9. ISSN 0009-921X. PMC 2628227. PMID 18836788. 5. ^ D W Rhodes, E R Mansfield, P A Bishop, J F Smith. The validity of the prone leg check as an estimate of standing leg length inequality measured by X-ray. J Manipulative Physiol Ther.; 18 (6):343-6 6. ^ Hanada E, Kirby RL, Mitchell M, Swuste JM (Jul 2001). "Measuring leg-length discrepancy by the "iliac crest palpation and book correction" method: reliability and validity". Arch Phys Med Rehabil. 82 (7): 938–42. doi:10.1053/apmr.2001.22622. PMID 11441382. 7. ^ "Adjusting the Joints, on season 12, episode 10". Scientific American Frontiers. Chedd-Angier Production Company. 2001–2002. PBS. Archived from the original on 2006.. Video discusses Activator technique and leg length 8. ^ Page 305 in: M. Lynn Palmer, Marcia E. Epler, Marcia F. Epler (1998). Fundamentals of Musculoskeletal Assessment Techniques. Lippincott Williams & Wilkins. ISBN 9780781710077.CS1 maint: multiple names: authors list (link) 9. ^ Page 269 in: Dror Paley (2002). Principles of Deformity Correction, Volume 1. Springer Science & Business Media. ISBN 9783540416654. 10. ^ Sabharwal, Sanjeev; Zhao, Caixia; McKeon, John; Melaghari, Todd; Blacksin, Marcia; Wenekor, Cornelia (2007). "Reliability Analysis for Radiographic Measurement of Limb Length Discrepancy". Journal of Pediatric Orthopaedics. 27 (1): 46–50. doi:10.1097/01.bpo.0000242444.26929.9f. ISSN 0271-6798. Rothbart BA 2006. Relationship of Functional Leg-Length Discrepancy to Abnormal Pronation. Journal American Podiatric Medical Association;96(6):499-507 ## External links[edit] Classification D * ICD-10: M21.7 * ICD-9-CM: 736.81, 755.30 * MeSH: D007870 * v * t * e Acquired musculoskeletal deformities Upper limb shoulder * Winged scapula * Adhesive capsulitis * Rotator cuff tear * Subacromial bursitis elbow * Cubitus valgus * Cubitus varus hand deformity * Wrist drop * Boutonniere deformity * Swan neck deformity * Mallet finger Lower limb hip * Protrusio acetabuli * Coxa valga * Coxa vara leg * Unequal leg length patella * Luxating patella * Chondromalacia patellae * Patella baja * Patella alta foot deformity * Bunion/hallux valgus * Hallux varus * Hallux rigidus * Hammer toe * Foot drop * Flat feet * Club foot knee * Genu recurvatum Head * Cauliflower ear General terms * Valgus deformity/Varus deformity * Joint stiffness * Ligamentous laxity * v * t * e Musculoskeletal examination Leg Hip examination * Galeazzi test * Allis test * Barlow maneuver * Ober's test * Ortolani test * Patrick's test * Thomas test * Trendelenburg's sign Knee examination * Ballottement * Clarke's test * Drawer test * Lachman test * Patellar tap * Pivot-shift test * Valgus stress test * meniscus * Apley grind test * McMurray test * ligament and meniscus * Unhappy triad Foot and ankle * Hubscher's maneuver * Mulder's sign * Simmonds' test * Thompson test * Ankle * Simmonds' test General * Straight leg raise * Lasègue's sign * Gait abnormality * Trendelenburg gait * Unequal leg length Arm Shoulder examination * Apprehension test * Jobe's test * Neer impingement sign * Yergason's test * rotator cuff * Hawkins–Kennedy test * Watson's test Elbow examination * Cozen's test * Elbow extension test Hand and wrist * Durkan's test * Finkelstein's test * Froment's sign * Lunotriquetral shear test * Phalen maneuver * Tinel sign * Watson's test Spine * Gaenslen's test * Low back pain * Waddell's signs * Lower back flexibility * Schober's test * sacroiliitis * Larrey's sign Other * Range of motion * Palpation * Codman triangle [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Unequal leg length	c0023221	29,023	wikipedia	https://en.wikipedia.org/wiki/Unequal_leg_length	2021-01-18T19:08:48	{"mesh": ["D007870"], "umls": ["C0023221"], "icd-9": ["755.30", "736.81"], "icd-10": ["M21.7", "Q72.9"], "wikidata": ["Q3027684"]}
Eosinophil peroxidase deficiency is a condition that affects certain white blood cells called eosinophils but causes no health problems in affected individuals. Eosinophils aid in the body's immune response. During a normal immune response, these cells are turned on (activated), and they travel to the area of injury or inflammation. The cells then release proteins and other compounds that have a toxic effect on severely damaged cells or invading organisms. One of these proteins is called eosinophil peroxidase. In eosinophil peroxidase deficiency, eosinophils have little or no eosinophil peroxidase. A lack of this protein does not seem to affect the eosinophils' ability to carry out an immune response. Because eosinophil peroxidase deficiency does not cause any health problems, this condition is often diagnosed when blood tests are done for other reasons or when a family member has been diagnosed with the condition. ## Frequency Approximately 100 individuals with eosinophil peroxidase deficiency have been described in the scientific literature. Based on blood test data, varying estimates of the prevalence of the condition have been reported in specific populations. Eosinophil peroxidase deficiency is estimated to occur in 8.6 in 1,000 Yemenite Jews, in 3 in 1,000 North-African Jews, and in 1 in 1,000 Iraqi Jews. In northeastern Italy, the condition occurs in approximately 1 in 14,000 individuals; in Japan it occurs in 1 in 36,000 people; and in Luxembourg, eosinophil peroxidase deficiency is thought to occur in 1 in 100,000 people. ## Causes Mutations in the EPX gene cause eosinophil peroxidase deficiency. The EPX gene provides instructions for making the eosinophil peroxidase protein. During an immune response, activated eosinophils release eosinophil peroxidase at the site of injury. This protein helps form molecules that are highly toxic to bacteria and parasites. These toxic molecules also play a role in regulating inflammation by fighting microbial invaders. EPX gene mutations reduce or prevent eosinophil peroxidase production or result in a protein that is unstable and nonfunctional. As a result, eosinophils have severely reduced amounts of eosinophil peroxidase or none at all. Other proteins within affected eosinophils are normal, and while the cells lacking eosinophil peroxidase are smaller and may have structural changes, the loss of eosinophil peroxidase does not appear to impair the function of eosinophils. ### Learn more about the gene associated with Eosinophil peroxidase deficiency * EPX ## 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Eosinophil peroxidase deficiency	c1850000	29,024	medlineplus	https://medlineplus.gov/genetics/condition/eosinophil-peroxidase-deficiency/	2021-01-27T08:25:47	{"gard": ["12361"], "mesh": ["C564893"], "omim": ["261500"], "synonyms": []}
Cerebral venous sinus thrombosis Other namesCerebral venous and sinus thrombosis, (superior) sagittal sinus thrombosis, dural sinus thrombosis, intracranial venous thrombosis, cerebral thrombophlebitis Dural veins SpecialtyNeurology TreatmentLow molecular weight heparin[1] Cerebral venous sinus thrombosis (CVST) is the presence of a blood clot in the dural venous sinuses, which drain blood from the brain. Symptoms may include headache, abnormal vision, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body, and seizures. The diagnosis is usually by computed tomography (CT scan) or magnetic resonance imaging (MRI) to demonstrate obstruction of the venous sinuses.[2] Testing may be done to try to determine the underlying cause. Treatment is typically with anticoagulants (medication that suppresses blood clotting) such as low molecular weight heparin.[1] Rarely, thrombolysis (enzymatic destruction of the blood clot) is used. The disease may be complicated by raised intracranial pressure, which may warrant surgical intervention such as the placement of a shunt.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Imaging * 3.2 D-dimer * 3.3 Further tests * 4 Pathogenesis * 5 Treatment * 6 Prognosis * 7 Epidemiology * 8 History * 9 Notable cases * 10 References * 11 External links ## Signs and symptoms[edit] Nine in ten people with sinus thrombosis have a headache; this tends to worsen over the period of several days, but may also develop suddenly (thunderclap headache).[2] The headache may be the only symptom of cerebral venous sinus thrombosis.[3] Many patients have symptoms of stroke: inability to move one or more limbs, weakness on one side of the face or difficulty speaking. This does not necessarily affect one side of the body as in the more common "arterial" stroke.[2] 40% of people have seizures, although it is more common in women who develop sinus thrombosis peripartum (in the period before and after giving birth).[4] These are mostly seizures affecting only one part of the body and unilateral (occurring on one side), but occasionally the seizures are generalised and rarely they lead to status epilepticus (persistent or recurrent seizure activity for a long period of time).[2] In the elderly, many of the aforementioned symptoms may not occur. Common symptoms in the elderly with this condition are otherwise unexplained changes in mental status and a depressed level of consciousness.[5] The pressure around the brain may rise, causing papilledema (swelling of the optic disc) which may be experienced as visual obscurations. In severely raised intracranial pressure, the level of consciousness is decreased, the blood pressure rises, the heart rate falls and the patient assumes an abnormal posture.[2] ## Causes[edit] Cerebral venous sinus thrombosis is more common in particular situations. 85% of people have at least one of these risk factors:[2] * Thrombophilia, a tendency to develop blood clots due to abnormalities in coagulation, e.g. factor V Leiden, deficiency of protein C, protein S or antithrombin, or related problems * Nephrotic syndrome, a kidney problem causing protein loss in the urine * Chronic inflammatory diseases, such as inflammatory bowel disease, lupus and Behçet's disease * Pregnancy and puerperium (the period after giving birth) * Particular blood disorders, especially polycythemia vera and paroxysmal nocturnal hemoglobinuria * Use of estrogen-containing forms of hormonal contraception * Meningitis and infections of the ear, nose and throat area such as mastoiditis and sinusitis * Direct injury to the venous sinuses * Medical procedures in the head and neck area * Sickle cell anemia * Dehydration, primarily in infants and children * Homocystinuria ## Diagnosis[edit] The diagnosis may be suspected on the basis of the symptoms, for example the combination of headache, signs of raised intracranial pressure and focal neurological abnormalities, or when alternative causes of headache and neurological abnormalities, such as a subarachnoid hemorrhage, have been excluded.[2] ### Imaging[edit] CT venogram showing a filling defect in the sagittal sinus (black arrow) A dural venous sinus thrombosis of the transverse sinus. Greater on the right than left. There are various neuroimaging investigations that may detect cerebral sinus thrombosis. Cerebral edema and venous infarction may be apparent on any modality, but for the detection of the thrombus itself, the most commonly used tests are computed tomography (CT) and magnetic resonance imaging (MRI), both using various types of radiocontrast to perform a venogram and visualise the veins around the brain.[2] Computed tomography, with radiocontrast in the venous phase (CT venography or CTV), has a detection rate that in some regards exceeds that of MRI. The test involves injection into a vein (usually in the arm) of a radioopaque substance, and time is allowed for the bloodstream to carry it to the cerebral veins - at which point the scan is performed. It has a sensitivity of 75-100% (it detects 75-100% of all clots present), and a specificity of 81-100% (it would be incorrectly positive in 0-19%). In the first two weeks, the "empty delta sign" may be observed (in later stages, this sign may disappear).[6] Magnetic resonance venography employs the same principles, but uses MRI as a scanning modality. MRI has the advantage of being better at detecting damage to the brain itself as a result of the increased pressure on the obstructed veins, but it is not readily available in many hospitals and the interpretation may be difficult.[6] Cerebral angiography may demonstrate smaller clots than CT or MRI, and obstructed veins may give the "corkscrew appearance".[2] This, however, requires puncture of the femoral artery with a sheath and advancing a thin tube through the blood vessels to the brain where radiocontrast is injected before X-ray images are obtained. It is therefore only performed if all other tests give unclear results or when other treatments may be administered during the same procedure. ### D-dimer[edit] There is an association between the D-dimer blood test and cerebral venous sinus thrombosis.[7] This association however is not strong enough to rule out the diagnosis alone.[7] ### Further tests[edit] In most patients, the direct cause for the cerebral sinus thrombosis is not readily apparent. Identifying a source of infection is crucial; it is common practice to screen for various forms of thrombophilia (a propensity to form blood clots).[2] ## Pathogenesis[edit] The veins of the brain, both the superficial veins and the deep venous system, empty into the dural venous sinuses, which carry blood back to the jugular vein and thence to the heart. In cerebral venous sinus thrombosis, blood clots usually form both in the veins of the brain and the venous sinuses. The thrombosis of the veins themselves causes venous infarction—damage to brain tissue due to a congested and therefore insufficient blood supply. This results in cerebral edema (both vasogenic and cytotoxic edema), and leads to small petechial haemorrhages that may merge into large haematomas. Thrombosis of the sinuses is the main mechanism behind the increase in intracranial pressure due to decreased resorption of cerebrospinal fluid (CSF). The condition does not lead to hydrocephalus, however, because there is no difference in pressure between various parts of the brain.[2] Any blood clot forms due to an imbalance between coagulation (the formation of the insoluble blood protein fibrin) and fibrinolysis. The three major mechanisms for such an imbalance are enumerated in Virchow's triad: alterations in normal blood flow, injury to the blood vessel wall, and alterations in the constitution of blood (hypercoagulability). Most cases of cerebral venous sinus thrombosis are due to hypercoagulability.[2] It is possible for the clot to break off and migrate (embolise) to the lungs, causing a pulmonary embolism.[2][4] An analysis of earlier case reports concludes that this occurs in about 10% of cases, but has a very poor prognosis.[8] ## Treatment[edit] Various studies have investigated the use of anticoagulation to suppress blood clot formation in cerebral venous sinus thrombosis. Before these trials had been conducted, there had been a concern that small areas of hemorrhage in the brain would bleed further as a result of treatment; the studies showed that this concern was unfounded.[9] Clinical practice guidelines now recommend heparin or low molecular weight heparin in the initial treatment, followed by warfarin, provided there are no other bleeding risks that would make these treatments unsuitable.[4][10][11] Some experts discourage the use of anticoagulation if there is extensive hemorrhage; in that case, they recommend repeating the imaging after 7–10 days. If the hemorrhage has decreased in size, anticoagulants are started, while no anticoagulants are given if there is no reduction.[12] The duration of warfarin treatment depends on the circumstances and underlying causes of the condition. If the thrombosis developed under temporary circumstances (e.g. pregnancy), three months are regarded as sufficient. If the condition was unprovoked but there are no clear causes or a "mild" form of thrombophilia, 6 to 12 months is advised. If there is a severe underlying thrombosis disorder, warfarin treatment may need to continue indefinitely.[4] Thrombolysis (removal of the blood clot with "clot buster" medication) has been described, either systemically by injection into a vein or directly into the clot during angiography. The 2006 European Federation of Neurological Societies guideline recommends that thrombolysis is only used in patients who deteriorate despite adequate treatment, and other causes of deterioration have been eliminated. It is unclear which drug and which mode of administration is the most effective. Bleeding into the brain and in other sites of the body is a major concern in the use of thrombolysis.[4] American guidelines make no recommendation with regards to thrombolysis, stating that more research is needed.[11] In those where a venous infarct or hemorrhage causes significant compression of surrounding brain structures, decompressive craniectomy is sometimes required.[13] Raised intracranial pressure, if severe or threatening vision, may require therapeutic lumbar puncture (removal of excessive cerebrospinal fluid), medication (acetazolamide), or neurosurgical treatment (optic nerve sheath fenestration or shunting).[2] In certain situations, anticonvulsants may be used to try to prevent seizures.[4] These situations include focal neurological problems (e.g. inability to move a limb) and focal changes of the brain tissue on CT or MRI scan.[4] Evidence to support or refute the use of antiepileptic drugs as a preventive measure, however, is lacking.[14] ## Prognosis[edit] In 2004 the first adequately large scale study on the natural history and long-term prognosis of this condition was reported; this showed that at 16 months follow-up 57.1% of patients had full recovery, 29.5%/2.9%/2.2% had respectively minor/moderate/severe symptoms or impairments, and 8.3% had died. Severe impairment or death were more likely in those aged over 37 years, male, affected by coma, mental status disorder, intracerebral hemorrhage, thrombosis of the deep cerebral venous system, central nervous system infection and cancer.[15] A subsequent systematic review of nineteen studies in 2006 showed that mortality is about 5.6% during hospitalisation and 9.4% in total, while of the survivors 88% make a total or near-total recovery. After several months, two thirds of the cases has resolution ("recanalisation") of the clot. The rate of recurrence was low (2.8%).[16] In children with CVST the risk of death is high.[17] Poor outcome is more likely if a child with CVST develops seizures or has evidence of venous infarction on imaging.[18] ## Epidemiology[edit] Cerebral venous sinus thrombosis is rare, with an estimated 3-4 cases per million annual incidence in adults. While it may occur in all age groups, it is most common in the third decade. 75% are female.[4] Given that older studies show no difference in incidence between men and women, it has been suggested that the use of oral contraceptives in women is behind the disparity between the sexes.[2] A 1995 report from Saudi Arabia found a doubled incidence at 7 cases per 100,000; this was attributed to the fact that Behçet's disease, which increases risk of CVST, is more common in the Middle East.[19] A 1973 report found that CVST could be found on autopsy (examination of the body after death) in nine percent of all people. Many of these were elderly and had neurological symptoms in the period leading up to their death, and many suffered from concomitant heart failure.[20] In children, a Canadian study reported in 2001 that CVST occurs in 6.7 per million annually. 43% occur in the newborn (less than one month old), and a further 10% in the first year of life. Of the newborn, 84% were already ill, mostly from complications after childbirth and dehydration.[18] ## History[edit] The first description of thrombosis of the cerebral veins and sinuses is attributed to the French physician Ribes, who in 1825 observed thrombosis of the sagittal sinus and cerebral veins in a man who had suffered from seizures and delirium.[21] Until the second half of the 20th century it remained a diagnosis generally made after death.[22] In the 1940s, reports by Dr Charles Symonds and others allowed for the clinical diagnosis of cerebral venous thrombosis, using characteristic signs and symptoms and results of lumbar puncture.[23][24] Improvements on the diagnosis of cerebral venous sinus thrombosis in life were made with the introduction of venography in 1951,[25] which also aided in the distinction from idiopathic intracranial hypertension,[26] which has similar presenting signs and symptoms in many cases.[22] The British gynecologist Stansfield is credited with the introduction, in 1942, of the just recently introduced anticoagulant heparin in the treatment of CVST in 1942.[22][24] Clinical trials in the 1990s finally resolved the concern about using anticoagulants in most cases of CVST.[4] ## Notable cases[edit] U.S. Secretary of State Hillary Clinton was hospitalized on December 30, 2012, for anticoagulation treatment of venous thrombosis of the right transverse sinus, which is located at the base of the brain. Clinton's thrombotic episode was discovered on an MRI scan done for follow-up of a cerebral concussion she had suffered 2.5 weeks before after she fell while suffering from gastroenteritis.[27] ## References[edit] 1. ^ a b Al Rawahi, B; Almegren, M; Carrier, M (September 2018). "The efficacy and safety of anticoagulation in cerebral vein thrombosis: A systematic review and meta-analysis". Thrombosis Research. 169: 135–139. doi:10.1016/j.thromres.2018.07.023. PMID 30056293. 2. ^ a b c d e f g h i j k l m n o p Stam J (2005). "Thrombosis of the cerebral veins and sinuses". N. Engl. J. Med. 352 (17): 1791–8. doi:10.1056/NEJMra042354. PMID 15858188. 3. ^ Cumurciuc R, Crassard I, Sarov M, Valade D, Bousser MG (2005). "Headache as the only neurological sign of cerebral venous thrombosis: a series of 17 cases". J. Neurol. Neurosurg. Psychiatry. 76 (8): 1084–7. doi:10.1136/jnnp.2004.056275. PMC 1739763. PMID 16024884. 4. ^ a b c d e f g h i Einhäupl K, Bousser MG, de Bruijn SF, et al. (2006). "EFNS guideline on the treatment of cerebral venous and sinus thrombosis". Eur. J. Neurol. 13 (6): 553–9. doi:10.1111/j.1468-1331.2006.01398.x. PMID 16796579. 5. ^ Ferro JM, Canhão P, Bousser MG, Stam J, Barinagarrementeria F (2005). "Cerebral vein and dural sinus thrombosis in elderly patients". Stroke. 36 (9): 1927–32. doi:10.1161/01.STR.0000177894.05495.54. PMID 16100024. 6. ^ a b Smith R, Hourihan MD (2007). "Investigating suspected cerebral venous thrombosis". BMJ. 334 (7597): 794–5. doi:10.1136/bmj.39154.636968.47. PMC 1852020. PMID 17431266. 7. ^ a b Smith, E; Kumar, V (June 2018). "BET 1: Does a normal D-dimer rule out cerebral venous sinus thrombosis (CVST)?". Emergency Medicine Journal. 35 (6): 396–397. doi:10.1136/emermed-2018-207777.1. PMID 29784833. 8. ^ Diaz JM, Schiffman JS, Urban ES, Maccario M (1992). "Superior sagittal sinus thrombosis and pulmonary embolism: a syndrome rediscovered". Acta Neurol. Scand. 86 (4): 390–6. doi:10.1111/j.1600-0404.1992.tb05106.x. PMID 1455986. 9. ^ Coutinho, Jonathan; de Bruijn, Sebastiaan Ftm; Deveber, Gabrielle; Stam, Jan (10 August 2011). "Anticoagulation for cerebral venous sinus thrombosis". Cochrane Database of Systematic Reviews (8): CD002005. doi:10.1002/14651858.CD002005.pub2. ISSN 1469-493X. PMC 7065450. PMID 21833941. 10. ^ National Institute for Health and Clinical Excellence. Clinical guideline 68: Stroke. London, 2008. 11. ^ a b Kernan, Walter N.; Ovbiagele, Bruce; Black, Henry R.; Bravata, Dawn M.; Chimowitz, Marc I.; Ezekowitz, Michael D.; Fang, Margaret C.; Fisher, Marc; Furie, Karen L.; Heck, Donald V.; Johnston, S. Claiborne (Clay); Kasner, Scott E.; Kittner, Steven J.; Mitchell, Pamela H.; Rich, Michael W.; Richardson, DeJuran; Schwamm, Lee H.; Wilson, John A. (July 2014). "Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack". Stroke. 45 (7): 2160–2236. doi:10.1161/STR.0000000000000024. 12. ^ Martinelli I, Franchini M, Mannucci PM (September 2008). "How I treat rare venous thromboses". Blood. 112 (13): 4818–23. doi:10.1182/blood-2008-07-165969. PMID 18805965. 13. ^ Avanali, Raghunath; Gopalakrishnan, M. S.; Devi, B. Indira; Bhat, Dhananjaya I.; Shukla, Dhaval P.; Shanbhag, Nagesh C. (15 May 2019). "Role of Decompressive Craniectomy in the Management of Cerebral Venous Sinus Thrombosis". Frontiers in Neurology. 10: 511. doi:10.3389/fneur.2019.00511. PMC 6529953. PMID 31156540. 14. ^ Price, Michelle; Günther, Albrecht; Kwan, Joseph SK (21 April 2016). "Antiepileptic drugs for the primary and secondary prevention of seizures after intracranial venous thrombosis". Cochrane Database of Systematic Reviews. 4: CD005501. doi:10.1002/14651858.cd005501.pub4. hdl:10722/226344. PMID 27098266. 15. ^ Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F (2004). "Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT)". Stroke. 35 (3): 664–70. doi:10.1161/01.STR.0000117571.76197.26. PMID 14976332. 16. ^ Dentali F, Gianni M, Crowther MA, Ageno W (2006). "Natural history of cerebral vein thrombosis: a systematic review". Blood. 108 (4): 1129–34. doi:10.1182/blood-2005-12-4795. PMID 16609071. 17. ^ Jackson, BF; Porcher, FK; Zapton, DT; Losek, JD (September 2011). "Cerebral sinovenous thrombosis in children: diagnosis and treatment". Pediatr. Emerg. Care. 27 (9): 874–80, quiz 881–3. doi:10.1097/PEC.0b013e31822c9ccc. PMID 21926891. 18. ^ a b deVeber G, Andrew M, Adams C, et al. (August 2001). "Cerebral sinovenous thrombosis in children". N. Engl. J. Med. 345 (6): 417–23. doi:10.1056/NEJM200108093450604. PMID 11496852. 19. ^ Daif A, Awada A, al-Rajeh S, et al. (1 July 1995). "Cerebral venous thrombosis in adults. A study of 40 cases from Saudi Arabia". Stroke. 26 (7): 1193–5. doi:10.1161/01.str.26.7.1193. PMID 7604412. 20. ^ Towbin A (1 May 1973). "The syndrome of latent cerebral venous thrombosis: its frequency and relation to age and congestive heart failure". Stroke. 4 (3): 419–30. doi:10.1161/01.str.4.3.419. PMID 4713031. 21. ^ Ribes MF (1825). "Des recherches faites sur la phlebite". Rev. Med. Fr. Etrang. 3: 5–41. 22. ^ a b c Bousser MG, Chiras J, Bories J, Castaigne P (1 March 1985). "Cerebral venous thrombosis--a review of 38 cases". Stroke. 16 (2): 199–213. doi:10.1161/01.str.16.2.199. PMID 3975957. 23. ^ Symonds CP (September 1940). "Cerebral thrombophlebitis". Br. Med. J. 2 (4158): 348–52. doi:10.1136/bmj.2.4158.348. PMC 2179068. PMID 20783290. 24. ^ a b Stansfield FR (April 1942). "Puerperal cerebral thrombophlebitis treated by heparin". Br. Med. J. 1 (4239): 436–438. doi:10.1136/bmj.1.4239.436. PMC 2164893. PMID 20784169. 25. ^ Ray BS, Dunbar HS, Dotter CT (January 1951). "Dural sinus venography as an aid to diagnosis in intracranial disease". J. Neurosurg. 8 (1): 23–37. doi:10.3171/jns.1951.8.1.0023. PMID 14804146. 26. ^ Ray BS, Dunbar HS (September 1951). "Thrombosis of the dural venous sinuses as a cause of pseudotumor cerebri". Ann. Surg. 134 (3): 376–86. doi:10.1097/00000658-195113430-00009. PMC 1802934. PMID 14869026. 27. ^ Paul Richter. "Hillary Clinton expected to make full recovery from blood clot". Los Angeles Times. Retrieved 1 January 2013. ## External links[edit] Classification D * ICD-10: G08, I63.6, I67.6 * ICD-9-CM: 325, 437.6 * MeSH: D012851 * DiseasesDB: 2242 External resources * eMedicine: neuro/642 radio/105 Wikimedia Commons has media related to Cerebral venous sinus thrombosis. * "Intracranial venous thrombosis - Patient UK". * UCH Institute for Child Health. "Clinical guideline Cerebral Venous Sinus Thrombosis in Children". Archived from the original on 2 February 2009. Retrieved 28 October 2007. * v * t * e Cerebrovascular diseases including stroke Ischaemic stroke Brain * Anterior cerebral artery syndrome * Middle cerebral artery syndrome * Posterior cerebral artery syndrome * Amaurosis fugax * Moyamoya disease * Dejerine–Roussy syndrome * Watershed stroke * Lacunar stroke Brain stem * Brainstem stroke syndrome * Medulla * Medial medullary syndrome * Lateral medullary syndrome * Pons * Medial pontine syndrome / Foville's * Lateral pontine syndrome / Millard-Gubler * Midbrain * Weber's syndrome * Benedikt syndrome * Claude's syndrome Cerebellum * Cerebellar stroke syndrome Extracranial arteries * Carotid artery stenosis * precerebral * Anterior spinal artery syndrome * Vertebrobasilar insufficiency * Subclavian steal syndrome Classification * Brain ischemia * Cerebral infarction * Classification * Transient ischemic attack * Total anterior circulation infarct * Partial anterior circulation infarct Other * CADASIL * Binswanger's disease * Transient global amnesia Haemorrhagic stroke Extra-axial * Epidural * Subdural * Subarachnoid Cerebral/Intra-axial * Intraventricular Brainstem * Duret haemorrhages General * Intracranial hemorrhage Aneurysm * Intracranial aneurysm * Charcot–Bouchard aneurysm Other * Cerebral vasculitis * Cerebral venous sinus thrombosis * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Cerebral venous sinus thrombosis	c0037198	29,025	wikipedia	https://en.wikipedia.org/wiki/Cerebral_venous_sinus_thrombosis	2021-01-18T18:45:05	{"mesh": ["D012851"], "umls": ["C0037198"], "icd-9": ["437.6", "325"], "icd-10": ["I67.6", "I63.6"], "wikidata": ["Q1428132"]}
Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which the body cannot properly regulate the number of immune system cells (lymphocytes). ALPS is characterized by the production of an abnormally large number of lymphocytes (lymphoproliferation). Accumulation of excess lymphocytes results in enlargement of the lymph nodes (lymphadenopathy), the liver (hepatomegaly), and the spleen (splenomegaly). Autoimmune disorders are also common in ALPS. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Most of the autoimmune disorders associated with ALPS target and damage blood cells. For example, the immune system may attack red blood cells (autoimmune hemolytic anemia), white blood cells (autoimmune neutropenia), or platelets (autoimmune thrombocytopenia). Less commonly, autoimmune disorders that affect other organs and tissues occur in people with ALPS. These disorders can damage the kidneys (glomerulonephritis), liver (autoimmune hepatitis), eyes (uveitis), or nerves (Guillain-Barre syndrome). Skin problems, usually rashes or hives (urticaria), can also occur in ALPS. ALPS can have varying patterns of signs and symptoms. Most commonly, lymphoproliferation becomes apparent during childhood. Enlargement of the lymph nodes and spleen frequently occur in affected individuals. Autoimmune disorders typically develop several years later, most frequently as a combination of hemolytic anemia and thrombocytopenia, also called Evans syndrome. People with this classic form of ALPS generally have a near-normal lifespan, but have a greatly increased risk of developing cancer of the immune system cells (lymphoma) compared with the general population. Some people have signs and symptoms that resemble those of ALPS, including lymphoproliferation, lymphadenopathy, splenomegaly, and low blood counts, but the specific pattern of these signs and symptoms or the genetic cause may be different. Researchers disagree whether individuals with these non-classic forms should be considered to have ALPS or a separate condition. ## Frequency ALPS is a rare disorder; its prevalence is unknown. ## Causes Mutations in the FAS gene cause ALPS in approximately 75 percent of affected individuals; these mutations are associated with the classic form of the disorder. The FAS gene provides instructions for making a protein involved in cell signaling that results in the self-destruction of cells (apoptosis). When the immune system is turned on (activated) to fight an infection, large numbers of lymphocytes are produced. Normally, these lymphocytes undergo apoptosis when they are no longer required. FAS gene mutations lead to an abnormal protein that interferes with apoptosis. As a result, excess lymphocytes accumulate in the body's tissues and organs and often begin attacking them, leading to autoimmune disorders. Interference with apoptosis allows cells to multiply without control, leading to the lymphomas that often occur in people with this disorder. Non-classic forms of ALPS may be caused by mutations in additional genes, some of which have not been identified. ### Learn more about the genes associated with Autoimmune lymphoproliferative syndrome * FAS * KRAS * MAGT1 * NRAS * PIK3CD * STAT3 Additional Information from NCBI Gene: * CASP10 * CTLA4 * FASLG ## Inheritance Pattern In most people with ALPS, including the majority of those with FAS gene mutations, this condition is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In these cases, an affected person usually inherits the mutation from one affected parent. Other cases with an autosomal dominant pattern result from new (de novo) gene mutations that occur early in embryonic development in people with no history of the disorder in their family. In a small number of cases, including some cases caused by FAS gene mutations, ALPS is inherited in an autosomal recessive pattern, which means both copies of a 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. ALPS can also arise from a mutation in lymphocytes that is not inherited but instead occurs during an individual's lifetime. This alteration is called a somatic mutation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autoimmune lymphoproliferative syndrome	c1328840	29,026	medlineplus	https://medlineplus.gov/genetics/condition/autoimmune-lymphoproliferative-syndrome/	2021-01-27T08:25:23	{"gard": ["8686"], "mesh": ["D056735"], "omim": ["601859"], "synonyms": []}
A rare acute leukemia of ambiguous lineage characterized by clonal proliferation of primitive hematopoietic cells, primarily in the bone marrow and blood, lacking lineage-specific markers and detectable genotypic alterations. The patients present with leukocytosis, anemia, variable platelet count and a variety of nonspecific symptoms related to ineffective hematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (lymphadenopathy, splenomegaly, hepatomegaly). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Acute undifferentiated leukemia	c0280141	29,027	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98835	2021-01-23T18:33:05	{"omim": ["601626"], "umls": ["C0280141", "C0856823"], "icd-10": ["C95.0"], "synonyms": ["Acute myeloid leukemia, minimal differentiation, FAB M0"]}
In 2 female fetuses born of first-cousin Pakistani parents, Thakker and Donnai (1991) described a syndrome of facial dysmorphism and multiple anomalies. The first fetus was delivered after therapeutic termination at 26 weeks' gestation for multiple structural abnormalities identified on ultrasound scanning. The palpebral fissures were long, downward slanting and widely separated; the nose was short and bulbous tipped; the mouth was small with downturned corners; and the neck was short and webbed. Autopsy showed dilatation of the ventricular system, Klippel-Feil anomaly, transposition of the great vessels with ventricular septal defect, and very short esophagus with intrathoracic stomach, small intestine, spleen, and pancreas. The umbilical cord had 4 vessels. The second affected sib was liveborn at 36 weeks' gestation. She had identical facial features, anal atresia associated with rectovaginal fistula, hemivertebra, agenesis of the corpus callosum, and tetralogy of Fallot. She died at age 53 days. Necropsy limited to a muscle biopsy showed uniform muscle atrophy compatible with a neurogenic origin. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation HEAD & NECK Ears \- Long ears \- Posteriorly rotated ears Eyes \- Hypertelorism \- Long palpebral fissures \- Downslanting palpebral fissures Nose \- Broad nasal bridge \- Short nose \- Bulbous nasal tip Mouth \- Small mouth \- Downturned corners of mouth Neck \- Short, webbed neck \- Low posterior hairline CARDIOVASCULAR Heart \- Transposition of the great vessels \- Ventricular septal defect \- Tetralogy of Fallot ABDOMEN Gastrointestinal \- Short esophagus \- Intrathoracic stomach \- Anal atresia \- Rectovaginal fistula GENITOURINARY Internal Genitalia (Female) \- Rectovaginal fistula Kidneys \- Hydronephrosis SKELETAL Spine \- Klippel-Feil anomaly \- Hemivertebrae SKIN, NAILS, & HAIR Hair \- Low posterior hairline NEUROLOGIC Central Nervous System \- Hydrocephalus \- Agenesis of corpus callosum \- Hypotonia PRENATAL MANIFESTATIONS Placenta & Umbilical Cord \- Four vessel umbilical cord ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	FACIAL DYSMORPHISM WITH MULTIPLE MALFORMATIONS	c2931219	29,028	omim	https://www.omim.org/entry/227255	2019-09-22T16:28:01	{"mesh": ["C536503"], "omim": ["227255"], "orphanet": ["1780"]}
CANOMAD syndrome is a rare chronic immune-mediated demyelinating polyneuropathy. CANOMAD stands for Chronic Ataxic Neuropathy Ophthalmoplegia IgM paraprotein Cold Agglutinins Disialosyl antibodies. Signs and symptoms of CANOMAD may include loss of muscle, tendon, and joint sensation, abnormal gait (walk), ataxia, tingling sensation on the skin around the mouth or extremities, paralysis of eye muscles, difficulty swallowing and speaking, and rarely respiratory muscle weakness. This condition is caused by the presence of anti-diasialosyl antibodies in the body. Oral or intravenous corticosteroids, ß-interferons, plasma exchange, intravenous immunoglobulin (IVIG), and cytotoxic drugs have all been used in treating CANOMAD with varying success. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CANOMAD syndrome	c2931684	29,029	gard	https://rarediseases.info.nih.gov/diseases/9778/canomad-syndrome	2021-01-18T18:01:38	{"mesh": ["C537980"], "umls": ["C2931684"], "orphanet": ["71279"], "synonyms": ["Chronic Ataxic Neuropathy Ophthalmoplegia M-protein Agglutination Disialosyl antibodies syndrome", "Chronic sensory ataxic neuropathy with anti-disialosyl antibodies"]}
Fear of spiders and other arachnids This article is about the specific phobia. For other uses, see Arachnophobia (disambiguation). Arachnophobia Other namesArachnephobia[1] Though many arachnids are harmless, a person with arachnophobia may still panic or feel uneasy around one. Sometimes, even an object resembling a spider can trigger a panic attack in an arachnophobic individual. The above cartoon is a depiction of the nursery rhyme "Little Miss Muffet", in which the title character is "frightened away" by a spider. Pronunciation * /əˌræknəˈfoʊbiə/ SpecialtyPsychiatry TreatmentExposure therapy[2] Arachnophobia is an intense and irrational fear of spiders and other arachnids such as scorpions.[3] Treatment is typically by exposure therapy, where the person is presented with pictures of spiders or the spiders themselves.[2] ## Contents * 1 Signs and symptoms * 2 Reasons * 2.1 Evolutionary * 2.2 Cultural * 3 Treatments * 4 Epidemiology * 5 See also * 6 References * 7 External links ## Signs and symptoms[edit] People with arachnophobia tend to feel uneasy in any area they believe could harbour spiders or that has visible signs of their presence, such as webs. If arachnophobes see a spider, they may not enter the general vicinity until they have overcome the panic attack that is often associated with their phobia. Some people run away, scream, cry, have emotional outbursts, experience trouble breathing, sweat, have increased heart rates, or even faint when they come in contact with an area near spiders or their webs. In some extreme cases, even a picture or a realistic drawing of a spider can trigger intense fear. ## Reasons[edit] Arachnophobia may be an exaggerated form of an instinctive response that helped early humans to survive[4] or a cultural phenomenon that is most common in predominantly European societies.[5] ### Evolutionary[edit] An evolutionary reason for the phobia remains unresolved. One view, especially held in evolutionary psychology, is that the presence of venomous spiders led to the evolution of a fear of spiders, or made acquisition of a fear of spiders especially easy. Like all traits, there is variability in the intensity of fear of spiders, and those with more intense fears are classified as phobic. Being relatively small, spiders do not fit the usual criterion for a threat in the animal kingdom where size is a factor, but they can have medically significant venom and/or cause skin irritation with their setae. [6] However, a phobia is an irrational fear as opposed to a rational fear.[7] By ensuring that their surroundings were free from spiders, arachnophobes would have had a reduced risk of being bitten in ancestral environments, giving them a slight advantage over non-arachnophobes in terms of survival. However, having a disproportionate fear of spiders in comparison to other, potentially dangerous creatures[8] present during Homo sapiens' environment of evolutionary adaptiveness may have had drawbacks.[citation needed] In The Handbook of the Emotions (1993), psychologist Arne Öhman studied pairing an unconditioned stimulus with evolutionarily-relevant fear-response neutral stimuli (snakes and spiders) versus evolutionarily-irrelevant fear-response neutral stimuli (mushrooms, flowers, and physical representation of polyhedra) on human subjects and found that ophidiophobia and arachnophobia required only one pairing to develop a conditioned response while mycophobia, anthophobia, and phobias of physical representations of polyhedra required multiple pairings and went extinct without continued conditioning while the conditioned ophidiophobia and arachnophobia were permanent.[9] Psychiatrists Isaac Marks and Randolph M. Nesse and evolutionary biologist George C. Williams have noted that people with systematically deficient responses to various adaptive phobias (e.g. arachnophobia, ophidiophobia, basophobia) are more temperamentally careless and more likely to end up in potentially fatal accidents and have proposed that such deficient phobia should be classified as "hypophobia" due to its selfish genetic consequences.[10][11][12] A 2001 study found that people could detect images of spiders among images of flowers and mushrooms more quickly than they could detect images of flowers or mushrooms among images of spiders. The researchers suggested that this was because fast response to spiders was more relevant to human evolution.[13] ### Cultural[edit] An alternative view is that the dangers, such as from spiders, are overrated and not sufficient to influence evolution.[attribution needed] Instead, inheriting phobias would have restrictive and debilitating effects upon survival, rather than being an aid. For some communities such as in Papua New Guinea and Cambodia spiders are included in traditional foods. This suggests arachnophobia may be a cultural, rather than genetic trait.[14][15] ## Treatments[edit] The fear of spiders can be treated by any of the general techniques suggested for specific phobias. The first line of treatment is systematic desensitization – also known as exposure therapy.[2] Before engaging in systematic desensitization, it is common to train the individual with arachnophobia in relaxation techniques, which will help keep the patient calm. Systematic desensitization can be done in vivo (with live spiders) or by getting the individual to imagine situations involving spiders, then modelling interaction with spiders for the person affected and eventually interacting with real spiders. This technique can be effective in just one session, although it generally takes more time.[16] Recent advances in technology have enabled the use of virtual or augmented reality spiders for use in therapy. These techniques have proven to be effective.[17] It has been suggested that exposure to short clips from the Spider-Man movies may help to reduce an individual's arachnophobia.[18] ## Epidemiology[edit] Arachnophobia affects 3.5 to 6.1 percent of the global population.[19] ## See also[edit] * Arachnophobia (film) * Apiphobia (fear of bees) * Entomophobia (fear of insects) * Myrmecophobia (fear of ants) * Zoophobia (fear of animals) ## References[edit] 1. ^ Patricia Bowen (ed.), Internal Medicine Words, Rayve Productions, 1997, p. 18. 2. ^ a b c Sperry, Len (2015). Mental Health and Mental Disorders: An Encyclopedia of Conditions, Treatments, and Well-Being [3 volumes]: An Encyclopedia of Conditions, Treatments, and Well-Being. ABC-CLIO. p. 430. ISBN 9781440803833. 3. ^ Heather Hatfield. "The Fear Factor: Phobias". Webmd.com 4. ^ Friedenberg, J.; Silverman, G. (2005). Cognitive Science: An Introduction to the Study of Mind. SAGE. pp. 244–245. ISBN 1-4129-2568-1. Retrieved 2008-10-11. 5. ^ Davey, G.C.L. (1994). "The "Disgusting" Spider: The Role of Disease and Illness in the Perpetuation of Fear of Spiders". Society and Animals. 2 (1): 17–25. doi:10.1163/156853094X00045. 6. ^ Isbister, Geoffrey; White, Julian (April 2004). "Clinical consequences of spider bites: recent advances in our understanding". Toxicon. 43 (5): 477–92. doi:10.1016/j.toxicon.2004.02.002. PMID 15066408. Retrieved 7 December 2020. 7. ^ https://www.webmd.com/anxiety-panic/features/fear-factor-phobias#1 8. ^ Gerdes, Antje B.M.; Uhl, Gabriele; Alpers, Georg W. (2009). "Spiders are special: fear and disgust evoked by pictures of arthropods" (PDF). Evolution and Human Behavior. 30: 66–73. doi:10.1016/j.evolhumbehav.2008.08.005. 9. ^ Öhman, Arne (1993). "Fear and anxiety as emotional phenomena: Clinical phenomenology, evolutionary perspectives, and information-processing mechanisms". In Lewis, Michael; Haviland, Jeannette M. (eds.). The Handbook of the Emotions (1st ed.). New York: Guilford Press. pp. 511–536. ISBN 978-0898629880. 10. ^ Nesse, Randolph; Williams, George C. (1994). Why We Get Sick: The New Science of Darwinian Medicine. New York: Vintage Books. pp. 212–214. ISBN 978-0679746744. 11. ^ Nesse, Randolph M. (2005). "32. Evolutionary Psychology and Mental Health". In Buss, David M. (ed.). The Handbook of Evolutionary Psychology (1st ed.). Hoboken, NJ: Wiley. pp. 911–913. ISBN 978-0471264033. 12. ^ Nesse, Randolph (2019). Good Reasons for Bad Feelings: Insights from the Frontier of Evolutionary Psychiatry. Dutton. pp. 64–76. ISBN 978-1101985663. 13. ^ Öhman, A., Flykt, A., & Esteves, F. (2001). "Emotion drives attention: Detecting the snake in the grass". Journal of Experimental Psychology: 130 (3), 466–478. 14. ^ Wagener, Alexandra L.; Zettle, Robert D. (2011). "Targeting Fear of Spiders With Control-, Acceptance-, and Information-Based Approaches" (PDF). The Psychological Record. 61 (1): 77–91. doi:10.1007/BF03395747. S2CID 44385538. Archived from the original (PDF) on 2011-06-14. 15. ^ Ohman, A; Mineka, S (2001). "Fears, Phobias, and Preparedness: Toward an Evolved Module of Fear and Fear Learning" (PDF). Psychological Review. 108 (3): 483–522. doi:10.1037/0033-295X.108.3.483. PMID 11488376. 16. ^ Ost, L. G. (1989). "One-session treatment for specific phobias". Behaviour Research and Therapy. 27 (1): 1–7. doi:10.1016/0005-7967(89)90113-7. PMID 2914000. 17. ^ Bouchard, S.; Côté, S.; St-Jacques, J.; Robillard, G.; Renaud, P. (2006). "Effectiveness of virtual reality exposure in the treatment of arachnophobia using 3D games". Technology and Healthcare. 14 (1): 19–27. 18. ^ Gabe Friedman (April 25, 2019). "Israeli Researchers: "Spider Man" movies decrease Spider Phobia". Arutz Sheva. Retrieved April 25, 2019. 19. ^ Schmitt, WJ; Müri, RM (2009). "Neurobiologie der Spinnenphobie". Schweizer Archiv für Neurologie. 160 (8): 352–355. Archived from the original on 23 August 2016. ## External links[edit] Classification D * ICD-10: F40.2 * Stiemerling, D. (1973). "Analysis of a spider and monster phobia". Z Psychosom Med Psychoanal (in German). 19 (4): 327–45. PMID 4129447. * National Geographic: "Fear of Snakes, Spiders Rooted in Evolution, Study Finds" * v * t * e Spiders Arachnology * Ballooning * Behavior * Cannibalism * Evolution * Classification * Glossary Taxonomy * Araneomorphae * Mesothelae * Mygalomorphae * Opisthothelae * List of families of spiders * Lists of spider species Anatomy * Arthropod leg * Book lung * Calamistrum * Cephalothorax * Chelicerae * Cheliceral fang * Cribellum * Epigyne * Exuviae * Opisthosoma * Pedipalp * Palpal bulb * Scopulae * Silk * Spinneret * Urticating hair Human interaction * Arachnophobia * Cultural depictions * Spider bite * Spider fighting Webs * Spider web * Web decorations * Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Arachnophobia	c0392331	29,030	wikipedia	https://en.wikipedia.org/wiki/Arachnophobia	2021-01-18T18:52:06	{"icd-10": ["F40.2"], "wikidata": ["Q220783"]}
Not to be confused with Systemic vasculitides. Necrotizing vasculitus SpecialtyRheumatology Necrotizing vasculitis, also called systemic necrotizing vasculitus (SNV),[1] is a category of vasculitis,[2] comprising vasculitides that present with necrosis.[3] Examples include giant cell arteritis,[4] microscopic polyangiitis, and granulomatosis with polyangiitis. ICD-10 uses the variant "necrotizing vasculopathy". ICD-9, while classifying these conditions together, does not use a dedicated phrase, instead calling them "polyarteritis nodosa and allied conditions". When using the influential classification known as the "Chapel Hill Consensus Conference", the terms "systemic vasculitis" or "primary systemic vasculitides" are commonly used.[5][6][7] Although the word necrotizing is omitted, the conditions described are largely the same. ## Contents * 1 Classification * 1.1 Large vessel vasculitis * 1.2 Medium vessel vasculitis * 1.3 Small vessel vasculitis * 1.3.1 Pauci-immune * 1.3.2 Immune complex * 1.3.3 Other/ungrouped * 2 Signs and symptoms * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Classification[edit] ### Large vessel vasculitis[edit] Giant-cell arteritis and Takayasu's arteritis have much in common,[8] but usually affect patients of different ages,[9] with Takayasu's arteritis affecting younger people, and giant-cell arteritis having a later age of onset. Aortitis can also be considered a large-vessel disease.[10] Takayasu arteritis. Primarily affects the aorta and its main branches. At least three out of six criteria yields sensitivity and specificity of 90.5 and 97.8%: * Onset < 40 years affects young and middle -aged women (ages 15–45) * Claudication of extremities * Decreased pulsation of one or both brachial arteries * At least 10 mmHg systolic difference in both arms * Bruit over one or both carotid arteries or abdominal aorta * Arteriographic narrowing of aorta, its primary branches, or large arteries in upper or lower extremities * Ocular manifestation * Visual loss or field defects * Retinal hemorrhages * Neurological abnormalities * Treatment: steroids Giant cell (temporal) arteritis. Chronic vasculitis of both large and medium vessels, primarily affecting cranial branches of the arteries arising from the aortic arch. At least three out of five criteria yields sensitivity and specificity of 95 and 91%: * Age at onset ≥ 50 years * New onset headache with localized tenderness * Temporal artery tenderness or decreased pulsation * Elevated ESR ≥ 50 mm/hour Westergren * Temporal artery biopsy showing vasculitis with mononuclear cell infiltrate or granulomatous inflammation, usually with multinucleated giant cells ### Medium vessel vasculitis[edit] These conditions are sometimes considered together with the small vessel vasculitides.[11] Polyarteritis nodosa (PAN). Systemic necrotizing vasculitis and aneurysm formation affecting both medium and small arteries. If only small vessels are affected, it is called microscopic polyangiitis, although it is more associated with granulomatosis with polyangiitis than to classic PAN. At least 3 out of 10 criteria yields sensitivity and specificity of 82 and 87%: * Unexplained weight loss > 4 kg * Livedo reticularis * Testicular pain * Myalgias, weakness * Abdominal pain, diarrhea, and GI bleeding * Mononeuropathy or polyneuropathy * New onset diastolic blood pressure > 90 mmHg * Elevated serum BUN (> 40 mg/dL) or serum creatinine (> 1.5 mg/dL) * Hepatitis B infection * Arteriographic abnormalities * Arterial biopsy showing polymorphonuclear cells Kawasaki disease. Usually in children (age<4), it affects large, medium, and small vessels, prominently the coronary arteries. Associated with a mucocutaneous lymph node syndrome. Diagnosis requires fever lasting five days or more with at least four out of five criteria: * Bilateral conjunctival injection * Injected or fissured lips, injected pharynx, or strawberry tongue * Erythema of palms/soles, edema of hands/feet, periungual desquamation * Polymorphous rash * Cervical lymphadenopathy (at least one node > 1.5 cm) Isolated cerebral vasculitis. Affects medium and small arteries over a diffuse CNS area, without symptomatic extracranial vessel involvement. Patients have CNS symptoms as well as cerebral vasculitis by angiography and leptomeningeal biopsy. ### Small vessel vasculitis[edit] There are several vasculitides that affect small vessels.[12] #### Pauci-immune[edit] Granulomatosis with polyangiitis (GPA). Systemic vasculitis of medium and small arteries, including venules and arterioles. Produces granulomatous inflammation of the respiratory tracts and necrotizing, pauci-immune glomerulonephritis. Most common cause of saddle nose deformity in USA (nose flattened due to destruction of nasal septum by granulomatous inflammation). Almost all patients with GPA have c-ANCA, but not vice versa. Current treatment of choice is cyclophosphamide. At least two out of four criteria yields sensitivity and specificity of 88 and 92%. * Nasal or oral inflammation (oral ulcers or purulent/bloody nasal discharge, may be painful) * Abnormal CXR showing nodules, infiltrates, cavities * Microscopic hematuria or RBC casts * Vessel biopsy shows granulomatous inflammation * Peak incidence: ages 40–60, males > females Eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome). Affects medium and small vessels with vascular and extravascular granulomatosis. Classically involves arteries of lungs and skin, but may be generalized. At least four criteria yields sensitivity and specificity of 85 and 99.7%. * Asthma (history of wheezeing or presently wheezing) * Eosinophilia > 10% on CBC * Mononeuropathy or polyneuropathy * Migratory or transient pulmonary opacities on chest x-ray (CXR) * Paranasal sinus abnormalities * Vessel biopsy showing eosinophils in extravascular areas Microscopic polyarteritis/polyangiitis. Affects capillaries, venules, or arterioles. Thought to be part of a group that includes granulomatosis with polyangiitis since both are associated with ANCA and similar extrapulmonary manifestations. Patients do not usually have symptomatic or histologic respiratory involvement. #### Immune complex[edit] Hypersensitivity vasculitis (allergic vasculitis). Usually due to a hypersensitivity reaction to a known drug. Drugs most commonly implicated are penicillin, sulphonamides and thiazide diuretics.[13] There is presence of skin vaculitis with palpable petechiae or purpura. Biopsy of these lesions reveal inflammation of the small vessels, termed leukocytoclastic vasculitis, which is most prominent in postcapillary venules. At least three out of five criteria yields sensitivity and specificity of 71 and 84%: * Age > 16 * Use of possible triggering drug in relation to symptoms * Palpable purpura * Maculopapular rash * Skin biopsy showing neutrophils around vessel IgA vasculitis (IgAV; formerly known as Henoch–Schonlein purpura). Systemic vasculitis due to tissue deposition of IgA-containing immune complexes. Biopsy of lesions shows inflammation of small vessels. It is considered a form of hypersensitivity vasculitis but is distinguished by prominent deposits of IgA. This is the most common vasculitis in children. Presence of three or more criteria yielded sensitivity of 87% while less than two criteria yielded hypersensitivity vasculitis in 74%: * Palpable purpura (usually of buttocks and legs) * Bowel angina * GI bleed * Hematuria * Onset < 20 years * No new medications Essential cryoglobulinemic vasculitis. Most often due to hepatitis C infection, immune complexes of cryoglobulins \--- proteins that consists of immunoglobulins and complement and precipitate in the cold while dissolving upon rewarming --- are deposited in walls of capillaries, venules, or arterioles. Therefore, complement will be low with histology showing vessel inflammation with immune deposits. #### Other/ungrouped[edit] Vasculitis secondary to connective tissue disorders. Usually secondary to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), relapsing polychondritis, Behçet's disease, and other connective tissue disorders. Vasculitis secondary to viral infection. Usually due to hepatitis B and C, HIV, cytomegalovirus, Epstein–Barr virus, and Parvo B19 virus. ## Signs and symptoms[edit] Patients usually present with systemic symptoms with single or multiorgan dysfunction. Common (and nonspecific) complaints include fatigue, weakness, fever, joint pains, abdominal pain, hypertension, chronic kidney disease, and neurologic dysfunction. The following symptoms should raise a strong suspicion of a vasculitis: * Mononeuritis multiplex. Also known as asymmetric polyneuropathy, in a non-diabetic this is suggestive of vasculitis. * Palpable purpura. If patients have this in isolation, it is most likely due to cutaneous leukocytoclastic vasculitis. If the purpura is in combination with systemic organ involvement, it is most likely to be Henoch–Schönlein purpura or microscopic polyangiitis. * Pulmonary-renal syndrome. Individuals who are coughing up blood and have kidney involvement are likely to have granulomatosis with polyangiitis, microscopic polyangiitis, or anti-GBM disease (Goodpasture syndrome). ## Diagnosis[edit] A detailed history is important to elicit any recent medications, any risk of hepatitis infection, or any recent diagnosis with a connective tissue disorder such as systemic lupus erythematosus (SLE). A thorough physical exam is needed as usual. * Lab tests. Basic lab tests may include a CBC, chem-7 (look for creatinine), muscle enzyme, liver function tests, ESR, hepatitis seroloties, urinalysis, CXR, and EKG. Additional, more specific tests include: * Antinuclear antibody (ANA) test can detect an underlying connective tissue disorder, especially SLE * Complement levels that are low can suggest mixed cryoglobulinemia, hepatitis C infection, and SLE, but not most other vasculitides. * Antineutrophil cytoplasmic antibody (ANCA) may highly suggest granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, or drug-induced vasculitis, but is not diagnostic. * Electromyography. It is useful if a systemic vasculitis is suspected and neuromuscular symptoms are present. * Arteriography. Arteriograms are helpful in vasculitis affecting the large and medium vessels but not helpful in small vessel vasculitis. Angiograms of mesenteri or renal arteries in polyarteritis nodosa may show aneurysms, occlusions, and vascular wall abnormalities. Arteriography are not diagnostic in itself if other accessible areas for biopsy are present. However, in Takayasu's arteritis, where the aorta may be involved, it is unlikely a biopsy will be successful and angiography can be diagnostic. * Tissue biopsy. This is the gold standard of diagnosis when biopsy is taken from the most involved area. ## Treatment[edit] Treatment is targeted to the underlying cause. However, most vasculitis in general are treated with steroids (e.g. methylprednisolone) because the underlying cause of the vasculitis is due to hyperactive immunological damage. Immunosuppressants such as cyclophosphamide and azathioprine may also be given. A systematic review of antineutrophil cytoplasmic antibody (ANCA) positive vasculitis identified best treatments depending on whether the goal is to induce remission or maintenance and depending on severity of the vasculitis.[14] ## References[edit] 1. ^ Cruz BA, Ramanoelina J, Mahr A, et al. (October 2003). "Prognosis and outcome of 26 patients with systemic necrotizing vasculitis admitted to the intensive care unit". Rheumatology. 42 (10): 1183–8. doi:10.1093/rheumatology/keg322. PMID 12777637. 2. ^ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. p. 534. ISBN 978-0-7216-0187-8. 3. ^ "systemic necrotizing vasculitis" at Dorland's Medical Dictionary 4. ^ Généreau T, Lortholary O, Pottier MA, et al. (December 1999). "Temporal artery biopsy: a diagnostic tool for systemic necrotizing vasculitis. French Vasculitis Study Group". Arthritis Rheum. 42 (12): 2674–81. doi:10.1002/1529-0131(199912)42:12<2674::AID-ANR25>3.0.CO;2-A. PMID 10616017. 5. ^ Jennette JC, Falk RJ, Andrassy K, et al. (February 1994). "Nomenclature of systemic vasculitides. Proposal of an international consensus conference". Arthritis Rheum. 37 (2): 187–92. doi:10.1002/art.1780370206. PMID 8129773. 6. ^ Sørensen SF, Slot O, Tvede N, Petersen J (June 2000). "A prospective study of vasculitis patients collected in a five year period: evaluation of the Chapel Hill nomenclature". Ann. Rheum. Dis. 59 (6): 478–82. doi:10.1136/ard.59.6.478. PMC 1753166. PMID 10834866. 7. ^ Gonzalez-Gay MA, Garcia-Porrua C, Guerrero J, Rodriguez-Ledo P, Llorca J (June 2003). "The epidemiology of the primary systemic vasculitides in northwest Spain: implications of the Chapel Hill Consensus Conference definitions". Arthritis Rheum. 49 (3): 388–93. doi:10.1002/art.11115. PMID 12794795. 8. ^ Churg J (September 1993). "Large vessel vasculitis". Clin. Exp. Immunol. 93 Suppl 1 (Suppl 1): 11–2. doi:10.1111/j.1365-2249.1993.tb06216.x. PMC 1554929. PMID 8103424. 9. ^ Weyand CM, Goronzy JJ (July 2003). "Medium- and large-vessel vasculitis". N. Engl. J. Med. 349 (2): 160–9. doi:10.1056/NEJMra022694. PMID 12853590. 10. ^ Hoffman GS (September 2003). "Large-vessel vasculitis: unresolved issues". Arthritis Rheum. 48 (9): 2406–14. doi:10.1002/art.11243. PMID 13130459. 11. ^ Seo P, Stone JH (December 2007). "Small-vessel and medium-vessel vasculitis". Arthritis Rheum. 57 (8): 1552–9. doi:10.1002/art.23105. PMID 18050229. 12. ^ Jennette JC, Falk RJ (1997). "Small-vessel vasculitis". N. Engl. J. Med. 337 (21): 1512–23. doi:10.1056/NEJM199711203372106. PMID 9366584. 13. ^ Axford J, O'Callaghan C, (eds). 2004. Medicine. Oxford. Blackwell Publishing. 14. ^ Bosch X, Guilabert A, Espinosa G, Mirapeix E (2007). "Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review". JAMA. 298 (6): 655–69. doi:10.1001/jama.298.6.655. PMID 17684188. ## External links[edit] Classification D * ICD-10: M30-M31 * ICD-9-CM: 446 * MeSH: D014657 External resources * Orphanet: 52759 * v * t * e Systemic vasculitis Large vessel * Takayasu's arteritis * Giant cell arteritis Medium vessel * Polyarteritis nodosa * Kawasaki disease * Thromboangiitis obliterans Small vessel Pauci-immune * c-ANCA * Granulomatosis with polyangiitis * p-ANCA * Eosinophilic granulomatosis with polyangiitis * Microscopic polyangiitis Type III hypersensitivity * Cutaneous small-vessel vasculitis * IgA vasculitis Ungrouped * Acute hemorrhagic edema of infancy * Cryoglobulinemic vasculitis * Bullous small vessel vasculitis * Cutaneous small-vessel vasculitis Other * Goodpasture syndrome * Sneddon's syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Systemic vasculitis	c0264939	29,031	wikipedia	https://en.wikipedia.org/wiki/Systemic_vasculitis	2021-01-18T18:56:11	{"mesh": ["D056647"], "icd-9": ["446"], "icd-10": ["M31", "M30"], "wikidata": ["Q7663822"]}
A number sign (#) is used with this entry because lissencephaly-4 (LIS4) is caused by homozygous mutation in the NDE1 gene (609449) on chromosome 16p13. Mutation in the NDE1 gene has also been reported in microhydranencephaly (MHAC; 605013). Description Lissencephaly-4 is an autosomal recessive neurodevelopmental disorder characterized by lissencephaly, severe brain atrophy, extreme microcephaly (head circumference of more than 10 standard deviations (SD) below the mean), and profound mental retardation. It has also been referred to as 'microlissencephaly' (summary by Bakircioglu et al., 2011 and Alkuraya et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432). Clinical Features Bakircioglu et al. (2011) reported 6 offspring from 3 consanguineous families with lissencephaly, extreme congenital microcephaly, and profound mental retardation. Two families were of Pakistani origin, and the third was of Turkish origin. The head circumferences of all patients were at least 10 SD below the mean, with onset at 18 weeks' gestation. Mental retardation was evident within the first few months of life; none of the children recognized their parents, and they showed little response to the outside world, even to painful stimuli. Seizures began by 3 months and evolved from occasional rhythmic jerks into complex partial and tonic-clonic seizures. The children gradually adopted a fetal position over the first 3 years of life, with a paucity of movements, but were not hypotonic or spastic. All but 1 died in the first 5 years of life of chest infections and aspiration. Brain imaging, available from 1 individual from each family, showed severe microcephaly, simplified gyral pattern of the cerebral cortex, small cerebellum, normal gross brain architecture, and normal cortical ribbon. Postmortem examination of 1 patient showed severe hypoplasia of the frontal lobes with abnormal gyral pattern. The temporal and occipital lobes were almost smooth, and the only major sulcus visible was the Sylvian fissure, consistent with lissencephaly. Cortical layering was abnormal, with several layers jumbled together and disorganized and a large loss of neurons. The disorder was described as a 'microlissencephaly.' Alkuraya et al. (2011) reported 2 unrelated consanguineous families from Saudi Arabia with lissencephaly and severe microcephaly (more than 11 SD below the mean). In the first family, 2 affected sisters showed marked hypertonia and lack of development but no seizures. Brain MRI of 1 girl showed severe microcephaly with a proportionate reduction in the size of most other brain structures, including the cerebellum and brain stem, associated with agenesis of the corpus callosum. The gyral folding of the cerebral cortex was extremely simplified; there were almost no detectable sulci other than the Sylvian fissure. Brain MRI of the second girl showed showed microcephaly, severe simplification of the gyral pattern, agenesis of the corpus callosum, and colpocephaly. In the second family, a brother and sister were similarly affected with extreme microcephaly. Clinical details on the girl were not available. At birth, CT scan of the boy showed small brain size. Seizures developed at age 2 months. Brain MRI at 11 months showed marked decrease in the size of both cerebral hemispheres, a large midline fluid-filled structure, dilatation of the right lateral ventricle, small cerebellum, and agenesis of the corpus callosum. All 4 patients reported by Alkuraya et al. (2011) showed overall poor growth. Inheritance Lissencephaly-4 is inherited in an autosomal recessive pattern (Bakircioglu et al., 2011). Molecular Genetics By linkage analysis followed by candidate gene sequencing, Bakircioglu et al. (2011) identified 2 different truncating mutations in the NDE1 gene (609449.0001 and 609449.0002, respectively) in affected members of 3 consanguineous families with lissencephaly-4. The disorder showed dual pathogenesis of profound early prenatal failure of neuron production and later prenatal deficiency of cortical lamination. The findings suggested that loss of NDE1 at the centrosomes of apical neuroepithelial cells plays a critical role in these processes, highlighting the importance of the centrosome in neurogenesis. Alkuraya et al. (2011) independently identified 2 truncating mutations in the NDE1 gene in affected members from 2 Saudi Arabian families with LIS4. Patient-derived lymphoblast cells showed spindle-structure defects, including tripolar spindles, misaligned mitotic chromosomes, nuclear fragmentation, and abnormal microtubule organizations, supporting an essential role for NDE1 in normal mitotic spindle function, neuronal proliferation, and human cerebral cortical neurogenesis. Animal Model Feng and Walsh (2004) found that Nde1-null mice were viable, but they showed a small-brain phenotype. At 6 to 8 weeks of age, the brains of Nde1-null mice were one-third smaller than their wildtype or heterozygous counterparts. The size reduction predominantly affected the cerebral cortex, while other brain structures, including the hippocampus, midbrain, and cerebellum, appeared normal or were only slightly reduced in size. Cortical lamination was mostly preserved, but the mutant cortex had fewer neurons and thin superficial cortical layers II to IV. Bromodeoxyuridine birthdating revealed retarded and modestly disorganized neuronal migration. More dramatic defects were found in mitotic progression, mitotic orientation, and chromosome localization in cortical progenitors. The small cerebral cortex of Nde1-null mice appeared to reflect both reduced progenitor cell division and altered neuronal cell fates. In vitro analysis demonstrated that Nde1 was essential for centrosome duplication and mitotic spindle assembly. Feng and Walsh (2004) concluded that mitotic spindle function and orientation are essential for normal cortical development. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature (in some patients) Other \- Poor growth HEAD & NECK Head \- Microcephaly, profound (at least 10 SD below mean) NEUROLOGIC Central Nervous System \- Mental retardation, profound \- Lack of psychomotor development \- Seizures (in some patients) \- Hypertonia (in some patients) \- Lissencephaly \- Small shrunken brain \- Simplified gyral pattern \- Thin cerebral cortex \- Abnormal cortical layering \- Reduced numbers of neurons \- Agenesis of the corpus callosum \- Small cerebellum MISCELLANEOUS \- Onset in utero \- Lack of psychomotor development \- Four families have been reported (last curated June 2011) MOLECULAR BASIS \- Caused by mutation in the homolog of the A. nidulans Nude 1 gene (NDE1, 609449.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	LISSENCEPHALY 4	c1956147	29,032	omim	https://www.omim.org/entry/614019	2019-09-22T15:56:46	{"doid": ["0050453"], "mesh": ["D008831"], "omim": ["614019"], "orphanet": ["1083"], "synonyms": ["Alternative titles", "LISSENCEPHALY 4 WITH MICROCEPHALY"]}
Dent disease is a chronic kidney disease that primarily affects males. While symptoms and severity vary, they usually begin in childhood and worsen over time. The most common feature of Dent disease is proteinuria (protein in the urine). Other common features include excess calcium in the urine (hypercalciuria); calcium deposits in the kidneys (nephrocalcinosis); and kidney stones. Less common features include rickets and mildy short stature. Progressive kidney problems often lead to kidney failure by early to mid-adulthood. There are two forms of Dent disease which are distinguished based on their genetic causes. Both forms are inherited in an X-linked recessive manner. * Dent disease type 1 is caused by a mutation in the CLCN5 gene. * Dent disease type 2 is caused by a mutation in the OCRL gene. Males with this form are also at increased risk for mild intellectual disability and hypotonia. Treatment is based on the symptoms present, aiming to delay progression of kidney disease and improve quality of life. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Dent disease	c1839874	29,033	gard	https://rarediseases.info.nih.gov/diseases/13105/dent-disease	2021-01-18T18:00:55	{"mesh": ["C545036"], "orphanet": ["1652"], "synonyms": ["Dent's disease", "Dents disease", "Dent syndrome", "Low-molecular-weight proteinuria with hypercalciuria and nephrocalcinosis", "Renal Fanconi syndrome with nephrocalcinosis and renal stones", "X-linked recessive hypercalciuric hypophosphatemic rickets", "X-linked recessive nephrolithiasis"]}
## Clinical Features Mayatepek and Flock (1998) described the inability to synthesize LTC4, thought to be due to a primary deficiency of LTC4 synthase (LTC4S; 246530), in an infant with a fatal developmental syndrome. The infant presented with muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly. The course of the disease was rapidly progressive and the infant died at the age of 6 months. The patient was the daughter of consanguineous Turkish parents. Mayatepek et al. (2000) reported another patient with LTC4S deficiency, a girl born at 33 weeks' gestation to consanguineous Italian parents. She had generalized muscular hypotonia with lack of facial expression from the first day of life. After the first week of life, she developed symmetric extension in the lower extremities, including stretching of the trunk musculature. During the course of the disease, severe muscular hypotonia and failure to thrive with tendency to microcephaly became rapidly progressive. There were no pyramidal tract signs, and deep tendon reflexes were not present. She had no psychomotor development and there was no visual contact at any time. It was impossible to extubate the patient, and the infant died at 6 months of age. INHERITANCE \- Autosomal recessive LABORATORY ABNORMALITIES \- Leukotriene C4 synthetase deficiency ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	LEUKOTRIENE C4 SYNTHASE DEFICIENCY	c3279662	29,034	omim	https://www.omim.org/entry/614037	2019-09-22T15:56:44	{"mesh": ["C565439"], "omim": ["614037"], "orphanet": ["79507"], "synonyms": ["Alternative titles", "LTC4 SYNTHASE DEFICIENCY"]}
Schisis association describes the combination of two or more of the following anomalies: neural tube defects (e.g. anencephaly, encephalocele, spina bifida cystica), cleft lip/palate, omphalocele and congenital diaphragmatic hernia (see these terms). These anomalies are associated at a higher frequency than would be expected with random combination rates. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Schisis association	c2931271	29,035	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=63862	2021-01-23T17:24:27	{"gard": ["246"], "mesh": ["C536633"], "umls": ["C2931271"], "icd-10": ["Q87.8"]}
Tick infestation SpecialtyInfectious disease A tick infestation is a condition where a tick acts as an ectoparasite. It is sometimes thought of as an animal disease. In humans, the primary concern from tick bites is often not the ectoparasitism itself, but the potential for the tick to transmit disease or tick paralysis. Still, in certain populations, it is possible for tick infestation to be clinically significant. There is some evidence that Ixodes ricinus infected with Borrelia burgdorferi may become more efficient at infestation.[1] Home remedies (such as vaseline or matches) have been used in the past, but are not currently recommended.[2] ## References[edit] Wikimedia Commons has media related to Tick infestation. 1. ^ Faulde MK, Robbins RG (February 2008). "Tick infestation risk and Borrelia burgdorferi s.l. infection-induced increase in host-finding efficacy of female Ixodes ricinus under natural conditions". Exp. Appl. Acarol. 44 (2): 137–45. doi:10.1007/s10493-008-9131-4. PMID 18273686. 2. ^ "cipm.ncsu.edu". Retrieved 2009-08-09. ## External links[edit] Classification D * ICD-10: B88.8 (ILDS B88.820) * MeSH: D013984 * v * t * e Tick-borne diseases and infestations Diseases Bacterial infections Rickettsiales * Anaplasmosis * Boutonneuse fever * Ehrlichiosis (Human granulocytic, Human monocytotropic, Human E. ewingii infection) * Scrub typhus * Spotted fever rickettsiosis * Pacific Coast tick fever * American tick bite fever * rickettsialpox * Rocky Mountain spotted fever) Spirochaete * Baggio–Yoshinari syndrome * Lyme disease * Relapsing fever borreliosis Thiotrichales * Tularemia Viral infections * Bhanja virus * Bourbon virus * Colorado tick fever * Crimean–Congo hemorrhagic fever * Heartland bandavirus * Kemerovo tickborne viral fever * Kyasanur Forest disease * Omsk hemorrhagic fever * Powassan encephalitis * Severe fever with thrombocytopenia syndrome * Tete orthobunyavirus * Tick-borne encephalitis Protozoan infections * Babesiosis Other diseases * Tick paralysis * Alpha-gal allergy * Southern tick-associated rash illness Infestations * Tick infestation Species and bites Amblyomma * Amblyomma americanum * Amblyomma cajennense * Amblyomma triguttatum Dermacentor * Dermacentor andersoni * Dermacentor variabilis Ixodes * Ixodes cornuatus * Ixodes holocyclus * Ixodes pacificus * Ixodes ricinus * Ixodes scapularis Ornithodoros * Ornithodoros gurneyi * Ornithodoros hermsi * Ornithodoros moubata Other * Rhipicephalus sanguineus * v * 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 This medical article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Tick infestation	c0040196	29,036	wikipedia	https://en.wikipedia.org/wiki/Tick_infestation	2021-01-18T19:01:31	{"mesh": ["D013984"], "umls": ["C0040196"], "icd-10": ["B88.8"], "wikidata": ["Q4199106"]}
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting). Signs and symptoms of LCHAD deficiency typically appear during infancy or early childhood and can include feeding difficulties, lack of energy (lethargy), low blood sugar (hypoglycemia), weak muscle tone (hypotonia), liver problems, and abnormalities in the light-sensitive tissue at the back of the eye (retina). Later in childhood, people with this condition may experience muscle pain, breakdown of muscle tissue, and a loss of sensation in their arms and legs (peripheral neuropathy). Individuals with LCHAD deficiency are also at risk for serious heart problems, breathing difficulties, coma, and sudden death. Problems related to LCHAD deficiency can be triggered when the body is under stress, for example during periods of fasting, illnesses such as viral infections, or weather extremes. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections. This disease summary is from MedlinePlus Genetics, an online health information resource from the National Institutes of Health. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	LCHAD deficiency	c1969443	29,037	gard	https://rarediseases.info.nih.gov/diseases/6867/lchad-deficiency	2021-01-18T17:59:30	{"mesh": ["C566945"], "omim": ["609016"], "umls": ["C0342786"], "orphanet": ["5"], "synonyms": ["Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency", "Long-chain 3-hydroxy acyl CoA dehydrogenase deficiency", "Long-chain 3-OH acyl-CoA dehydrogenase deficiency", "3-hydroxyacyl-CoA dehydrogenase long chain deficiency"]}
The ischemic (ischaemic) cascade is a series of biochemical reactions that are initiated in the brain and other aerobic tissues after seconds to minutes of ischemia (inadequate blood supply).[1] This is typically secondary to stroke, injury, or cardiac arrest due to heart attack. Most ischemic neurons that die do so due to the activation of chemicals produced during and after ischemia.[2] The ischemic cascade usually goes on for two to three hours but can last for days, even after normal blood flow returns.[3] A cascade is a series of events in which one event triggers the next, in a linear fashion. Thus "ischemic cascade" is actually a misnomer, since the events are not always linear: in some cases they are circular, and sometimes one event can cause or be caused by multiple events.[4] In addition, cells receiving different amounts of blood may go through different chemical processes. Despite these facts, the ischemic cascade can be generally characterized as follows: 1. Lack of oxygen causes the neuron's normal process for making ATP for energy to fail. 2. The cell switches to anaerobic metabolism, producing lactic acid. 3. ATP-reliant ion transport pumps fail, causing the cell to become depolarized, allowing ions, including calcium (Ca2+), to flow into the cell. 4. The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high. 5. The presence of calcium triggers the release of the excitatory amino acid neurotransmitter glutamate. 6. Glutamate stimulates AMPA receptors and Ca2+-permeable NMDA receptors, which open to allow more calcium into cells. 7. Excess calcium entry overexcites cells and causes the generation of harmful chemicals like free radicals, reactive oxygen species and calcium-dependent enzymes such as calpain, endonucleases, ATPases, and phospholipases in a process called excitotoxicity.[5][6] Calcium can also cause the release of more glutamate. 8. As the cell's membrane is broken down by phospholipases, it becomes more permeable, and more ions and harmful chemicals flow into the cell. 9. Mitochondria break down, releasing toxins and apoptotic factors into the cell. 10. The caspase-dependent apoptosis cascade is initiated, causing cells to "commit suicide." 11. If the cell dies through necrosis, it releases glutamate and toxic chemicals into the environment around it. Toxins poison nearby neurons, and glutamate can overexcite them. 12. If and when the brain is reperfused, a number of factors lead to reperfusion injury. 13. An inflammatory response is mounted, and phagocytic cells engulf damaged but still viable tissue. 14. Harmful chemicals damage the blood–brain barrier. 15. Cerebral edema (swelling of the brain) occurs due to leakage of large molecules like albumins from blood vessels through the damaged blood brain barrier. These large molecules pull water into the brain tissue after them by osmosis. This "vasogenic edema" causes compression of and damage to brain tissue (Freye 2011; Acquired Mitochondropathy-A New Paradigm in Western Medicine Explaining Chronic Diseases). ## Mitigation of effects[edit] The fact that the ischemic cascade involves a number of steps has led doctors to suspect that neuroprotectants such as calcium channel blockers or glutamate antagonists could be produced to interrupt the cascade at a single one of the steps, blocking the downstream effects. Though initial trials for such neuroprotective drugs led many to be hopeful, until recently, human clinical trials with neuroprotectants such as NMDA receptor antagonists were unsuccessful.[citation needed] ## References[edit] 1. ^ "eMedicine - Stroke, Ischemic : Article by Joseph U Becker". 2. ^ Stroke Center Archived 2018-01-30 at the Wayback Machine of the Washington University School of Medicine. 3. ^ "Stroke: Hope Through Research: National Institute of Neurological Disorders and Stroke (NINDS)". 4. ^ Hinkle JL, Bowman L (April 2003). "Neuroprotection for ischemic stroke". J Neurosci Nurs. 35 (2): 114–8. doi:10.1097/01376517-200304000-00008. PMID 12795039. 5. ^ Jill Conway. 2000. "Diseases at the Cellular Level Lecture Handout Archived 2005-07-10 at the Wayback Machine" and Inflammation and Repair Lecture Handout " University of Illinois College of Medicine. Retrieved on January 9, 2007. 6. ^ "eMedicine - Acute Stroke Management : Article by Edward C Jauch". [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ischemic cascade	None	29,038	wikipedia	https://en.wikipedia.org/wiki/Ischemic_cascade	2021-01-18T18:30:32	{"wikidata": ["Q2940871"]}
A rare chromosomal anomaly syndrome, resulting from the partial duplication of the long arm of chromosome 22, with a highly variable phenotype principally characterized by developmental delay, intellectual disability, behavioral anomalies, and non-specific craniofacial dysmorphism. Congenital heart malformations, visual and hearing impairment, urogenital abnormalities, and seizures have also been reported. Penetrance is incomplete. In 70% of cases, the duplication is inherited from as asymptomatic parent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Distal 22q11.2 microduplication syndrome	c4706942	29,039	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261337	2021-01-23T18:19:53	{"icd-10": ["Q92.3"], "synonyms": ["Distal dup(22)(q11.2)", "Distal trisomy 22q11.2"]}
## Description Primary basilar impression of the skull is a developmental defect of the cranium in which there is invagination of the foramen magnum upward into the posterior cranial fossa. Basilar impression is often associated with other malformations of the notochord and craniovertebral junction, such as occipitalization of the atlas, Klippel-Feil anomaly (see 118100), Chiari type I malformation (118420), and syringomyelia (186700) (Paradis and Sax, 1972; Bhangoo and Crockard, 1999). Secondary basilar impression occurs as a result of generalized skeletal diseases, including hyperparathyroidism (see 145000), Paget disease (see 167250), and osteogenesis imperfecta (see, e.g., 166200). Platybasia refers to a skull base with an abnormally obtuse angle between the planes of the clivus and the anterior fossa. Platybasia may occur in basilar impression, but it is not of medical significance on its own (Bhangoo and Crockard, 1999). Historically, basilar impression was defined radiologically by numerous parameters, including the lines defined by Chamberlain (1939), McGregor (1948), and Fischgold and Metzger (1952), and the angle defined by Bull et al. (1955). Nomenclature Bhangoo and Crockard (1999) noted that there is confusion as to the correct usage of the terms basilar impression and invagination with some authors insisting that the terms are not interchangeable. They suggested that basilar impression and invagination are terms that can be used interchangeably and describe the invagination of the foramen magnum into the posterior cranial fossa and the concomitant translocation of the upper cervical vertebrae into this cranial depression. Clinical Features Although basilar impression has been recognized for centuries, basilar impression with associated neurologic symptoms was first described in modern literature by Homen (1901) (Paradis and Sax, 1972). Bull et al. (1955) reported the radiographic finding of primary basilar impression in 20 individuals. Of 39 available relatives, 11 also showed basilar impression. Despite consanguinity in 1 case, the authors suggested autosomal dominant inheritance. Of the 20 probands, 10 were asymptomatic, 7 had a previous diagnosis of syringomyelia, and 3 had symptoms and signs explicable by a local lesion at the level of the foramen magnum. Brocher (1955) described affected mother and daughter. Morariu and Taranu (1968) reported 2 families with primary basilar impression. Sajid and Copple (1968) reported 2 brothers with basilar impression associated with X-linked aqueductal stenosis (HSAS; 307000). Paradis and Sax (1972) reported a family in which at least 6 individuals spanning 3 generations had primary basilar impression. The proband was a 32-year-old male who had associated syringomyelia with neurologic signs. He presented with weakness mainly in the left arm and leg. Other features included short neck, craniofacial asymmetry, left Horner syndrome, depressed reflexes in the arms, scoliosis, and lower limb hyperreflexia with extensor plantar responses. Other affected family members had short neck and atrophy of the cervical paravertebral muscles, but no other neurologic signs. Paradis and Sax (1972) suggested autosomal dominant inheritance with incomplete penetrance and variable expressivity. In a review article, Bhangoo and Crockard (1999) stated that symptomatic basilar impression can result in upper and lower motor neuron signs, cranial nerve abnormalities, hydrocephalus, cerebellar dysfunction, syringomyelia, and syringobulbia. Symptoms likely occur when there is brainstem compression from the clivus or translocated odontoid peg impinging on the anterior craniospinal neuraxis. Other contributory factors include altered CSF dynamics, traction on the brainstem, and possibly obstruction of the vertebrobasilar blood supply. INHERITANCE \- Autosomal dominant HEAD & NECK Neck \- Short neck \- Hypoplasia of cervical paravertebral muscles SKELETAL Skull \- Invagination of the foramen magnum upward into the posterior cranial fossa \- Translocation of the upper cervical vertebrae into the cranial depression \- Occipitalization of the atlas \- Base of the skull is flattened on the cervical spine \- Platybasia MUSCLE, SOFT TISSUES \- Hypoplasia of cervical paravertebral muscles NEUROLOGIC Central Nervous System \- Neurologic symptoms, if present, usually result from associated syringomyelia MISCELLANEOUS \- Variable expressivity \- Incomplete penetrance \- Often associated with syringomyelia ( 186700 ) \- Often associated with Chiari type I malformation (CM1, 118420 ) \- Often associated with Klippel-Feil anomaly ( 118100 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BASILAR IMPRESSION, PRIMARY	c1862299	29,040	omim	https://www.omim.org/entry/109500	2019-09-22T16:44:29	{"mesh": ["C566226"], "omim": ["109500"], "orphanet": ["2285"]}
Post-lingual deafness is a deafness which develops after the acquisition of speech and language, usually after the age of six. Post-lingual hearing impairments are far more common than prelingual deafness. Typically, hearing loss is gradual, and often detected by family and friends of the people so affected long before the patients themselves will acknowledge the disability. ## Contents * 1 Causes * 2 Treatment * 3 Social impact * 4 References * 5 See also ## Causes[edit] In some cases, the loss is extremely sudden and can be traced to specific diseases, such as meningitis, or to ototoxic medications, such as Gentamicin. In both cases, the final degree of loss varies. Some experience only partial loss, while others become profoundly deaf. Hearing aids and cochlear implants may be used to regain a sense of hearing, with different people experiencing differing degrees of success. It is possible that the affected person may need to rely on speechreading and/or sign language for communication. In most cases the loss is a long term degradation in hearing loss. Discrediting earlier notions of presbycusis, Rosen demonstrated that long term hearing loss is usually the product of chronic exposure to environmental noise in industrialized countries (Rosen, 1965). The U.S. Environmental Protection Agency has asserted the same sentiment and testified before the U.S. Congress that approximately 34 million Americans are exposed to noise pollution levels (mostly from roadway and aircraft noise) that expose humans to noise health effects including the risk of hearing loss (EPA, 1972). Certain genetic conditions can also lead to post-lingual deafness. In contrast to genetic causes of pre-lingual deafness, which are frequently autosomal recessive, genetic causes of post-lingual deafness tend to be autosomal dominant. ## Treatment[edit] In cases where the causes are environmental, the treatment is to eliminate or reduce these causes first of all, and then to fit patients with a hearing aid, especially if they are elderly. When the loss is due to heredity, total deafness is often the end result. On the one hand, persons who experience gradual deterioration of their hearing are fortunate in that they have learned to speak. Ultimately the affected person may bridge communication problems by becoming skilled in sign language, speech-reading, using a hearing aid, or accepting elective surgery to use a prosthetic devices such as a cochlear implant. ## Social impact[edit] Those who lose their hearing later in life, such as in late adolescence or adulthood, face their own challenges. For example, they must adjust to living with the adaptations that make it possible for them to live independently. They may have to adapt to using hearing aids or a cochlear implant, develop speech-reading skills, and/or learn sign language. The affected person may need to use a TTY, a videophone, an interpreter, or relay service to communicate over the telephone. Loneliness and depression can arise as a result of isolation (from the inability to communicate with friends and loved ones) and difficulty in accepting their disability. The challenge is made greater by the need for those around them to adapt to the person's hearing loss. ## References[edit] * S. Rosen and P. Olin, Hearing Loss and Coronary Heart Disease, Archives of Otolaryngology, 82:236 (1965) * Senate Public Works Committee, Noise Pollution and Abatement Act of 1972, S. Rep. No. 1160, 92nd Cong. 2nd session ## See also[edit] * Noise Pollution * Noise regulation * Hearing impairment [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Post-lingual deafness	None	29,041	wikipedia	https://en.wikipedia.org/wiki/Post-lingual_deafness	2021-01-18T18:43:13	{"wikidata": ["Q2359757"]}
Sound to color synesthesia 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 is written like a personal reflection, personal essay, or argumentative essay that states a Wikipedia editor's personal feelings or presents an original argument about a topic. Please help improve it by rewriting it in an encyclopedic style. (April 2015) (Learn how and when to remove this template message) This article possibly contains original research. Please improve it by verifying the claims made and adding inline citations. Statements consisting only of original research should be removed. (April 2015) (Learn how and when to remove this template message) (Learn how and when to remove this template message) A keyboard depicting note-color associations. Note that the colors are experienced with the sounding of the note, and are not necessarily localized to piano keys. Chromesthesia or sound-to-color synesthesia is a type of synesthesia in which sound involuntarily evokes an experience of color, shape, and movement.[1][2] Individuals with sound-color synesthesia are consciously aware of their synesthetic color associations/perceptions in daily life.[3] Synesthetes that perceive color while listening to music, experience the colors in addition to the normal auditory sensations. The synesthetic color experience supplements, but does not obscure real, modality-specific perceptions.[3] As with other forms of synesthesia, individuals with sound-color synesthesia perceive it spontaneously, without effort, and as their normal realm of experience.[3] Chromesthesia can be induced by different auditory experiences, such as music, phonemes, speech, and/or everyday sounds.[1] ## Contents * 1 Individual variance * 2 History * 3 Mechanisms * 3.1 Cross-activation theory * 3.2 Disinhibited feedback model * 4 Research * 4.1 Involvement of specific brain regions * 4.2 Definitional bias * 5 Drug-induced chromesthesia * 6 Music and chromesthesia * 6.1 Composers with chromesthesia * 6.1.1 Alexander Scriabin * 7 References ## Individual variance[edit] The color associations, that is, which color is associated to which sound, tone, pitch, or timbre is highly idiosyncratic, but in most cases, consistent over time.[2][4] Individuals with synesthesia have unique color pairings. However, studies to date have reported that synesthetes and non-synesthetes alike associate high pitched sounds with lighter or brighter colors and low pitched sounds with darker colors, indicating that a common mechanism may underlie those associations in normal adult brains.[5] There are forms of pseudo-chromesthesia that may be explained by associations synesthetes have made and forgotten from childhood.[6] As with other types of synesthesia, sound-color synesthesia can be divided into groups based on the way the colors are experienced. Those that 'see' or perceive the color in external space are called projectors, and those that perceive the color in the mind's eye are often called associators, but these terms can be misleading to understanding the nature of the experience.[2][3] For most synesthetes, the condition is not wholly sensory/perceptual.[3] For some individuals, chromesthesia is only triggered by speech sounds, while others' chromesthesia can be triggered by any auditory stimuli.[7] In a study investigating variability within categories of synesthesia, 40% of subjects with chromesthesia for spoken words reported that voice pitch, accent, and prosody influenced the synesthetic color, whereas few subjects reported that volume or speed of talking had any influence.[8] Within these subjects, many reported that the speaker's emotional inflection could influence the synesthetic color, but only two reported that their own mood had such influence.[8] Of participants categorized as having synesthesia for music in this study, 75% reported concurrents exclusively when listening to notes being played.[8] When asked whether the experience of the concurrent could be voluntarily controlled, only 33% of participants indicated an ability to smother, ignore, or willfully evoke their concurrents without great effort.[8] Attention to the inducing stimulus was reported as influential in 59% of participants.[8] Other contributing factors included concentration level, fatigue, sleep habits, fever, emotions, and substances, such as caffeine or alcohol.[8] Sound-color synesthesia is far more common than color-sound synesthesia, although there are reported cases where sounds and colors activate bidirectionally. One individual, JR, sees colors when she hears sounds and also hears sounds when she sees colors.[7] This type of synesthesia interferes greatly with daily life. This individual's associations were highly consistent over time, but the associations were not necessarily the same in either direction.[7] Another individual, D, had absolute pitch, as well as Chromesthesia, claimed that her absolute pitch was less stable than her Chromesthesia[9] There may be an effect of semantic mediation in some individuals with sound-color synesthesia. One subject, MH, self-triggered notes on a synthesizer and noted the color associations. When the synthesizer was transposed without her knowledge, she reported identical color associations to the notes that she believed she was hearing, rather than the absolute pitch of the tones.[4] ## History[edit] > For History of Synesthesia: History of synesthesia research The terms synesthesia and chromesthesia have developed and evolved considerably throughout history. The first documented synesthete was Georg Tobias Ludwig Sachs in 1812.[10] Although he did not give a specific name to his experience, in a medical dissertation regarding his albinism (written in Latin), he mentioned obscure ideas and described how colored ideas appeared to him. [11] Even earlier than Sachs, however, Johann Gottfried Herder discussed similar ideas in his Treatise on the Origin of Language in 1772.[10] He talked about how people, "through a sudden onset immediately associate with this sound that color".[12] The first concrete term associated with chromesthesia was given by Charles-Auguste-Édouard Cornaz in an eye disease dissertation in 1848. Color blindness was a common condition known as chromatodysopsia and, since Cornaz saw chromesthesia as the opposite, he named it hyperchromatopsia or perception of too many colors.[10] In 1881, Eugen Bleuler and Karl Bernhard Lehmann were the first to establish six different types of what they called secondary sensations or secondary imaginations.[10] The first, which was the most common, was sound photisms. They described it as "light, color, and form sensations which are elicited through hearing".[13] Their book was reviewed by an Austrian newspaper, where the term colored hearing, still commonly used today to describe chromesthesia, first appeared.[10] Research on synesthesia in the United States began in 1892. And, since 1895, the term finally expanded from pure sound-to-color experiences (chromesthesia) to a wide range of phenomena, including grapheme-color synesthesia, mirror-touch synesthesia, and lexical-gustatory synesthesia.[10] The rise of behaviorism between 1920 and 1940 resulted in a considerable decline in interest for synesthesia,[1] as it was seen as "little more than a learned association".[14] The number of scientific papers on the topic rebounded around 1980 [1] and exponentially increased in the 21st century, where substantial progress has been made to study it empirically and understand the mechanisms at work.[14] ## Mechanisms[edit] Synesthesia is established in early childhood, when the brain is most plastic. There is a genetic predisposition for the condition, but the specific type is determined by environment and learning, which explains why "mappings differ across individuals, but are not strictly random".[1] Furthermore, it manifests as the dominant process in distributed systems, or neural networks, which are dynamic, auto-assemble and self-calibrate.[1] That is what is understood so far, but the specific mechanisms by which synesthesia occurs are still unclear and a general consensus has not yet been reached. There are two main hypotheses: Cross-activation theory and Disinhibited feedback model.[15] ### Cross-activation theory[edit] The cross-activation theory of synesthesia was formulated by V.S. Ramachandran and E.M. Hubard, based on converging evidence from studies of synesthesia that sensory areas for processing real and synesthetic information tend to be neighboring brain regions.[16] This is most apparent in grapheme-color synesthesia, because the brain regions for color processing and visual word form processing are adjacent.[17] Individuals with chromesthesia show activation of brain areas involved in visual processing, such as V4, immediately after the auditory perception, indicating an automatic linking of sounds and colors.[16] Neonates have increased connectivity between different brain areas, but these hyper-connections are cut back during development.[1] The reason for this cross-activation is unclear, but one hypothesis is that the increased connectivity between adjacent brain regions is due to a reduction in the pruning of neuronal networks during childhood.[16] Another hypothesis is that unusual branching of neurons causes more numerous synaptic connections and cross-activation. These hypotheses align with Daphne Maurer's neonatal hypothesis, which states that all newborns are synesthetes, but the condition disappears at around the age of three months.[1] Cross-activation may occur at the fusiform gyrus in projector synesthetes (who perceive photisms in external space) and at the angular gyrus in associator synesthetes (who perceive photisms, which come from learned associations, in their mind).[15] One problem with the cross-activation theory is that synesthesia should be present from birth, but is only evident from mid-childhood.[1] ### Disinhibited feedback model[edit] The disinhibited feedback model is an alternative to the cross-activation theory.[16] The disinhibited feedback model rejects the assumption of increased connectivity in synesthetes and proposes that the cross-activation is due to a decrease of inhibition in the networks present in the normal adult brain.[16] Disinhibited feedback could account for the fact that chromesthesia can be acquired by damage to the retino-cortical pathway [5] or transiently induced through chemical agents, sensory deprivation, meditation, etc.[1] In all brains, there are anatomical cross-connections where inhibition and excitation are counterbalanced.[1] However, excitation prevails in synesthetes and this disinhibits other structures "to elicit sensory sensations in a second sensory area".[15] One theory that explains how this occurs is neurotransmitter-mediated inhibition. Local inhibitory networks are supposed to confine cortical firing to a specific region, but it leads to a spread of cortical firing, when these networks are blocked by bicuculline.[1] Forward feeding connections in the brain that receive converging signals from multiple pathways are reciprocated by feedback connections.[18] In most people, feedback connections are sufficiently inhibited to avoid synesthetic induction of a concurrent perception. In synesthetes, it is suggested that feedforward signaling in the inducer pathway could activate neurons, to which both inducer and concurrent pathways converge, and that feedback signaling is capable of propagating down the concurrent pathway to activate the concurrent representation.[18] In this mechanism, feedforward activity from the inducer leads to feedback activation of the concurrent representation.[18] ## Research[edit] The mechanism by which synesthesia occurs has yet to be identified. Given that synesthetes and non-synesthetes both match sounds to colors in a non-arbitrary way and that the ingestion of hallucinogenic drugs can induce synesthesia in under an hour, some researchers suggest that synesthetic experience uses existing pathways in the normal brain.[5] The cause of synesthesia is also unclear, although evidence points to a genetic predisposition. Synesthesia runs in families, though the condition may present idiosyncratically within a family.[16] Synesthesia may skip a generation.[16] However, there are cases of monozygotic twins where only one has synesthesia, indicating there may be additional factors.[16] Differences between synesthetic and non-synesthetic brains may reflect direct hard-wired connections between unimodal auditory and visual regions in the brain, or they may reflect feedback pathways from multimodal audiovisual regions to unimodal visual regions present in all brains.[5] ### Involvement of specific brain regions[edit] In addition to high interconnectivity in synesthesia, there is an apparent contribution from the inferior parietal cortex during synesthetic experiences, possibly serving as the mechanism to bind the real and synesthetic perceptions into one experience.[16][19] Parietal lobe activation is most apparent when the synesthete is directing attentional focus to the synesthetic experience.[16] Functional magnetic resonance imaging studies implicate the left superior temporal sulcus for the integration of auditory and visual information. This brain region responds most strongly to congruent pairs of visual and auditory information, such as congruent lip movements and speech.[5] ### Definitional bias[edit] The literature contains conflicting definitional criteria for synesthesia, which could bias selection of research subjects and interpretation of results. Synesthesia has long been described as a 'merging of the senses' or as a kind of 'cross-sensory' experience; however, the condition is not purely sensory/perceptual in all individuals. While this description of synesthesia is useful in describing the condition, it should not be interpreted literally and used as selection criteria for scientific exploration.[3] Another common defining characteristic of synesthesia is that synesthetic associations are consistent over time. This is generally determined by having individuals report color pairings twice, with several months separating the test from the re-test. Consistency has been described as so fundamental to synesthesia that the test of consistency has become the behavioral 'gold standard' for identifying the genuine condition, and selecting subjects for research.[3] This creates a circular bias, in which virtually all research subjects show consistency over time because they have been selected for it.[3] While consistency, to some extent, may be characteristic of synesthesia, there are individuals that fit all other criteria of synesthesia, but report that their synesthetic associations are not consistent over time.[3] Another misleading defining characteristic of synesthesia has been that synesthetic concurrents are spatially extended, and the individuals should be able to indicate a spatial location in which the concurrent is experienced. In the case of sound-color synesthesia, those who experience colored photisms from listening to music can often describe the direction of movement of these photisms.[3] While the majority of synesthetes experience a spatial quality to the synesthetic experience, there are still many that report no such quality.[3] In addition to definitional inclusion/exclusion criteria for synesthesia research, self-report bias is also likely relevant to many studies. This self-report bias, if it exists, would perpetuate itself because the condition would become defined by those cases that become known, and not by those that remain hidden.[3] This is significant because many synesthetic individuals may exclude themselves on the basis of not fitting the prescribed definitional criteria. This is also significant to the extent that synesthetic individuals have a limited ability to differentiate their experience from that of nonsynesthetic individuals. A possible resolution of these issues would involve defining synesthesia on a neurological basis.[3] Such a unifying neurobiological cause has yet to be found, but if it exists, it would deepen understanding of the phenomenon in ways that the behavioral definition has failed to do.[3] ## Drug-induced chromesthesia[edit] Gautier, under the influence of hashish, depicted his chromesthetic perceptions over the piano as lines of color arising from the music. Chromesthesia can be transiently induced with chemical agents through the manipulation of neurotransmitters. These substances can also modulate existing synesthesia.[1] Psychoactive drugs including LSD, mescaline, psilocybin, and ayahuasca are non-selective serotonin agonists that elicit spontaneous synesthesia, specially sound-to-color.[20] The first to report drug-induced chromesthesia was Théophile Gautier in 1845.[1] Under the influence of hashish, he described: "My hearing was developed extraordinarily; I heard the noise of colors. Green, red, blue, yellow sounds reached me in perfectly distinguishable waves".[21] Gautier made a sketch of Gustave Moreau playing the piano, where he depicted his chromesthetic experiences as lines of color above the instrument.[21] Recent scientific studies, with enhanced methodologies, suggest that drug-induced synesthesia is substantially different from congenital synesthesia. Psychoactive substances "affect ongoing streams of transmission rather than causing stimulus-induced activation".[1] The most common type of synesthesia elicited with chemical agents is chromesthesia. Still, frequent inducers include auditory and visual stimuli, especially music - which could explain the prevalence of sound-to-color synesthesia over other types of synesthesia.[20] Heinrich Klüver's form constants: Tunnels, Spirals, Honeycombs Gratings, and Cobwebs Heinrich Klüver categorized recurring geometric shapes under the influence of peyote in the 1920s.[1] He called these the form constants: Tunnels, Spirals, Honeycombs Gratings, and Cobwebs. These also apply to both drug-induced and natural hallucinations, which appear in near-death experiences, sensory deprivation, waking up or falling asleep, and during migraines.[22] According to Klüver, all hallucinations consist of shapes in one of these categories and 'atypical' hallucinations are simply variations. The form constants are common in chromesthetic experiences.[1] Psychedelics greatly enhance suggestibility, so it is fairly common to mistaken hallucinations with chromesthesia;[20] especially considering that all measures of color perception including brightness, saturation, luminance, contrast, and hue are affected due to chemical agents. Drug-induced chromesthesia, as opposed to congenital chromesthesia, is not consistent or automatic. Furthermore, bottom-up processing is responsible for experiences under drug influence, so external stimuli and context are not as critical.[1] Several studies, both direct (intentionally trying to induce synesthesia) and indirect (participants respond to a set of questions, including one about synesthetic experiences), suggest that the induction of synesthesia with chemical agents is possible. Nevertheless, most studies "suffer from a large number of limitations including a lack of placebo control, double-blinds, and randomized allocation".[20] ## Music and chromesthesia[edit] Individuals with chromesthesia are more likely to play musical instruments and be artistically inclined. Furthermore, "both the hobbies and occupations of synesthetes are skewed toward the creative industries." [14] People with synesthetic propensities are more metaphorical since the same genes cause them to relate concepts and ideas and, thus, be more creative. This could explain the higher incidence of musicians who have synesthesia.[23] However, musical experience does not assist the ability to consistently match colors to tones. Against natural expectation, studies have found that possession of absolute pitch increased local variance in matching ability.[4] One possible explanation for this is that because absolute pitch is subject to chance error, occasionally incorrectly inferred note names could compete with the pitch-induced color on particular trials.[4] Another possibility is that people with absolute pitch can label tighter pitch recognition categories than normal, introducing a greater number of category boundaries to cross between distinct tones.[4] ### Composers with chromesthesia[edit] Franz Liszt is a composer who was known for asking performers to play with color. He was noted telling his orchestra to play the music in a "Bluer Fashion," [24] since that is what the tone required. Synesthesia was not a common term in Liszt's time; people thought he was playing a trick on them when he referred to a color instead of a musical term. Leonard Bernstein openly discussed his chromesthesia, which he described as a "timbre to color." [24] Although he does not reference specific songs as being a certain color, he does explain the way it should sound to the artist performing. There are recordings of him stopping orchestras and singers when they are changing the "timbre."[25] If someone changes the “timbre” or tone in a piece, it does not necessarily change the sound to the listener, but the composer with Chromesthesia will automatically know. Amy Beach was another composer who had synesthesia. According to her perspective, each key signature was associated with a particular color. If an artist changed the key to suit their voice, then she would become upset because it would change the intended sound, portrayal, and emotion of the piece.[24] Olivier Messiaen was influenced by the color of musical keys for his compositions.[14] Alexander Scriabin. It is debatable whether Scriabin had chromesthesia or if his analogies were purely associative #### Alexander Scriabin[edit] Main articles: Alexander Scriabin and Clavier à lumières The Theosophist "meanings of colors" of thought-forms and human aura associated with feelings and emotions Alexander Scriabin was a Russian composer and pianist. He is famously regarded as a synesthete, but there is a lot of controversy surrounding whether he had chromesthesia or not.[26] Scriabin was a major proponent of Theosophy, which had a system associating colors to feelings and emotions.[27] This influenced the musician, who distinguished "spiritual" tonalities (like F-sharp major) from "earthly, material" ones (C major, F major).[26] Furthermore, Alexander Scriabin developed a "keyboard with lights" or clavier à lumières, which directly matched musical notes with colors.[26] "Scriabin believed integration of colored light within a symphonic work would act as a 'powerful psychological resonator for the listener'".[28] That is why he created the clavier à lumières for his color-symphony Prometheus: The Poem of Fire.This consisted of a color organ, which projected colors on a screen.[28] The musicologist Sabaneyev first published a table of Scriabin's sound-to-color mapping in 1911:[26] Scriabin's sound-to-color associations [26] Note Color C Red G Orange-pink D Yellow A Green E Whitish-blue B Similar to E F♯ Blue, bright D♭ Violet A♭ Purplish-violet E♭ Steel color with metallic sheen B♭ Similar to E flat F Red, dark Scriabin was friends with composer Nikolai Rimsky-Korsakov, who was a synesthete, and their sound-to-color associations were not the same. Specifically, Rimsky-Korsakov made a distinction between major and minor scales and his associations had a "more neutral, spontaneous character".[26] Still, different individuals respond to some sounds and not others, and sound-to-color associations vary greatly between them.[1] Scriabin's sound-to-color associations arranged into a circle of fifths, demonstrating its spectral quality When the notes are ordered by the circle of fifths, the colors are in order of a spectrum, which casts doubt on whether Scriabin experienced chromesthesia:[29] Scriabin's sound-to-color circle of fifths [26] Note Color C Red, intense G Orange D Yellow A Green E Sky blue B Blue F♯/ G♭ Bright blue or violet D♭ Violet or purple A♭ Violet or lilac E♭ Flesh or steel B♭ Rose F Deep red Whether Scriabin had chromesthesia or not, his work was greatly influenced by the particularities of this phenomenon. He created a system that associated colors to tones and aimed to create holistic sensory experiences with his compositions. Not only did he experiment with colors, but also with "the generation of scents and sensation of touch and taste".[30] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s Cytowic RE (2018). Synesthesia. Cambridge, MA: MIT Press. ISBN 9780262535090. 2. ^ a b c Cytowic RE, Eagleman DM (2009). Wednesday is Indigo Blue: Discovering the Brain of Synesthesia (with an afterword by Dmitri Nabokov). Cambridge: MIT Press. p. 309. ISBN 978-0-262-01279-9. 3. ^ a b c d e f g h i j k l m n Simner J (February 2012). "Defining synaesthesia" (PDF). British Journal of Psychology. London, England. 103 (1): 1–15. doi:10.1348/000712610X528305. PMID 22229768. 4. ^ a b c d e de Thornley Head P (February 2006). "Synaesthesia: pitch-colour isomorphism in RGB-space?". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 42 (2): 164–74. doi:10.1016/s0010-9452(08)70341-1. PMID 16683490. S2CID 53179317. 5. ^ a b c d e Ward J, Huckstep B, Tsakanikos E (February 2006). "Sound-colour synaesthesia: to what extent does it use cross-modal mechanisms common to us all?". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 42 (2): 264–80. doi:10.1016/s0010-9452(08)70352-6. PMID 16683501. S2CID 4481009. 6. ^ Calkins MW (1893-07-01). "A Statistical Study of Pseudo-Chromesthesia and of Mental-Forms". The American Journal of Psychology. 5 (4): 439–464. doi:10.2307/1411912. JSTOR 1411912. 7. ^ a b c Goller AI, Otten LJ, Ward J (October 2009). "Seeing sounds and hearing colors: an event-related potential study of auditory-visual synesthesia". Journal of Cognitive Neuroscience. 21 (10): 1869–81. doi:10.1162/jocn.2009.21134. PMID 18823243. S2CID 17434150. 8. ^ a b c d e f Niccolai V, Jennes J, Stoerig P, Van Leeuwen TM (2012). "Modality and variability of synesthetic experience". The American Journal of Psychology. 125 (1): 81–94. doi:10.5406/amerjpsyc.125.1.0081. PMID 22428428. 9. ^ Haack, Paul A.; Radocy, Rudolf E. (1981-07-01). "A Case Study of a Chromesthetic". Journal of Research in Music Education. 29 (2): 85–90. doi:10.2307/3345016. ISSN 0022-4294. JSTOR 3345016. S2CID 144842634. 10. ^ a b c d e f Jewanski J, Simner J, Day SA, Rothen N, Ward J (November 2019). "The evolution of the concept of synesthesia in the nineteenth century as revealed through the history of its name". Journal of the History of the Neurosciences. 29 (3): 259–285. doi:10.1080/0964704X.2019.1675422. PMC 7446036. PMID 31702956. 11. ^ Jewanski J, Day SA, Ward J (July 2009). "A colorful albino: the first documented case of synaesthesia, by Georg Tobias Ludwig Sachs in 1812". Journal of the History of the Neurosciences. 18 (3): 293–303. doi:10.1080/09647040802431946. PMID 20183209. S2CID 8641750. 12. ^ Forster MN, ed. (2002-09-05). "Treatise on the Origin of Language (1772)". Herder: Philosophical Writings (1st ed.). Cambridge University Press. pp. 65–164. doi:10.1017/cbo9781139164634.007. ISBN 978-0-521-79088-8. Retrieved 2020-06-22. 13. ^ "Zwangsmässige Lichtempfindungen durch Schall und verwandte Erscheinungen auf dem Gebiete der anderen Sinnesempfindungen". Nature. 24 (603): 51–52. May 1881. Bibcode:1881Natur..24...51.. doi:10.1038/024051a0. ISSN 0028-0836. S2CID 43201081. 14. ^ a b c d Ward J (2013-01-03). "Synesthesia". Annual Review of Psychology. 64 (1): 49–75. doi:10.1146/annurev-psych-113011-143840. PMID 22747246. 15. ^ a b c Zdzinski SF, Ireland SJ, Wuttke BC, Belen KE, Olesen BC, Doyle JL, Russell BE (February 2019). "An Exploratory Neuropsychological Case Study of Two Chromesthetic Musicians". Research Perspectives in Music Education. 20 (1): 65–82. 16. ^ a b c d e f g h i j Specht K (March 2012). "Synaesthesia: cross activations, high interconnectivity, and a parietal hub". Translational Neuroscience. 3 (1): 15–21. doi:10.2478/s13380-012-0007-z. S2CID 143228367. 17. ^ Brang D, Williams LE, Ramachandran VS (May 2012). "Grapheme-color synesthetes show enhanced crossmodal processing between auditory and visual modalities". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 48 (5): 630–7. doi:10.1016/j.cortex.2011.06.008. PMID 21763646. S2CID 10497638. 18. ^ a b c Grossenbacher PG, Lovelace CT (January 2001). "Mechanisms of synesthesia: cognitive and physiological constraints". Trends in Cognitive Sciences. 5 (1): 36–41. doi:10.1016/s1364-6613(00)01571-0. PMID 11164734. S2CID 15092606. 19. ^ Dovern A, Fink GR, Fromme AC, Wohlschläger AM, Weiss PH, Riedl V (May 2012). "Intrinsic network connectivity reflects consistency of synesthetic experiences". The Journal of Neuroscience. 32 (22): 7614–21. doi:10.1523/JNEUROSCI.5401-11.2012. PMC 6703581. PMID 22649240. 20. ^ a b c d Luke DP, Terhune DB (October 2013). "The induction of synaesthesia with chemical agents: a systematic review". Frontiers in Psychology. 4: 753. doi:10.3389/fpsyg.2013.00753. PMC 3797969. PMID 24146659. 21. ^ a b van Campen C (2019-09-09). "Exploring Drug-Induced Synesthesia". The MIT Press Reader. Retrieved 2020-06-23. 22. ^ Bressloff PC, Cowan JD, Golubitsky M, Thomas PJ, Wiener MC (March 2002). "What geometric visual hallucinations tell us about the visual cortex". Neural Computation. 14 (3): 473–91. doi:10.1162/089976602317250861. PMID 11860679. S2CID 207683037. 23. ^ Robertson LC, Sagiv N (2004-10-14). Synesthesia: Perspectives from Cognitive Neuroscience. Oxford University Press. ISBN 978-0-19-029028-3. 24. ^ a b c "Synesthete-composers-and-musicians". www.daysyn.com. Retrieved 2019-10-15. 25. ^ "Tenor Keeps Screwing Up while Bernstein Conducts - Awkward Sequence" – via www.youtube.com. 26. ^ a b c d e f g Galeyev BM, Vanechkina IL (2001). "Was Scriabin a Synesthete?". Leonardo. 34 (4): 357–361. doi:10.1162/00240940152549357. ISSN 0024-094X. JSTOR 1577166. S2CID 57564192. 27. ^ Altman MJ (2017-08-24). "The Theosophical Quest for Occult Power". Oxford Scholarship Online. doi:10.1093/acprof:oso/9780190654924.003.0005. 28. ^ a b Peacock K (1985). "Synesthetic Perception: Alexander Scriabin's Color Hearing". Music Perception: An Interdisciplinary Journal. 2 (4): 483–505. doi:10.2307/40285315. ISSN 0730-7829. JSTOR 40285315. 29. ^ Harrison JE (2001). Synaesthesia : the strangest thing. Oxford: Oxford University Press. ISBN 0-19-263245-0. OCLC 45446164. 30. ^ Altenmüller E (2015). "Alexander Scriabin: his chronic right-hand pain and Its impact on his piano compositions". Progress in Brain Research. 216: 197–215. doi:10.1016/bs.pbr.2014.11.031. ISBN 978-0-444-63410-8. PMID 25684291. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Chromesthesia	None	29,042	wikipedia	https://en.wikipedia.org/wiki/Chromesthesia	2021-01-18T18:51:40	{"wikidata": ["Q2088820"]}
A number sign (#) is used with this entry because autosomal recessive spastic paraplegia-35 (SPG35) and its related phenotypes are caused by homozygous mutation in the gene encoding fatty acid 2-hydroxylase (FA2H; 611026). Description Autosomal recessive spastic paraplegia-35 is a complicated form of SPG characterized by childhood onset of gait difficulties due to progressive spastic paraparesis, dysarthria, and mild cognitive decline associated with leukodystrophy on brain imaging. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur (summary by Dick et al., 2010). In addition, some patients with mutations in the FA2H gene have radiographic evidence of neurodegeneration with brain iron accumulation (NBIA), thus expanding the phenotype. Kruer et al. (2010) referred to this phenotypic spectrum of disorders as fatty acid hydrolase-associated neurodegeneration (FAHN). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). Clinical Features Dick et al. (2008) identified a large consanguineous Omani family in which 7 individuals had spastic paraplegia. Affected individuals presented between 6 and 11 years with foot drop and difficulty walking. There was rapid progression over the following 2 to 4 years with steadily increasing lower and then upper limb spasticity with hyperreflexia and extensor plantar responses, resulting in complete dependence by age 25. Variable features included dysarthria, ankle clonus, and increased muscle tone in the lower limbs. Two individuals had minor well-controlled seizures, 1 had urinary frequency and nocturnal enuresis, and most had progressive cognitive decline. Brain MRI of the proband showed no abnormalities. Four patients became wheelchair-bound in early adulthood, and the disorder made normal schooling impossible. Dick et al. (2010) provided follow-up of the family reported by Dick et al. (2008). Brain MRI of 1 affected individual at age 9 years showed T2 hyperintense lesions in the parietal and occipital periventricular white matter as well as scattered subcortical T2 hyperintensities. Edvardson et al. (2008) reported 2 sisters, from a consanguineous Arab Muslim family, who developed walking difficulties due to spasticity at ages 4 and 6 years, respectively. Brain MRI in 1 was normal; brain MRI was not performed in the other child. There was no disease progression by ages 12 and 10, respectively. Edvardson et al. (2008) considered the phenotype in these patients to be consistent with a form of hereditary spastic paraplegia, and noted that SPG35 maps to chromosome 16q, close to the FA2H gene. Edvardson et al. (2008) reported 7 patients from 2 consanguineous Arab Muslim families who presented at age 4 to 6 years with lower limb spasticity and gait disturbance after normal early childhood development. There was rapid progression of the disorder, with generalized dystonia, upper limb spasticity, dysarthria, and cognitive decline with loss of ability to read and write. Five of the 7 became wheelchair-bound by age 14 years. Other features included cerebellar signs with dysmetria and dysdiadochokinesis, and extensor plantar responses. Visual evoked potentials were delayed in 1 patient who was tested, suggesting a demyelinating process. Brain MRI of several affected individuals from both families revealed prolonged relaxation time of the posterior periventricular white matter, which progressed to involve the posterior limbs of the internal capsules and the corticospinal tracts. There was thinning of the corpus callosum and the pons, as well as cerebellar atrophy. Sural nerve biopsy was essentially normal, suggesting sparing of peripheral myelin. Edvardson et al. (2008) noted that the phenotype in these 2 families was consistent with a form of complicated SPG, but emphasized the MRI findings, and suggested that it should also be regarded as a new form of leukodystrophy. Dick et al. (2010) reported a consanguineous Pakistani family in which 4 individuals had SPG35. The proband developed gait disturbances due to spastic paraparesis at age 4 years, and became wheelchair-bound at age 10. She also developed progressive dysarthria, bilateral optic atrophy, ophthalmoplegia, and dystonia. She had a low IQ of 59, attributable mainly to a hypoxic episode in infancy. However, other affected family members were reported to have a similar disorder with cognitive defects, and 2 had died at a young age. Brain MRI of the proband showed T2 hyperintensities in the white matter, involving the internal capsules, cerebrum, and cerebellum. There was atrophy of the corpus callosum, brainstem, and cerebellum. Kruer et al. (2010) reported 3 Italian brothers from a consanguineous family who presented with gait impairment and frequent falls due to spastic paraplegia between ages 4 and 5 years. The disorder was progressive, with later development of ataxia, dysmetria, spastic quadriparesis, optic atrophy, ocular apraxia, dysarthria, and scoliosis. Two died from respiratory complications in their late twenties, and 1 developed seizures. Cognition was relatively preserved. Two brothers from an Albanian family had a similar disorder, with mild cognitive impairment, dystonia, dysarthria, and bladder and bowel incontinence. Brain imaging in 1 brother from each family showed T2 hypointensity in the globus pallidus bilaterally, consistent with iron deposition. There was also pontocerebellar atrophy, mild generalized cortical atrophy, thinning of the corpus callosum, and periventricular T2 white matter hyperintensities. On retrospective brain image analysis of a patient reported by Edvardson et al. (2008) and Dick et al. (2010), Kruer et al. (2010) noted that both patients also had evidence of brain iron accumulation in the globus pallidus. Pierson et al. (2012) reported a 10-year-old boy, born of unrelated parents, with a complicated form of SPG35. The patient developed normally until age 3 years, when he developed progressive neurodegeneration following a febrile illness. He had lower extremity weakness and atrophy, spasticity, dystonic foot inversion, and poor balance. He also had dysarthria, neck weakness, mask-like facies, hunched posture, and mild cognitive deficits, but did not have optic atrophy or seizures. Serial brain MRIs showed progressive neurodegenerative changes, with white matter abnormalities, cerebellar and brainstem atrophy, thin corpus callosum, and evidence of demyelination. He also had an axonal sensory neuropathy. High-throughput sequencing identified compound heterozygosity for a missense mutation and deletion involving the FA2H gene (611026.0007 and 611026.0008). Mapping By genomewide linkage analysis of an Omani family with autosomal recessive spastic paraplegia, Dick et al. (2008) identified a homozygous candidate region on chromosome 16q21-q23.1 between markers rs149428 and rs9929635 (maximum multipoint lod score of 4.86). This 20.4-Mb (3.25-cM) region, designated SPG35, cosegregated with disease status and was not homozygous in the unaffected family members. Genetic sequencing excluded mutations in the VPS4A (609982) and DYNC1LI2 (611406) genes. Molecular Genetics In affected members of 2 unrelated consanguineous families with complicated spastic paraparesis and leukodystrophy, Edvardson et al. (2008) identified a homozygous mutation in the FA2H gene (611026.0001). Affected individuals from a third family with spastic paraparesis were found to have a different homozygous mutation in the FA2H gene (611026.0002). The relatively late onset of the disorders was consistent with the proposed need for FA2H at later stages of myelin maturation. In affected members of an Omani family (Dick et al., 2008) and a Pakistani family with complicated SPG35, Dick et al. (2010) identified 2 different homozygous mutations in the FA2H gene (611026.0003 and 611026.0004, respectively). The findings indicated that mutations in FA2H are associated with SPG35, and that abnormal hydroxylation of myelin galactocerebroside lipid components can lead to a severe progressive phenotype, with a clinical presentation of complicated SPG and radiological features of leukodystrophy. Kruer et al. (2010) identified 2 different homozygous mutations in the FA2H gene (611026.0005 and 611026.0006) in affected members from 2 unrelated families with progressive complicated spastic paraplegia associated with brain iron deposition in the globus pallidus. The authors noted the connection between leukodystrophy and neurodegeneration with brain iron accumulation. Pathogenesis Drecourt et al. (2018) found that cells derived from patients with FA2H mutations showed a significant increase (10- to 30-fold change) in cellular iron content when incubated with iron compared to controls. In response to high iron, patient cells showed a normal and appropriate decrease in transferrin receptor (TFRC; 190010) mRNA levels, but the amount of TFRC did not decrease in patient cells, suggesting impaired posttranslational lysosomal-based degradation of TFRC. Patient cells showed impaired transferrin (190000) and TFRC trafficking and recycling compared to controls, with clustering at the surface and in the perinuclear region, as well as abnormally enlarged lysosomes. Patient cells also showed decreased palmitoylation of TFRC, which is necessary for regulating TFRC endocytosis. Addition of the antimalarial agent artesunate rescued abnormal TFRC palmitoylation and decreased iron content in cultured patient fibroblasts. Similar findings were observed in studies of cells from NBIA patients due to mutations in other NBIA-associated genes. Drecourt et al. (2018) concluded that these forms of NBIA result from defective endosomal recycling and should be regarded as disorders of cellular trafficking, whatever the original genetic defect. Population Genetics Donkervoort et al. (2014) identified a homozygous 2-bp deletion in the FA2H gene (c.509_510delAC; 611026.0006) in a brother and sister from Montenegro with SPG35. Both children had typical features of the disorder, but no brain iron accumulation was seen on brain MRI. Donkervoort et al. (2014) noted that this mutation had been identified by Kruer et al. (2010) in 2 brothers from Albania who had a similar neurodegenerative disorder with brain iron accumulation, suggesting that it may represent a founder mutation in individuals from the Balkan region. The findings indicated that additional factors likely contribute to phenotypic variability in this disorder. Liao et al. (2015) identified pathogenic biallelic mutations in the FA2H gene in 3 patients from 2 unrelated Chinese families with SPG35. The patients were ascertained from a larger cohort of 97 probands with autosomal recessive SPG who underwent direct sequencing of the FA2H gene; mutations in several common forms of autosomal recessive SPG had been excluded in these patients. The phenotype was similar to that previously reported: patients had onset of progressive spasticity of the lower limbs in the first or second decade and variable cognitive impairment. The patient with no family history also had ocular motility deficits, ataxia, and seizures. Liao et al. (2015) concluded that SPG35 accounts for 2.1% of autosomal recessive SPG in the Chinese population. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- External ophthalmoplegia (less common) \- Optic atrophy \- Nystagmus \- Strabismus GENITOURINARY Bladder \- Urinary urgency \- Incontinence (variable) NEUROLOGIC Central Nervous System \- Spasticity, primarily lower limbs, but upper limbs may be involved \- Gait difficulties \- Spastic quadriparesis \- Ataxia \- Hyperreflexia \- Dystonia \- Dysarthria \- Dysmetria \- Cognitive decline \- Poor school performance \- Extensor plantar responses \- Seizures \- Thinning of the corpus callosum \- Brainstem atrophy \- Cerebellar atrophy \- Leukodystrophy, dysmyelinating \- Periventricular white matter abnormalities \- White matter hyperintensities in T2 imaging \- Iron deposition in the globus pallidus (variable) MISCELLANEOUS \- Onset between 3 and 11 years of age \- Progressive disorder \- Most patients become wheelchair-bound in adolescence or as young adults MOLECULAR BASIS \- Caused by mutation in the fatty acid 2-hydroxylase gene (FA2H, 611026.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE	c3668943	29,043	omim	https://www.omim.org/entry/612319	2019-09-22T16:01:49	{"doid": ["0110786"], "mesh": ["C580102"], "omim": ["612319"], "orphanet": ["329308", "171629"], "synonyms": ["Alternative titles", "FATTY ACID HYDROXYLASE-ASSOCIATED NEURODEGENERATION", "LEUKODYSTROPHY, DYSMYELINATING, AND SPASTIC PARAPARESIS WITH OR WITHOUT DYSTONIA"], "genereviews": ["NBK56080"]}
Glycogen storage disease type 0 (also known as GSD 0) is a condition caused by the body's inability to form a complex sugar called glycogen, which is a major source of stored energy in the body. GSD 0 has two types: in muscle GSD 0, glycogen formation in the muscles is impaired, and in liver GSD 0, glycogen formation in the liver is impaired. The signs and symptoms of muscle GSD 0 typically begin in early childhood. Affected individuals often experience muscle pain and weakness or episodes of fainting (syncope) following moderate physical activity, such as walking up stairs. The loss of consciousness that occurs with fainting typically lasts up to several hours. Some individuals with muscle GSD 0 have a disruption of the heart's normal rhythm (arrhythmia) known as long QT syndrome. In all affected individuals, muscle GSD 0 impairs the heart's ability to effectively pump blood and increases the risk of cardiac arrest and sudden death, particularly after physical activity. Sudden death from cardiac arrest can occur in childhood or adolescence in people with muscle GSD 0. Individuals with liver GSD 0 usually show signs and symptoms of the disorder in infancy. People with this disorder develop low blood sugar (hypoglycemia) after going long periods of time without food (fasting). Signs of hypoglycemia become apparent when affected infants begin sleeping through the night and stop late-night feedings; these infants exhibit extreme tiredness (lethargy), pale skin (pallor), and nausea. During episodes of fasting, ketone levels in the blood may increase (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars (such as glycogen) are unavailable. These short-term signs and symptoms of liver GSD 0 often improve when food is eaten and sugar levels in the body return to normal. The features of liver GSD 0 vary; they can be mild and go unnoticed for years, or they can include developmental delay and growth failure. ## Frequency The prevalence of GSD 0 is unknown; fewer than 10 people with the muscle type and fewer than 30 people with the liver type have been described in the scientific literature. Because some people with muscle GSD 0 die from sudden cardiac arrest early in life before a diagnosis is made and many with liver GSD 0 have mild signs and symptoms, it is thought that GSD 0 may be underdiagnosed. ## Causes Mutations in the GYS1 gene cause muscle GSD 0, and mutations in the GYS2 gene cause liver GSD 0. These genes provide instructions for making different versions of an enzyme called glycogen synthase. Both versions of glycogen synthase have the same function, to form glycogen molecules by linking together molecules of the simple sugar glucose, although they perform this function in different regions of the body. The GYS1 gene provides instructions for making muscle glycogen synthase; this form of the enzyme is produced in most cells, but it is especially abundant in heart (cardiac) muscle and the muscles used for movement (skeletal muscles). During cardiac muscle contractions or rapid or sustained movement of skeletal muscle, glycogen stored in muscle cells is broken down to supply the cells with energy. The GYS2 gene provides instructions for making liver glycogen synthase, which is produced solely in liver cells. Glycogen that is stored in the liver can be broken down rapidly when glucose is needed to maintain normal blood sugar levels between meals. Mutations in the GYS1 or GYS2 gene lead to a lack of functional glycogen synthase, which prevents the production of glycogen from glucose. Mutations that cause GSD 0 result in a complete absence of glycogen in either liver or muscle cells. As a result, these cells do not have glycogen as a source of stored energy to draw upon following physical activity or fasting. This shortage of glycogen leads to the signs and symptoms of GSD 0. ### Learn more about the genes associated with Glycogen storage disease type 0 * GYS1 * GYS2 ## 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Glycogen storage disease type 0	c1855861	29,044	medlineplus	https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-0/	2021-01-27T08:25:19	{"gard": ["2513"], "mesh": ["C565485"], "omim": ["240600", "611556"], "synonyms": []}
A rare, acquired, subepidermal autoimmune bullous disease characterized by polymorphic cutaneous lesions (blisters, urticarial lesions or scars/milia) associated with imunoglubulin G deposition in the basement membrane zone. Lesions are frequently localized on extremities, trunk, palmoplantar and cephalic areas as well as mucous membranes. ## Epidemiology Approximately 115 cases been reported in the literature to date. A male predominant of about 2:1 is observed. ## Clinical description The disease predominantly affects elderly people (mean age 66 years, range 28-91). Cutaneous lesions are polymorphic, but typically include itchy erythematous lesions and tense blisters, vesicles, and erosions on trunk and extremities, with possibly predominant palmoplantar involvement. In some cases, patients can have annularly arranged lesions. Usually, lesions heal without scarring, and milia formation has only been reported in few cases. About half of the patients have mucosal involvement affecting either oral or anogenital mucosa, or both. In Japanese patients, coexisting (mostly preexisting) psoriasis may be present (30% of cases). ## Etiology The exact etiology is unknown, but may be related to laminin gamma-1, consistent with the identified characteristics of the p200 protein (an acidic non-collagenous N-linked glycoprotein localized within the lower lamina lucida outside of hemidesmosomes). ## Diagnostic methods Diagnosis is based on the combination of the clinical features and direct immunofluorescence microscopy showing linear deposits of IgG and/or C3 at the dermal-epidermal junction in an n-serrated pattern and is confirmed by detection of a 200-kDa band by immunoblotting of patients' serum on human dermal extracts. About 90% of patients' sera are positive for anti-laminin-gamma 1 reactivity on ELISA or immunoblotting. ## Differential diagnosis Differential diagnosis includes bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid, IgA linear bullous dermatosis, pemphigus herpetiform, and pemphigus. ## Management and treatment The treatment may follow that of bullous pemphigoid. Super-potent topical corticosteroids may be applied on the whole-body surface or tapering doses of prednisolone 0.5 mg/kg/day, frequently associated with dapsone. Doxycycline, azathioprine and ciclosporine can also be used. ## Prognosis Prognosis is variable. Most patients achieve complete remission on therapy. The use of systemic corticosteroid treatment may contribute to higher mortality rate in the older patients. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Anti-p200 pemphigoid	None	29,045	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=454710	2021-01-23T17:29:34	{"icd-10": ["L12.8"]}
For a general phenotypic description of insulin-dependent diabetes mellitus, see IDDM1 (222100). Mapping To identify novel loci predisposing to insulin-dependent diabetes mellitus, Field et al. (1994) studied 250 families with more than one diabetic child. Affected sib-pair linkage analysis revealed strong evidence for an IDDM susceptibility locus near D15S107 on chromosome 15q26. Field et al. (1994) designated the locus IDDM3. In an independent study, Luo et al. (1995) confirmed linkage to 15q. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	DIABETES MELLITUS, INSULIN-DEPENDENT, 3	c1838262	29,046	omim	https://www.omim.org/entry/600318	2019-09-22T16:16:17	{"mesh": ["C563960"], "omim": ["600318"], "synonyms": ["Alternative titles", "INSULIN-DEPENDENT DIABETES MELLITUS 3"]}
A number sign (#) is used with this entry because Cockayne syndrome A (CSA) is caused by homozygous or compound heterozygous mutation in the gene encoding the group 8 excision repair cross-complementing protein (ERCC8; 609412) on chromosome 5q11. Description Cockayne syndrome is characterized by abnormal and slow growth and development that becomes evident within the first few years after birth. 'Cachectic dwarfism' describes the outward appearance of afflicted individuals. Other features include cutaneous photosensitivity, thin, dry hair, a progeroid appearance, progressive pigmentary retinopathy, sensorineural hearing loss, dental caries, and a characteristic stance in the ambulatory patient. Patients often show disproportionately long limbs with large hands and feet, and flexion contractures of joints are usual skeletal features. Knee contractures result in a 'horse-riding stance.' There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. The mean age at death in reported cases is 12.5 years, although a few affected individuals have lived into their late teens or twenties. Remarkably, in striking contrast with xeroderma pigmentosum, patients with CS have no significant increase in skin cancer or infection (Nance and Berry, 1992). Lowry (1982) noted that there is an early-onset form of Cockayne syndrome in which patients may show abnormalities at birth and have a shorter survival. Lowry (1982) thus suggested that CS could be divided clinically into the more common type I, with classic CS symptoms that manifest within the first few years or life, and the less common type II, with more severe symptoms that manifest prenatally. Mallery et al. (1998) found no correlation between genotype and phenotype among 16 patients with CS of varying severities, and concluded that clinical differences were based on other genetic backgrounds or the intrauterine environment. ### Genetic Heterogeneity of Cockayne Syndrome Cockayne syndrome is a genetically heterogeneous disorder, and certain types show some overlap with certain forms of xeroderma pigmentosum (XP), another disorder caused by defective DNA repair. See also Cockayne syndrome B (133540), caused by mutation in the ERCC6 gene (609413) on chromosome 10q11; XPG/CS (see 278780), caused by mutation in the ERCC5 gene (133530) on chromosome 13q33; XPB/CS (see 610651), caused by mutation in the ERCC3 gene (133510) on chromosome 2q21; and XPF/CS (see 278760), caused by mutation in the ERCC4 gene (133520) on chromosome 16p13. Rapin et al. (2000) reviewed the clinical, pathologic, and molecular features of Cockayne syndrome, xeroderma pigmentosum, and the XP-CS complex. Clinical Features In 2 sibs of nonconsanguineous parents, Neill and Dingwall (1950) described a progeria-like syndrome characterized by dwarfism, microcephaly, severe mental retardation, 'pepper-and-salt' chorioretinitis, and intracranial calcification. The diagnosis may have been Cockayne syndrome. Death from early atherosclerosis occurred in these sibs, as in progeria (Neill, 1966). Examination of the brain of the 2 sibs showed massive pericapillary calcification in the putamina, thalami and cerebellar white matter superficial to the dentate nuclei. In the larger vessels the calcification was mainly in the adventitial coat (Norman, 1963). Paddison et al. (1963) reported a striking pedigree with Cockayne syndrome. In 4 patients with Cockayne syndrome, Brumback et al. (1978) noted development of the triad of normal pressure hydrocephalus: dementia, gait disturbance, and incontinence. Higginbottom et al. (1979) noted that hypertension and renal disease are frequent complications of Cockayne syndrome. Bensman et al. (1982) found decreased or undetectable thyroid hormone in the serum of 7 cases of CS. Sato et al. (1988) reviewed renal lesions. Early onset was described by Houston et al. (1982) and by Moyer et al. (1982). In studies of 3 sibs with Cockayne syndrome, Smits et al. (1982) found segmental de- and remyelination with onion-bulb formation in sural nerve biopsies and disturbed visual and brainstem auditory evoked responses indicative of CNS demyelination. They suggested that this finding supports the theory that Cockayne syndrome is a leukodystrophy, as first proposed by Moosa and Dubowitz (1970). Patton et al. (1989) described 2 cases of early-onset Cockayne syndrome in unrelated infants. In both, striking failure of growth and developmental deterioration began around 6 months of age. Studies of cultured fibroblasts showed the characteristics typical of Cockayne syndrome, and examination of the brain in 1 patient who died at the age of 34 months showed leukodystrophy with 'tigroid' demyelinization similar to that reported in later-onset cases of Cockayne syndrome. Although the disorder resembled cerebrooculofacioskeletal syndrome (COFS; 214150), the pathologic and fibroblast studies seemed to indicate that it was the same as Cockayne syndrome. Traboulsi et al. (1992) described the ocular findings in 8 patients varying in age from 1 to 25 years. Strabismus was present in 4 patients and cataracts in 2, while 3 had nystagmus. Visual acuity was relatively well preserved in 6 patients, including a 25-year-old man with a visual acuity of 20/60 in each eye despite advanced retinal pigmentary changes. In an exhaustive review, Nance and Berry (1992) commented that in contrast to other disorders of DNA repair, cancer has not been reported as a feature of classic CS. Furthermore, there appears to be no predisposition to infectious complications. The authors emphasized probable heterogeneity. Mahmoud et al. (2002) reported 3 sisters showing clinical features and investigational findings of CS. The 12-year-old proband had typical features of CS. She had no apparent problems until the end of the first year when growth and developmental delay prompted medical evaluation. Brain CT, bone x-rays, and auditory and ophthalmologic evaluation confirmed the clinical impression of CS. Her 2 sisters were later found to have CS. The sisters varied in clinical severity as 2 of them, including the proband, had cataracts and early global delay and died early of inanition and infection. The third had a normal course until the age of 2 years when she started to show deceleration in growth and delay in development. She exhibited mental retardation but did not have cataract and was still ambulatory at the age of 10 years. The parents were not related and the father was married to 2 other wives with 11 unaffected children. Upon analysis of cerebrospinal fluid neurotransmitters in a 16-year-old Sri Lankan male with Cockayne syndrome, Ellaway et al. (2000) found a decreased level of 5-hydroxyindole acetic acid and a normal level of homovanillic acid, with a consequent low 5-hydroxyindole acetic acid:homovanillic acid ratio. Peripheral serotonin levels, platelet serotonin, and urinary 5-hydroxyindole acetic acid levels, plasma phenylalanine levels, and dihydropteridine reductase activity were all normal. In view of these findings, the primary disorder of central serotonin metabolism was considered and the proband was treated with 5-hydroxytryptophan. There was no clinical improvement over a period of 2 years, but his cognitive function, tremor, and gait did not deteriorate. Ellaway et al. (2000) also measured resting energy expenditure and found this to be 75% of the predicted value; they suggested that this situation in Cockayne syndrome might be similar to that of anorexia nervosa, where resting energy expenditure is reduced but normalizes upon refeeding, with concomitant increases in body weight. Wilson et al. (2016) reviewed the features and made recommendations regarding the evaluation of 102 patients, 44 females and 58 males, with Cockayne syndrome A or B. The mean age of recruited individuals was 11.5 years, with a range of 3 months to 39 years. All patients were microcephalic and had growth failure leading to proportionate short stature. At the time of the analysis, 28 individuals had died, with a mean age of death of 8.4 years with a range of 17 months to 30 years. The most prevalent features were cold extremities and abnormal brain imaging present in over 80% of individuals, followed by weakness, hearing loss, clinical photosensitivity, tremor, joint contractures, abnormal liver function tests, and abnormal bowel movements, present in over 60% but less than 80%. Cataracts were present in about 50% and were likely to be seen by age 4 years. The majority of patients with abnormal brain imaging had calcifications and white matter changes, with a minority having cerebellar corpus callosum or ventriculomegaly abnormalities. Lower extremity joint contractures were more common than upper extremity ones. Cataracts were more likely to be bilateral. Most patients had low-normal birth growth parameters but rapidly fell off the growth charts postnatally. The authors noted that early development may appear to be normal and suggested that developmental delay may be a poor discriminating factor for early diagnosis. The authors suggested that Cockayne syndrome should be suspected in any child with postnatal growth failure, microcephaly, and any 2 of the following: persistently cold hands and feet, bilateral hearing loss, dermal photosensitivity, intention tremor, joint contractures, progressive loss of body fat, cataracts, or typical facial features. Using these criteria increased clinical recognition of Cockayne syndrome in their cohort of 102 patients to around 90%. The authors cautioned that metronidazole causes acute hepatic failure in Cockayne syndrome, which may be fatal and should be avoided in anyone with a suspected diagnosis of Cockayne syndrome. The authors noted that the phenotypic discordance between sibs is not unusual. The only identified association with younger age at death in Cockayne syndrome was with early onset of cataracts (less than 3 years of age). This association was statistically significant (p = 1.36 x 10(-6)); at 5 years, survival is about 60% for those patients with early cataracts and 95% for those without. Wilson et al. (2016) also found a significant association between early cataracts and the time to development of hearing loss and of contractures, but not of tremor or loss of subcutaneous fat. Degree of photosensitivity was not associated with survival or time until the onset of tremor. Biochemical Features Schmickel et al. (1977) showed that fibroblasts from 2 unrelated children with Cockayne syndrome exhibited increased sensitivity to UV irradiation, but not to X-irradiation, as measured by colony-forming ability. In addition, both cell lines showed normal rates of removal of thymidine dimers. Andrews et al. (1978) found that CS fibroblasts had markedly decreased post-UV light colony-forming ability compared to controls. However, the patients' fibroblasts had normal rates of UV-induced unscheduled DNA synthesis, indicating that the defect in these cells was not due to abnormal DNA excision repair. The findings differentiated CS from xeroderma pigmentosum, in which DNA excision repair is deficient. Hoar and Waghorne (1978) found normal UV-induced unscheduled DNA synthesis and normal post-replication repair in CS cells. Mayne and Lehmann (1982) showed that cells from patients with Cockayne syndrome failed to recover RNA synthesis after UV irradiation despite normal excision and daughter-strand repair pathways. The findings indicated that recovery of RNA synthesis is an important early response to UV irradiation. Schweiger et al. (1987) suggested that the defect in DNA repair in Cockayne syndrome is located beyond incision, exonuclease reaction, and DNA synthesis, and that it may involve a defect in DNA ligase. Venema et al. (1990) demonstrated a defect in preferential DNA repair of transcriptionally active DNA in Cockayne syndrome. Cells from normal controls repaired UV-induced pyrimidine dimers at a faster rate in transcriptionally active DNA when compared to a nontranscribed locus or to the genome overall. In contrast, cells from CS patients were unable to repair transcriptionally active DNA as rapidly and efficiently as normal cells, although repair occurred at a slower rate similar to that of untranscribed DNA. Venema et al. (1990) concluded that CS fibroblasts have lost the preferential repair of active genes but are proficient in overall genome repair. Venema et al. (1990) suggested that the results help to elucidate the pleiotropic clinical effects associated with disorders having defects in the repair of DNA damage. In particular, neurodegeneration appeared to be associated with the loss of preferential repair of active genes and not simply correlated with reduced levels of overall repair. Lehmann et al. (1993) found failure of RNA synthesis to recover to normal rates after UV irradiation in cells from 29 of 52 patients for whom the clinical diagnosis of Cockayne syndrome was considered a possibility; the other 23 had a normal response. From review of the clinical details, they concluded that, apart from the cardinal features of dwarfism and mental retardation, sun sensitivity correlated best with a positive cellular diagnosis. Pigmentary retinopathy, gait defects, and dental caries were also good indicators, although several patients with a positive cellular diagnosis did not have these features. Van Oosterwijk et al. (1996) examined the sensitivity of CSA and CSB fibroblast cells to the DNA damaging agent N-acetoxy-2-acetylaminofluorene (NA-AAF), which mimics UV irradiation. They found that although CS cells are 3-fold more sensitive to NA-AAF than are normal cells and are unable to recover the ability to synthesize RNA, this sensitivity is not due to defective transcription-coupled repair of active genes. They concluded that a transcription defect is the underlying cause of the hypersensitivity and prolonged repressed RNA synthesis. ### Complementation Groups A and B Tanaka et al. (1981) used cell fusion techniques to demonstrate that there are at least 2 complementation groups in Cockayne syndrome. Fusion between certain cell lines allowed recovery of a nearly normal rate of semiconservative DNA synthesis after UV irradiation. Lehmann (1982) performed cell fusion studies on cultured cells from 11 patients with Cockayne syndrome. The 11 cell lines were assigned to 3 complementation groups: 2 to group A, 8 to group B, and 1 to group C. The group C patient was thought to have xeroderma pigmentosum also and was the sole known representative of the XP complementation group B (133510). The patient had clinical as well as biologic features of both disorders. See 610651. Jaeken et al. (1989) studied 3 patients with unusually severe CS. Unlike classic CS, the disorder had its onset in the first weeks of life and led to unusually early death. Fibroblasts from 2 of the patients showed a complete defect in the repair of UV-induced thymine dimer lesions; the fibroblasts were unable to remove thymine dimer lesions from their DNA, had a severe reduction of RNA synthesis rates after UV irradiation, and showed no reactivation of a UV-inactivated indicator gene and no DNA recondensation after UV irradiation. DNA repair investigated in these 2 strains resembled that of xeroderma pigmentosum cells of complementation group A (278700). In contrast, fibroblasts from the third patient showed the same in vitro repair characteristics as classic CS cells. The findings in the 2 patients with a complete defect of thymine dimer removal supported the suggestion of Marshall et al. (1980) that there are transitional forms between CS and XP, since in the various forms of the latter condition (with the exception of XP variant), removal of pyrimidine dimer lesions is the underlying defect. Preliminary complementation experiments indicated that the 3 patients belonged to CS complementation group A. Stefanini et al. (1996) analyzed cell cultures from 22 Cockayne syndrome donors from different countries and different racial groups. In particular, they tested the cultures for complementation, which they defined as the restoration of normal RNA synthesis rates in UV-irradiated heterokaryons. Cultures from 5 patients were assigned to complementation group A and the remaining 17 were assigned to complementation group B. The authors detected no distinctions (racial, clinical, or cellular) between the 2 complementation groups. Diagnosis ### Prenatal Diagnosis Sugita et al. (1982) made the prenatal diagnosis of Cockayne syndrome on the basis of sensitivity of amniocytes to ultraviolet light. Colony-forming ability of the cells from the affected fetus was reduced after UV exposure as compared with normals. Lehmann et al. (1985) demonstrated the feasibility of prenatal diagnosis by study of RNA synthesis in cultured amniotic cells after irradiation with ultraviolet light. Not only are cultured cells from CS patients hypersensitive to the lethal effects of UV and some chemical carcinogens, but also the normal recovery in DNA and RNA synthesis after UV exposure does not occur (Mayne and Lehmann, 1982). A prenatal test based on this observation is simple and rapid and its outcome is unambiguous. Clinical Management Neilan et al. (2008) reported 3 adolescent patients with Cockayne syndrome who showed a clear reduction in tremors and improvement in fine hand movements, including handwriting, following treatment with carbidopa-levodopa. The findings implicated the dopaminergic pathway in the pathogenesis of this disorder. One of the patients ('patient 3') described by Neilan et al. (2008) was later found to have a different disorder (see 616541). Molecular Genetics Henning et al. (1995) identified mutations in the ERCC8 gene in CSA cDNAs of all CSA cell lines examined, including an identical mutation in 2 CSA sibs (609412.0001). In a cell line from an 11-year-old girl with photophobia, dwarfism, mental retardation, cataracts, retinopathy, and optic atrophy, Cao et al. (2004) identified compound heterozygosity for a nonsense mutation (E13X; 609412.0003) and a missense mutation (A205P; 609412.0005) in the ERCC8 gene. In a cell line from a patient with CSA, Ridley et al. (2005) identified compound heterozygosity for an E13X mutation and a novel missense mutation (A160V; 609412.0004) in the ERCC8 gene. Bertola et al. (2006) analyzed the ERCC8 gene in 8 patients from 6 Brazilian families with typical CSA and identified homozygosity or compound heterozygosity for ERCC8 mutations in all of them. The authors stated that there was no obvious genotype/phenotype correlation across the mutation spectrum. Khayat et al. (2010) analyzed the Y322X ERCC8 mutation (609412.0002) in the Arab Christian population of northern Israel and found a carrier frequency of 6.79. Haplotype analysis as well as the high carrier frequency suggested that Y322X is an ancient founder mutation that may have originated in the Christian Lebanese community. History Edward Alfred Cockayne (1880-1956) was a London physician who concentrated on diseases of children, particularly hereditary diseases. His 'Inherited Abnormalities of the Skin and its Appendages,' published in 1933, was an extensive collation of pedigrees from the literature. Forty years later, McKusick (1973) reviewed the subject of 'genetics and dermatology' under the subtitle 'If I were to rewrite Cockayne's Inherited Abnormalities of the Skin.' McKusick (1973) also provided biographic information on Cockayne, including his important contributions to entomology. Czeizel and Marchalko (1995) used the designation Cockayne syndrome type III for the disorder in a teenaged girl with characteristic somatic manifestations of Cockayne syndrome, particularly a cachectic phenotype. She was not dwarfed (stature was 158 cm) but weighed only 30 kg. Her appearance was normal at birth and during the first postnatal years. Loss of adipose tissue occurred after a third year, resulting in thin, atrophic skin, unusual facies with a slender nose and moderately sunken eyes, and a precociously senile appearance. Bilateral impaired hearing of nerve type occurred from 13 years of age with progression. Ocular abnormalities, starting with bilateral corneal infiltrates and band keratopathy, were noted from the age of 14. Menarche occurred at age 13 years with regular menstrual cycles following. The Wechsler test showed an IQ of 128. Werner syndrome (277700) was excluded on the basis of lack of scleroderma-like skin changes. Lack of cataract and the presence of sensitivity to sunlight and bilateral impaired hearing were also noted. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation \- Severe postnatal growth deficiency \- Cachectic dwarfism HEAD & NECK Head \- Microcephaly \- Mandible prognathism Face \- Loss of facial adipose tissue \- Wizened face Ears \- Malformed ears \- Sensorineural hearing loss Eyes \- Salt and pepper retinal pigmentation \- Pigmentary retinopathy \- Optic atrophy \- Strabismus \- Hyperopia \- Corneal opacity \- Decreased lacrimation \- Nystagmus \- Cataracts Nose \- Slender nose Teeth \- Dental caries \- Delayed eruption of deciduous teeth \- Malocclusion \- Absent/hypoplastic teeth CARDIOVASCULAR Heart \- Cardiac arrhythmias Vascular \- Hypertension ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly GENITOURINARY External Genitalia (Male) \- Cryptorchidism \- Micropenis Kidneys \- Proteinuria \- Renal failure SKELETAL Skull \- Thickened calvarium Spine \- Kyphosis \- Vertebral body abnormalities Pelvis \- Small, squared off pelvis \- Hypoplastic iliac wings Limbs \- Mild to moderate joint limitation Hands \- Sclerotic ivory phalangeal epiphyses SKIN, NAILS, & HAIR \- Precociously senile appearance Skin \- Photosensitivity \- Scarring \- Pigmentation \- Atrophy \- Anhidrosis \- Dry skin \- Decreased subcutaneous adipose tissue Hair \- Thin, dry hair MUSCLE, SOFT TISSUES \- Decreased subcutaneous adipose tissue NEUROLOGIC Central Nervous System \- Mental retardation \- Normal pressure hydrocephalus \- Dementia \- Basal ganglia calcifications \- Patchy demyelination of subcortical white matter \- Seizures \- Cerebral atrophy \- Dysarthric speech Peripheral Nervous System \- Dysmyelination \- Gait disturbance \- Ataxia \- Tremor \- Weakness \- Peripheral neuropathy \- Slowed nerve conduction velocities ENDOCRINE FEATURES \- Irregular menstrual cycles \- Hypogonadism LABORATORY ABNORMALITIES \- Thymic hormone decreased \- At least 2 complementation groups \- Abnormal myelination in sural nerve biopsies \- Disturbed visual and brainstem auditory evoked responses indicative of CNS demyelination \- Increased cellular sensitivity to UV light MISCELLANEOUS \- Phenotypic overlap with xeroderma pigmentosum (see, e.g., 278700 ) \- Genetic heterogeneity (see, e.g., Cockayne syndrome type B, 133540 ) MOLECULAR BASIS \- Caused by mutations in the excision-repair cross-complementing group 8 gene (ERCC8, 609412.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	COCKAYNE SYNDROME A	c0751038	29,047	omim	https://www.omim.org/entry/216400	2019-09-22T16:29:32	{"doid": ["2962"], "mesh": ["D003057"], "omim": ["216400"], "orphanet": ["90322", "191", "90321", "90324"], "genereviews": ["NBK1342"]}
A number sign (#) is used with this entry because of evidence that variation in high density lipoprotein cholesterol levels is associated with variation in the LIPC gene (151670). Molecular Genetics In a metaanalysis of 25 published reports on a SNP in the promoter region of the hepatic lipase gene (-514C-T; 151670.0003), involving 24,000 individuals with measurements of gene activity and lipid profiles, Isaacs et al. (2004) found significant associations between the -514 genotype and hepatic lipase activity and HDL levels. In 5,414 subjects from the cardiovascular cohort of the Malmo Diet and Cancer Study, Kathiresan et al. (2008) studied SNPs in 9 genes, including rs1800775 of LIPC, that had previously been associated with elevated LDL or lower HDL. Kathiresan et al. (2008) replicated the associations with each SNP and created a genotype score on the basis of the number of unfavorable alleles. With increasing genotype scores, the level of LDL cholesterol increased, whereas the level of HDL cholesterol decreased. At 10-year follow-up, the genotype score was found to be an independent risk factor for incident cardiovascular disease (myocardial infarction, ischemic stroke, or death from coronary heart disease); the score did not improve risk discrimination but modestly improved clinical risk reclassification for individual subjects beyond standard clinical factors. Grarup et al. (2008) investigated the effect of a -250G-A variant of the LIPC gene (rs2070895; 151670.0004) on metabolic traits and risk of type 2 diabetes (see 125853) in 5,585 middle-aged treatment-naive Danish individuals from a randomized population-based study and found significant association with fasting serum HDL cholesterol (p = 8 x 10(-10)); the association was replicated in 8,407 high-risk individuals. The authors observed no association with type 2 diabetes in a cross-sectional design in this study. Iijima et al. (2008) analyzed alphalipoprotein (HDL) levels in 2 independent Japanese populations consisting of 2,970 and 1,638 individuals, respectively, and found significant association with a 2-SNP haplotype in intron 1 of the LIPC gene (151670.0005) in both populations (p = 0.00011 and 0.00070, respectively). The authors concluded that variation at the LIPC locus influences HDL metabolism. Aulchenko et al. (2009) reported the first genomewide association (GWA) study of loci affecting total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. This study included a total of 17,797 to 22,562 individuals aged 18 to 104 years from geographic regions spanning from the Nordic countries to Southern Europe. Aulchenko et al. (2009) established 22 loci associated with serum lipid levels at a genomewide significance level (P less than 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The region near the LIPC gene identified by rs1532085 was significantly associated with HDL cholesterol levels (P = 9.7 x 10(-36)). In a metaanalysis of plasma lipid concentrations in greater than 100,000 individuals of European descent, Teslovich et al. (2010) identified rs1532085 as having an effect on HDL cholesterol concentrations with an effect size of +1.45 mg per deciliter and a P value of 3 x 10(-96). This variant was also found to be an expression quantitative trait locus (eQTL) regulating the expression of the LIPC gene. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	HIGH DENSITY LIPOPROTEIN CHOLESTEROL LEVEL QUANTITATIVE TRAIT LOCUS 12	c2675071	29,048	omim	https://www.omim.org/entry/612797	2019-09-22T16:00:37	{"omim": ["612797"]}
Severe cutaneous adverse reactions Other namesSCARs SpecialtyDermatology Severe cutaneous adverse reactions are a group of potentially lethal adverse drug reactions that involve the skin and mucous membranes of various body openings such as the eyes, ears, and inside the nose, mouth, and lips. In more severe cases, SCARs also involves serious damage to internal organs. SCARs includes five syndromes: Drug reaction with eosinophilia and systemic symptoms (i.e. DRESS syndrome, also termed Drug-induced hypersensitivity syndrome [DIHS]); Stevens–Johnson syndrome (SJS); Toxic epidermal necrolysis (TEN), Stevens-Johnson/toxic epidermal necrolysis overlap syndrome (SJS/TEN); and Acute generalized exanthematous pustulosis (AGEP). The five disorders have similar pathophysiologies, i.e. disease-causing mechanisms, for which new strategies are in use or development to identify individuals predisposed to develop the SCARs-inducing effects of specific drugs and thereby avoid treatment with them.[1] Maculopapular rash (MPR) is a less-well defined and benign form of drug-induced adverse skin reactions; while not classified in the SCARs group, it shares with SCARS a similar pathophysiology and is caused by some of the same drugs which cause SCARs.[2] Adverse drug reactions are major therapeutic problems estimated to afflict up to 20% of inpatients and 25% of outpatients. About 90% of these adverse reactions take the form of benign morbilliform rash hypersensitivity drug reactions such as MPR. However, they also include more serious reactions: a) pseudo-allergic reactions in which a drug directly stimulates mast cells, basophils, and/or eosinophils to release pro-allergic mediators (e.g. histamine); b) Type I, Type II, and Type III hypersensitivity reactions of the adaptive immune system mediated by IgE, IgG, and/or IgM antibodies; and c) SCARs and MPR which are Type IV hypersensitivity reactions of the innate immune system initiated by lymphocytes of the T cell type and mediated by various types of leukocytes and cytokines.[3] Type IV hypersensitivity reactions are off-target drug reactions, i.e. reactions in which a drug causes toxicity by impacting a biological target other than the one(s) for which it is intended. They are T cell-initiated delayed hypersensitivity reactions occurring selectively in individuals who may be predisposed to do so because of the genetically-based types of human leukocyte antigens (i.e. HLA) or T-cell receptors they express; the efficiency with which they absorb, distribute to tissues, metabolize, and eliminate a drug or drug metabolite; or less well-defined idiosyncrasies.[1][4][5] SCARs are here considered as a group focusing on the similarities and differences in their pathophysiologies, clinical presentations, instigating drugs, and recommendations for drug avoidance. Further details on these syndromes can be found on their individual Wikipedia pages. ## Contents * 1 Types * 1.1 SJS, TEN, and SJS/TEN * 1.2 DRESS syndrome * 1.3 AGEP * 2 Pathophysiology * 2.1 HLA proteins * 2.2 T-cell receptors * 2.3 ADME * 2.4 Other factors * 2.4.1 Virus reactivation * 2.4.2 Infections * 2.4.3 Autoimmune Disorders * 2.5 Effectors of tissue injury * 3 Prevention * 4 References ## Types[edit] ### SJS, TEN, and SJS/TEN[edit] Main article: Stevens–Johnson syndrome Main article: Toxic epidermal necrolysis Stevens–Johnson syndrome, toxic epidermal necrolysis, and Stevens–Johnson syndrome/Toxic epidermal necrolysis overlap syndrome are a spectrum of Type IV, Subtype IVc, delayed hypersensitivity reactions, i.e. reactions initiated by CD8+ T cells and natural killer T cells.[2] They are characterized initially by fever and flu-like symptoms followed within days by skin as well as mucous membrane blisters and denudation. Differentiation of the three disorders is based on the extent of disease with SJS involving <10%, SGS/TEN involving 10% to 30%, and TEN involving >30% of the total bodily skin area. This spectrum of disorders is complicated by inflammation in and damage to internal organs such as the liver and, less commonly, kidney and heart. More importantly, they are also complicated by sepsis due to the loss of skin and mucous membrane epithelial barriers. In one study, SJS, TEN, and SJS/TEN mortality rates were 4.8%, 19.4%, and 14.8%, respectively, with an important portion of the deaths due to bacterial sepsis, particularly in the acute, early stage of these disorders.[6][7] The drugs most commonly triggering the SJS, TEN, and SJS/TEN spectrum of disorders are anti-infective sulfonamides, anticonvulsants (e.g. carbamazepine and lamotrigine), non-steroidal anti-inflammatory drugs, allopurinol, nevirapine, and chlormezanone. Allopurinol appears in some studies to be the most common instigator of these disorders. Any new biological or herbal remedy, it is suggested, should be considered a possible cause of these disorders under the proper clinical circumstances.[6] ### DRESS syndrome[edit] Main article: DRESS syndrome The DRESS syndrome is a Type IV, Subtype IVb, hypersensitivity drug reaction, i.e. a reaction dependent on CD4(+) cells and the cell- and tissue-injuring action of eosinophils.[2][8] Skin lesions inflict 73% to 100% of afflicted individuals; they are generally infiltrative macules and plaques. About 75% of cases exhibit facial edema. The syndrome is also associated with other maladies caused by high levels of blood eosinophils such as the various hypereosinophilia-related disorders: persistent asthma and allergic rhinitis and, more significantly, eosinophil-based and lymphocyte-based inflammation of the liver (>70% of cases), kidney (20% to 40% of cases), lung (~33% of cases), heart (4% to 27% of cases), and, uncommonly, the meninges, brain, gastrointestinal tract, and spleen.[4] The disorder is lengthened and worsened in individuals that develop reactivation of latent viruses of the herpes viruses.[4][9] The estimated mortality rate for the DRESS syndrome is about 10%. Allopurinol and sulfasalazine account for almost 66% of DRESS syndrome cases with minocycline being the third most common cause of the disorder; Strontium ranelate, leflunomide, dapsone, and nonsteroidal anti-inflammatory drugs (diclofenac, celecoxib, ibuprofen, and phenylbutazone) are less common causes of the disorder.[10] ### AGEP[edit] Main article: Acute generalized exanthematous pustulosis AGEP is a rare Type IV, subtype IVd, hypersensitivity reaction dependent on neutrophils and characterized by the rapid formation of skin pustules on an erythematous background.[2][11] In one study of 28 patients, the disorder was complicated by involvement of the kidney (36% of cases), lung (27%), and liver (11%).[12] It is the least severe of the SCARs disorders, typically shows a mild course, and is rarely associated with severe complications although superinfection of skin lesions may be life-threatening.[2][13][11] ## Pathophysiology[edit] Individuals are predisposed to develop SCARs in response to a given drug based on the types of human leukocyte antigen (i.e. HLA) proteins and T-cell receptors that they express; their ability to process an instigating drug or the drug's metabolite(s); and other less well-defined factors. These predispositions are a consequence of the HLA allele and T-cell receptor variants that individuals express in their antigen presentation immune pathways; their ADME, i.e. efficiency in Absorbing, Distributing to tissues, Metabolizing, and/or Eliminating a drug or drug metabolite; and other less well-defined factors. ### HLA proteins[edit] Drugs can cause SCARs by subverting the antigen presentation pathways which recognize and trigger immune responses to non-self epitopes (i.e. antigens) on foreign proteins. These proteins are taken up by antigen-presenting cells (APC) and degraded into small peptides. The peptides are inserted into a groove on HLA proteins that are part of major histocompatibility complexes (i.e. MHC) and presented to T-cell receptors (TCR) on nearby cytotoxic T cells (i.e. CD8+ T cells) or T helper cells (i.e. CD4+ T cells). T-cell receptors are heterologous; only a small fraction of them can bind a particular epitope on presented peptides and this binding is restricted to non-self epitopes. Upon binding a non-self epitope on a presented peptide, a T-cell receptor becomes active in stimulating its parent cell to mount one of two types of immune responses based on whether the APC presenting the peptide is professional or non-professional in type. Non-professional APC include all nucleated cells; these cells load the processed peptides onto MHC class I (i.e. HLA-A, HLA-B, or HLA-C) proteins and thereon present the peptides to CD8+ T cells. Those CD8+ T cells whose T-cell receptors bind a non-self epitope on the peptides are stimulated to attack cells or pathogens expressing this epitope. Professional APC are dendritic cells, macrophages, and B cells. They load processed peptides onto MHC class II (i.e. HLA-DM, HLA-DO, HLA-DP, HLA-DQ, or HLA-DR) proteins and thereon present the peptides to CD4+ T cells. Those CD4+ T cells whose T-cell receptors bind a non-self epitope on presented peptides are stimulated to orchestrate various immune reactions that attack soluble proteins, pathogens, and host cells and tissues that express the non-self epitope. SCARs-inducing drugs can act through these pathways to cause CD8+ or CD4+ T cells to mount immune responses that are inappropriately directed against bodily tissues. Four models propose the underlying mechanisms by which SCARs-inducing drugs may activate T cells to mount immune responses against self:[3][13] * Hapten model: A drug (here termed a hapten) covalently binds to a host protein to create a non-self epitope; the protein is degraded in APC to drug-bound peptides which are loaded onto the groove in HLA proteins and then presented to T cells. Those T cells whose T-cell receptors bind the drug-related epitope on a presented peptide are thereby activated. * Pro-hapten model: This model is identical to the hapten model except that a drug's metabolite rather than the drug acts as the hapten that forms the non-self epitope. * p-i Model: A drug or its metabolite fits into the groove in HLA proteins to become a non-self epitope which is presented to and activates T cells whose T-cell receptors bind the drug-related epitope; alternatively, the drug binds to T-cell receptors on and thereby directly activates the receptors' parent T cells. * Altered peptide repertoire model: A drug or its metabolite binds directly to a HLA protein outside of its groove to alter the HLA protein's structure; the altered HLA protein thereby contains a non-self epitope which activates those T cells whose T-cell receptors bind the drug-created epitope. HLA genes are highly polymorphic, i.e. have many different serotypes (i.e. alleles) while T-cell receptor genes receptors are edited. i.e. altered to encode proteins with different amino acid sequences. Humans, it is estimated, express more than 10,000 different HLA class I proteins, 3,000 different HLA class II proteins, and 100 trillion different T-cell receptors. An individual, however, expresses only a fraction of these polymorphic or edited gene products. Since a SCARs-inducing drug interacts with only one or a few types of HLA proteins or T-cell receptors, its ability to induce a SCARs disorder is limited to those individuals who express those HLA proteins that make the appropriate HLA/non-self peptide or the T cell that expresses the T-cell receptor that recognize the non-self epitope created by the drug.[3][13] Thus, only rare individuals are predisposed to develop a SCARs disorder in response to a particular drug on the bases of their expression of specific HLA protein or T-cell receptor types.[5] SCARs disorders are triggered by wide range of drugs[4] with the most commonly reported offenders being Carbamazepine, allopurinol, abacavir, phenytoin, and nevirapine.[3] These drugs evoke SCARs by interacting with one or just a few HLA proteins. The following table list drugs repeatedly implicated in eliciting SCARs; it also gives the drugs' therapeutic targets, HLA serotypes through which they act, the types of SCARs disorders they trigger, the negative and positive predictive values for the drugs (where known), and the populations afflicted.[1][3] Positive predictive values give the true percentages of individuals with the indicated HLA gene allele (identified as a serotype) that develop the cited drug-induced SCARs; negative predictive values give the percentage of individuals without the indicated serotype that fail to develop the cited drug-induced SCARs. For example, Chinese, Korean, Japanese, and European individuals that express the HLA-A31:01 allele have a 1% true chance of developing the DRESS syndrome while HLA-A31:01 negative individuals in these specific populations have a 99.9% true chance of not developing the DRESS syndrome when treated with carbamazepine. In this particular example, the HLA-A31:01 allele is virtually necessary but clearly not sufficient for developing the DRESS syndrome in response to carbamazepine. The table also shows that: positive predictive values lie between 0.59-55%, i.e. far below 100%; positive as well as negative predictive values vary with the population tested; a drug may cause more than one type of SCARs disorder or interact with more than one HLA serotype to cause SCARs; and the level of susceptibility to a drug varies between populations. These findings indicate that other factors, generally regarded as due to unspecified population-related genetic differences, contribute decisively to developing SCARs.[3][4][13][14] Drug Drug action HLA gene and allele SCARs disorder triggered Positive predictive value Negative predictive value Populations afflicted Carbamazepine anticonvulsant HLA-A31:01 DRESS syndrome 1% 99.9% Chinese, Koreans, Japanese, European Carbamazepine anticonvulsant HLA-A31:01 SJS, TEN, SJS/TEN 0.89% 99.98% European Carbamazepine anticonvulsant HLA-A31:01 SJS, TEN, SJS/TEN 0.59% 99.97% Chinese Carbamazepine anticonvulsant HLA-A31:01 SJS, TEN, SJS/TEN ? ? Northern European, Japanese, Korean Carbamazepine anticonvulsant HLA-B15:02 SJS, TEN, SJS/TEN 3% 100% Chinese, Tai, Malaysian, Koreans, Indian Carbamazepine anticonvulsant HLA-A31:01 MPE 34/9% 96.7% Han Chinese Oxcarbazepine anticonvulsant HLA-B15:01 SJS, TEN, SJS/TEN ? ? Han Chinese, Taiwanese Phenytoin anticonvulsant HLA-B13:01 or HLA-B51:01 DRESS syndrome, MPE ? ? Han Chinese Phenytoin anticonvulsant HLA-B15:02, HLA-Cw08:01, or HLA-DRB116:02 DRESS syndrome ? ? Han Chinese Lamotrigine anticonvulsant HLA-B15:02 or HLA-B38 SJS, TEN, SJS/TEN ? ? Han Chinese Lamotrigine anticonvulsant HLA-B38, HLA-B58:01, or HLA:68:01 SJS, TEN, SJS/TEN ? ? European Lamotrigine anticonvulsant HLA-Cw07, HLA-DQB06:09, or HLA-DRB113:01 SJS, TEN, SJS/TEN ? ? European Oxicam anti-inflammatory HLA-B73, HLA-A2, or HLA-B12 SJS, TEN, SJS/TEN ? ? European various sulfa drugs antibiotic HLA-Cw4 SJS, TEN, SJS/TEN ? ? Han Chinese various sulfa drugs antibiotic HLA-B38 SJS, TEN, SJS/TEN ? ? European Methazolamide lowers intraocular pressure HLA-B59:01 or HLA-CW01:02 SJS, TEN, SJS/TEN ? ? Korean, Japanese Dapsone antibiotic, anti-inflammatory HLA-B13:01 DRESS syndrome 7.8% 99.8% Han Chinese Allopurinol anti-gout drug HLA-B58:01 DRESS syndrome, SJS, TEN, SJS/TEN 3% 100% in Han Chinese Han Chinese, Korean, Thai, European Nevirapine anti-retroviral HLA-DRB101:01 or HLA-DRB101:012 DRESS syndrome 18% 96% Australian, European, South African Nevirapine anti-retroviral HLA-Cw8 or HLA-Cw8:-B14 DRESS syndrome 18% 96% Italian, Japanese Nevirapine anti-retroviral HLA-B35, HLA-B35:01, or HLA-B35:05 SJS, TEN, SJS/TEN ? ? Asian Nevirapine anti-retroviral HLA-C04:01 SJS, TEN, SJS/TEN ? ? Malawian Abacavir anti-retroviral HLA-B57:01 DRESS syndrome 55% 100% European, African ### T-cell receptors[edit] Due to gene editing. the number of diverse T-cell receptors expressed is estimated to be as high as 10 trillion. This has made it difficult to identify specific T-cell receptor types that are uniquely associated with the development of SCARs. One study, however, identified the preferential presence of the TCR-V-b and complementarity-determining region 3 in T-cell receptors found on the T cells in the blisters of patients with allopurinol-induced SCARs. This finding is compatible with the notion that specific types of T-cell receptors are involved in the development of specific drug-induced SCARs.[15] ### ADME[edit] Certain variations in ADME (i.e. absorption, distribution, metabolism, and excretion of a drug) are associated with the development of SCARs. These variations influence the levels and duration of a drug or drug metabolite in tissues and thereby impact the drug's or drug metabolite's ability to evoke SCARs.[1] A prominent example of an ADME-based genetic predisposition to SCARs involves the CYP2CP3 allele of the CYP2C9 gene. CYP2C9, a cytochrome P450 enzyme, metabolizes various substances including phenytoin. The CYP2CP3 variant of CYP29C has reduced catalytic activity. Individuals studied in Japan or Malaysia, and the Han Chinese in Taiwan that express this variant have an increased chance of developing the DRESS syndrome, SJS, SJS/TEN, or TEN when taking phenytoin while Africans in Mozambique expressing this variant taking phenytoin have an increase risk of developing SJS, SJS/TEN, or TEN. These reactions appear due to increases in the drug's blood and tissue levels.[16] In a second example of a genetically based ADME defect causing SCARs, Japanese individuals bearing slow acetylating variants of the N-acetyltransferase 2 gene, (NAT2), viz., NAT26A and NAT27B, acetylate sulfasalazine more slowly than individuals homozygous for the wild type gene. Individuals expressing the NAT26A and NAT27 variants have an increased risk for developing a particularly severe form of the DRESS syndrome-like reactions to this anti-inflammatory drug.[10] None-genetic ADME factors are also associated with increased risks of developing SCARs. For example, allopurinol is metabolized to oxipurinol, a product with a far slower renal excretion rate than its parent compound. Renal impairment is associated with abnormally high blood levels of oxipurinol and an increased risk of developing the DRESS syndrome, particularly the more severe forms of this disorder. Dysfunction of the kidney and liver are also suggested to promote SCARs responses to other drugs due to the accumulation of SCARs-inducing drugs or metabolites in blood and tissues.[1][6] Currently, it is suspected that the expression of particular HLA proteins and T-cell receptors interact with ADME factors to promote SCARs particularly in their more serious forms.[1][16] ### Other factors[edit] #### Virus reactivation[edit] During the progression of the DRESS syndrome certain viruses which previously infected an individual and then became latent are reactivated and proliferate. Viruses known to do so include certain members of the Herpesviridae family of Herpes viruses viz., Epstein–Barr virus, human herpesvirus 6, human herpesvirus 7, and cytomegalovirus. Individuals suffering the DRESS syndrome may exhibit sequential reactivation of these four virus, typically in the order just given. Reactivation of these viruses is associated with sequential flare-ups in symptoms, a prolonged course, and increased disease severity which includes significant organ involvement and the development of certain autoimmune diseases viz., systemic lupus erythematosus, autoimmune thyroiditis, and type 1 diabetes mellitus. While these viral reactivations, particularly of human herpes virus 6, have been suggested to be an important factor in the pathogenesis of the DRESS syndrome, studies to date have not clearly determined if they are a cause or merely a consequence of T cell-mediated tissue injury. Rare case reports have associated the SJS/TEN spectrum of SCARs with reactivation of human herpesvirus 6; reactivation of cytomegalovirus has also been proposed to be associated with AGEP although a large study failed to observe the latter association. In all cases, the relationships of viral reactivation to the development and severity of any SCARs disorder is uncertain and requires further study.[1][4] #### Infections[edit] Although more than 90% of AGEP are associated with the intake of a presumptively offending drug, reports have associated infection with Parvovirus B19, mycoplasma, cytomegalovirus, coxsackie B4 virus, Chlamydophila pneumoniae, E. coli, and Echinococcus with the drug-independent development of this disorder. The pathophysiology for the development of these drug-independent cases of AGEP is unclear.[11] Viral infections have also been observed to be associated with the development of SJS, SJS/TEN, and TEN in the absence of a causative drug.[6] #### Autoimmune Disorders[edit] Individuals suffering autoimmune disorders such as systemic lupus erythematosus may have an increased incidence of developing SCARs. While the cause for this possible predilection has not been determined, the altered immune system and the excessive production of cytokines occurring in these disorders could be contributing factors.[2][6] ### Effectors of tissue injury[edit] The tissue injury in SCARs is initiated principally by CD8+ or CD4+ T cells. Once drug-activated, these lymphocytes elicit immune responses to self tissues that can result in SCARs drug reactions by mechanisms which vary with the type of disorder that develops. Salient elements mediating tissue injury for each type of disorder include:[2][13] SJS, SJS/TEN, and TEN: These three SCARs are variants of a common epidermal necrolysis disorder that differ only in severity. Key down-stream elements that promote tissue injury in this spectrum of disorders are natural killer cells; death-inducing ligands that kill cells (viz., Fas ligand, TRAIL, and TNFSF12); cellular receptors for these ligands (viz., Fas receptor, death receptor 4, death receptor 5, and TNFRSF12A); cell-injuring proteins made by CD8+ and natural killer cells, (viz., granulysin, granzyme B, and perforin); and two cytokines that stimulate the proliferation and activation of natural killer and T cells (viz., interleukin 5 and annexin A1). * DRESS syndrome: Key elements promoting tissue injury in the DRESS syndrome are: Th2 cells and eosinophils; and cytokiness which either activate eosinophils (viz.,. Interleukin 5), promote adaptive and allergic immune responses (viz., Interleukin 4), promote allergic responses and tissue fibrosis (viz., Interleukin 13), promote innate, adaptive, and auto-immune responses (viz., interferon gamma); or cause cell death (viz., tumor necrosis factor alpha). * AGEP: Key elements promoting tissue injury in AGEP are: neutrophils; recruiters and activators of neutrophils (viz., Interleukin 8 and Interleukin 17); a promoter of innate immune and autoimmune responses (viz., Interleukin 22); and a cytokine which promotes the function of neutrophils, other granulocyte types, and monocytes as well as the production of these cells from their stem cells (viz., GM-CSF). Future studies may find that drugs which neutralize one or more of these effectors to be useful for treating SCARs disorders. ## Prevention[edit] Screening individuals for the expression of certain variant alleles of HLA genes before initiating treatment with particular SCARs-inducing drugs is recommended. These recommendations typically apply only to specific populations that have a significant chance of expressing the indicated variant since screening of populations with extremely low incidences of expressing the variant allele is considered cost-ineffective.[17] Individuals expressing the HLA allele associated with sensitivity to an indicated drug should not be treated with the drug. These recommendations include:[1][18] * Carbamazepine: The Taiwan and USA Food and Drug Administrations recommend screening for HLA-B15:02 in certain Asian groups before carbamazepine treatment. This has been implemented in Taiwan, Hong Kong, Singapore, and many medical centers in Thailand and Mainland China. Allopurinol: The American College of Rheumatology guidelines for the management of gout recommend HLA-B58:01 screening before allopurinol treatment. This is provided in many medical centers in Taiwan, Hong Kong, Thailand, and Mainland China. Abacavir: The USA Food and Drug Administration recommends screening for HLA-B57:01 in the treatment of HIV with abacovir in Caucasian populations. This screening is widely implemented. It has also been suggested that all individuals found to express this HLA serotype avoid treatment with abacovir. Current trials are underway to evaluate the cost-effectiveness of genetic screening for HLA-B13:01 to prevent dapsone-induced SCARs in China and Indonesia. Similar trials are underway in Taiwan to prevent phenytoin-induced SCARs in individuals expressing the CYP2C93 allele of CYP2C9 or a series of HLA alleles.[18] ## References[edit] 1. ^ a b c d e f g h Adler NR, Aung AK, Ergen EN, Trubiano J, Goh MS, Phillips EJ (2017). "Recent advances in the understanding of severe cutaneous adverse reactions". The British Journal of Dermatology. 177 (5): 1234–1247. doi:10.1111/bjd.15423. PMC 5582023. PMID 28256714. 2. ^ a b c d e f g Hoetzenecker W, Nägeli M, Mehra ET, Jensen AN, Saulite I, Schmid-Grendelmeier P, Guenova E, Cozzio A, French LE (2016). "Adverse cutaneous drug eruptions: current understanding". Seminars in Immunopathology. 38 (1): 75–86. doi:10.1007/s00281-015-0540-2. PMID 26553194. 3. ^ a b c d e f Garon SL, Pavlos RK, White KD, Brown NJ, Stone CA, Phillips EJ (2017). "Pharmacogenomics of off-target adverse drug reactions". British Journal of Clinical Pharmacology. 83 (9): 1896–1911. doi:10.1111/bcp.13294. PMC 5555876. PMID 28345177. 4. ^ a b c d e f Cho YT, Yang CW, Chu CY (2017). "Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System". International Journal of Molecular Sciences. 18 (6): 1243. doi:10.3390/ijms18061243. PMC 5486066. PMID 28598363. 5. ^ a b Pichler WJ, Hausmann O (2016). "Classification of Drug Hypersensitivity into Allergic, p-i, and Pseudo-Allergic Forms". International Archives of Allergy and Immunology. 171 (3–4): 166–179. doi:10.1159/000453265. PMID 27960170. 6. ^ a b c d e Lerch M, Mainetti C, Terziroli Beretta-Piccoli B, Harr T (2017). "Current Perspectives on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis". Clinical Reviews in Allergy & Immunology. 54 (1): 147–176. doi:10.1007/s12016-017-8654-z. PMID 29188475. 7. ^ Schneider JA, Cohen PR (2017). "Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Concise Review with a Comprehensive Summary of Therapeutic Interventions Emphasizing Supportive Measures". Advances in Therapy. 34 (6): 1235–1244. doi:10.1007/s12325-017-0530-y. PMC 5487863. PMID 28439852. 8. ^ Uzzaman A, Cho SH (2012). "Chapter 28: Classification of hypersensitivity reactions". Allergy and Asthma Proceedings. 33 Suppl 1 (3): S96–9. doi:10.2500/aap.2012.33.3561. PMID 22794701. 9. ^ Corneli HM (2017). "DRESS Syndrome: Drug Reaction With Eosinophilia and Systemic Symptoms". Pediatric Emergency Care. 33 (7): 499–502. doi:10.1097/PEC.0000000000001188. PMID 28665896. 10. ^ a b Adwan MH (2017). "Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome and the Rheumatologist". Current Rheumatology Reports. 19 (1): 3. doi:10.1007/s11926-017-0626-z. PMID 28138822. 11. ^ a b c Feldmeyer L, Heidemeyer K, Yawalkar N (2016). "Acute Generalized Exanthematous Pustulosis: Pathogenesis, Genetic Background, Clinical Variants and Therapy". International Journal of Molecular Sciences. 17 (8): 1214. doi:10.3390/ijms17081214. PMC 5000612. PMID 27472323. 12. ^ Alniemi DT, Wetter DA, Bridges AG, El-Azhary RA, Davis MD, Camilleri MJ, McEvoy MT (2017). "Acute generalized exanthematous pustulosis: clinical characteristics, etiologic associations, treatments, and outcomes in a series of 28 patients at Mayo Clinic, 1996-2013". International Journal of Dermatology. 56 (4): 405–414. doi:10.1111/ijd.13434. PMID 28084022. 13. ^ a b c d e Duong TA, Valeyrie-Allanore L, Wolkenstein P, Chosidow O (2017). "Severe cutaneous adverse reactions to drugs". Lancet. 390 (10106): 1996–2011. doi:10.1016/S0140-6736(16)30378-6. PMID 28476287. 14. ^ Fan WL, Shiao MS, Hui RC, Su SC, Wang CW, Chang YC, Chung WH (2017). "HLA Association with Drug-Induced Adverse Reactions". Journal of Immunology Research. 2017: 3186328. doi:10.1155/2017/3186328. PMC 5733150. PMID 29333460. 15. ^ Wang CW, Dao RL, Chung WH (2016). "Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions". Current Opinion in Allergy and Clinical Immunology. 16 (4): 339–45. doi:10.1097/ACI.0000000000000286. PMID 27362322. 16. ^ a b Chung WH, Wang CW, Dao RL (July 2016). "Severe cutaneous adverse drug reactions". The Journal of Dermatology. 43 (7): 758–66. doi:10.1111/1346-8138.13430. PMID 27154258. 17. ^ Chong HY, Mohamed Z, Tan LL, Wu DB, Shabaruddin FH, Dahlui M, Apalasamy YD, Snyder SR, Williams MS, Hao J, Cavallari LH, Chaiyakunapruk N (2017). "Is universal HLA-B15:02 screening a cost-effective option in an ethnically diverse population? A case study of Malaysia". The British Journal of Dermatology. 177 (4): 1102–1112. doi:10.1111/bjd.15498. PMC 5617756. PMID 28346659. 18. ^ a b Su SC, Hung SI, Fan WL, Dao RL, Chung WH (2016). "Severe Cutaneous Adverse Reactions: The Pharmacogenomics from Research to Clinical Implementation". International Journal of Molecular Sciences. 17 (11): 1890. doi:10.3390/ijms17111890. PMC 5133889. PMID 27854302. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Severe cutaneous adverse reactions	None	29,049	wikipedia	https://en.wikipedia.org/wiki/Severe_cutaneous_adverse_reactions	2021-01-18T18:45:37	{"umls": ["C1869024"], "wikidata": ["Q55632923"]}
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: "Periodontal abscess" – news · newspapers · books · scholar · JSTOR (May 2016) (Learn how and when to remove this template message) Periodontal abscess A gingival abscess between the lower left canine and first premolar. SpecialtyDentistry A periodontal abscess (also termed lateral abscess,[1] or parietal abscess),[1] is a localized collection of pus (i.e. an abscess) within the tissues of the periodontium. It is a type of dental abscess. A periodontal abscess occurs alongside a tooth, and is different from the more common[2] periapical abscess, which represents the spread of infection from a dead tooth (i.e. which has undergone pulpal necrosis). To reflect this, sometimes the term "lateral (periodontal) abscess" is used. In contrast to a periapical abscess, periodontal abscesses are usually associated with a vital (living) tooth. Abscesses of the periodontium are acute bacterial infections[3] classified primarily by location.[4] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Classification * 4 Treatment * 5 References * 6 External links ## Signs and symptoms[edit] The main symptom is pain, which often suddenly appears, and is made worse by biting on the involved tooth, which may feel raised and prominent in the bite. The tooth may be mobile, and the lesion may contribute to destruction of the periodontal ligament and alveolar bone.[4] The pain is deep and throbbing. The oral mucosa covering an early periodontal abscess appears erythematous (red), swollen and painful to touch.[3] The surface may be shiny due to stretching of the mucosa over the abscess. Before pus has formed, the lesion will not be fluctuant, and there will be no purulent discharge. There may be regional lymphadenitis. When pus forms, the pressure increases, with increasing pain, until it spontaneously drains and relieves the pain. When pus drains into the mouth, a bad taste and smell are perceived. Usually drainage occurs via the periodontal pocket, or else the infection may spread as a cellulitis or a purulent odontogenic infection. Local anatomic factors determine the direction of spread (see fascial spaces of the head and neck). There may be systemic upset, with an onset of pain and fever. ## Causes[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (May 2016) (Learn how and when to remove this template message) A periodontal abscess most commonly occurs as a complication of advanced periodontal disease (which is normally painless). A periodontal pocket contains dental plaque, bacteria and subgingival calculus. Periodontal pathogens continually find their way into the soft tissues, but normally they are held in check by the immune system. A periodontal abscess represents a change in this balance, related to decreased local or systemic resistance of the host. An inflammatory response occurs when bacteria invade and multiply within the soft tissue of the gingival crevice/periodontal pocket. A pus-filled abscess forms when the immune system responds and attempts to isolate the infection from spreading. Communication with the oral environment is maintained via the opening of the periodontal pocket. However, if the opening of a periodontal pocket becomes obstructed, as may occur if the pocket has become very deep (e.g. with furcation involvement), then plaque and calculus are trapped inside. Food packing may also obstruct a periodontal pocket. Food packing is usually caused by failure to accurately reproduce the contact points when dental restorations are placed on the interproximal surfaces of teeth. Another potential cause occurs when a periodontal pocket is scaled incompletely. Following this procedure, the gingival cuff tightens around the tooth, which may be enough to trap the bacteria left in the pocket. A gingival retraction cord which is accidentally left in situ is an occasional cause of a periodontal abscess. Penetrating injury to the gingiva--for example, with a toothbrush bristle, fishbone, toothpick or periodontal instrument--may inoculate bacteria into the tissues. Trauma to the tissues, such as serious impact on a tooth or excessive pressure exerted on teeth during orthodontic treatment, can be a possible cause as well. Occlusal overload may also be involved in the development of a periodontal abscess, but this is rare and usually occurs in combination with other factors. Bruxism is a common cause of excessive occlusal forces. Systemic immune factors such as diabetes can predispose a person to the formation of periodontal abscesses. Perforation of a root canal during endodontic therapy can also lead to a periodontal abscess. ## Diagnosis[edit] Periodontal abscesses may be difficult to distinguish from periapical abscesses. Since the management of a periodontal abscess is different from a periapical abscess, this differentiation is important to make (see Dental abscess#Diagnostic approach) For example, root canal therapy is unnecessary and has no impact on pain in a periodontal abscess. ### Classification[edit] There are four types of abscesses that can involve the periodontal tissues:[3] 1. Gingival abscess—a localized, purulent infection involves only the soft gum tissue near the marginal gingiva or the interdental papilla.[3] 2. Periodontal abscess—a localized, purulent infection involving a greater dimension of the gum tissue, extending apically and adjacent to a periodontal pocket.[3] 3. Pericoronal abscess—a localized, purulent infection within the gum tissue surrounding the crown of a partially or fully erupted tooth.[3] Usually associated with an acute episode of pericoronitis around a partially erupted and impacted mandibular third molar (lower wisdom tooth). 4. combined periodontal/endodontic abscess ## Treatment[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (May 2016) (Learn how and when to remove this template message) An important factor is whether the involved tooth is to be extracted or retained. Although the pulp is usually still vital, a history of recurrent periodontal abscesses and significantly compromised periodontal support indicate that the prognosis for the tooth is poor and it should be removed. The initial management of a periodontal abscess involves pain relief and control of the infection. The pus needs to be drained, which helps both of these aims. If the tooth is to be removed, drainage will occur via the socket. Otherwise, if pus is already discharging from the periodontal pocket, this can be encouraged by gentle irrigation and scaling of the pocket whilst massaging the soft tissues. If this does not work, incision and drainage is required, as described in Dental abscess#Treatment. Antibiotics are of secondary importance to drainage, which if satisfactory renders antibiotics unnecessary. Antibiotics are generally reserved for severe infections, in which there is facial swelling, systemic upset and elevated temperature. Since periodontal abscesses frequently involve anaerobic bacteria, oral antibiotics such as amoxicillin, clindamycin (in penicillin allergy or pregnancy) and/or metronidazole are given. Ideally, the choice of antibiotic is dictated by the results of microbiological culture and sensitivity testing of a sample of the pus aspirated at the start of any treatment, but this rarely occurs outside the hospital setting. Other measures that are taken during management of the acute phase might include reducing the height of the tooth with a dental drill, so it no longer contacts the opposing tooth when biting down; and regular use of hot salt water mouth washes (antiseptic) that encourages further drainage of the infection. The management following the acute phase involves removing any residual infection, and correcting the factors that lead to the formation of the periodontal abscess. Usually, this will be therapy for periodontal disease, such as oral hygiene instruction and periodontal scaling. ## References[edit] 1. ^ a b Newman MG, Takei HH, Klokkevold PR, Carranza FA, eds. (2012). Carranza's clinical periodontology (11th ed.). St. Louis, Mo.: Elsevier/Saunders. p. 137. ISBN 978-1-4377-0416-7. 2. ^ Hupp JR, Ellis E, Tucker MR (2008). Contemporary oral and maxillofacial surgery (5th ed.). St. Louis, Mo.: Mosby Elsevier. p. 293. ISBN 9780323049030. 3. ^ a b c d e f American Academy of Periodontology (May 2000). "Parameter on acute periodontal diseases. American Academy of Periodontology" (PDF). J. Periodontol. 71 (5 Suppl): 863–6. doi:10.1902/jop.2000.71.5-S.863. PMID 10875694. Archived from the original (PDF) on 2010-11-28. 4. ^ a b American Academy of Periodontology (1999). "Consensus report: Abscesses of the Periodontium". Ann. Periodontol. 4 (1): 83. doi:10.1902/annals.1999.4.1.83. ## External links[edit] Classification D * ICD-10: K05.2 * MeSH: D005491 * v * t * e Dentistry involving supporting structures of teeth (Periodontology) Anatomy * Periodontium * Alveolar bone * Biologic width * Bundle bone * Cementum * Free gingival margin * Gingiva * Gingival fibers * Gingival sulcus * Junctional epithelium * Mucogingival junction * Periodontal ligament * Sulcular epithelium * Stippling Disease Diagnoses * Chronic periodontitis * Localized aggressive periodontitis * Generalized aggressive periodontitis * Periodontitis as a manifestation of systemic disease * Periodontosis * Necrotizing periodontal diseases * Abscesses of the periodontium * Combined periodontic-endodontic lesions Infection * A. actinomycetemcomitans * Capnocytophaga sp. * F. nucleatum * P. gingivalis * P. intermedia * T. forsythia * T. denticola * Red complex * Entamoeba gingivalis (amoebic) * Trichomonas tenax Other * Calculus * Clinical attachment loss * Edentulism * Fremitus * Furcation defect * Gingival enlargement * Gingival pocket * Gingival recession * Gingivitis * Horizontal bony defect * Linear gingival erythema * Occlusal trauma * Periodontal pocket * Periodontal disease * Periodontitis * Plaque * Vertical bony defect Treatment and prevention * Periodontal examination * Ante's law * Brushing * Bleeding on probing * Chlorhexidine gluconate * Flossing * Hydrogen peroxide * Mouthwash * Oral hygiene * Tetracycline * Triclosan * Host modulatory therapy Treatment Conventional therapy * Debridement * Scaling and root planing * Full mouth disinfection * Full mouth ultrasonic debridement Surgery * Apically positioned flap * Bone graft * Coronally positioned flap * Crown lengthening * Free gingival graft * Gingival grafting * Gingivectomy * Guided bone regeneration * Guided tissue regeneration * Enamel matrix derivative * Implant placement * Lateral pedicle graft * Open flap debridement * Pocket reduction surgery * Socket preservation * Sinus lift * Subepithelial connective tissue graft * Tools * Curette * Membrane * Probe * Scaler Important personalities * Tomas Albrektsson * Frank Beube * Per-Ingvar Brånemark * Robert Gottsegen * Gary Greenstein * Jan Lindhe * Brian Mealey * Preston D. Miller * Willoughby D. Miller * Carl E. Misch * John Mankey Riggs * Jay Seibert * Jørgen Slots * Paul Roscoe Stillman * Dennis P. Tarnow * Hom-Lay Wang * James Leon Williams * W. J. Younger Other specialties * Endodontology * Orthodontology * Prosthodontology [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Periodontal abscess	c0031085	29,050	wikipedia	https://en.wikipedia.org/wiki/Periodontal_abscess	2021-01-18T18:50:49	{"mesh": ["D010508"], "wikidata": ["Q4669671"]}
## Clinical Features In an inbred North-Swedish family, Jagell et al. (1987) found an ichthyosis-mental retardation syndrome apparently distinct from the Sjogren-Larsson syndrome (SLS; 270200), which is unusually frequent in the same area. The disorder differed from SLS by the presence of alopecia, eclabium, and ectropion and by the absence of spastic diplegia or other neurologic changes and of glistening dots in the fundus of the eye typical of SLS. Although patients in the present study were originally included in the series of Sjogren and Larsson (1957), Jagell et al. (1987) could find no genealogic connection between these patients and SLS patients published by Sjogren and Larsson in studies going back to 1700. Inheritance Autosomal recessive inheritance seemed clear in the patients reported by Jagell et al. (1987); 2 brothers and an aunt and uncle were affected and all 4 parents of the affected sibships shared at least one common ancestral couple. HEENT \- Eclabion \- Ectropion Inheritance \- Autosomal recessive Neuro \- Mental retardation Skin \- Ichthyosis \- Alopecia ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ICHTHYOSIS WITH ALOPECIA, ECLABIUM, ECTROPION, AND MENTAL RETARDATION	c1855788	29,051	omim	https://www.omim.org/entry/242510	2019-09-22T16:26:25	{"mesh": ["C537364"], "omim": ["242510"], "orphanet": ["2269"]}
Schnitzler syndrome is a rare autoinflammatory condition. Signs and symptoms of the condition vary but may include urticaria; recurrent fevers; joint pain and inflammation; organomegaly (abnormally enlarged organs); and/or blood abnormalities. The exact underlying cause of the condition is unknown; however, most cases occur sporadically in people with no family history of the condition. Treatment is focused on alleviating the signs and symptoms associated with the condition and may include various medications and/or phototherapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Schnitzler syndrome	c0524988	29,052	gard	https://rarediseases.info.nih.gov/diseases/12390/schnitzler-syndrome	2021-01-18T17:57:48	{"mesh": ["D019873"], "orphanet": ["37748"], "synonyms": ["Chronic urticaria with gammapathy", "Chronic urticaria with macroglobulinemia", "Chronic urticaria with gammopathy"]}
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: "Acne fulminans" – news · newspapers · books · scholar · JSTOR (April 2009) (Learn how and when to remove this template message) Acne fulminans SpecialtyDermatology Acne fulminans (also known as "acute febrile ulcerative acne"[1]:686) is a severe form of the skin disease, acne, which can occur after unsuccessful treatment for another form of acne, acne conglobata. The condition is thought to be an immunologically induced disease in which elevated level of testosterone causes a rise in sebum and population of Cutibacterium acnes bacteria. The increase in the amount of C acnes or related antigens may trigger the immunologic reaction in some individuals and lead to an occurrence of acne fulminans.[2] In addition to testosterone, isotretinoin may also precipitate acne fulminans, possibly related to highly increased levels of C acnes antigens in the patient's immune system.[3] Acne fulminans is a rare disease. Over the past several years, fewer cases of this disease have occurred, possibly because of earlier and better treatment of acne. Approximately 100 patients with acne fulminans have been described.[4] ## Contents * 1 Signs and symptoms * 2 Treatment * 3 History * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] Acne fulminans begins as pain and inflammation in the joints. It eventually progresses into a swelling of the lymph nodes located at the base of the neck, causing inflexibility in the neck within weeks after the nodes swell. This swelling will eventually decrease, but this decrease will be accompanied by an increased inflammation and swelling of the joints, as well as a complete loss of appetite, though these symptoms are often ignored. After some time, the disease will cause an extreme loss of weight and atrophy of the muscles, leading to the decline of physical abilities.[5] ## Treatment[edit] Treatment should be sought immediately in order to avoid hospitalization. If not treated, hospitalization for an extended period of time (usually two weeks) is likely. During hospitalization, the patient is tested for signs of system degradation, especially of the skeletal structure and the digestive tract. By this time open sores will develop on the upper torso. Some will be the size of dimes, others will be large enough to stick a couple fingers into. They will crust up, causing cohesion to any fabric the sores touch, which is extremely painful to remove. It is recommended to sleep on one's sides until the cystic condition subsides, in order to avoid any uncomfortable situations. Debridement and steroid therapy is preferred over antibiotics.[6] Recurrent AF is extremely rare. Bone lesions typically resolve with treatment, but residual radiographic changes, such as sclerosis and hyperostosis, may remain. Scarring and fibrosis may result from this acute inflammatory process. The disease activates at the height of puberty, usually at around 13 years of age. Acne fulminans predominantly affects young males aged 13 to 22 years with a history of acne. ## History[edit] In 1958, at a meeting of the Detroit Dermatological Society, Burns and Colville presented a 16-year-old white boy with acute febrile disease and acne conglobata. Many similar cases have been reported since then.[7] Genetic factors may play an important role in some patients; 4 sets of identical twins who developed an identical pattern of acne fulminans have been documented.[8] ## See also[edit] * 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. ^ http://reference.medscape.com/medline/abstract/2522757 3. ^ http://reference.medscape.com/medline/abstract/16004026 4. ^ http://reference.medscape.com/medline/abstract/21029206 5. ^ http://reference.medscape.com/medline/abstract/14007467 6. ^ http://reference.medscape.com/medline/abstract/15858507 7. ^ Burns RE, Colville JM. Acne conglobata with septicemia. Arch Dermatol. 1959 8. ^ http://reference.medscape.com/medline/abstract/84495 ## External links[edit] Classification D * ICD-10: L70.8 (ILDS L70.812) * ICD-9-CM: 706.1 * 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]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Acne fulminans	c0263445	29,053	wikipedia	https://en.wikipedia.org/wiki/Acne_fulminans	2021-01-18T19:04:53	{"icd-9": ["706.1"], "icd-10": ["L70.8"], "wikidata": ["Q766442"]}
MPI-CDG is a form of congenital disorders of N-linked glycosylation, characterized by cyclic vomiting, profound hypoglycemia, failure to thrive, liver fibrosis, gastrointestinal complications (protein-losing enteropathy with hypoalbuminaemia, life-threatening intestinal bleeding of diffuse origin), and thrombotic events (protein C and S deficiency, low anti-thrombine III levels), whereas neurological development and cognitive capacity is usually normal. The clinical course is variable even within families. The disease is caused by loss of function of the gene MPI (15q24.1). [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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MPI-CDG	c1865145	29,054	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79319	2021-01-23T18:53:12	{"gard": ["9830"], "mesh": ["C535740"], "omim": ["602579"], "umls": ["C1865145"], "icd-10": ["E77.8"], "synonyms": ["CDG syndrome type Ib", "CDG-Ib", "CDG1B", "Carbohydrate deficient glycoprotein syndrome type Ib", "Congenital disorder of glycosylation type 1b", "Congenital disorder of glycosylation type Ib", "Phosphomannose isomerase deficiency"]}
Tick paralysis SpecialtyEmergency medicine Tick paralysis is the only tick-borne disease that is not caused by an infectious organism. The illness is caused by a neurotoxin produced in the tick's salivary gland. After prolonged attachment, the engorged tick transmits the toxin to its host. The incidence of tick paralysis is unknown. Patients can experience severe respiratory distress (similar to anaphylaxis). ## Contents * 1 Signs and symptoms * 2 Pathogenesis * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Research * 7 Culture * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] Tick paralysis results from injection of a toxin from tick salivary glands during a blood meal. The toxin causes symptoms within 2–7 days, beginning with weakness in both legs that progresses to paralysis. The paralysis ascends to the trunk, arms, and head within hours and may lead to respiratory failure and death. The disease can present as acute ataxia without muscle weakness. Patients may report minor sensory symptoms, such as local numbness, but constitutional signs are usually absent. Deep tendon reflexes are usually decreased or absent, and ophthalmoplegia and bulbar palsy can occur. Electromyographic (EMG) studies usually show a variable reduction in the amplitude of compound muscle action potentials, but no abnormalities of repetitive nerve stimulation studies. These appear to result from a failure of acetylcholine release at the motor nerve terminal level. There may be subtle abnormalities of motor nerve conduction velocity and sensory action potentials. ## Pathogenesis[edit] Tick paralysis is believed to be due to toxins found in the tick's saliva that enter the bloodstream while the tick is feeding. The two ticks most commonly associated with North American tick paralysis are the Rocky Mountain wood tick (Dermacentor andersoni) and the American dog tick (Dermacentor variabilis); however, 43 tick species have been implicated in human disease around the world.[1] Most North American cases of tick paralysis occur from April to June, when adult Dermacentor ticks emerge from hibernation and actively seek hosts.[2] In Australia, tick paralysis is caused by the tick Ixodes holocyclus. Prior to 1989, 20 fatal cases were reported in Australia.[3] Although tick paralysis is of concern in domestic animals and livestock in the United States as well, human cases are rare and usually occur in children under the age of 10. Tick paralysis occurs when an engorged and gravid (egg-laden) female tick produces a neurotoxin in its salivary glands and transmits it to its host during feeding. Experiments have indicated that the greatest amount of toxin is produced between the fifth and seventh day of attachment (often initiating or increasing the severity of symptoms), although the timing may vary depending on the species of tick. Unlike Lyme disease, ehrlichiosis, and babesiosis, which are caused by the systemic proliferation and expansion of parasites in their hosts long after the offending tick is gone, tick paralysis is chemically induced by the tick and therefore usually only continues in its presence. Once the tick is removed, symptoms usually diminish rapidly. However, in some cases, profound paralysis can develop and even become fatal before anyone becomes aware of a tick's presence. ## Diagnosis[edit] Diagnosis is based on symptoms and upon finding an embedded tick, usually on the scalp. In the absence of a tick, the differential diagnosis includes Guillain–Barré syndrome. Early signs of tick poisoning could be a change of an animals' ‘voice’, weakness in the back legs or vomiting.[citation needed] ## Prevention[edit] No human vaccine is currently available for any tick-borne disease, except for tick-borne encephalitis. Individuals should therefore take precautions when entering tick-infested areas, particularly in the spring and summer months. Preventive measures include avoiding trails that are overgrown with bushy vegetation, wearing light-coloured clothes that allow one to see the ticks more easily, and wearing long pants and closed-toe shoes. Tick repellents containing DEET (N,N, diethyl-m-toluamide) are only marginally effective and can be applied to skin or clothing. Rarely, severe reactions can occur in some people who use DEET-containing products. Young children may be especially vulnerable to these adverse effects. Permethrin, which can only be applied to clothing, is much more effective in preventing tick bites. Permethrin is not a repellent but rather an insecticide; it causes ticks to curl up and fall off the protected clothing.[weasel words] ## Treatment[edit] Removal of the offending tick usually results in resolution of symptoms within several hours to days. If the tick is not removed, the toxin can be fatal. A 1969 study of children reported mortality rates of 10 – 12 percent,[4] mostly due to respiratory paralysis. The tick is best removed by grasping it as close to the skin as possible and pulling in a firm steady manner.[5] Because the toxin lies in the tick's salivary glands, care must be taken to remove the entire tick (including the head), or symptoms may persist. It is important to note that, unlike the toxin of other tick species, the toxin of Ixodes holocyclus (Australian paralysis tick) may still be fatal even if the tick is removed. For affected animals, food and water intake can worsen the outcome, as the toxin can prevent the animal from swallowing properly. If you find a tick on your animal, remove it immediately and seek veterinary assistance if the animal shows any signs of illness. The tick can be placed in a tightly sealed plastic bag and taken to a veterinarian for identification.[6][7] ## Research[edit] Although several attempts have been made to isolate and identify the neurotoxin since the first isolation in 1966, the exact structure of the toxin has still not been published.[8] The 40-80 kDa protein fraction contains the toxin.[9] The neurotoxin structure and gene, at least for the tick species Ixodes holocyclus have since been identified and are called holocyclotoxins after the species. At least three members (HT-1,[10] HT-3,[11] and HT-12[12]) trigger paralysis by presynaptic inhibition of neurotransmitter release via a calcium dependent mechanism resulting in a reduction of quantal content, and loss of effective neuromuscular synaptic transmission.[13] ## Culture[edit] In the TV show, Hart of Dixie, Season 1, Episode 2, a patient is diagnosed with tick paralysis who has been deer hunting. In the TV show, Emergency!, Season 5, Episode 4, "Equipment" (first aired Oct. 4, 1975), Dr. Joe Early diagnoses a young boy who has fallen from a tree with tick paralysis, after eliminating polio as a cause.[14] In the TV show, House, Season 2, Episode 16, "Safe", Dr House diagnoses a patient (played by Michelle Trachtenberg) with tick paralysis.[15] In the TV show, Remedy, Season 1 Episode 7, "Tomorrow, the Green Grass", Rebecca is diagnosed with tick paralysis. In the TV show, Royal Pains, Season 1 Episode 3, "Strategic Planning", a US Senator's teenage son is diagnosed with and overcomes tick paralysis. In the TV show, Chicago Med, Season 3, Episode 5, "Mountains and Molehills", a young girl returning from Australia with increasing paralysis is diagnosed with tick paralysis. ## See also[edit] * Polyneuropathy in dogs and cats for tick paralysis in dogs * Tick-borne disease ## References[edit] 1. ^ Gothe R, Kunze K, Hoogstraal H (1979). "The mechanisms of pathogenicity in the tick paralyses". J Med Entomol. 16 (5): 357–69. doi:10.1093/jmedent/16.5.357. PMID 232161. 2. ^ Dworkin MS, Shoemaker PC, Anderson D (1999). "Tick paralysis: 33 human cases in Washington state, 1946–1996". Clin Infect Dis. 29 (6): 1435–9. doi:10.1086/313502. PMID 10585792. 3. ^ Masina S; Broady K. W. (1999). "Tick paralysis: development of a vaccine". International Journal for Parasitology. 29 (4): 535–541. doi:10.1016/S0020-7519(99)00006-5. PMID 10428629. 4. ^ Schmitt N, Bowmer EJ, Gregson JD (1969). "Tick paralysis in British Columbia". Can Med Assoc J. 100 (9): 417–21. PMC 1945728. PMID 5767835. 5. ^ Needham GR (1985). "Evaluation of five popular methods for tick removal". Pediatrics. 75 (6): 997–1002. PMID 4000801. 6. ^ Cannon, Michael. "Envenomation: Tick Paralysis" (PDF). Retrieved June 11, 2018. 7. ^ O’Keefe, Dr Janette. "Australian Paralysis Tick" (PDF). Retrieved June 9, 2018. 8. ^ Doube B. M. (1975). "Cattle and Paralysis Tick Ixodes-Holocyclus". Australian Veterinary Journal. 51 (11): 511–515. doi:10.1111/j.1751-0813.1975.tb06901.x. PMID 1220655. 9. ^ B. F. Stone; K. C. Binnington; M. Gauci; J. H. Aylward (1989). "Tick/host interactions forIxodes holocyclus: Role, effects, biosynthesis and nature of its toxic and allergenic oral secretions". Experimental and Applied Acarology. 7 (1): 59–69. doi:10.1007/BF01200453. PMID 2667920. 10. ^ "Ixodes holocyclus holocyclotoxin-1 (HT1) mRNA, complete cds - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-07-29. 11. ^ "Ixodes holocyclus holocyclotoxin 3 (HT3) mRNA, complete cds - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-07-29. 12. ^ "Ixodes holocyclus holocyclotoxin 12 (HT12) mRNA, complete cds - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-07-29. 13. ^ Chand, Kirat K.; Lee, Kah Meng; Lavidis, Nickolas A.; Rodriguez-Valle, Manuel; Ijaz, Hina; Koehbach, Johannes; Clark, Richard J.; Lew-Tabor, Ala; Noakes, Peter G. (2016-07-08). "Tick holocyclotoxins trigger host paralysis by presynaptic inhibition". Scientific Reports. 6 (1): 29446. Bibcode:2016NatSR...629446C. doi:10.1038/srep29446. ISSN 2045-2322. PMC 4937380. PMID 27389875. 14. ^ "IMDB". 15. ^ "House MD Episode Guide: Season Two #216 'Safe'". housemd-guide.com. Retrieved August 11, 2012. ## External links[edit] Classification D * ICD-10: T63.4 * ICD-9-CM: 989.5 * MeSH: D013985 * DiseasesDB: 31779 * SNOMED CT: 74225001 External resources * MedlinePlus: 001359 * v * t * e * Poisoning * Toxicity * Overdose History of poison Inorganic Metals Toxic metals * Beryllium * Cadmium * Lead * Mercury * Nickel * Silver * Thallium * Tin Dietary minerals * Chromium * Cobalt * Copper * Iron * Manganese * Zinc Metalloids * Arsenic Nonmetals * Sulfuric acid * Selenium * Chlorine * Fluoride Organic Phosphorus * Pesticides * Aluminium phosphide * Organophosphates Nitrogen * Cyanide * Nicotine * Nitrogen dioxide poisoning CHO * alcohol * Ethanol * Ethylene glycol * Methanol * Carbon monoxide * Oxygen * Toluene Pharmaceutical Drug overdoses Nervous * Anticholinesterase * Aspirin * Barbiturates * Benzodiazepines * Cocaine * Lithium * Opioids * Paracetamol * Tricyclic antidepressants Cardiovascular * Digoxin * Dipyridamole Vitamin poisoning * Vitamin A * Vitamin D * Vitamin E * Megavitamin-B6 syndrome Biological1 Fish / seafood * Ciguatera * Haff disease * Ichthyoallyeinotoxism * Scombroid * Shellfish poisoning * Amnesic * Diarrhetic * Neurotoxic * Paralytic Other vertebrates * amphibian venom * Batrachotoxin * Bombesin * Bufotenin * Physalaemin * birds / quail * Coturnism * snake venom * Alpha-Bungarotoxin * Ancrod * Batroxobin Arthropods * Arthropod bites and stings * bee sting / bee venom * Apamin * Melittin * scorpion venom * Charybdotoxin * spider venom * Latrotoxin / Latrodectism * Loxoscelism * tick paralysis Plants / fungi * Cinchonism * Ergotism * Lathyrism * Locoism * Mushrooms * Strychnine 1 including venoms, toxins, foodborne illnesses. * Category * Commons * WikiProject * v * t * e Tick-borne diseases and infestations Diseases Bacterial infections Rickettsiales * Anaplasmosis * Boutonneuse fever * Ehrlichiosis (Human granulocytic, Human monocytotropic, Human E. ewingii infection) * Scrub typhus * Spotted fever rickettsiosis * Pacific Coast tick fever * American tick bite fever * rickettsialpox * Rocky Mountain spotted fever) Spirochaete * Baggio–Yoshinari syndrome * Lyme disease * Relapsing fever borreliosis Thiotrichales * Tularemia Viral infections * Bhanja virus * Bourbon virus * Colorado tick fever * Crimean–Congo hemorrhagic fever * Heartland bandavirus * Kemerovo tickborne viral fever * Kyasanur Forest disease * Omsk hemorrhagic fever * Powassan encephalitis * Severe fever with thrombocytopenia syndrome * Tete orthobunyavirus * Tick-borne encephalitis Protozoan infections * Babesiosis Other diseases * Tick paralysis * Alpha-gal allergy * Southern tick-associated rash illness Infestations * Tick infestation Species and bites Amblyomma * Amblyomma americanum * Amblyomma cajennense * Amblyomma triguttatum Dermacentor * Dermacentor andersoni * Dermacentor variabilis Ixodes * Ixodes cornuatus * Ixodes holocyclus * Ixodes pacificus * Ixodes ricinus * Ixodes scapularis Ornithodoros * Ornithodoros gurneyi * Ornithodoros hermsi * Ornithodoros moubata Other * Rhipicephalus sanguineus Authority control * LCCN: sh85135249 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Tick paralysis	c0040197	29,055	wikipedia	https://en.wikipedia.org/wiki/Tick_paralysis	2021-01-18T18:34:34	{"gard": ["7771"], "mesh": ["D013985"], "umls": ["C0040197"], "icd-9": ["989.5"], "icd-10": ["T63.4"], "wikidata": ["Q4223496"]}
## Clinical Features Verloes et al. (1990) described 2 male sibs with a hitherto undescribed multiple congenital anomaly/mental retardation (MCA/MR) syndrome. The brothers shared the following clinical characteristics: postnatal growth deficiency, obesity, coarse facial features with deep-set small eyes, and severe genital anomalies resulting in sexual ambiguity. Mental retardation was profound in one; the other sib was only slightly retarded. Although the features suggested the Borjeson-Forssman-Lehmann syndrome (BFLS; 301900), the patients were thought not to fit completely with any previously known syndrome. De Die-Smulders et al. (1994) reported a moderately mentally retarded adult male with genital anomalies and facial features resembling those in the patients of Verloes et al. (1990). As illustrated in the figures, the patient had short neck with low posterior hairline and lateral webbing. Radiography demonstrated cervical spina bifida. There had been no speech development and audiologic testing showed severe sensorineural hearing loss. On eye examination, he was found to have bilateral coloboma of the choroid and temporal displacement of both maculae. At the time of the report, the patient was 42 years old. Inheritance The transmission pattern of this disorder is consistent with autosomal recessive or X-linked recessive inheritance (de Die-Smulders et al., 1994). INHERITANCE \- Autosomal recessive GROWTH Weight \- Obesity Other \- Postnatal growth deficiency HEAD & NECK Face \- Coarse facies Ears \- Sensorineural hearing loss, severe Eyes \- Small eyes \- Deep-set eyes \- Coloboma of choroid \- Temporal displacement of maculae Neck \- Short neck \- Lateral neck webbing \- Low posterior hairline GENITOURINARY External Genitalia (Male) \- Male pseudohermaphroditism \- Sexual ambiguity SKELETAL Spine \- Cervical spina bifida SKIN, NAILS, & HAIR Hair \- Low posterior hairline NEUROLOGIC Central Nervous System \- Mental retardation, mild to profound \- No speech development (in some patients) MISCELLANEOUS \- X-linked inheritance possible ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MALE PSEUDOHERMAPHRODITISM/MENTAL RETARDATION SYNDROME, VERLOES TYPE	c2931233	29,056	omim	https://www.omim.org/entry/600122	2019-09-22T16:16:34	{"mesh": ["C536539"], "omim": ["600122"], "orphanet": ["2983"], "synonyms": ["Alternative titles", "VERLOES SYNDROME"]}
This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Progressive disease" – news · newspapers · books · scholar · JSTOR (May 2020) (Learn how and when to remove this template message) Progressive disease or progressive illness is a disease or physical ailment whose course in most cases is the worsening, growth, or spread of the disease. This may happen until death, serious debility, or organ failure occurs. Some progressive diseases can be halted and reversed by treatment. Many can be slowed by medical therapy. Some cannot be altered by current treatments. Though the time distinctions are imprecise, diseases can be rapidly progressive (typically days to weeks) or slowly progressive (months to years). Virtually all slowly progressive diseases are also chronic diseases in terms of time course; many of these are also referred to as degenerative diseases. Not all chronic diseases are progressive: a chronic, non-progressive disease may be referred to as a static condition. Progressive disease can also be a clinical endpoint i.e. an endpoint in a clinical trial. ## Examples[edit] There are examples of slowly and rapidly progressive diseases affecting all organ systems and parts of the body. The following are some examples of rapidly and slowly progressive diseases affecting various organ systems: * Brain: Creutzfeldt–Jakob disease progresses rapidly compared to Alzheimer's disease. * Eyes: Cataracts can be static or slowly progressive. Macular degeneration is slowly progressive, while retinal detachment is rapidly progressive. * Lungs: Emphysema due to alpha-1 antitrypsin deficiency is a slowly progressive pulmonary disease. * Kidneys: Goodpasture's syndrome is a rapidly progressive glomerulonephritis, while diabetic glomerulosclerosis is slowly progressive. * Pancreas: Type 1 diabetes mellitus involves rapidly progressive loss of insulin secretory capacity compared to type 2 diabetes mellitus, in which the loss of insulin secretion is slowly progressive over many years. MODY 2, due to GCK mutation, is a relatively static form of reduced insulin secretion. * Joints: Both osteoarthritis and rheumatoid arthritis are slowly progressive forms of arthritis. * Nerves: Essential tremor is a slowly progressive neurological disorder which is usually genetically passed down. ## References[edit] [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Progressive disease	c1335499	29,057	wikipedia	https://en.wikipedia.org/wiki/Progressive_disease	2021-01-18T18:52:08	{"wikidata": ["Q1951525"]}
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 possibly contains original research. Please improve it by verifying the claims made and adding inline citations. Statements consisting only of original research should be removed. (August 2011) (Learn how and when to remove this template message) 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: "Irlen syndrome" – news · newspapers · books · scholar · JSTOR (August 2011) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Irlen syndrome Pseudomedical diagnosis RisksNocebo Irlen syndrome, occasionally referred to as scotopic sensitivity syndrome (SSS) or Meares-Irlen syndrome,[1] is a proposed disorder of vision or image-processing in the brain. Irlen syndrom is also sometimes referred to as asfedia or visual stress.[citation needed] Many mainstream professionals are skeptical of the concept.[2] Research on Irlen syndrome has produced mixed results, finding a possible neurological basis for the condition[3] but little or no evidence supporting the most commonly proposed treatment using tinted eyeglasses or overlays to aid reading.[4] ## Contents * 1 History * 2 Research * 3 Treatment * 3.1 Irlen Method * 4 Scientific repudiation * 4.1 Terminology * 5 References * 6 Further reading ## History[edit] In 1980, New Zealand teacher Olive Meares described the visual distortions some individuals reported when reading from white paper. In 1983, American psychologist Helen Irlen wrote a paper about the use of coloured overlays aiding the reading abilities of some people. Similar symptoms were separately described by Meares and Irlen—each unaware of the other's work. Irlen, who was the first to systematically define the condition, named her findings "scotopic sensitivity", though in the discussions and debates over the following years, some referred to it as Meares-Irlen syndrome. The Irlen Institute, founded by Helen Irlen, describes scotopic senstivity as "a perceptual processing disorder" related to brain interpretations of colors and light.[5] It remains controversial whether non-Irlen-certified Meares-Irlen syndrome and the original Irlen syndrome are the same condition. Irlen syndrome, for example, seems to include a broader array of symptoms, including severe variants of the core condition. Basic testing for scotopic sensitivity was tried by optometrists, opticians, and orthoptists in UK hospitals, and by optometrists and opticians in private practice employing a technique that used the Intuitive Colorimeter, developed under Medical Research Council license. An alternative approach to correct Irlen syndrome was tried by Orthoscopics franchise in the UK, with wide colour coverage and tints manufactured by Hoyato match. Other commercial organisations have produced sets of therapeutic tints, although most have not received scientific evaluation.[6] Studies investigating Irlens' syndrome as a treatable condition have been criticised for having a biased and subjective approach to their research.[7] Treatments offered by Irlens' practitioners have not been found to be effective in improving reading ability.[8] ## Research[edit] The disorders have been studied in several institutions, including the Psychology Department at Essex University, the former Applied Psychology Unit, Cambridge University in England, and in the case of Meares-Irlen syndrome, Visual Unit at Glasgow Caledonian University in Scotland. As of 2012[update] the Visual Stress Unit offered non-commercial diagnostic and therapeutic services to individuals, and provided advice to the Scottish National Health Service. In Australia, Irlen syndrome was researched by Paul Whiting at the University of Sydney. Whiting set up the first Irlen Dyslexia Centre in Australia, which operated in the Children's Centre at Sydney University for more than 15 years.[9] Irlen syndrome was also studied in Australia by Greg Robinson (1944–2008) at the University of Newcastle. He was director of the Special Education Centre at the School of Education.[10] In the US, peer-reviewed literature on the topic suggests that much is unknown about the cause of these disorders, ranging from the 2011 study in a journal of the American Academy of Pediatrics, "Irlen Colored Overlays Do not Alleviate Reading Difficulties"[4] and the 2012 study in the journal Brain Topography, "A Functional Neuroimaging Case Study of Meares–Irlen Syndrome".[3] The first, purely in relation to Meares-Irlen syndrome, finds that there is no evidence for one of the fundamental claims of therapeutic benefit. The second, which focused primarily on Irlen syndrome, found compelling evidence of unique brain function linked to the syndrome. ## Treatment[edit] The College of Optometrists (UK) has specified guidelines for optometrists who use the colorimeter system. A society for coloured lens prescribers has been established to provide a list of eye-care practitioners with expertise in the provision of coloured lenses for the treatment of visual stress.[11] ### Irlen Method[edit] The Irlen Method uses coloured overlays and tinted lenses in the form of glass or contact lenses. The method is intended to reduce or eliminate perceptual processing errors; it is claimed the resultant retiming of visual signals in the brain improves the reading difficulties associated with scotopic sensitivity syndrome.[12] ## Scientific repudiation[edit] Skepticism relating to scotopic sensitivity syndrome's exact pathology has evolved on several fronts: 1. Whether it exists as a distinct, predictably identifiable disease with a reasonable pathophysiological mechanism, or whether a range of symptoms from other conditions are being placed under this convenient heading; 2. Whether it is causally or incidentally related to dyslexia, autism, or other conditions; and 3. Whether existing methods of scotopic sensitivity syndrome treatment are appropriate and effective. A 2009 report by the American Academy of Pediatrics (AAP) does not believe that there is conclusive scientific evidence for the use of coloured lenses (one treatment used to relieve symptoms of scotopic sensitivity syndrome) although it acknowledges anecdotal evidence in support of customized colored lenses.[13] When discussing its scientific basis, the AAP mentions that "[t]he method used to select the lens or filter color has been highly variable, the color selection has also shown considerable variability, and the test-retest consistency has been poor" (p. 843). The association of scotopic sensitivity syndrome and dyslexia has been challenged by many authors in the optometric and ophthalmologic communities.[2] Furthermore, many special education departments at universities challenge the validity of coloured lenses as an effective treatment for the condition as outlined by the Macquarie University Special Education Centre.[14] > In a joint statement, The American Academy of Ophthalmology, American Academy of Pediatrics, American Association for Pediatric Ophthalmology and Strabismus and American Association of Certified Orthoptists firmly repudiated the use of lenses, stating that there was no scientific evidence supporting their use. The expense of such treatment is unwarranted and may divert resources from evidence-based treatment. Critics claim that the symptoms of those with Scotopic Sensitivity Syndrome are related to already known visual perceptual and neurological disorders.[15] According to a statement released by the American Optometric Association in 2004:[16] > There is evidence that the underlying symptoms associated with specifically Meares Irlen Syndrome, are related to identifiable vision anomalies, e.g., accommodative, binocular, and ocular motor dysfunctions, in many patients seeking help from coloured lenses. Furthermore, such conditions return to normal function when appropriately treated with lenses, prisms, or vision therapy. When patients exhibiting Meares Irlen Syndrome were treated with vision therapy, their symptoms were relieved. These patients were no longer classified as exhibiting this syndrome, and therefore did not demonstrate a need for the coloured overlays or tinted lenses. As outlined by Hyatt, Stephenson and Carter (2009)[17] > In 1990, the Journal of Learning Disabilities published a special issue that provided intensive coverage of Irlen lenses. In the preface to the issue, the editor in chief, Wiederholt, noted that each of the studies had serious theoretical, medical/physical, and methodological flaws, but were published along with articles critiquing the studies to provide readers with an overview of the Irlen procedures as well as guidance for conducting quality research studies. He, along with Hoyt (1990),[18] Parker (1990),[19] and Solan (1990),[20] noted that these initial studies by Blaskey et al. (1990),[21] O’Connor, Sofo, Kendall, and Olsen (1990),[22] and Robinson and Conway (1990)[23] failed to support the treatment validity of colored overlays. ### Terminology[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (March 2020) (Learn how and when to remove this template message) Critics maintain that the term "scotopic sensitivity" is a misnomer given that the symptoms of "scotopic sensitivity syndrome" reportedly occur during photopic conditions. The term "scotopic sensitivity" seems dubious, given that scotopic vision is the vision of the eye under low light conditions and as such vision is provided by rod cells on the retina, which have little if any role in colour vision; it does not make sense that a coloured lens or coloured overlay would have any impact upon "scotopic sensitivity syndrome". However, under low light conditions, the condition may exhibit itself in a distinctive manner (i.e. perceptions/visual disturbances of light, tones, and tracers that are not otherwise visually recordable or present). ## References[edit] 1. ^ "Irlen Syndrome vs. Visual Stress: Simple Semantics or Something More". irlen.com. 2. ^ a b Cotton M, Evans K (1990). "A review of the use of Irlen (tinted) lenses". Aust N Z J Ophthalmol. 18 (3): 307–12. doi:10.1111/j.1442-9071.1990.tb00625.x. PMID 2261178. 3. ^ a b Chouinard BD, Zhou CI, Hrybouski S, Kim ES, Cummine J (July 2012). "A functional neuroimaging case study of Meares-Irlen syndrome/visual stress (MISViS)". Brain Topogr. 25 (3): 293–307. doi:10.1007/s10548-011-0212-z. PMID 22124535. S2CID 13065620. 4. ^ a b Ritchie SJ, Della Sala S, McIntosh RD (October 2011). "Irlen colored overlays do not alleviate reading difficulties". Pediatrics. 128 (4): e932–8. doi:10.1542/peds.2011-0314. PMID 21930551. S2CID 27034274. 5. ^ https://irlen.com/what-is-irlen-syndrome/ What is Irlen Syndrome? The Irlen Institute, accessed 2020-10-08 6. ^ American Academy Of Pediatrics, Section on Ophthalmology; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology Strabismus; American Association of Certified Orthoptists (August 2009). "Joint statement—Learning disabilities, dyslexia, and vision" (PDF). Pediatrics. 124 (2): 837–44. doi:10.1542/peds.2009-1445. PMID 19651597. S2CID 15631430. 7. ^ https://sciencebasedmedicine.org/irlen-syndrome/ 8. ^ Ritchie, S. J.; Della Sala, S.; McIntosh, R. D. (2011). "Irlen colored overlays do not alleviate reading difficulties". Pediatrics. 128 (4): e932-8. doi:10.1542/peds.2011-0314. PMID 21930551. S2CID 27034274. 9. ^ "Archived copy". Archived from the original on 25 January 2014. Retrieved 2014-03-28.CS1 maint: archived copy as title (link) 10. ^ "Archived copy". Archived from the original on 25 January 2014. Retrieved 2014-03-28.CS1 maint: archived copy as title (link) 11. ^ "Society for Coloured Lens Prescribers". www.s4clp.org. 12. ^ "The University of Newcastle, Australia". www.newcastle.edu.au. 13 November 2015. Archived from the original on 12 January 2007. 13. ^ "American Academy of Pediatrics, 2009". 14. ^ Hyatt, KJ (2010). "Irlen Tinted Lenses and Overlays" (PDF). MUSEC Briefings. Macquarie University Special Education Centre. 22. 15. ^ Solan H, Richman J (1990). "Irlen lenses: a critical appraisal". J Am Optom Assoc. 61 (10): 789–96. PMID 2136527. 16. ^ "The Use of Tinted Lenses and Colored Overlays for the Treatment of Dyslexia and Other Related Reading and Learning Disorders". Aoa.org. Archived from the original on 2 October 2009. Retrieved 13 October 2009. 17. ^ Keith j. Hyatt; Jennifer Stephenson; Mark Carter (2009). "A Review of Three Controversial Educational Practices: Perceptual Motor Programs, Sensory Integration, and Tinted Lenses". Project MUSE - Education and Treatment of Children. 32 (2): 313–342. doi:10.1353/etc.0.0054. S2CID 143983625. 18. ^ Hoyt CS (December 1990). "Irlen lenses and reading difficulties". J Learn Disabil. 23 (10): 624–6. doi:10.1177/002221949002301010. PMID 2280171. S2CID 30863520. 19. ^ Parker RM (December 1990). "Power, control, and validity in research". J Learn Disabil. 23 (10): 613–20. doi:10.1177/002221949002301008. PMID 2280169. S2CID 21369939. 20. ^ Solan HA (December 1990). "An appraisal of the Irlen technique of correcting reading disorders using tinted overlays and tinted lenses". J Learn Disabil. 23 (10): 621–3, 626. doi:10.1177/002221949002301009. PMID 2280170. S2CID 40223496. 21. ^ Blaskey P, Scheiman M, Parisi M, Ciner EB, Gallaway M, Selznick R (December 1990). "The effectiveness of Irlen filters for improving reading performance: a pilot study". J Learn Disabil. 23 (10): 604–12. doi:10.1177/002221949002301007. PMID 2280168. S2CID 32063320. 22. ^ O'Connor PD, Sofo F, Kendall L, Olsen G (December 1990). "Reading disabilities and the effects of colored filters" (PDF). J Learn Disabil. 23 (10): 597–603, 620. doi:10.1177/002221949002301006. PMID 2280167. S2CID 19142994. Archived from the original (PDF) on 20 September 2010. 23. ^ Robinson GL, Conway RN (December 1990). "The effects of Irlen colored lenses on students' specific reading skills and their perception of ability: a 12-month validity study". J Learn Disabil. 23 (10): 589–96. doi:10.1177/002221949002301005. PMID 2280166. S2CID 37587288. ## Further reading[edit] * Hyatt, Keith J (February 2010). "Irlen Tinted Lenses and Overlay" (PDF). MUSEC Briefings. Macquarie University Special Education Centre (22). Archived from the original (PDF) on 29 August 2017. Retrieved 22 April 2017. * Wilkins, Arnold J. (2003). Reading through color: how colored filters can reduce reading difficulty, eye strain, and headaches. Chichester: John Wiley & Sons. ISBN 0-470-85116-3. OCLC 78883050. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Irlen syndrome	c1272174	29,058	wikipedia	https://en.wikipedia.org/wiki/Irlen_syndrome	2021-01-18T18:44:04	{"wikidata": ["Q7435732"]}
A number sign (#) is used with this entry because hereditary intrinsic factor deficiency is caused by homozygous or compound heterozygous mutation in the gene encoding gastric intrinsic factor (GIF; 609342) on chromosome 11q12. Description Congenital pernicious anemia (PA), or intrinsic factor deficiency, is a rare disorder characterized by the lack of gastric intrinsic factor in the presence of normal acid secretion and mucosal cytology and the absence of GIF antibodies that are found in the acquired form of pernicious anemia (170900). See also pernicious anemia due to defect in the receptor for vitamin B12/intrinsic factor (261100). Clinical Features Cases of childhood pernicious anemia have been reported in which, although the gastric mucosa was histologically normal, intrinsic factor was lacking from the acid gastric juice. No antibodies to intrinsic factor or to gastric parietal cells were detected in the patients' serum. Studies in sibs, parents, and grandparents showed no abnormality in the secretion of gastric acid or intrinsic factor and normal vitamin B12 absorption (McIntyre et al., 1965). In 1 such family (Herbert et al., 1964), 2 sibs were affected. Juvenile 'congenital' pernicious anemia was the designation suggested by Miller et al. (1966) for vitamin B12 deficiency due to congenital lack of gastric intrinsic factor without other apparent abnormality of the stomach or its secretions. Furthermore, serum antibodies to intrinsic factor and gastric parietal cells are conspicuously absent. McNicholl and Egan (1968) described a brother and sister with congenital PA and stated that 28 cases had been described. They noted that the defect seems to be one of failure of intrinsic factor secretion despite normal gastric acidity and mucosal morphology. The disorder is distinct from juvenile pernicious anemia due to selective intestinal malabsorption of vitamin B12 with proteinuria (261100) and pernicious anemia associated with the polyglandular autoimmune syndrome (240300). It is also distinct from classic adult-onset pernicious anemia (170900). The congenital form is manifest by megaloblastic anemia presenting at about 1 year of age and mental retardation. Katz et al. (1972) described a 13-year-old male from a consanguineous marriage with normal gastric intrinsic factor by immunoassay but none by biologic test. By means of a new second-antibody radioimmunoassay, Carmel (1983) could detect no immunoreactive intrinsic factor in any of 6 patients studied. One patient, a female Mexican physician, was first diagnosed at age 23 years. The delay in diagnosis was attributable to the fact that after a severe illness, said to be amebiasis, at age 1, the mother had given her monthly liver injections; these had been continued until age 16. At age 23, she was investigated for pancytopenia and found to have florid megaloblastic changes in the circulating blood and bone marrow. Although the author works in Los Angeles, it may be significant that all of his cases were Mexicans distributed in 3 kindreds. Juvenile PA due apparently to production of intrinsic factor unusually susceptible to degradation in the lumen of the GI tract was described by Levine et al. (1981). See Yang et al. (1985). Katz et al. (1974) described a type of congenital intrinsic factor defect in which intrinsic factor had normal cobalamin-binding ability and immunoreactivity but showed very poor affinity for the intestinal receptor for intrinsic factor. In a 26-year-old man, the offspring of first-cousin parents, Remacha et al. (1992) found a defect in vitamin B12 absorption by Schilling test, which was corrected by adding intrinsic factor. The parents and sibs had normal serum vitamin B12 levels, but the father and a sister in whom gastric examination was performed showed decreased IF secretion compatible with heterozygosity. The proband came to medical attention because of an episode of jaundice and anemia. He had recovered from similar crises at ages 2, 4, 8, 16, 22, and 24 years of age with administration of parenteral vitamins complex including vitamin B12. He was found to have macrocytic anemia, moderate leukopenia, and bilirubinemia. Molecular Genetics Hewitt et al. (1991) found that Southern analysis of genomic GIF DNA from patients with congenital pernicious anemia due to lack of intrinsic factor showed normal restriction fragment patterns, suggesting that a sizable gene deletion is not responsible for the deficiency. Gordon et al. (2004) sequenced all the exons of the GIF gene in 5 patients with intrinsic factor deficiency and in the parents of 4 of the patients. A single-nucleotide substitution at position 2 of codon 5 (68A-G) in 1 or both copies of the GIF gene was identified in all of the subjects, with additional changes observed in 2 patients. When COS-7 cells were transfected with plasmids containing either the normal or the mutant cDNA, the secreted GIF proteins had a similar rate of secretion and sensitivity to pepsin degradation. Three subjects were homozygous for the missense mutation, changing codon 5 from CAG (glutamine) to CGG (arginine). Three subjects were homozygous for the mutation and 2 subjects were heterozygous, 1 of whom was apparently a compound heterozygote at positions 1 and 2 of the fifth codon. The other patient heterozygous for position 2 had 1 heterozygous unaffected parent. Most parents were heterozygous for this base exchange, confirming the pattern of autosomal recessive inheritance for congenital IF deficiency. cDNA encoding GIF was mutated at basepair g.68A-G. The apparent size, secretion rate, and sensitivity to pepsin hydrolysis of the expressed IF were similar to native intrinsic factor. The allelic frequency of 68A-G was 0.067 and 0.038 in 2 control populations from Germany and Spain, respectively. Gordon et al. (2004) concluded that the Q5R variant (609342.0001) was not the cause of the phenotype but was associated with congenital IF deficiency in such a way as to serve as a marker for inheritance of this disorder. In an 11-year-old girl with severe anemia and cobalamin (Cbl) deficiency, Yassin et al. (2004) identified a 4-base deletion in the coding region of the GIF gene (609342.0002). The bone marrow showed frank megaloblastic morphology, and the Schilling test indicated a failure to absorb Cbl that was corrected by coadministration of intrinsic factor. Pentagastrin administration induced acid secretion, but the gastric juice lacked intrinsic factor as determined by Cbl binding and other tests. In 7 families previously diagnosed with Imerslund-Grasbeck syndrome (261100) due to inconclusive results on radiocobalamin absorption tests, but who were negative for mutations in the cubilin (CUBN; 602997) or the AMN (605799) gene, Tanner et al. (2005) identified homozygosity for 6 different mutations in the GIF gene (609342.0002-609342.0007). Tanner et al. (2005) proposed that rather than radiocobalamin absorption tests, mutation analysis of the CUBN, AMN, and GIF genes may be the diagnostic method of choice for cobalamin absorption disorders. INHERITANCE \- Autosomal recessive ABDOMEN Gastrointestinal \- Vitamin B12 deficiency caused by intestinal malabsorption \- Absence of intrinsic factor by immunoassay of gastric juices \- Normal gastric mucosa \- Normal gastric acid secretion \- Normal pepsin secretion NEUROLOGIC Peripheral Nervous System \- Sensory impairment \- Paresthesias \- Peripheral neuropathy HEMATOLOGY \- Megaloblastic anemia \- Increased mean corpuscular volume \- Bone marrow biopsy shows megaloblastic erythroid hyperplasia IMMUNOLOGY \- Absence of auto-antibodies to intrinsic factor or parietal cells LABORATORY ABNORMALITIES \- Decreased serum B12 levels MISCELLANEOUS \- Onset in childhood MOLECULAR BASIS \- Caused by mutation in the gastric intrinsic factor gene (GIF, 609342.0001 ). ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	INTRINSIC FACTOR DEFICIENCY	c0340957	29,059	omim	https://www.omim.org/entry/261000	2019-09-22T16:23:35	{"doid": ["0050734"], "omim": ["261000"], "orphanet": ["332"], "synonyms": ["Alternative titles", "PERNICIOUS ANEMIA, CONGENITAL, DUE TO DEFECT OF INTRINSIC FACTOR"]}
A number sign (#) is used with this entry because of evidence that susceptibility to idiopathic generalized epilepsy-13 (EIG13), including juvenile myoclonic epilepsy-5 (EJM5) and childhood absence epilepsy-4 (ECA4), can be conferred by heterozygous mutation in the GABRA1 gene (137160) on chromosome 5q34. Description Childhood absence epilepsy and juvenile myoclonic epilepsy are both subtypes of what has classically been called idiopathic generalized epilepsy (IGE, EIG; see 600669). For a phenotypic description and a discussion of genetic heterogeneity of idiopathic generalized epilepsy, see 600669. For a phenotypic description and a discussion of genetic heterogeneity of juvenile myoclonic epilepsy and childhood absence epilepsy, see ECA1 (600131) and JME (254770), respectively. Clinical Features Cossette et al. (2002) reported a French Canadian family in which 14 members over 4 generations had juvenile myoclonic epilepsy. All affected members had a similar phenotype, with no history of febrile seizures. Lachance-Touchette et al. (2011) reported 2 unrelated French Canadian families with idiopathic generalized epilepsy. In 1 family, 3 affected individuals had late-onset afebrile, generalized tonic-clonic seizures as well as photosensitivity. In the other family, 4 affected individuals had mainly febrile seizures, with or without generalized tonic-clonic and absence seizures. Inheritance The transmission pattern of EJM5 in the family reported by Cossette et al. (2002) was consistent with autosomal dominant inheritance. The transmission pattern of EIG13 in the families reported by Lachance-Touchette et al. (2011) was consistent with autosomal dominant inheritance and incomplete penetrance. Molecular Genetics In 14 members of a French Canadian family with juvenile myoclonic epilepsy, Cossette et al. (2002) identified a heterozygous mutation in the GABRA1 gene (A322D; 137160.0001). Among 98 German individuals with IGE, Maljevic et al. (2006) identified 1 boy with a heterozygous mutation in the GABRA1 gene (137160.0002). He had childhood absence epilepsy with onset of short episodes of loss of consciousness in daily clusters between 3 and 5 years of age. There were no febrile seizures and no family history of the disorder. In affected members of 2 unrelated French Canadian families with EIG, Lachance-Touchette et al. (2011) identified 2 different heterozygous mutations in the GABRA1 gene (137160.0006 and 137160.0007, respectively). In vitro studies showed that the mutations reduced surface expression of the proteins and altered neurotransmitter effectiveness, resulting in a detrimental effect on inhibitory control of neuronal circuits. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 13	c0270853	29,060	omim	https://www.omim.org/entry/611136	2019-09-22T16:03:35	{"doid": ["0111314"], "mesh": ["D020190"], "omim": ["611136", "600131"], "orphanet": ["64280", "307"], "synonyms": ["Pyknolepsy"]}
Chondrosarcoma is a malignant bone tumor arising from cartilaginous tissue, most frequently occuring at the ends of the femur and tibia, the proximal end of the humerus and the pelvis; and presenting with a palpable mass and progressive pain. Chondrosarcoma is usually slow growing at low histological grades and can be well managed by intralesional curettage or en-block wide resection. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Chondrosarcoma	c0008479	29,061	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=55880	2021-01-23T17:56:39	{"gard": ["6055"], "mesh": ["D002813"], "omim": ["215300"], "umls": ["C0008479"], "icd-10": ["C49.9"]}
Thinking seizures is a rare neurologic disease characterized by seizures induced by specific cognitive tasks, such as calculation or solving arithmetic problems (e.g. Sudoku puzzle), playing thinking games (e.g. Rubik's cube, chess, cards), thinking, making decisions and abstract reasoning. Idiopathic generalized seizures are mainly involved, but partial epilepsies may, in rare cases, be observed. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Thinking seizures	c4706523	29,062	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166424	2021-01-23T17:38:18	{"icd-10": ["G40.5"]}
Fetal alcohol syndrome (FAS) is a rare malformation syndrome caused by excessive maternal consumption of alcohol during pregnancy. It is characterized by prenatal and/or postnatal growth deficiency (weight and/or height <10th percentile), a unique cluster of minor facial anomalies (short palpebral fissures, flat and smooth philtrum, and thin upper lip) and severe central nervous system (CNS) abnormalities including microcephaly, and cognitive and behavioral impairment (intellectual disability, deficit in general cognition, learning and language, executive function, visual-spatial processing, memory, and attention). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Fetal alcohol syndrome	c0015923	29,063	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1915	2021-01-23T18:36:23	{"gard": ["599"], "mesh": ["D063647", "D005310"], "umls": ["C0015923", "C0814154", "C2985290", "C3146244"], "icd-10": ["Q86.0"], "synonyms": ["ARBD", "ARND", "Alcohol-related birth defects", "Alcohol-related neurodevelopmental disorder", "FAS", "FASD", "Fetal alcohol spectrum disorders"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant primary microcephaly-18 (MCPH18) is caused by heterozygous mutation in the WDFY3 gene (617485) on chromosome 4q21. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200). Clinical Features Kadir et al. (2016) reported a 3-generation family in which multiple individuals had microcephaly with mild to moderate intellectual disability. None had apparent dysmorphic features or ocular malformations. Brain imaging showed no structural defects. Inheritance The transmission pattern of MCPH18 in the family reported by Kadir et al. (2016) was consistent with autosomal dominant inheritance. Molecular Genetics In affected members of a family with autosomal dominant MCPH18, Kadir et al. (2016) identified a heterozygous missense mutation in the WDFY3 gene (R2637W; 617485.0001). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in the family. In vitro functional expression studies showed that cells transfected with the mutation had increased levels of DVL3 (601368) compared to controls. This was suggested to cause abnormal activation of WNT signaling and continued generation of apical progenitor cells without transition to differentiation and generation of the basal progenitor cell layer in the cerebral cortex, thus resulting in impaired cortical development and microcephaly. The mutation acted through a dominant-negative effect rather than haploinsufficiency. The findings indicated that autophagic attenuation of WNT signaling through removal of DVL3 aggregates by WDFY3 acts in determining human brain size. Animal Model Kadir et al. (2016) found that Drosophila transfected with mutant human WDFY3 (R2637W; 617485.0001) had smaller brains. Compared to wildtype, mutant fly brains were 40 to 60% smaller in volume, denser, and very fragile and malformed, and showed clusters of disorganized cells containing WDFY3-labeled aggregates. Mutant flies also showed an abnormal rough eye phenotype with disorganized and/or fused omatids and disorganized bristles. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Microcephaly (<3 SD below mean per age) NEUROLOGIC Central Nervous System \- Intellectual disability, mild to moderate \- No structural brain abnormalities MISCELLANEOUS \- One family has been reported (last curated June 2017) MOLECULAR BASIS \- Caused by mutation in the WD repeat- and FYVE domain-containing protein 3 gene (WDFY3, 617485.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MICROCEPHALY 18, PRIMARY, AUTOSOMAL DOMINANT	c4479608	29,064	omim	https://www.omim.org/entry/617520	2019-09-22T15:45:46	{"omim": ["617520"]}
Rare neural tube defect characterised by fusion of the occiput with the spine Iniencephaly Other namesIniencephaly clausus Iniencephaly showing a stargazing head and an enlarged skull SymptomsNeural malformations Usual onsetCongenital DurationLong term TypesIniencephaly apertus, Iniencephaly clausus CausesUnknown Diagnostic methodPrenatal screening Differential diagnosisKlippel–Feil syndrome PreventionPrenatal screening TreatmentNone MedicationNone PrognosisMostly stillborn FrequencyRare Iniencephaly is a rare type of cephalic disorder[1][2] characterised by three common characteristics: a defect to the occipital bone, spina bifida of the cervical vertebrae and retroflexion (backward bending) of the head on the cervical spine.[3] Stillbirth is the most common outcome, with a few rare examples of live birth, after which death almost invariably occurs within a short time. The disorder was first described by Étienne Geoffroy Saint-Hilaire in 1836. The name is derived from the Ancient Greek word ἰνίον inion, for the occipital bone/nape of the neck. ## Contents * 1 Classifications * 2 Signs and symptoms * 2.1 Additional symptoms * 3 Causes * 3.1 Chromosomal abnormalities * 3.2 Environmental factors * 3.3 Drugs * 3.4 Obesity * 3.5 History of iniencephaly * 4 Pathogenesis * 5 Diagnosis * 5.1 Differential diagnosis * 6 Prevention * 7 Treatment * 8 Prognosis * 9 Epidemiology * 10 References * 11 External links ## Classifications[edit] There are two types of iniencephaly. The more severe group is iniencephaly apertus (open iniencephaly), involving the development of an encephalocele. In the other group, iniencephaly clausus (closed iniencephaly), the encephalocele is absent.[4] ## Signs and symptoms[edit] The affected infant tends to be short, with a disproportionately large head. The fetal head of infants born with iniencephaly are hyperextended while the foramen magnum is enlarged and opens through the widened pedicles. The defective neural arches directly into the upper cervical reach of the spinal canal, causing the formation of a common cavity between most of the spinal cord and the brain. The skin of the anterior chest is connected directly to the face, bypassing the formation of a neck, while the scalp is directly connected to the skin of the back. Because of this, those born with this anomaly either have a highly shortened neck or no neck at all. This causes extreme retroflexion, or backward bending, of the head in a "star-gazing" fashion. The spine is severely distorted as well along with significant shortening due to marked lordosis. The vertebrae, especially cervical, are fused together in abnormal shapes and their numbers are reduced. The spinal cord is almost always defective while the ventricular system is often dilated and the cortex is thinned. Sometimes, in the case of iniencephaly apertus, an encephalocele (sac-like protrusions of the brain through an opening in the cranium) forms.[4][5][6] ### Additional symptoms[edit] Additional symptoms include:[4][7] * anencephaly (failure of major sections of the brain to form) * encephalocele (cranial contents protrudes from the skull) * cyclopia (the two eye cavities fuse into one) * agnathia * cleft palate * arthrogryposis * clubfeet * holoprosencephaly * spina bifida * low-set ears * pulmonary hypoplasia * omphalocele * gastroschisis * cardiovascular disorders * diaphragmatic hernias * gastrointestinal atresia * single umbilical artery * renal abnormalities * genu recurvatum * hydramnios ## Causes[edit] Though the iniencephaly is not genetic with its cause unknown, studies have shown that there are certain factors that can increase the risk of mothers giving birth to children with these anomalies. ### Chromosomal abnormalities[edit] Abnormalities in chromosomes such as trisomy 18, trisomy 13, and monosomy X have been shown to be tied to this disorder.[1] ### Environmental factors[edit] Mothers with poor socioeconomic conditions, poor nutrition, low parity, and lack of folic acid supplementation, and/or hyperhomocysteinemia have shown to be at larger risk.[1] ### Drugs[edit] Animal studies have shown that administration of the drugs vinblastine, streptonigrin, triparano, sulfonamide, tetracycline, antihistamines, and antitumor agents to pregnant mothers have resulted in offspring born with iniencephaly.[7] The drug clomiphene, a drug commonly used for ovulation stimulation in fertility treatments, has also been seen to be associated with iniencephaly.[8] ### Obesity[edit] Studies have shown that obesity of the mother increases the risk of neural tube disorders such as iniencephaly by 1.7 fold while severe obesity increases the risk by over 3 fold.[9] ### History of iniencephaly[edit] Once a mother has given birth to a child with iniencephaly, risk of reoccurrence increases to 1-5%.[4] ## Pathogenesis[edit] The exact pathogenesis of iniencephaly is still unknown though there are proposed theories, most of which view the neural tube malformation from the primary neural anomaly standpoint. Marin-Padilla and MarinPadilla have proposed that the cause for the abnormalities has to do with a deficiency in the primary mesoderm. P. Erdinçler, et al. suggests from their findings that the cause of the anomaly is actually a defect in the occipital bone and rachischisis of the posterior vertebral arches leading to herniation of neural tissue through the opening in the bone during gestation.[3] ## Diagnosis[edit] The most accurate method of diagnosis is prenatal screening through real-time fetal images. However, since maternal body habitus leads to diagnostic difficulties using this method, MRI and sonography are the most commonly used technique since there is no exposure to ionizing radiation.[4] At the beginning of the second trimester, the central nervous system (CNS) and anatomic structures of the fetus can be clearly visualized and the characteristic malformations of iniencephaly, such as a shortened trunk, marked lordosis in the cervicothoracic vertebrae, absence or partial absence of the occipital squama, abnormal fusion of vertebrae, closed vertebral arches, formation of an encephalocele (for iniencephaly apertus), and dorsiflexion of the head in respect to the spine, can be precisely diagnosed as well as the severity and location established. Once established, further decisions can be made with regard to terminating the pregnancy or providing a plan of adequate postnatal care.[7] ### Differential diagnosis[edit] Since many of the characteristics of iniencephaly, such as congenital retroflexion of the spine and fusion of the cervical vertebrae, are shared with other disorders, key differences are important to note. While anencephaly experiences a partial to total lack of the neurocranium, iniencephaly does not. In anencephaly, the retroflexed head is not covered with skin while in iniencephaly, the retroflexed head is covered with skin entirely. Cervical vertebrae are malformed and reduced in iniencephaly while they are almost normal in anencephaly. Even though KFS does experience malformed cervical vertebra due to failure of segmentation during early fetal development, there is not retroflexion of the head as seen in iniencephaly. While iniencephaly clausus is fatal, KFS is not and can be surgically corrected. Therefore, it is crucial to correctly diagnose KFS and not mistake it for iniencephaly clausus.[1] ## Prevention[edit] Pregnant mothers are advised to take folic acid supplements to reduce risk of iniencephaly by up to 70%. Pregnant mothers are also advised not to take antiepileptic drugs, diuretics, antihistamines, and sulfa drugs, all of which have been associated with increased risk for neural tube defects.[6] ## Treatment[edit] Since newborns with iniencephaly so rarely survive past childbirth, a standard treatment does not exist. ## Prognosis[edit] Iniencephaly of both types carry a lethal prognosis, sometimes even ending in spontaneous abortion or stillborns. Most infants die within hours of childbirth. There are only seven reported cases of relatively long-term survival of those born with iniencephaly.[1] ## Epidemiology[edit] Iniencephaly is thought to make up around 1% of all fetal abnormalities,[5] with an incidence rate estimated at 0.1 to 10 in 10,000 deliveries. For unknown reasons, this disease seems to occur most often in newborn females (about 90%).[4] ## References[edit] 1. ^ a b c d e Kulkarni, PR; Rao, RV; Alur, MB; Joshi, SK (July 2011). "Iniencephaly clausus: A case report with review of literature". Journal of Pediatric Neurosciences. 6 (2): 121–3. doi:10.4103/1817-1745.92831 (inactive 2021-01-11). PMC 3296405. PMID 22408660.CS1 maint: DOI inactive as of January 2021 (link) 2. ^ Hemal U, Solanki RS, Varsheney A, Baliga S (2004). "Prenatal diagnosis of iniencephaly on ultrasound". Indian J Radiol Imaging. 14: 265–6. 3. ^ a b Erdinçler Pamir; Kaynar Mehmet Y.; et al. (1998). "Iniencephaly: Neuroradiological and Surgical Features". Journal of Neurosurgery. 89 (2): 317–20. doi:10.3171/jns.1998.89.2.0317. PMID 9688130. 4. ^ a b c d e f Pungavkar Sona A.; et al. (2007). "Antenatal Diagnosis of Iniencephaly: Sonographic and MR Correlation: A Case Report". Korean Journal of Radiology. 8 (4): 351–5. doi:10.3348/kjr.2007.8.4.351. PMC 2627161. PMID 17673848. 5. ^ a b Cimmino Christian V (1962). "Iniencephaly". Radiology. 79 (6): 942–44. doi:10.1148/79.6.942. PMID 14021377. 6. ^ a b "NINDS Iniencephaly Information Page." National Institute of Neurological Disorders and Stroke (NINDS). NINDS, 13 Feb. 2007. Web. 30 Nov. 2012. 7. ^ a b c Akdemir Yeşim; et al. (2010). "Iniencephaly with Mediastinal Bronchogenic Cyst: A Case Report". Journal of Prenatal Medicine. 4 (4): 74–76. PMC 3279188. PMID 22439066. 8. ^ Bhambhani Vikas; George Sanila (2004). "Association of Clomiphene with Iniencephaly". Indian Pediatrics. 41 (5): 517. PMID 15181310. 9. ^ Rasmussen S; et al. (2008). "Maternal Obesity and Risk of Neural Tube Defects: A Metaanalysis". American Journal of Obstetrics and Gynecology. 198 (6): 611–19. doi:10.1016/j.ajog.2008.04.021. PMID 18538144. ## External links[edit] Classification D * ICD-10: Q00.2 * ICD-9-CM: 740.2 External resources * Orphanet: 63259 * v * t * e Congenital malformations and deformations of nervous system Brain Neural tube defect * Anencephaly * Acephaly * Acrania * Acalvaria * Iniencephaly * Encephalocele * Chiari malformation Other * Microcephaly * Congenital hydrocephalus * Dandy–Walker syndrome * other reduction deformities * Holoprosencephaly * Lissencephaly * Microlissencephaly * Pachygyria * Hydranencephaly * Septo-optic dysplasia * Megalencephaly * Hemimegalencephaly * CNS cyst * Porencephaly * Schizencephaly * Polymicrogyria * Bilateral frontoparietal polymicrogyria Spinal cord Neural tube defect * Spina bifida * Rachischisis Other * Currarino syndrome * Diastomatomyelia * Syringomyelia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Iniencephaly	c0152234	29,065	wikipedia	https://en.wikipedia.org/wiki/Iniencephaly	2021-01-18T18:48:19	{"gard": ["10506"], "mesh": ["D009436"], "umls": ["C0152234"], "icd-9": ["740.2"], "icd-10": ["Q00.2"], "orphanet": ["63259"], "wikidata": ["Q3315335"]}
Aromatase deficiency Other namesCongenital estrogen deficiency[1] AES results when the function of aromatase is impaired. The aromatase protein (pictured) is required for the biosynthesis of oestrogens like oestradiol in the human body. SpecialtyEndocrinology ComplicationsVirilisation, tall stature, primary amenorrhea, multicystic ovaries, Usual onsetAdulthood DurationLifetime TypesEndocrine Disruptive Disorder CausesGenetic mutations of CPY19 Diagnostic methodExtremely low level of oestrogen and elevated level of androgens TreatmentTransdermal oestradiol replacement, hormone replacement therapy Aromatase deficiency is a very rare condition characterised by the extremely low or absence of the enzyme aromatase activity in the body. [2] It is an autosomal recessive disease resulted from various mutations of gene CPY19 (P450arom) which can lead to delayed puberty in females, osteoporosis in males and virilisation in pregnant mothers. As of 2016, only 35 cases have been described in medical literature. [3] ## Contents * 1 Signs and symptoms * 1.1 Female * 1.2 Male * 1.3 During pregnancy * 1.4 Comorbidity * 1.5 Complications * 1.5.1 Pregnant mother * 1.5.2 Female * 1.5.3 Male * 2 Cause * 2.1 Gene Mutation * 3 Diagnosis * 4 Treatment * 5 History * 6 See also * 7 References * 8 Further reading * 9 External links ## Signs and symptoms[edit] The deficiency causes the virilization of XX fetuses. The onset of the symptoms usually displayed during adolescent or early adulthood. The lack of estrogen results in the presentation of primary amenorrhea and tall stature. The taller than expected height occurs because estrogen normally causes fusion of the epiphyseal growth plates in the bones, and in its absence, the patient will keep growing longer. The gonadotropins LH and FSH will both be elevated and patients present with polycystic ovaries. Furthermore, the low oestrogen will predispose those with the condition to osteoporosis.[2] ### Female[edit] * After birth, female infant usually displays ambiguous genitalia including labioscrotal fusion, clitoromegaly, and phallic-structure genitalia. Hyperandrogenism is present at birth along with low level of estrogen in the blood. However, they have normal internal female genitalia. [4]Other presented symptoms assist with the correct diagnostics. * During pubertal age, progressive sign of virilisation such as growing of body hair can be observed along with puberty failure due to the lack of estradiol action.[2] The disruption of the LHRH-LH/FSH axis causes bone age to delay with the absence of growth spurt. * In adulthood, symptoms include virilisation, absent of breast development, primary amenorrhea and infertility, and multicystic ovaries. [4] * Other symptoms include hypergonadotropic hypogonadism, polycystic ovaries, hypoplastic ovaries and tall stature. [3] ### Male[edit] Symptoms are generally manifested in adulthood: * Tall stature, osteopenia, osteoporosis, Type II Diabetes, hyperinsulinemia, acanthusis nigricans, lipid metabolism disorders and liver function impairment. [4] ### During pregnancy[edit] During gestation, a baby with Aromatase Deficiency can cause a mother to become virilised by causing the deepening of the voice, cystic acne, cliteromegaly, and hirsutism.[3] The mother also has an increased level of circulating testosterone. [5] However, the symptoms normally regress post-partum. [2] ### Comorbidity[edit] Aromatase deficiency may be comorbid with Autism through their mutual relationship with RORA deficiency. This affects both males and females however the effect on males is more common due to the female protective effect. RORA is the gene for aromatase, an enzyme that converts male to female hormones. Thus, RORA deficiency is linked to aromatase deficiency, which in turn can lead to elevated testosterone levels, a proposed risk factor for autism. [6] ### Complications[edit] #### Pregnant mother[edit] Aromatase is an estrogen synthase that synthesize estrone (E1) and estradiol (E2) from Androstenedione and Testosterone respectively.[7] During pregnancy, the placenta, which is fetal tissue, synthesizes large amounts of the intermediates in the biosynthesis of the estrogens, androstenedione and testosterone, but cannot convert them to estrogens due to the absence of aromatase.[7] The levels of accumulated androgens in the mother can elevate 100-fold higher than normal cycling levels which subsequently virilise both the mother and the fetus. The mother will experience cystic acne, deepening of the voice and hirsutism.[2] However, these symptoms are normally resolved following parturition.[2] If the fetus is a male, it will develop a normal male genitalia and will proceed to grow normally and exhibit secondary male sex characteristics.[8] If the fetus is a female, it will be born with ambiguous genitalia including labioscrotal fusion and a greatly enlarged phallus.[7] #### Female[edit] Aromatase deficient female cannot synthesize estrone or estradiol in the absence of aromatase. The amount of androgen will accumulate at a very high rate in the blood, disrupting the LHRH-LH/FSH axis that can potentially lead to polycystic ovaries in adulthood.[4] In the absence of estrogen, high level of circulating LH and FSH can results in Hypergonadotropic hypogonadism. [9] While females begin to virilise and grow hair in various places during adolescent, they are unable to menstruate without the presence of estradiol, subsequently causing primary amenorrhea, clitormegaly, and absence of breast development. [2]As puberty fails, the growth spurt is absence and bone age is delayed.[4] Without treatment, the collection of excessive androgen in the blood can lead to development of polycystic ovaries. [2] #### Male[edit] Aromatase deficient males experience a normal growth into adulthood. With a very low level of circulating estrogen (<7pg/mL), resulting in a higher level of FSH and LH in the blood. [2] Elevated level of androgens do not contribute to harmonic skeletal muscle growth like estrogen, thus, patients exhibits eunuchoid body habitus.[4] Patients are generally tall in stature and have a pattern of persistent linear bone growth into adulthood.[2][7] Without estrogen, the epiphyseal plates cannot fuse together properly, resulting in continuous height growth. As a necessary steroid to maintain bone homeostasis, low level of estrogen also result osteopenia and osteoporosis of the lumbar spine and cortical bone.[2][4] Estrogen is also thought to be linked to the abnormal lipid profile and hyperinsulinemia in men, however, the detail mechanism is unknown. [2] Similarly, men with aromatase deficiency are likely to present with different degrees of type II diabetes and acanthosis nigricans.[citation needed] ## Cause[edit] ### Gene Mutation[edit] Autosomal recessive Aromatase deficiency is an autosomal recessive disease with most of the mutations occur along the highly conservative regions of the gene. Both homozygous and heterozygous mutations have been identified along various location of the exon on the P450 arom (CYP19) gene localized on chromosome15p21.1.[8] In addition, mutations in cytochrome P450 oxidoreductase (POR), which is required for enzymatic activity of aromatase, can also cause aromatase deficiency.[10] Table 1. Summary of known homozygous mutations in P450 arom (CPY19) gene [2] [4] [9] Gender Mutation Transcription Results Aromatase Activity (%) Female GT to GC at the 5’ Terminus of intron VI An extra 87 bp insertion, between exon VI and intron VI 0.3% Female/Male Single base change at bp 1123: C to T in exon X Cysteine being transcribed instead of Arginine at position 375 (R375C) 0.2% Female Point mutation (R457X) in exon X No Transcription \- Female Mutation Valine 370 to Methionine in exon IX - \- Female 1600 bp deletion in exon V Aromatase lacking 59 Amino Acids \- Female Point mutation in exon X (R435C) Missense mutation that causes loss of function \- Female Deletion of a single Phenylalanine residue at codon 234 in exon VI - \- Female 568C insertion in CYP19A1 190 Leucine was changed to Proline \- Female Single base change at bp 1094 (G to A) in exon IX Glutamine instead of Arginine being transcribed at position 365 (R365Q) 0.4 Male C-base deletion in exon V Resulting in a stop codon after 21 codons 0.0 Male C to A substitution in intron V, at 3’ splicing acceptor site before exon VI Premature stop codon \- Male Insertion of 21 bp at the codon 353 in exon IX - \- Male Single base change at bp 628 (G to A) in the last nucleotide of exon V Glutamic acid instead of a Lysine being transcribed at position 210 (E210K) 1.0 Table 2. Summary of known heterozygous mutations in P450 arom (CPY19) gene [4] Gender Mutation Transcription Results Aromatase Activity (%) Female Single base changes in exon X at bp 1303: C to T Cysteine was transcribed instead of Arginine at position 435 (R435C) 1.1 Single base changes in exon X at bp 1310: G to A Tyrosine was transcribed instead of Cysteine at position 437 (C437Y) 0.0 Female Point mutation (G to A) at the splicing point between exon and intron III No transcription 0.0 Base pair deletion occurring at P408 (CCC) in exon IX Nonsense codon 111 bp were transcribed down in the CYP19 0.0 Female Point mutation (GAA to AAA) at bp 628 in exon V Glutamic acid transcribed instead of lysine at position 210 (E210K) 0.0 A Base pair deletion occurring at E412 in exon IX Transcribed a stop codon 98 bp downstream 0.0 Male Point mutation (ATG to AGG) at bp 380 in exon IV Methionine was transcribed instead of arginine at position 127 (M127R) \- Point mutation (CGC CAC) at bp 1123 in exon IX 2\. Arginine was transcribed instead of histidine at position 375 (R375H) \- Male 23 bp deletion in exon IV Premature stop codon in exon IV \- Point mutation (G to T) at first bp in intron IX Alternative splicing? \- ## Diagnosis[edit] A fetus can be predicted to be suffering from aromatase deficiency when its pregnant mother is displaying virilisation. A female infant can be physically diagnosed due to the abnormal genitalia along with hormonal blood test.[4] Excessively low level of estrogen and elevated level of androgens are diagnostic markers for aromatase deficiency in both males and females.[9] Testosterone level in the urine may be normal or elevated.[4] ## Treatment[edit] In males, transdermal estradiol replacement enable epiphyseal plates closure, increases bone density, promote skeletal maturation, lower FSH and LH level to normal and decrease insulin blood concentration. [4] In a young man with high stature due to unfused epiphysis, estrogen patch treatment daily possibly for life resolved the issue with further growth and osteoporosis.[citation needed] In females, hormonal replacement therapy such as cyclic oral therapy of conjugated estrogen leads to breast development, menses, pubertal growth spurt, resolution of ovarian cysts, suppression of elevated FSH and LH levels in the blood, and proper bone growth.[4] Ambiguous genitalia, clitoromegaly, and ovarian cysts can be remove in surgery. [2] ## History[edit] Aromatase deficiency was first recorded in literature in 1991 by Shouz and colleagues.[11] The pregnant mother had low estrogen serum level and high androgens level in the third trimester along with signs of progressive virilisation. Upon delivery, the female infant exhibited pseudohermaphroditism. Aromatase activity of the placenta was approximately ten times less than the normal range.[citation needed] ## See also[edit] * Aromatase excess syndrome * Congenital estrogen deficiency * Disorders of sex development * Estrogen insensitivity syndrome * Inborn errors of steroid metabolism * Cytochrome P450 oxidoreductase deficiency ## References[edit] 1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Aromatase deficiency". www.orpha.net. Retrieved 14 April 2019. 2. ^ a b c d e f g h i j k l m n Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K (December 1995). "Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of oestrogens". J. Clin. Endocrinol. Metab. 80 (12): 3689–98. doi:10.1210/jc.80.12.3689. PMID 8530621. 3. ^ a b c Akçurin S, Türkkahraman D, Kim WY, Durmaz E, Shin JG, and Lee SJ (2016). "HA novel null mutation in P450 aromatase gene (CYP19A1) associated with development of hypoplastic ovaries in humans". J Clin Res Pediatr Endocrinol. 8 (2): 205–10. doi:10.4274/jcrpe.2761. PMC 5096477. PMID 27086564. 4. ^ a b c d e f g h i j k l m Zirilli L, Rochira V, Diazzi C, Caffagni G, Carani C (April 2008). "Human models of aromatase deficiency". J. Steroid Biochem. Mol. Biol. 109 (3–5): 212–8. doi:10.1016/j.jsbmb.2008.03.026. PMID 18448329. 5. ^ Jones ME, Boon WC, McInnes K, Maffei L, Carani C, Simpson ER (May 2007). "Recognizing rare disorders: aromatase deficiency". Nat Clin Pract Endocrinol Metab. 3 (5): 414–21. doi:10.1038/ncpendmet0477. PMID 17452968. 6. ^ Valerie W Hu et al. Investigation of sex differences in the expression of RORA and its transcriptional targets in the brain as a potential contributor to the sex bias in autism. Molecular Autism, May 2015 DOI: 10.1186/2040-2392-6-7 7. ^ a b c d Blakemore J, Naftolin F (July 2016). "Aromatase: Contributions to Physiology and Disease in Women and Men". Physiology. 31 (4): 258–269. doi:10.1152/physiol.00054.2015. PMID 27252161. 8. ^ a b Bulun, Serdar E. (2014). "Aromatase and estrogen receptor α deficiency". Fertility and Sterility. 101 (2): 323–329. doi:10.1016/j.fertnstert.2013.12.022. ISSN 0015-0282. PMC 3939057. PMID 24485503. 9. ^ a b c Mazen I, Mcelreavey K, Elaidy A, Kamel AK, Abdel-Hamid MS (January 2018). "Aromatase deficiency due to homozygous CYP19A1 mutation in a 46, XX Egyptian patient with ambiguous genitalia". Sex Dev. 11 (5–6): 275–279. doi:10.1159/000485278. PMID 29324451. 10. ^ Parween, Shaheena; Fernández-Cancio, Mónica; Benito-Sanz, Sara; Camats, Núria; Velazquez, Maria Natalia Rojas; López-Siguero, Juan-Pedro; Udhane, Sameer S.; Kagawa, Norio; Flück, Christa E.; Audí, Laura; Pandey, Amit V. (2020). "Molecular basis of CYP19A1 deficiency in a 46, XX patient with R550W mutation in POR: Expanding the PORD phenotype". The Journal of Clinical Endocrinology & Metabolism. doi:10.1210/clinem/dgaa076. PMID 32060549. 11. ^ Shouzu M, Akasofu K, Harada T, Kubota Y (March 1991). "A new cause of female pseudohermaphroditism: placental aromatase deficiency". J. Clin. Endocrinol. Metab. 72 (3): 560–566. doi:10.1210/jcem-72-3-560. PMID 1825497. ## Further reading[edit] * Bulun SE (2014). "Aromatase and estrogen receptor α deficiency". Fertil. Steril. 101 (2): 323–9. doi:10.1016/j.fertnstert.2013.12.022. PMC 3939057. PMID 24485503. ## External links[edit] Classification D * ICD-10: E25.8 * OMIM: 107910 * MeSH: C537436 * DiseasesDB: 29906 External resources * Orphanet: 91 * v * t * e Inborn errors of steroid metabolism Mevalonate pathway * HMG-CoA lyase deficiency * Hyper-IgD syndrome * Mevalonate kinase deficiency To cholesterol * 7-Dehydrocholesterol path: Hydrops-ectopic calcification-moth-eaten skeletal dysplasia * CHILD syndrome * Conradi-Hünermann syndrome * Lathosterolosis * Smith–Lemli–Opitz syndrome * desmosterol path: Desmosterolosis Steroids Corticosteroid (including CAH) * aldosterone: Glucocorticoid remediable aldosteronism * cortisol/cortisone: CAH 17α-hydroxylase * CAH 11β-hydroxylase * both: CAH 3β-dehydrogenase * CAH 21-hydroxylase * Apparent mineralocorticoid excess syndrome/11β-dehydrogenase Sex steroid To androgens * 17α-Hydroxylase deficiency * 17,20-Lyase deficiency * Cytochrome b5 deficiency * 3β-Hydroxysteroid dehydrogenase deficiency * 17β-Hydroxysteroid dehydrogenase deficiency * 5α-Reductase deficiency * Pseudovaginal perineoscrotal hypospadias To estrogens * Aromatase deficiency * Aromatase excess syndrome Other * X-linked ichthyosis * Antley–Bixler syndrome * v * t * e Gonadal disorder Ovarian * Polycystic ovary syndrome * Premature ovarian failure * Estrogen insensitivity syndrome * Hyperthecosis Testicular Enzymatic * 5α-reductase deficiency * 17β-hydroxysteroid dehydrogenase deficiency * aromatase excess syndrome Androgen receptor * Androgen insensitivity syndrome * Familial male-limited precocious puberty * Partial androgen insensitivity syndrome Other * Sertoli cell-only syndrome General * Hypogonadism * Delayed puberty * Hypergonadism * Precocious puberty * Hypoandrogenism * Hypoestrogenism * Hyperandrogenism * Hyperestrogenism * Postorgasmic illness syndrome * Cytochrome P450 oxidoreductase deficiency * Cytochrome b5 deficiency * Androgen-dependent condition * Aromatase deficiency * Complete androgen insensitivity syndrome * Mild androgen insensitivity syndrome * Hypergonadotropic hypogonadism * Hypogonadotropic hypogonadism * Fertile eunuch syndrome * Estrogen-dependent condition * Premature thelarche * Gonadotropin insensitivity * Hypergonadotropic hypergonadism [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Aromatase deficiency	c1960539	29,066	wikipedia	https://en.wikipedia.org/wiki/Aromatase_deficiency	2021-01-18T19:01:08	{"gard": ["365"], "mesh": ["C537436"], "orphanet": ["91"], "wikidata": ["Q4795506"]}
Piloleiomyomas are a cutaneous condition that present as dermal reddish-brown, pink or skin-colored papules or nodules that can be solitary or multiple.[1] ## See also[edit] * Palisaded encapsulated neuroma * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Piloleiomyoma	c1709540	29,067	wikipedia	https://en.wikipedia.org/wiki/Piloleiomyoma	2021-01-18T18:42:59	{"umls": ["C1709540"], "wikidata": ["Q7194301"]}
Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. It usually develops as a single, painless, bump on sun-exposed skin. The bump may be skin-colored or red-violet, and tends to grow rapidly over weeks to months. It may spread quickly to surrounding tissues, nearby lymph nodes, or more distant parts of the body. Factors associated with developing MCC include increasing age, fair skin, a history of extensive sun exposure, chronic immune suppression, and the Merkel cell polyomavirus. This virus has been detected in about 80% of people with MCC. Treatment may include surgery, radiation therapy, and/or chemotherapy. Treatment options and prognosis depend on the location(s) and size of the cancer, whether it has just been diagnosed or has come back (recurred), and how deeply it has grown into the skin. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Merkel cell carcinoma	c0007129	29,068	gard	https://rarediseases.info.nih.gov/diseases/9266/merkel-cell-carcinoma	2021-01-18T17:59:08	{"mesh": ["D015266"], "umls": ["C0007129"], "orphanet": ["79140"], "synonyms": ["Merkel cell cancer", "Merkle tumors", "Carcinoma, merkel cell", "Cutaneous neuroendocrine carcinoma"]}
This possibly 'new' syndrome described by Goldblatt and Viljoen (1987) was manifested in varying degrees in a father and 2 daughters. The father had a flattened nasal bridge, chronic blocked nose related to choanal stenosis, convergent squint, and hypoplastic left thumb with hypoplasia of the muscles of the forearm and left thenar eminence. The older daughter had flattened nasal bridge, left convergent strabismus, and hypoplastic left forearm and thumb, the latter being distally placed. The younger daughter had bilateral choanal atresia, markedly flattened nasal bridge, esotropia, absence of the left radius and left thumb, and small, distally implanted right thumb. Eyes \- Convergent strabismus Inheritance \- Autosomal dominant Nose \- Flat nasal bridge \- Chronic blocked nose \- Choanal stenosis \- Choanal atresia Limbs \- Hypoplastic thumb \- Hypoplastic forearm muscles \- Hypoplastic thenar eminence \- Distally placed thumb ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	RADIAL RAY HYPOPLASIA WITH CHOANAL ATRESIA	c0339838	29,069	omim	https://www.omim.org/entry/179270	2019-09-22T16:35:20	{"mesh": ["C536263"], "omim": ["179270"], "orphanet": ["3026"]}
## Summary The purpose of this overview is to increase the awareness of clinicians regarding genetic causes of heritable pulmonary arterial hypertension (HPAH) and related genetic counseling issues. The goals of this overview are the following: ### Goal 1. Describe the clinical characteristics of HPAH. ### Goal 2. Review the genetic causes of HPAH. ### Goal 3. Provide an evaluation strategy to identify the genetic cause of HPAH in a proband (when possible). ### Goal 4. Inform genetic risk assessment and surveillance of at-risk relatives for detection of early treatable manifestations of HPAH. ### Goal 5. Review a high-level view of management of HPAH. ## Diagnosis ## Clinical Characteristics ## Differential Diagnosis ## Management [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Heritable Pulmonary Arterial Hypertension Overview	None	29,070	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1485/	2021-01-18T21:19:45	{"synonyms": []}
## Clinical Features Gollop et al. (1980) described 2 brothers, each with 1 normal upper limb; 1 had tridactylous ectrodactyly of 1 hand with normal radius and ulna, and the other had monodactyly of 1 hand with absent ulna. Both had monodactyly of the feet, absence of the tibias, and unilateral bifurcation of the femur. A sister of the paternal grandfather was purportedly similarly affected. The mode of inheritance was considered unclear. Wolfgang (1984) reported an Amish newborn with a rare combination of congenital anomalies, including bifurcation of the right femur with ipsilateral complete tibial hemimelia, congenital diastasis of the left ankle, and bilateral central defects of the hand. Kohn et al. (1989) reported 2 unrelated families, each with 2 affected offspring with bifid femur, absent tibia, and ectrodactyly. In each family, the healthy parents were consanguineous. The authors suggested that these observations established this combination of malformations as a causally heterogeneous disorder with both autosomal dominant (119100) and autosomal recessive forms and, therefore, as a developmental field defect. Lurie and Ilyina (1986) proposed the eponym Gollop-Wolfgang complex (GWC) for the combination of femoral bifurcation with hand ectrodactyly. Endo et al. (1998) found a total of 12 reported cases and added the case of a Japanese girl with a unique form of this malformation complex. Both hands and feet were involved and the involvement was bilateral. Autosomal recessive inheritance seemed to obtain in the case of a child described by Raas-Rothschild et al. (1999). Features were bifid femur, absent tibiae, hypoplastic hallux, bilateral clubfeet, congenital heart defects, and segmentation anomalies of the spine and ribs. The parents were an Arab Muslim couple related as first cousins once removed who came from a region where other consanguineous families with similarly affected individuals had been reported (Kohn et al., 1989). Raas-Rothschild et al. (1999) suggested that identification of the responsible gene(s) will shed light on whether both a dominant and a recessive form of tibial aplasia with ectrodactyly/Gollop-Wolfgang complex exist. Erickson (2005) reported 2 unrelated infants with absent tibiae and bifid femur showing phenotypic overlap with the Gollop-Wolfgang complex. Both also had clubfeet and congenital heart defects, similar to the patient reported by Raas-Rothschild et al. (1999). Additional features included cleft lip and palate, increased spinal fluid, and lissencephaly in 1 patient and tracheoesophageal fistula in the other patient. Both patients died in infancy. Fiogbe et al. (2010) described 3 unrelated infants from Benin, West Africa, 2 boys and a girl, with femoral bifurcation and tibial aplasia. One boy had right-sided femoral bifurcation with agenesis of the patella, tibia, talus, and 1 metatarsal, and varus equinus of the right foot; he also had an absent third ray of the left foot and partial syndactyly of the first and second toes. The second boy had bilateral tibial aplasia and varus equinus, with right-sided femoral bifurcation. The girl had right-sided femoral bifurcation, tibial agenesis, pseudarthrosis of the fibula and varus equinus; her left lower extremity was normal. Cytogenetics Asamoah et al. (2004) described a patient with a deletion in the proximal part of chromosome 8q: 46,XY,del(8)(q11.23q13.3). The patient was severely affected with a variety of congenital malformations, including femoral bifurcation and bilateral absence of the fibula. Asamoah et al. (2004), like others before them, suggested that there may be genes important in bone/limb formation in the proximal region of 8q. Okumus and Uner (2007) suggested that the patient described by Asamoah et al. (2004) did not have bilateral absence of the fibula but rather bilateral absence of the tibia, consistent with the diagnosis of Gollop-Wolfgang complex. Asamoah (2007) argued that this patient did not have Gollop-Wolfgang complex but a multiple congenital anomaly syndrome secondary to the 8q chromosomal deletion (8q11-q13). Skel \- Ectrodactyly of hand \- Monodactyly of hand \- Absent ulna \- Monodactyly of feet \- Absent tibia \- Bifurcated femur 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	FEMUR, UNILATERAL BIFID, WITH MONODACTYLOUS ECTRODACTYLY	c1856789	29,071	omim	https://www.omim.org/entry/228250	2019-09-22T16:27:54	{"mesh": ["C537917"], "omim": ["228250"], "orphanet": ["1986"], "synonyms": ["Alternative titles", "GOLLOP-WOLFGANG COMPLEX"]}
Rare non-syndromic intellectual disability is a rare, hereditary, neurologic disease characterized by early-onset cognitive impairment as a sole disability. The disease may be associated with autism, epilepsy and neuromuscular deficits. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Rare non-syndromic intellectual disability	None	29,072	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101685	2021-01-23T17:29:25	{"gard": ["12633"], "synonyms": ["Rare NSID"]}
A number sign (#) is used with this entry because congenital disorder of glycosylation type Ip (CDG1P) is caused by homozygous or compound heterozygous mutation in the ALG11 gene (613666) on chromosome 13q14. For a discussion of the classification of CDGs, see CDG1A (212065). Clinical Features Rind et al. (2010) reported 2 sibs, born of consanguineous Turkish parents, with a multisystem metabolic disorder characterized by hypotonia, seizures, developmental retardation, and death by age 2 years. The first affected child showed poor feeding, recurrent vomiting, and muscular hypotonia in the first weeks of life. Other features included seizures, instability of body temperature, delayed pupil reaction and fixation, no blink reflex, and abnormal brainstem auditory response consistent with deafness. Dysmorphic features, including small head, high forehead with low hairline, and inverted nipples, were also noted. She died at age 2 years. The second affected child showed a similar disease course with hypotonia, generalized epilepsy, and opisthotonus. Dysmorphic features were not noted. Isoelectric focusing of serum transferrin from patient fibroblasts showed an increased amount of di- and asialo-transferrin with a decrease of tetrasialo-transferrin, consistent with CDG type I. Further studies showed an accumulation of shortened dolichol-linked oligosaccharides, indicating a defect at the step adding the fourth and fifth mannose residues. Thiel et al. (2012) reported 3 unrelated patients with CDG1P. All had severely delayed psychomotor development and mental retardation with onset in the first year of life. Communication was absent, and social interaction very limited. All also had seizures and strabismus. Two had axial hypotonia and peripheral hypertonia. The most severely affected child had dysmorphic features, including long philtrum, retrognathia, and high forehead, scoliosis, fat pads, inverted nipples, oscillations of body temperature, dry scaly skin, and lack of visual tracking or light response. None were deaf. Biochemical analysis showed a CDG type I pattern. However, the pathologic glycosylation phenotype was only apparent after glucose starvation in patient fibroblasts; then, analysis of dolichol-linked oligosaccharides led to the emergence of pathologic shortened intermediate dolichol-linked oligosaccharides, indicating a defect in biosynthesis. Molecular Genetics In 2 Turkish sibs, born of consanguineous parents, with congenital disorder of glycosylation type Ip, Rind et al. (2010) identified a homozygous mutation (L86S; 613666.0001) in the ALG11 gene. In 3 unrelated patients with CDG1P, Thiel et al. (2012) identified compound heterozygous or homozygous mutations in the ALG11 gene (613666.0002-613666.0006). All mutations occurred in conserved residues, and the cellular biochemical defects could be rescued by retroviral complementation with wildtype ALG11. Glucose starvation prior to metabolic labeling of patient-derived fibroblasts was a crucial step for the correct biochemical diagnosis. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Small head (rare) Face \- High forehead (rare) Ears \- Sensorineural deafness (rare) Eyes \- Delayed pupillary responses (in some patients) \- Lack of blink reflex (in some patients) \- Poor response to light (in some patients) \- Strabismus CHEST Breasts \- Inverted nipples (rare) ABDOMEN Gastrointestinal \- Poor feeding \- Recurrent vomiting SKIN, NAILS, & HAIR Hair \- Low hairline (rare) NEUROLOGIC Central Nervous System \- Psychomotor retardation, severe \- Lack of speech \- Poor social interaction \- Hypotonia, neonatal \- Seizures \- Peripheral hypertonia \- Opisthotonus METABOLIC FEATURES \- Body temperature instability LABORATORY ABNORMALITIES \- Abnormal isoelectric focusing of serum transferrin (type 1 pattern) \- Increased di- and asialo-transferrin \- Decreased tetrasialo-transferrin \- Accumulation of shortened dolichol-linked oligosaccharides in patient fibroblasts MISCELLANEOUS \- Onset in first year of life MOLECULAR BASIS \- Caused by mutation in the homolog of the S. cerevisiae Alg11 gene (ALG11, 613666.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ip	c3150913	29,073	omim	https://www.omim.org/entry/613661	2019-09-22T15:58:00	{"doid": ["0080567"], "omim": ["613661"], "orphanet": ["280071"], "synonyms": ["CDG syndrome type Ip", "CDG-Ip", "CDG1P", "Carbohydrate deficient glycoprotein syndrome type Ip", "Congenital disorder of glycosylation type 1p", "Congenital disorder of glycosylation type Ip"], "genereviews": ["NBK1332"]}
A rare ophthalmic disorder characterized by mostly unilateral failure of the regression of a fetal ocular vessel component, the tunica vasculosa lentis and/or the hyaloid system, resulting in an anterior (presenting with microphthalmia, leukocoria, cataract, glaucoma, elongated ciliary processes, shallow anterior chamber, and retrolental fibrovascular membranes, among others) or posterior disease subtype (with microphthalmia, leukocoria, presence of a retinal fold or detachment, hypo- or dysplastic optic nerve, and vitreous membranes and stalk), respectively. Most patients present with a combination of the two subtypes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Persistent hyperplastic primary vitreous	c0266568	29,074	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91495	2021-01-23T18:23:50	{"mesh": ["D054514"], "omim": ["221900", "611308"], "umls": ["C0266568", "C1857299"], "icd-10": ["Q14.0"], "synonyms": ["Congenital retinal detachment", "NCRNA disease", "Non-syndromic congenital retinal non-attachment", "PFVS", "PHPV", "Persistent fetal vasculature syndrome"]}
A number sign (#) is used with this entry because primary ciliary dyskinesia-27 (CILD27) is caused by homozygous mutation in the CCDC65 gene (611088) on chromosome 12q13. Description Primary ciliary dyskinesia-27 is an autosomal recessive disorder caused by defective ciliary movement. Affected individuals have neonatal respiratory distress, recurrent upper and lower airway disease, and bronchiectasis. Respiratory cilia from patients show defects in the inner dynein arms and nexin links. Situs inversus has not been reported in these patients (summary by Austin-Tse et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see 244400. Clinical Features Austin-Tse et al. (2013) reported 2 brothers and an unrelated girl, all of Ashkenazi Jewish descent, with primary ciliary dyskinesia. The patients had recurrent bronchitis, sinusitis, and/or otitis media, but no situs inversus. Fertility status could not be ascertained. Cilia ultrastructure showed normal outer dynein arms, radial spokes, and central pairs, but there was a reduction in inner dynein arms and nexin links. Microtubule disorganization was also observed in 5 to 15% of cilia cross-sections, suggesting that the reduction in nexin links may lead to overall structural instability in a subset of cilia. Live imaging of patient nasal epithelial cilia showed a stiff, dyskinetic cilia waveform. Horani et al. (2013) reported an 18-year-old boy of Ashkenazi Jewish descent with primary ciliary dyskinesia without laterality defects. He presented in early infancy with recurrent respiratory infections resulting in cystic bronchiectasis. Nasal nitric oxide levels were reduced. Nasal respiratory epithelial cells showed normal ciliary axonemal structure on electron microscopy, but the ciliary beat pattern was abnormally stiff and hyperkinetic compared to controls. Inheritance The transmission pattern of CILD27 in the families reported by Austin-Tse et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 3 Ashkenazi Jewish patients, including 2 brothers, with primary ciliary dyskinesia-27, Austin-Tse et al. (2013) identified a homozygous truncating mutation in the CCDC65 gene (611088.0001). The patients were ascertained from a larger cohort of 295 individuals with CILD. Horani et al. (2013) also identified a homozygous truncating mutation in the CCDC65 gene (611088.0001) in a CILD27 patient of Ashkenazi Jewish descent. The patient did not have laterality defects. Immunohistochemical studies of patient nasal epithelial cells showed absence of the CCDC65 protein as well as absence of GAS8 (605178), another member of the nexin-dynein regulatory complex (N-DRC). Similar results were obtained after shRNA knockdown of CCDC65 in control respiratory epithelial cells. Animal Model Austin-Tse et al. (2013) found that morpholino knockdown of the CCDC65 gene in zebrafish resulted in a strong ciliopathy phenotype, including pronephric cysts, axis curvature, left-right asymmetry defects, and hydrocephalus. Immunostaining for certain ciliary proteins did not detect structural abnormalities, and ultrastructure analysis showed that the outer dynein arms were not missing. High-speed video microscopy showed paralyzed or dyskinetic cilia, consistent with a motility defect. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Sinusitis, recurrent Ears \- Otitis media, recurrent Nose \- Rhinitis, recurrent RESPIRATORY \- Respiratory insufficiency due to defective ciliary clearance \- Respiratory infections, recurrent Airways \- Chronic bronchitis LABORATORY ABNORMALITIES \- Electron microscopy of patient respiratory cells shows reduced inner dynein arms and nexin links \- Microtubule disorganization in some cilia \- Dyskinetic ciliary motility \- Decreased nasal nitric oxide MISCELLANEOUS \- Onset in infancy or neonatal period MOLECULAR BASIS \- Caused by mutation in the coiled-coil domain-containing protein 65 (CCDC65, 611088.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CILIARY DYSKINESIA, PRIMARY, 27	c3809701	29,075	omim	https://www.omim.org/entry/615504	2019-09-22T15:51:53	{"doid": ["0110611"], "omim": ["615504", "244400"], "orphanet": ["244"], "synonyms": ["Alternative titles", "PCD", "CILIARY DYSKINESIA, PRIMARY, 27, WITHOUT SITUS INVERSUS"], "genereviews": ["NBK1122"]}
In the usual patient with selective IgA deficiency (137100), both serum and secretory IgA are absent. Strober et al. (1976) described a 15-year-old boy with chronic intestinal candidiasis who had normal serum IgA levels and no IgA in his secretions. Unlike normal persons as well as patients with selective IgA deficiency, he had no detectable free secretory component in saliva and jejunal juice. This component is synthesized by epithelial cells; later called polymeric immunoglobulin receptor (Mostov et al., 1984), it transports dimeric IgA produced by mucosal B cells through the epithelial cells into the secretions. It was thought that the patient might have a genetic defect in its synthesis; however, Plaut and Ridker (1992) provided a follow-up which suggested that the secretory component deficiency was an acquired, transient defect. The patient reported by Strober et al. (1976) sought medical consultation because of concern that his children might inherit a defect in secretory immunity. Except for intermittent, self-limited diarrhea, he had been in excellent health since the late 1970s. Mixed saliva obtained from the patient in June 1991 contained secretory component according to Western blot analysis. Furthermore, the IgA content of the saliva was within the normal range. Immunology \- Selective IgA deficiency \- Normal serum IgA \- Absent secretory IgA \- Chronic intestinal candidiasis GI \- Intermittent, self-limited diarrhea 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	SECRETORY COMPONENT DEFICIENCY	c0398709	29,076	omim	https://www.omim.org/entry/269650	2019-09-22T16:22:26	{"doid": ["0060025"], "mesh": ["C562869"], "omim": ["269650"], "synonyms": ["Alternative titles", "IgA DEFICIENCY, SECRETORY"]}
Fibrillary glomerulonephritis is an uncommon cause of glomerular disease. A more rare disorder known as immunotactoid glomerulpathy is a very similar condition. Both disorders probably result from deposits derived from immunoglobulins but in most cases the cause is idiopathic (unknown). The diagnosis is made with a kidney biopsy and by electron microscopy. Fibrillary glomerulonephritis and immunotactoid glomerulopathy can be differentiated from each other by electron microscopy; the fibrils in fibrillary glomerulonephritis are smaller and randomly oriented as opposed to the larger and often organized fibrils of immunotactoid glomerulopathy. The signs and symptoms include blood (hematuria) and protein (proteinuria) in the urine, kidney insufficiency and high blood pressure. Both fibrillary glomerulonephritis and immunotactoid glomerulopathy have been associated with hepatitis C virus infection and with malignancy and autoimmune disease. Because of this, patients should be screened for these conditions. Treatment is generally determined by the severity of the kidney problems. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Fibrillary glomerulonephritis	c4273674	29,077	gard	https://rarediseases.info.nih.gov/diseases/12740/fibrillary-glomerulonephritis	2021-01-18T18:00:29	{"orphanet": ["97566"], "synonyms": ["Congo red-negative amyloidosis-like glomerulopathy", "Non-amyloid fibrillary glomerulonephritis", "Non-amyloid fibrillary glomerulopathy"]}
Not to be confused with Catalepsy. Cataplexy Pronunciation * /ˈkætəˌplɛksi/ SpecialtyNeurology, Psychiatry Cataplexy is a sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically triggered by emotions such as laughing, crying, or terror.[1] Cataplexy affects approximately 70% of people who have narcolepsy,[2] and is caused by an autoimmune destruction of hypothalamic neurons that produce the neuropeptide hypocretin (also called orexin), which regulates arousal and has a role in stabilization of the transition between wake and sleep states.[3] Cataplexy without narcolepsy is rare and the cause is unknown. The term cataplexy originates from the Greek κατά (kata, meaning "down"), and πλῆξις (plēxis, meaning "strike")[4] and it was first used around 1880 in German physiology literature to describe the phenomenon of tonic immobility also known as "playing possum" (in reference to the opossum's behavior of feigning death when threatened).[4] In the same year the French neuropsychiatrist Jean-Baptiste Gélineau coined the term 'narcolepsy' and published some clinical reports that contain details about two patients who have similar condition as the narcoleptic cases nowadays.[5] Nevertheless, the onset reported by him was in adulthood as compared to the nowadays cases reported in childhood and adolescence.[6] Even if he preferred the term ‘astasia’ instead of ‘cataplexy’ the case described by him remained iconic for the full narcoleptic syndrome.[4] ## Contents * 1 Signs and symptoms * 2 Mechanism * 2.1 Theories for episodes * 2.2 Hypocretin * 3 Diagnosis * 4 Treatment * 4.1 Gamma-hydroxybutyrate * 4.2 Antidepressants * 4.3 Future treatments for cataplexy * 4.3.1 Immune-based therapies * 4.3.2 Histaminergic H3 receptor inverse agonist * 5 Research * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Cataplexy manifests itself as muscular weakness which may range from a barely perceptible slackening of the facial muscles to complete muscle paralysis with postural collapse.[7] Attacks are brief, most lasting from a few seconds to a couple of minutes, and typically involve dropping of the jaw, neck weakness, and/or buckling of the knees. Even in a full-blown collapse, people are usually able to avoid injury because they learn to notice the feeling of the cataplectic attack approaching and the fall is usually slow and progressive.[8] Speech may be slurred and vision may be impaired (double vision, inability to focus), but hearing and awareness remain normal.[citation needed] Cataplexy attacks are self-limiting and resolve without the need for medical intervention. If the person is reclining comfortably, he or she may transition into sleepiness, hypnagogic hallucinations, or a sleep-onset REM period. While cataplexy worsens with fatigue, it is different from narcoleptic sleep attacks and is usually, but not always, triggered by strong emotional reactions such as laughter, anger, surprise, awe, and embarrassment, or by sudden physical effort, especially if the person is caught off guard.[9] One well known example of this was the reaction of 1968 Olympic long jump medalist Bob Beamon on understanding that he had broken the previous world record by over 0.5 meters (almost 2 feet).[10][additional citation(s) needed][medical citation needed] Cataplectic attacks may occasionally occur spontaneously, with no identifiable emotional trigger.[11] ## Mechanism[edit] In this simplified brain circuit, damage to orexin-secreting neurons in the hypothalamus can lead to inhibition of motor neurons, thus lowering muscle tone. Cataplexy is considered secondary when it is due to specific lesions in the brain that cause a depletion of the hypocretin neurotransmitter. Secondary cataplexy is associated with specific lesions located primarily in the lateral and posterior hypothalamus. Cataplexy due to brainstem lesions is uncommon particularly when seen in isolation. The lesions include tumors of the brain or brainstem and arterio-venous malformations. Some of the tumors include astrocytoma, glioblastoma, glioma, and subependynoma. These lesions can be visualized with brain imaging, however in their early stages they can be missed. Other conditions in which cataplexy can be seen include ischemic events, multiple sclerosis, head injury, paraneoplastic syndromes, and infections such as encephalitis. Cataplexy may also occur transiently or permanently due to lesions of the hypothalamus that were caused by surgery, especially in difficult tumor resections. These lesions or generalized processes disrupt the hypocretin neurons and their pathways. The neurological process behind the lesion impairs pathways controlling the normal inhibition of muscle tone drop, consequently resulting in muscle atonia.[12] ### Theories for episodes[edit] A phenomenon of REM sleep, muscular paralysis, occurs at an inappropriate time. This loss of tonus is caused by massive inhibition of motor neurons in the spinal cord. When this happens during waking, the victim of a cataplectic attack loses control of his or her muscles. As in REM sleep, the person continues to breathe and is able to control eye movements.[9] ### Hypocretin[edit] The hypothalamus region of the brain regulates basic functions of hormone release, emotional expression and sleep. A study in 2006 in "Tohoku Journal of Experimental Medicine" concluded that the neurochemical hypocretin, which is regulated by the hypothalamus, was significantly reduced in study participants with symptoms of cataplexy. Orexin, also known as Hypocretin, is a primary chemical important in regulating sleep as well as states of arousal. Hypocretin deficiency is further associated with decreased levels of histamine and epinephrine, which are chemicals important in promoting wakefulness, arousal and alertness.[13] ## Diagnosis[edit] The diagnosis of narcolepsy and cataplexy is usually made by symptom presentation. Presenting with the tetrad of symptoms (Excessive daytime sleepiness, sleep onset paralysis, hypnagogic hallucinations, cataplexy symptoms) is strong evidence of the diagnosis of narcolepsy. A Multiple Sleep Latency Test (MSLT) is often conducted in order to quantify daytime sleepiness.[14] ## Treatment[edit] Cataplexy is treated with medications. The treatments for narcolepsy and cataplexy can be divided in treatments that act on the excessive daytime sleepiness (ESD) and those which improve the cataplexy. For most of the patients, this will represent a lifelong medication.[15] Nevertheless, most of the treatments in humans will act only symptomatically and do not target the loss of the orexin producing neurons.[16] When treating cataplexy, all three systems: adrenergic, cholinergic and dopaminergic must be considered. In the studies made both in vitro and in vivo, it was proven that the adrenergic system can be inhibited by the antidepressants. In the mouse models the cataplexy is regulated by the dopaminergic system via the D2-like receptor, which blocked decreases the cataplexic attacks[clarification needed]. The cholinergic system was also observed in the animal models, and it was suggested that stimulations of this system led to severe cataplexy episodes in canine model.[17] There are no behavioral treatments. People with narcolepsy will often try to avoid thoughts and situations that they know are likely to evoke strong emotions because they know that these emotions are likely to trigger cataplectic attacks.[9] ### Gamma-hydroxybutyrate[edit] Gamma-hydroxybutyrate (GHB, also known as sodium oxybate) has been found to be effective at reducing the number of cataplexy episodes.[18][19] Sodium oxybate is generally safe [19] and is typically the recommended treatment.[20] Sodium oxybate (GHB) is a natural metabolite of GABA. Its main target is the dopaminergic system because at pharmacological concentration it acts as an agonist and modulates the dopamine neurotransmitters and dopaminergic signalling.[17] GHB was used to treat narcolepsy and cataplexy for more than 15 years[4] and it is the only drug authorised by the EMA to treat the whole disease in adults, and by the FDA to treat patients who suffer from cataplexy with the indication to be used for combating excessive daytime sleepiness.[20] This drug helps to normalise the sleep architecture, pushing the REM sleep toward its normal setting, and inhibits the intrusion during the day of its elements like the paralysis in cataplexy.[4] ### Antidepressants[edit] If the above treatment is not possible venlafaxine is recommended.[20] Evidence for benefit is not as good[clarification needed].[20] Previous treatments include tricyclic antidepressants such as imipramine, clomipramine or protriptyline.[8] Monoamine oxidase inhibitors may be used to manage both cataplexy and the REM sleep-onset symptoms of sleep paralysis and hypnagogic hallucinations.[21] In the clinical practice, venlafaxine (doses 75–225 mg daily) or clomipramine (25–100 mg daily) are the most common antidepressants used to treat cataplexy. If the patient wishes to have a sedative effect then clomipramine is prescribed. The effect of this drugs is to suppress the REM component and to increase the brainstem monoaminergic levels.[4] The venlafaxine is a norepinephrine and serotonin reuptake inhibitor whereas the clomipramine is a tricyclic antidepressant. Their effects can be seen within 48 hours after the drug is administrated and at doses smaller than the ones used in depression.[17] Nevertheless, the EMA and the FDA do not approve this antidepressants for the treatment of cataplexy.[20] Frequently, tolerance is developed by the patients and typically the risk of cataplexy rebound or “status cataplecticus” appears when their intake is abruptly interrupted.[17] ### Future treatments for cataplexy[edit] #### Immune-based therapies[edit] Narcolepsy with cataplexy is considered an autoimmune-mediated disorder, so some therapies based on this hypothesis were developed. The immune-based therapies developed were more or less effective and include:[20] * Corticosteroid: after testing in 1 human and 1 canine case it proved to be ineffective so is less likely to be further used. * Intravenous immunoglobulins (IVIgs): it may decrease the symptoms but its effectiveness is still subjective and unconfirmed by the placebo-controlled trials. It was also suggested that sometimes it might have life-threatening side effects.[16] Nevertheless, after giving this treatment to a patient with undetectable orexin levels in the cerebrospinal fluid after only 15 days after the disease onset, the cataplexy was improved and the orexin levels started to normalise.[17] * Plasmapheresis: should be similar with IVIgs but it is more invasive and for it even less data is available.[16] * Immunoadsorption * Alemtuzumab #### Histaminergic H3 receptor inverse agonist[edit] The histaminergic neurons have a very important role in preserving consciousness and in helping maintain wakefulness and remain active during cataplexy. In narcolepsy, there seems to be an increase in these neurons, possibly to compensate for hypocretin loss.[22] A promising therapy would be to increase the activation of histaminergic neurons by an inverse agonist of the histamine H3 receptor, which enhances histamine release in hypothalamus.[17] An inverse agonist of the histamine H3 is Pitolisant.[23] Results after drug testing on animals have indicated increased wakefulness in normal animals, decreased sleepiness and blocked the abnormal transitions from REM sleep to awake state in the hypocretin knock-out mice.[17] Also placebo-controlled studies suggest some positive effects of Pitolisant on cataplexy symptoms increasing the levels of alertness and wakefulness.[4] ## Research[edit] Research is being conducted on hypocretin gene therapy and hypocretin cell transplantation for narcolepsy-cataplexy.[24][25] ## See also[edit] * Neurodegenerative disease * Niemann Pick disease ## References[edit] 1. ^ Seigal, Jerome (January 2001). "Narcolepsy". Scientific American: 77. 2. ^ "Narcolepsy Fact Sheet". Retrieved 2011-06-23. 3. ^ Elphick, Heather; Staniforth, Teya; Blackwell, Jane; Kingshott, Ruth (2017). "Narcolepsy and cataplexy – a practical approach to diagnosis and managing the impact of this chronic condition on children and their families" (PDF). Paediatrics and Child Health. 272 (7): 343–347. doi:10.1016/j.paed.2017.02.007. 4. ^ a b c d e f g Reading, Paul (2019). "Cataplexy". Practical Neurology. 19 (1): 21–27. doi:10.1136/practneurol-2018-002001. PMID 30355740. S2CID 219207393. 5. ^ Anderson, M.; Salmon, M.V. (1977). "Symptomatic cataplexy". Journal of Neurology, Neurosurgery & Psychiatry. 40 (2): 186–191. doi:10.1136/jnnp.40.2.186. PMC 492636. PMID 864483. 6. ^ Mignot, Emmanuel J.M. (2014). "History of narcolepsy at Stanford University". Immunologic Research. 58 (2–3): 315–339. doi:10.1007/s12026-014-8513-4. PMC 4028550. PMID 24825774. 7. ^ Bourgoin, Jean-Maxime. "Il s'endort au volant de sa voiture" (in French). Sun Media. Le Journal de Montréal. Retrieved 11 May 2015. 8. ^ a b Michelle Cao; Christian Guilleminault (2008). "Cataplexy". Scholarpedia. 3 (1): 3317. Bibcode:2008SchpJ...3.3317C. doi:10.4249/scholarpedia.3317. 9. ^ a b c Carlson, Neil R. (2012). Physiology of Behavior. Boston, MA: Pearson Education, Inc. ISBN 978-0-205-66627-0. 10. ^ Great Olympic Moments - Sir Steve Redgrave, 2011 11. ^ van Nues SJ, van der Zande WL, Donjacour CE, van Mierlo P, Jan Lammers G (2011). "The clinical features of cataplexy: A questionnaire study in narcolepsy patients with and without hypocretin-1 deficiency". Sleep Medicine. 12 (1): 12–18. doi:10.1016/j.sleep.2010.05.010. PMID 21145280. 12. ^ Dauvilliers, Yves; Isabelle Arnulf; Emmanuel Mignot (10 February 2007). "Narcolepsy with Cataplexy". The Lancet. 39 (9560): 499–511. doi:10.1016/S0140-6736(07)60237-2. PMID 17292770. S2CID 11041392. Retrieved April 30, 2012. 13. ^ Walding, Aureau. "Causes of Cataplexy". Demand Media, Inc. Retrieved April 30, 2012. 14. ^ Carskadon, Mary A. (1986). "Guidelines for the Multiple Sleep Latency Test (MSLT): A Standard Measure of Sleepiness". Sleep. 9 (4): 519–524. doi:10.1093/sleep/9.4.519. PMID 3809866. 15. ^ Elphick, Heather; Staniforth, Teya; Blackwell, Jane; et, al. (2017). "Narcolepsy and cataplexy – a practical approach to diagnosis and managing the impact of this chronic condition on children and their families" (PDF). Paediatrics and Child Health. 27 (7): 343–347. doi:10.1016/j.paed.2017.02.007. ISSN 1751-7222. 16. ^ a b c Mignot, Emmanuel; Nishino, Seiji (2005). "Emerging Therapies in Narcolepsy-Cataplexy". Sleep. 28 (6): 754–763. doi:10.1093/sleep/28.6.754. PMID 16477963. 17. ^ a b c d e f g Dauvilliers, Yves; Siegel, Jerry M.; Lopez, Regies; Torontali, Zoltan A.; Peever, John H. (2014). "Cataplexy – clinical aspects, pathophysiology and management strategy". Nature Reviews Neurology. 10 (7): 386–395. doi:10.1038/nrneurol.2014.97. PMID 24890646. S2CID 2369989. 18. ^ Boscolo-Berto, R; Viel, G; Montagnese, S; Raduazzo, DI; Ferrara, SD; Dauvilliers, Y (October 2012). "Narcolepsy and effectiveness of gamma-hydroxybutyrate (GHB): a systematic review and meta-analysis of randomized controlled trials". Sleep Medicine Reviews. 16 (5): 431–443. doi:10.1016/j.smrv.2011.09.001. PMID 22055895. 19. ^ a b Alshaikh, MK; Tricco, AC; Tashkandi, M; Mamdani, M; Straus, SE; BaHammam, AS (15 August 2012). "Sodium oxybate for narcolepsy with cataplexy: systematic review and meta-analysis". Journal of Clinical Sleep Medicine. 8 (4): 451–458. doi:10.5664/jcsm.2048. PMC 3407266. PMID 22893778. 20. ^ a b c d e f Lopez, R; Dauvilliers, Y (May 2013). "Pharmacotherapy options for cataplexy". Expert Opinion on Pharmacotherapy. 14 (7): 895–903. doi:10.1517/14656566.2013.783021. PMID 23521426. S2CID 7219704. 21. ^ Thomas F. Anders, MD (2006). "Narcolepsy". Childhood Sleep Disorders. Armenian Medical Network. Retrieved 2007-09-19. 22. ^ Elliott, Linnea; Swick, Todd (2015). "Treatment paradigms for cataplexy in narcolepsy: past, present, and future". Nature and Science of Sleep. 7: 159–69. doi:10.2147/NSS.S92140. PMC 4686331. PMID 26715865. 23. ^ Schwartz, Jean-Charles (2011). "The histamine H3 receptor: from discovery to clinical trials with pitolisant: H3 Receptor: from discovery to clinical trials". British Journal of Pharmacology. 163 (4): 713–721. doi:10.1111/j.1476-5381.2011.01286.x. PMC 3111674. PMID 21615387. 24. ^ "Emerging Therapies in Narcolepsy-Cataplexy" (PDF). Archived from the original (PDF) on 2012-12-03. Retrieved 2011-06-23. 25. ^ Weidong, W.; Fang, W.; Yang, Z.; Menghan, L.; Xueyu, L. (2009). "Two patients with narcolepsy treated by hypnotic psychotherapy". Sleep Medicine. 10 (10): 1167. doi:10.1016/j.sleep.2009.07.011. PMID 19766057. ## External links[edit] Classification D * ICD-10: G47.4 * ICD-9-CM: 347 * MeSH: D002385 * DiseasesDB: 16311 External resources * Patient UK: Cataplexy * v * t * e Sleep and sleep disorders Stages of sleep cycles * Rapid eye movement (REM) * Non-rapid eye movement * Slow-wave Brain waves * Alpha wave * Beta wave * Delta wave * Gamma wave * K-complex * Mu rhythm * PGO waves * Sensorimotor rhythm * Sleep spindle * Theta wave Sleep disorders Dyssomnia * Excessive daytime sleepiness * Hypersomnia * Insomnia * Kleine–Levin syndrome * Narcolepsy * Night eating syndrome * Nocturia * Sleep apnea * Catathrenia * Central hypoventilation syndrome * Obesity hypoventilation syndrome * Obstructive sleep apnea * Periodic breathing * Sleep state misperception Circadian rhythm disorders * Advanced sleep phase disorder * Cyclic alternating pattern * Delayed sleep phase disorder * Irregular sleep–wake rhythm * Jet lag * Non-24-hour sleep–wake disorder * Shift work sleep disorder Parasomnia * Bruxism * Nightmare disorder * Night terror * Periodic limb movement disorder * Rapid eye movement sleep behavior disorder * Sleepwalking * Somniloquy Benign phenomena * Dreams * Exploding head syndrome * Hypnic jerk * Hypnagogia / Sleep onset * Hypnopompic state * Sleep paralysis * Sleep inertia * Somnolence * Nocturnal clitoral tumescence * Nocturnal penile tumescence * Nocturnal emission Treatment * Sleep diary * Sleep hygiene * Sleep induction * Hypnosis * Lullaby * Somnology * Polysomnography Other * Sleep medicine * Behavioral sleep medicine * Sleep study Daily life * Bed * Bunk bed * Daybed * Four-poster bed * Futon * Hammock * Mattress * Sleeping bag * Bed bug * Bedding * Bedroom * Bedtime * Bedtime story * Bedtime toy * Biphasic and polyphasic sleep * Chronotype * Dream diary * Microsleep * Mouth breathing * Nap * Nightwear * Power nap * Second wind * Siesta * Sleep and creativity * Sleep and learning * Sleep deprivation / Sleep debt * Sleeping while on duty * Sleepover * Snoring * v * t * e Disorders of consciousness Unconsciousness * Minimally conscious state * Persistent vegetative state * Obtundation * Coma * Brain stem death * Stupor * Sopor * Sleep * Somnolence * Cataplexy Syncope * Heat syncope * Vasovagal episode Alteration of consciousness * Locked-in syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Cataplexy	c0007384	29,078	wikipedia	https://en.wikipedia.org/wiki/Cataplexy	2021-01-18T18:49:35	{"mesh": ["D002385"], "umls": ["C0007384"], "icd-9": ["347"], "icd-10": ["G47.4"], "wikidata": ["Q944473"]}
A number sign (#) is used with this entry because van der Woude syndrome-1 (VWS1) is caused by heterozygous mutation in the gene encoding interferon regulatory factor-6 (IRF6; 607199) on chromosome 1q32. Description Van der Woude syndrome (VWS) is a dominantly inherited developmental disorder characterized by pits and/or sinuses of the lower lip, and cleft lip and/or cleft palate (CL/P, CP). It is the most common cleft syndrome. ### Genetic Heterogeneity of van der Woude Syndrome Also see VWS2 (606713), caused by mutation in the GRHL3 gene (608317) on chromosome 1p36. Clinical Features In 3 generations of a family, Levy (1962) found malformations of the lower lip consisting of symmetrical lumps. Two sibs had cleft palate in addition to the lip anomaly. The literature on this syndrome was analyzed by van der Woude (1954), who found confirmation for the autosomal dominant mode of inheritance. It is possible that in some affected families, because of the variable expressivity of the gene, the syndrome is expressed only as pits. Baker (1964) reported such a pedigree with affected members in 3 generations showing pits as the only malformation. On the other hand, only harelip and/or cleft palate without pits could segregate in families as a dominant trait. Test and Falls (1947) described the condition transmitted through 5 generations. The rule that cleft palate alone and cleft lip with or without cleft palate behave differently does not hold in this disorder, in which either type of cleft alone or the 2 in combination may occur. Janku et al. (1980) traced the van der Woude syndrome through 7 generations. Lip pits, the most common manifestation, were present in 88% of the affected and were the only manifestation in 64%. Clefts of lip and palate occurred in 21%. Penetrance was 96.7%. Ranta and Rintala (1983) analyzed the 'microforms' of the van der Woude syndrome in cases of cleft palate. Conical elevations (CE) on the lower lip at the site of sinuses were present in 39.3% of cleft palate cases, 0.8% of cleft lip with or without cleft palate cases, and 0.7% of noncleft cases. In CP cases with CE, the familial occurrence of clefts was statistically higher (30%) than in CP cases without CE. The corresponding figures for hypodontia were 40.7% and 24.7%, respectively. See review by Schinzel and Klausler (1986). Burdick et al. (1987) reported 2 unrelated families from the area of Beijing, China. Ankyloglossia was found in the proband in each family. Sorricelli et al. (1966) also described this association. Kocer et al. (2001) described a child with symmetrical lower lip pits and cleft palate whose mother had only a single lower lip pit in the right paramedian region. (The possibility of mosaicism in the mother might be raised. VAM) Birnbaum et al. (2008) analyzed the IRF6 gene in 63 families with what was believed to be isolated CL/P or CP and identified a deletion/insertion and duplication in 2 families, respectively. Despite 'credible denials' of a history of lip pits in family members, upon reinterviewing and retrieval of preoperative photographs, the presence of lip pits in both families confirmed the diagnosis of VWS. Birnbaum et al. (2008) noted that this is important for genetic counseling, because the recurrence risk of VWS is higher than the recurrence risk for nonsyndromic clefts. Other Features Nopoulos et al. (2007) reported brain MRI results in 7 adult men and 7 adult women with VWS. Seven of the affected patients belonged to a single large kindred; the remaining patients each came from a different family. Individuals with VWS had markedly larger gray matter volumes of the anterior cerebrum compared to controls, and there was a negative correlation between anterior gray matter volume and IQ, indicating that the changes had functional significance. Men with VWS also had decreased volumes of the posterior cerebrum. Nopoulos et al. (2007) concluded that brain structure is altered in individuals with VWS, similar to that observed in patients with isolated cleft lip/palate (see 119530 and Nopoulos et al., 2002), suggesting that both disorders reflect abnormal brain development. Cytogenetics Bocian and Walker (1987) described a patient with an interstitial deletion of chromosome 1q, del(1q32-q41). Among other anomalies, the patient had congenital lower lip pits similar to those found in association with the van der Woude syndrome and with the popliteal pterygium syndrome. Bocian and Walker (1987) suggested that the van der Woude syndrome may be due to a submicroscopic deletion of chromosome 1q in the area stated. A tentative assignment of the locus, symbolized PIT, to 1q32-q41 was made on the basis of this report. Sander et al. (1994) reported a microdeletion involving 1q32-q41 in a family with VWS. They found allelic loss of the stable and highly polymorphic microsatellite D1S205. They estimated that the upper bound of the size of the deletion was 4 Mb. Schutte et al. (1999) screened a panel of 37 VWS families for loss of transmission of an allele using a highly polymorphic marker (D1S3753) from the VWS critical region. Allele loss, indicating the presence of a deletion, was identified in 1 family. In this family, the phenotype in 3 generations of affected individuals was confined to the cardinal signs of VWS, in contrast to previously reported deletions in which developmental delay and other anomalies accompanied features of VWS (Bocian and Walker, 1987; Sander et al., 1994). Houdayer et al. (2000) performed a microsatellite-based screening test for 1q32-q41 haploinsufficiency on 14 family triads with VWS and identified no additional microdeletions. Mapping Wienker et al. (1987) excluded linkage of VDWS with a considerable number of marker loci in studies of a kindred segregating for the disorder through 5 generations. Only linkage with Duffy blood group (110700) showed a uniformly positive lod score (lod = 1.31 at theta = 0.0). Murray et al. (1988) found linkage of LPS to the renin gene (REN; 179820); lod = 4.62 at theta = 0.04. Studies by Nishimura et al. (1989) raised the maximum lod score to 8.62 at theta = 0.02 for linkage of LPS and REN. Murray et al. (1988) and Nishimura et al. (1989) also adopted a candidate gene approach and investigated whether the laminin B2 (150290) gene might be the site of the mutation in VDWS. The finding of several recombinants ruled out this possibility. Nishimura et al. (1989) used the same approach to investigate decay accelerating factor (125240) as the site of the mutation and found no recombinants (lod = 2.22). Murray et al. (1990) reported a multipoint linkage analysis that indicated flanking of the VDWS locus by REN and D1S65 at a lod score of 10.83. Schutte et al. (1996) constructed a 3.5-Mb YAC contig and sequence tagged site (STS) map extending from D1S245 to D1S414 in the region containing the VWS locus. They also carried out deletion mapping on a somatic cell hybrid derived from a patient with VWS due to a microdeletion. Analysis of this hybrid and genetic analysis in an additional family narrowed the VWS critical region to a 1.6-cM region flanked by D1S491 and D1S205. The authors noted that the STS markers that flank this critical region and the proximal and distal ends of the microdeletion are present in a single 850-kb YAC. Houdayer et al. (1999) studied the linkage of 6 microsatellite markers in the 1q32-q41 region to the disease phenotype in 5 Caucasian VWS kindreds. A maximum cumulative lod score of 3.27 at a recombination fraction of 0.00 was obtained with marker D1S245. The inner 4 markers were found to be tightly linked to one another without recombination. The authors concluded that the results favored locus homogeneity. In studies of 4 multiplex Caucasian VWS families that had been recruited at 3 different locations in the U.S., Beiraghi et al. (1999) found positive lod scores without any recombination in the candidate region of 1q. The largest 2-point lod score was 5.87. They used an assay method for short tandem repeat (STR) markers that provided highly accurate size estimation of marker allele fragment sizes, enabling them to determine the specific alleles segregating with the VWS gene in each of the 4 families. They observed a striking pattern of STR allele sharing at several closely linked loci among the 4 VWS families. These results suggested the possibility of a unique (i.e., single) origin for the mutation responsible for many or most cases of VWS. Lees et al. (1999) reported clinical features and linkage analysis in 3 families with popliteal pterygium syndrome. Linkage analysis showed a multipoint lod score of 2.7 with no evidence of recombination using the markers D1S205, D1S491, and D1S3753 in the critical region for VWS on chromosome 1q32, supporting the hypothesis that these 2 conditions are allelic. The cardinal features of van der Woude syndrome are lip pits and cleft lip with or without cleft palate or cleft palate (alone) (119540). Since none of these traits is present in all mutation carriers, some individuals or familial VWS cases, especially those lacking lip pits, are indiscernible from nonsyndromic CL/P (119530), raising the question of whether allelic variation at the VWS locus could underlie nonsyndromic CL/P. Houdayer et al. (2001) addressed this question using parametric linkage (lod score) analysis in 21 multiplex nonsyndromic CL/P families based on a tightly linked microsatellite marker (D1S3753) and nonparametric analysis using the transmission/disequilibrium test in 106 nonsyndromic CL/P triads (2 parents and an offspring) and 3 selecting markers on chromosome 1. No evidence for linkage of nonsyndromic CL/P to VWS was found on the 21 families using the lod score approach. In contrast, the transmission/disequilibrium test yielded a significant P value of 0.04 for D1S205, supporting involvement of VWS in nonsyndromic CL/P in a complex, modifying/polygenic manner rather than as a monogenic/major disease locus. Wong et al. (2001) performed linkage analysis in 5 Finnish families with VWS. Three of these families were linked to the 1q32-q41 region. A recombination in an unaffected individual reduced the critical region to a 200-kb interval bounded by the markers at D1S491 and D1S3753. The authors expressed caution about the use of apparently unaffected individuals in a condition with low expressivity. Linkage disequilibrium suggested that the critical region was 130 kb bounded by the markers at D1S491 and D1S2136. ### Modifier Loci The expression of VWS, which has incomplete penetrance, is highly variable. Both the occurrence of cleft lip/palate and cleft palate within the same kindred and a recurrence risk of less than 40% for cleft palate among descendants with VWS suggested that the development of clefts in this syndrome is influenced by modifying genes at other loci. To test this hypothesis, Sertie et al. (1999) conducted linkage analysis in a large Brazilian kindred with VWS, considering as affected the individuals with CP, regardless of whether it was associated with other clinical signs of VWS. The results suggested that a gene at 17p11.2-p11.1 (604547), together with the VWS gene at 1q32, enhances the probability of CP in an individual carrying the 2 at-risk genes. Sertie et al. (1999) stated that if this hypothesis is confirmed in other VWS pedigrees, it will represent one of the first examples of a gene, mapped through linkage analysis, that modifies the expression of a major gene. Molecular Genetics In efforts to clone the VWS gene, Watanabe et al. (2001) analyzed 900 kb of genomic sequence from the critical region of 1q32-q41. They found a polymorphism within a polymorphism that is a deletion/insertion (del/ins) polymorphism with a TTCC short tandem repeat (STR) embedded within it. They suggested that this be called a 'matroshka' polymorphism, after the Russian doll that has additional dolls nested inside. Kondo et al. (2002) performed direct sequence analysis of genes and presumptive transcripts in the 350-kb VWS critical region identified by linkage analysis and identified mutations in the IRF6 gene, encoding interferon regulatory factor-6. They found a nonsense mutation in exon 4 of the IRF6 gene (607199.0001) in the affected twin of a pair of monozygotic twins who were discordant for VWS. Subsequently, they identified mutations in 45 additional unrelated families with VWS and distinct mutations in 13 families with popliteal pterygium syndrome (119500). In a family whose affected members showed cleft lip with or without cleft palate and isolated cleft palate, Kondo et al. (2002) found that all affected members regardless of phenotype shared the 18-bp deletion (607199.0002) found in the proband. The authors hypothesized that marked phenotypic variation in their cohort strongly implicated the action of stochastic factors or modifier genes on IRF6 function. Ghassibe et al. (2004) screened the IRF6 gene in 6 families with VWS and identified 6 heterozygous missense mutations, respectively, all affecting either the DNA-binding or the protein-binding domain. In a 4-generation VWS family in which affected individuals carried an L22P mutation (607199.0014), 2 of the patients displayed additional features: 1 had finger syndactyly, and the other had toe syndactyly and oral synechiae. Ghassibe et al. (2004) stated that because syndactyly and synechiae are major signs for PPS, these 2 patients were considered to have PPS, whereas the 6 other affected family members were classified as VWS, thus demonstrating that a single mutation could be responsible for both syndromes. Yeetong et al. (2009) reported 3 female patients with lower lip anomalies, all of whom had heterozygous mutations in the IRF6 gene. One patient was a 16-year-old girl with bilateral conical elevations without pits, joining at the midline of the lower lip, giving the appearance of a heart-shaped mass; she was heterozygous for a nonsense mutation (Q49X; 607199.0017). Her mother and other relatives were reported to have similar findings, but were unavailable for evaluation. Malik et al. (2010) identified 16 Pakistani probands with VWS from more than 1,200 individuals with CL/P, for a frequency of approximately 1% in Pakistan. Analysis of IRF6 in the 16 VWS probands identified mutations in 12 of them (see, e.g., 607199.0009 and 607199.0018), including 2 missense mutations that previously had been identified in patients with popliteal pterygium syndrome (PPS). While no clinical signs of PPS were identified or reported by these patients or their families, Malik et al. (2010) noted that subtler signs of PPS such as genital hypoplasia may have been present but were not evaluated in this study. To test whether DNA variants in regulatory elements cause VWS, Fakhouri et al. (2014) sequenced 3 conserved elements near IRF6 in 70 VWS families who were negative for mutations with IRF6 exons and identified a duplication (350dupA) within a highly conserved sequence in the MCS9.7 enhancer element in a 3-generation Brazilian family. The duplication was present in 3 affected individuals as well as in 2 unaffected family members, but it was not found in 100 unaffected controls or in 1,092 genomes from 14 populations in the NHLBI Exome Sequencing Project database. Functional analysis demonstrated that the 350dupA mutation disrupted MCS9.7 enhancer activity in 2 different cell lines as well as in vivo in a transgenic mouse embryo assay. ### Van der Woude Syndrome-Popliteal Pterygium Syndrome Spectrum In a patient with overlapping features of VWS and PPS (unilateral cleft lip and palate, ankyloblepharon, paramedian lip pits) as well as unilateral renal aplasia and coronal hypospadias, de Medeiros et al. (2008) identified a novel heterozygous mutation in the IRF6 gene (607199.0013). The patient and his brother, who had hypospadias and nephrocalcinosis but no IRF6 mutation, were both conceived by in vitro fertilization. De Medeiros et al. (2008) suggested that the hypospadias and renal aplasia may have been due to the method of fertilization rather than the IRF6 mutation. They noted that a lethal PPS syndrome (263650) has renal aplasia as a feature. INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Lower lip pits \- Cleft lip \- Cleft palate \- Cleft uvula Teeth \- Hypodontia MOLECULAR BASIS \- Caused by mutation in the interferon regulatory factor 6 gene (IRF6, 607199.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	VAN DER WOUDE SYNDROME 1	c0175697	29,079	omim	https://www.omim.org/entry/119300	2019-09-22T16:43:18	{"doid": ["0060239"], "mesh": ["C536528"], "omim": ["119300"], "icd-10": ["Q38.0"], "orphanet": ["888"], "synonyms": ["Alternative titles", "VDWS", "LIP-PIT SYNDROME", "CLEFT LIP AND/OR PALATE WITH MUCOUS CYSTS OF LOWER LIP"], "genereviews": ["NBK1407"]}
A group of rare acute leukemias of ambiguous lineage characterized by the presence of separate populations of blasts of more than one lineage (bilineal), a single population of blasts coexpressing antigens of more than one lineage (biphenotypic), or a combination thereof. The diagnosis relies on immunophenotyping, the T-cell component being characterized by strong expression of cytoplasmic CD3, usually in the absence of surface CD3, the B-cell component expressing CD19, almost always together with CD10, cCD79a, CD22, or PAX5, while the most specific hallmark of the myeloid component is the presence of myeloperoxidase in the blast cytoplasm. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Mixed phenotype acute leukemia	c0023467	29,080	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=530995	2021-01-23T17:16:59	{"mesh": ["D015470"], "omim": ["601626"], "icd-10": ["C95.0"], "synonyms": ["MPAL"]}
PSP-corticobasal syndrome (PSP-CBS) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease. ## Epidemiology It is rare, and probably accounts for less than 10% of all cases of PSP-tau pathology, which prevalence is estimated at about 1/16,600. ## Clinical description The disease manifests during the sixth or seventh decade of life with a progressive, often asymmetric dystonia, dyspraxia, and cortical sensory loss. Limb rigidity, bradykinesia and slowed vertical saccadic eye movements are also observed. Postural instability and axial rigidity develop as the disease progresses. The disease is characterized neuropathologically by gliosis with astrocytic plaques, accumulation of tau-immunoreactive neurofibrillary tangles and neuronal loss in specific brain areas, especially in the midfrontal and inferior parietal cortices. ## Etiology PSP is a 4R tauopathy composed of a preponderance of four-repeat (exon 10 positive) tau isoforms and a characteristic biochemical profile (doublet tau 64 and tau 69). The MAPT H1-clade specific sub-haplotype, H1c, is a risk factor for this disease. The factors that initiate tau-neurodegeneration are unknown. ## Diagnostic methods Diagnosis is based on the clinical picture and neuropsychological evaluation. ## Differential diagnosis Differential diagnosis includes corticobasal degeneration (CBD), Parkinson disease and other atypical parkinsonian disorders (APD) (see these terms). ## Management and treatment There is no treatment curing the disease. Patients do not respond to levodopa treatment. Botulinum toxin and splinting may improve painful dystonic posturing of the hand. ## Prognosis Progressively, patients become wheel-chair dependant due to the frequent falls. Difficulties in breathing and swallowing, and infections are the main causes of death, generally 6-12 years after onset of the disease. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Progressive supranuclear palsy-corticobasal syndrome	None	29,081	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=240103	2021-01-23T16:55:41	{"icd-10": ["G23.1"], "synonyms": ["PSP-CBS", "PSP-corticobasal syndrome"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2017) BENTA Disease Other namesB-cell expansion with NF-kB and T-cell anergy disease For each child an affected parent has, there is a 50% chance of passing on the mutation, regardless of the sex of the child autosomal dominant SpecialtyImmunology BENTA disease is a rare genetic disorder of the immune system. BENTA stands for "B cell expansion with NF-κB and T cell anergy" and is caused by germline heterozygous gain-of-function mutations in the gene CARD11 (see OMIM entry #607210). This disorder is characterized by polyclonal B cell lymphocytosis with onset in infancy, splenomegaly, lymphadenopathy, mild immunodeficiency, and increased risk of lymphoma. Investigators Andrew L. Snow and Michael J. Lenardo at the National Institute of Allergy and Infectious Disease at the U.S. National Institutes of Health first characterized BENTA disease in 2012. Dr. Snow's current laboratory at the Uniformed Services University of the Health Sciences is now actively studying this disorder.[1][2] ## Contents * 1 Presentation * 2 Genetics * 2.1 Inheritance * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Presentation[edit] Individuals with BENTA disease have polyclonal B cell lymphocytosis (i.e. excess B cells) developing in infancy, in addition to splenomegaly and lymphadenopathy. Patients may have low serum IgM and mildly anergic T cells. These features likely contribute to the mild immunodeficiency seen with BENTA disease. Patients are generally susceptible to recurrent sinopulmonary and ear infections in childhood, and may be more susceptible to certain viruses including Epstein-Barr virus, BK virus, and molluscum contagiosum.[1] ## Genetics[edit] Representation of the CARD11 protein showing the general domain structure and two different gain-of-function missense mutations associated with BENTA disease located just upstream of the coiled-coil (CC) domain[2] BENTA disease is caused by germline-encoded gain-of-function mutations in the gene CARD11. This is a 138 kB gene mapping to chromosome 7p22 with 26 exons encoding a 1,154 amino acid protein.[3][4] The CARD11 protein (also known as CARMA1) is a scaffolding protein required for NF-κB activation in both B and T lymphocytes. Gain-of-function mutations drive constitutive NF-κB activation in both types of cells. Most mutations are localized within or just upstream of the coiled-coil domain (exons 4-9) of the protein. Patient phenotypes also suggest that B cell differentiation might be partially impaired in BENTA disease, contributing to a low percentage of class-switched and memory B cells.[1][2] Germline gain-of-function mutations in CARD11 manifest a less severe illness than loss-of-function mutations seen in CARD11 deficiency (OMIM #615206), an autosomal recessive condition manifesting in severe combined immunodeficiency.[1] The gain-of-function CARD11 mutations associated with BENTA disease may also predispose patients to B cell malignancy. Importantly, overactive NF-κB is frequently associated with B cell malignancy and, specifically, somatic gain-of-function CARD11 mutations are seen frequently in diffuse large B cell lymphoma (DLBCL). However, most BENTA patients present with polyclonal B cell accumulation with no evidence of oligoclonal or monoclonal populations (i.e. malignancy). These mutations do not appear to be associated with T cell malignancies.[2] ### Inheritance[edit] This disorder is inherited in an autosomal dominant manner. Autosomal refers to the fact that every person has two CARD11 alleles, one inherited from each parent. This is in contrast to sex-linked chromosomes. Dominant means that the abnormal allele dominates the matching, normal allele. Only one of the two copies (alleles) of CARD11 needs to be abnormal for a person to have BENTA disease. BENTA disease can also arise spontaneously in a patient as the result of a de novo mutations in CARD11, which means that the mutation was not inherited from the parents. In this case the patient could still pass on the mutation to his/her children. Children of a parent who carries a CARD11 mutation have a 50% chance of inheriting the mutation. In a family, each child’s risk of inheriting the mutated CARD11 allele is independent of whether or not other siblings inherited the mutation. For example, if the first four children in a family have the mutation, the next child has the same 50% risk of inheriting the mutation. Children who do not inherit the mutation will not develop BENTA disease nor pass it on to their children. ## Diagnosis[edit] The majority of patient peripheral blood mononucleated cells are polyclonal naïve mature B cells, with a significant increase in immature, transitional B cell numbers (identified as CD10+).[5] Percentages of circulating class-switched and memory B cells are very low, and in vitro studies show poor B cell differentiation and immunoglobulin secretion. Serum IgM is low in most patients, while total IgG and IgA may be on the low end of normal. Patients demonstrate defective antibody production against T cell-independent, polysaccharide-based vaccines. Some patients may not mount protective antibody titers to other vaccines, such as measles and varicella zoster virus.[2][6] T cell counts are generally within or just above the normal range. In vitro stimulation of T cells demonstrates that both CD4+ and CD8+ T cells are less responsive than normal, suggesting mild T cell anergy in patients.[1] A diagnosis of leukemia can generally be ruled out in these patients based on the unremarkable appearance of small resting lymphocytes in the blood; however, patients must be closely monitored for any signs of monoclonal or oligoclonal B cell expansion because there may be an increased risk for B cell malignancy. Specifically, one patient with BENTA disease was reported as having developed B cell chronic lymphocytic leukemia (B-CLL) as an adult.[1] ## Treatment[edit] There is currently minimal therapeutic intervention available for BENTA disease. Patients are closely monitored for infections and for signs of monoclonal or oligoclonal B cell expansion that could indicate B cell malignancy. Splenectomy is unlikely to reduce B cell burden; peripheral blood B cell counts rose significantly in three patients who underwent the procedure. It remains to be determined whether immunosuppressive drugs, including B cell-depleting drugs such as rituximab, could be effective for treating BENTA disease.[1] ## References[edit] 1. ^ a b c d e f g Turvey, SE; Durandy, A; Fischer, A; Fung, SY; Geha, RS; Gewies, A; Giese, T; Greil, J; Keller, B; McKinnon, ML; Neven, B; Rozmus, J; Ruland, J; Snow, AL; Stepensky, P; Warnatz, K (2014). "The CARD11-BCL10-MALT1 (CBM) signalosome complex: Stepping into the limelight of human primary immunodeficiency". The Journal of Allergy and Clinical Immunology. 134 (2): 276–84. doi:10.1016/j.jaci.2014.06.015. PMC 4167767. PMID 25087226. 2. ^ a b c d e Snow, A. L.; Xiao, W.; Stinson, J. R.; Lu, W.; Chaigne-Delalande, B.; Zheng, L.; Pittaluga, S.; Matthews, H. F.; Schmitz, R.; Jhavar, S.; Kuchen, S.; Kardava, L.; Wang, W.; Lamborn, I. T.; Jing, H.; Raffeld, M.; Moir, S.; Fleisher, T. A.; Staudt, L. M.; Su, H. C.; Lenardo, M. J. (5 November 2012). "Congenital B cell lymphocytosis explained by novel germline CARD11 mutations". Journal of Experimental Medicine. 209 (12): 2247–2261. doi:10.1084/jem.20120831. PMC 3501355. PMID 23129749. 3. ^ "CARD11 caspase recruitment domain family, member 11 [ Homo sapiens (human) ]". NCBI > Genes & Expression > Gene. NCBI. Retrieved 4 September 2014. 4. ^ "Caspase recruitment domain-containing protein 11 [Homo sapiens]". NCBI. Retrieved 4 September 2014. 5. ^ Chung JB1, Silverman M, Monroe JG. (June 2003). "Transitional B cells: step by step towards immune competence". Trends Immunol. 24 (6): 343–9. doi:10.1016/s1471-4906(03)00119-4. PMID 12810111.CS1 maint: uses authors parameter (link) 6. ^ Kniffin, Cassandra. "#606445 Persistent polyclonal B-cell lymphocytosis; PPBL". OMIM. Johns Hopkins University. Archived from the original on 24 September 2015. Retrieved 4 September 2014. ## External links[edit] Classification D * OMIM: 616452 External resources * Orphanet: 464336 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BENTA disease	c4551967	29,082	wikipedia	https://en.wikipedia.org/wiki/BENTA_disease	2021-01-18T19:00:15	{"gard": ["13339"], "omim": ["616452"], "umls": ["CN231446"], "orphanet": ["464336"], "synonyms": ["B-cell expansion with NF-kB and T-cell anergy disease"], "wikidata": ["Q25339136"]}
From in situ hybridization studies, Price et al. (1973) suggested that a D-group chromosome contains on its long arm DNA complementary to the RNA of the oncogenic virus RD114. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	VIRUS RD114 RNA COMPLEMENTARITY	c1860423	29,083	omim	https://www.omim.org/entry/193070	2019-09-22T16:31:58	{"omim": ["193070"]}
Bauxite fibrosis Other namesShaver's disease, Corundum smelter's lung, Bauxite lung or Bauxite smelters' disease Bauxite with unweathered rock core SpecialtyPulmonology Bauxite pneumoconiosis, is a progressive form of pneumoconiosis usually caused by occupational exposure to bauxite fumes which contain aluminium and silica particulates.[1] It is typically seen in workers involved in the smelting of bauxite to produce corundum.[2] ## Contents * 1 Presentation * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Presentation[edit] Initially, the disease appears as alveolitis, and then progresses to emphysema.[3] Patients may develop pneumothorax (collapsed lung). ## Diagnosis[edit] This section is empty. You can help by adding to it. (September 2017) ## Treatment[edit] This section is empty. You can help by adding to it. (September 2017) ## References[edit] 1. ^ Tamotsu Takishima (1994-05-23). Basic and Clinical Aspects of Pulmonary Fibrosis. CRC Press. pp. 391–. ISBN 978-0-8493-8927-6. 2. ^ WYATT JP, RIDDELL AC (1949). "The morphology of bauxite-fume pneumoconiosis". Am. J. Pathol. 25 (3): 447–65. PMC 1942907. PMID 18127135. 3. ^ Lippincott (2012-11-05). Professional Guide to Diseases. Lippincott Williams & Wilkins. pp. 1200–. ISBN 978-1-4511-7892-0. ## External links[edit] Classification D * ICD-10: J63.1 * ICD-9-CM: 503 * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis This article about a medical condition affecting the respiratory system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Bauxite fibrosis	c0264437	29,084	wikipedia	https://en.wikipedia.org/wiki/Bauxite_fibrosis	2021-01-18T18:31:32	{"icd-9": ["503"], "icd-10": ["J63.1"], "wikidata": ["Q4873613"]}
Cat with noticeable jaundice from late-stage hepatic lipidosis. Note the ears and eye-membrane Feline hepatic lipidosis, also known as feline fatty liver syndrome, is one of the most common forms of liver disease of cats.[1] The disease officially has no known cause, though obesity is known to increase the risk.[2] The disease begins when the cat stops eating from a loss of appetite, forcing the liver to convert body fat into usable energy. If this process continues for too long, fat builds up in the cells of the liver, and the disease has officially onset.[1] Prognosis varies depending on the stage of the disease, with both a high recovery and mortality rate at different stages. The disease is reversible through intense feeding.[3] Treatment may involve the insertion of a temporary feeding tube to ensure adequate caloric intake for cats that have stopped eating as a result of this disease.[4] ## Contents * 1 Causes * 2 Symptoms * 2.1 Early Stage * 2.2 Late Stage * 3 Diagnosis * 4 Treatment * 5 References ## Causes[edit] One of the reasons a cat may stop eating is separation anxiety and the emotional stress that results. Moving, gaining or losing housemates or pets, going on vacation, or prolonged boarding are all common situations that pet owners report just prior to the onset of the disease, but it may develop without these conditions existing. Obesity is known to increase the risk of hepatic lipidosis; however, there is no known "official" cause of the disease.[2] Severe anorexia usually precedes the onset of the disease. When the cat has no energy from eating, the liver must metabolize fat deposits in the body into usable energy to sustain life. The cat liver, however, is poor at metabolizing fat,[5] causing a buildup of fat in the cells of the liver, leading to fatty liver. At this point the disease can be diagnosed; however, it will often not be diagnosed, and many animals are euthanized due to improper or no diagnosis. ## Symptoms[edit] Anorexia always precedes liver disease, with the cat refusing to eat enough food for days, or weeks. This may be amplified by frequent vomiting when the cat does choose to eat. A lack of appetite causes the cat to refuse any food, even after it has purged its system of all stomach contents. Severe weight loss proceeds as the liver keeps the cat alive off body fat, causing a yellowing of the skin (jaundice). When the cat runs out of fat to process, severe muscle wasting (cachexia) takes place as the body converts protein into energy.[2] Eventually the body cannot give the brain enough energy to function properly and the cat dies from malnutrition. In addition, an overworked liver can eventually fail causing total system collapse. ### Early Stage[edit] * Anorexia * Lack of appetite * Vomiting ### Late Stage[edit] * Jaundice * Seizures * Drooling * Coma ## Diagnosis[edit] Feline hepatic lipidosis shares similar symptoms to other problems, including liver disease, kidney failure, feline leukemia, Feline infectious peritonitis, and some cancers. Diagnosis requires tests that target the liver to make an accurate diagnosis. Jaundice is highly indicative of the disease. Blood tests and a liver biopsy will confirm the presence of the disease. ## Treatment[edit] Cat receiving treatment for hepatic lipidosis. An esophageal feeding tube can be seen extending from the neck. A syringe containing a nutrient slurry can also be seen. Untreated, the disease has a mortality rate upwards of 90%. Cats treated in the early stages can have a recovery rate of 80–90%.[6] Left untreated, the cats usually die from severe malnutrition or complications from liver failure. Treatment usually involves aggressive feeding through one of several methods. Cats can have a feeding tube inserted by a veterinarian so that the owner can feed the cat a liquid diet several times a day. If the cat stops vomiting and regains its appetite, it can be fed in a food dish normally. The key is aggressive feeding so the body stops converting fat in the liver. The cat liver has a high regeneration rate and the disease will eventually reverse assuming that irreparable damage has not been done to the liver. The best method to combat feline hepatic lipidosis is prevention and early detection. Obesity increases the chances of onset. In addition, if a cat stops eating for 1–2 days, it should be taken to a vet immediately. The longer the disease goes untreated, the higher the mortality rate. ## References[edit] 1. ^ a b Welcome to Healthypet.com! Archived 2007-09-28 at the Wayback Machine 2. ^ a b c "Feline Hepatic Lipidosis (Fatty Liver Syndrome)". Archived from the original on 2007-08-29. Retrieved 2007-09-02. 3. ^ Feline Hepatic Lipidosis—Fatty Liver Disease in Cats 4. ^ [1] 5. ^ Sarah Wootten DVM, " Why Is My Cat Not Eating?", The Idle Cat 6. ^ Fatty Liver Syndrom—Ways to encourage anorexic cats to eat * v * t * e Domestic cats Felinology * Anatomy * Genetics * Dwarf cat * Kitten * Odd-eyed cat * Squitten Coat genetics Bicolor cat Black cat Calico cat Tabby cat Tortoiseshell cat Health * Aging * Declawing * Diet * dental health * senior * Neutering * Spaying * Vaccination Behavior * Body language * Catfight * Catnip * valerian * Communication * Meow * Purr * Kneading * Intelligence * Play and toys * Righting reflex * Senses Human–cat interaction * Ailurophobia * Animal-assisted therapy * Bodega cat * Cat cafés * Cat massage * Cat meat * Cat-scratch disease * Cat show * Cats in ancient Egypt * Cultural depictions * Internet * Farm cat * Feral cat * Cats and Islam * Lolcat * National Cat Day * Puppy cat * Ship's cat * Zoonosis Registries * American Cat Fanciers 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receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Feline hepatic lipidosis	None	29,085	wikipedia	https://en.wikipedia.org/wiki/Feline_hepatic_lipidosis	2021-01-18T19:00:35	{"wikidata": ["Q1607635"]}
Severe congenital neutropenia is an immunodeficiency characterized by low levels of granulocytes (< 200/mm3) without an associated lymphocyte deficit. ## Epidemiology The prevalence in the general population is estimated at 1-1.7/333,300. Annual incidence is around 1/250,000 births. ## Clinical description This neutropenia leads to repeated bacterial or mycotic infections in various locations, mostly cutaneo-mucous, ear, nose, and throat, and pulmonary. Stomatological signs are almost always present after 2 years of age and are distinguished by erosive gingivitis, hemorrhage and pain, associated with papilla on the tongue and mucous membranes. Infections may be very severe or even lethal. Around 15% of patients evolve to acute leukemia or a myelodysplastic syndrome. ## Etiology To date, mutations in four genes have been implicated in severe congenital neutropenia. These include the neutrophil elastase gene (ELA2), the GFI1 gene, the HAX1 gene and activation genes of Wiskott Aldrich disease (WASP). The combination of these mutations leads to a deficit in the production of neutrophils. ## Diagnostic methods The defining characteristic is cytology showing profound neutropenia associated with monocytosis. An isolated blockage at the promyelocyte stage of the myeloid series associated with eosinophilia and monocytosis is seen on myelogram. ## Differential diagnosis On the discovery of these features a complete biological assessment should be conducted to rule out several differential diagnoses, particularly lymphocytic immune deficiencies and autoimmune neutropenia. ## Antenatal diagnosis Prenatal diagnosis may be offered if the genotype is known. ## Genetic counseling The four mutations are transmitted differently: ELA2 and GFI1 are autosomal dominant, HAX1 is autosomal recessive, and WASP is X-linked recessive. Genetic counseling is essential and should take into account family history and the causal mutation. ## Management and treatment All febrile episodes or infections should be reviewed by a hospital and treated actively. Prophylactic antibiotics are used to prevent infections. If this is ineffective, hematopoietic growth factors (G-CSF in particular) can correct both neutropenia and the susceptibility to infections and can be administered either in response to infections or continuously. The dose of G-CSF required varies greatly. Continuous high dose G-CSF (more than 20µg/kg/day) encourages the onset of leukemia in the long term and therefore, in cases requiring continuous high dose treatment, bone marrow transplant should be considered. ## Prognosis The prognosis depends heavily on the quality of care and timeliness of treatment of severe infections, but also on the possibility of a bone marrow transplant, particularly in cases with malignant transformation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Severe congenital neutropenia	c1853118	29,086	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=42738	2021-01-23T17:11:29	{"mesh": ["C537592"], "umls": ["C1853118"], "icd-10": ["D70"]}
A number sign (#) is used with this entry because Bardet-Biedl syndrome-16 (BBS16) is caused by homozygous or compound heterozygous mutations in the SDCCAG8 gene (613524) on chromosome 1q43. Mutations in the SDCCAG8 gene can also result in Senior-Loken syndrome-7 (613615), an autosomal recessive ciliopathy. Description BBS16 is an autosomal recessive ciliopathy characterized by retinal degeneration, obesity, renal disease, and cognitive impairment. Although polydactyly is considered a primary feature of BBS overall, it has not been reported in any BBS16 patient (Billingsley et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900). Clinical Features Billingsley et al. (2012) studied 2 female sibs of East Indian descent with BBS. Both subjects, aged 16 and 13 year, respectively, developed end-stage renal disease that required transplantation at 11 and 9 years of age, respectively. Both had obesity, short stature, and mild cognitive impairment. The younger patient had nonalcoholic fatty liver disease. This patient also had trace mitral and tricuspid regurgitation. Visual acuity and central fields were preserved in the teenage years in both patients. Optical coherence tomography showed preservation of the retinal lamination at the fovea; fundus autofluorescence demonstrated a perifoveal ring of hyperfluorescence consistent with retinitis pigmentosa. Full-field ERG showed rod function to be more severely affected than cone function in both cases. Polydactyly was not present. Schaefer et al. (2010) clinically characterized the patients reported by Otto et al. (2010) and described a previously unreported patient. The 2 consanguineous families studied by Otto et al. (2010) were a Gypsy and a French family, respectively. The phenotype in all families was characterized by obesity, chronic renal failure, cone-rod dystrophy, and developmental delay. Also present were conductive hearing loss/recurrent otitis, respiratory infection, and asthma. Polydactyly was not present in any affected individual. Molecular Genetics Otto et al. (2010) carried out an independent homozygosity mapping study on 22 consanguineous families diagnosed with Bardet-Biedl syndrome in whom no mutation had been detected in any of the 12 BBS genes known at that time. They identified homozygosity for mutation in the SDCCAG8 gene in 2 families (613524.0004, 613524.0005). Sequencing of SDCCAG8 in 96 unrelated individuals identified 2 further families in which compound heterozygous loss-of-function mutations seemed to be sufficient to cause the disorder (613524.0006, 613524.0007). Two unique heterozygous alleles were found in 2 additional families. In 2 sibs of East Indian descent with BBS, Billingsley et al. (2012) identified the same compound heterozygous truncating mutations in the SDCCAG8 gene that had been identified by Otto et al. (2010). Billingsley et al. (2012) referred to the changes observed at the protein level as Thr482LysfsTer12 and Asp543AlsfsTer24. The mutations segregated with the disorder in the family and were not found in 69 matched control individuals. Functional studies of the variants were not performed. INHERITANCE \- Autosomal recessive GROWTH Weight \- Obesity HEAD & NECK Ears \- Otitis media, recurrent \- Hearing impairment, conductive Eyes \- Retinitis pigmentosa \- Retinal degeneration RESPIRATORY \- Respiratory infections, recurrent, chronic \- Respiratory distress \- Bronchiolitis GENITOURINARY External Genitalia (Male) \- Hypogonadism \- Hypogenitalism Kidneys \- Renal anomalies \- Renal agenesis \- Dysplastic kidneys \- Abnormal corticomedullary differentiation \- Renal cysts \- Renal failure SKELETAL Hands \- No polydactyly NEUROLOGIC Central Nervous System \- Developmental delay \- Learning disabilities \- Cognitive impairment \- Mental retardation MISCELLANEOUS \- Early-onset severe renal disease MOLECULAR BASIS \- Caused by mutation in the serologically defined colon cancer antigen 8 gene (SDCCAG8, 613524.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BARDET-BIEDL SYNDROME 16	c0752166	29,087	omim	https://www.omim.org/entry/615993	2019-09-22T15:50:17	{"doid": ["0110138"], "mesh": ["D020788"], "omim": ["615993"], "orphanet": ["110"]}
Frasier syndrome is a condition that affects the kidneys and genitalia. Frasier syndrome is characterized by kidney disease that begins in early childhood. Affected individuals have a condition called focal segmental glomerulosclerosis, in which scar tissue forms in some glomeruli, which are the tiny blood vessels in the kidneys that filter waste from blood. In people with Frasier syndrome, this condition often leads to kidney failure by adolescence. Although males with Frasier syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear completely female. The internal reproductive organs (gonads) are typically undeveloped and referred to as streak gonads. These abnormal gonads are nonfunctional and often become cancerous, so they are usually removed surgically early in life. Affected females usually have normal genitalia and gonads and have only the kidney features of the condition. Because they do not have all the features of the condition, females are usually given the diagnosis of isolated nephrotic syndrome. ## Frequency Frasier syndrome is thought to be a rare condition; approximately 50 cases have been described in the scientific literature. ## Causes Mutations in the WT1 gene cause Frasier syndrome. The WT1 gene provides instructions for making a protein that regulates the activity of other genes by attaching (binding) to specific regions of DNA. On the basis of this action, the WT1 protein is called a transcription factor. The WT1 protein plays a role in the development of the kidneys and gonads (ovaries in females and testes in males) before birth. The WT1 gene mutations that cause Frasier syndrome lead to the production of a protein with an impaired ability to control gene activity and regulate the development of the kidneys and reproductive organs, resulting in the signs and symptoms of Frasier syndrome. Frasier syndrome has features similar to another condition called Denys-Drash syndrome, which is also caused by mutations in the WT1 gene. Because these two conditions share a genetic cause and have overlapping features, some researchers have suggested that they are part of a spectrum and not two distinct conditions. ### Learn more about the gene associated with Frasier syndrome * WT1 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Frasier syndrome	c0950122	29,088	medlineplus	https://medlineplus.gov/genetics/condition/frasier-syndrome/	2021-01-27T08:24:46	{"gard": ["2375"], "mesh": ["D052159"], "omim": ["136680"], "synonyms": []}
Congenital muscular dystrophy with intellectual disability and severe epilepsy is a rare, fatal, inborn error of metabolism disorder characterized by respiratory distress and severe hypotonia at birth, severe global developmental delay, early-onset intractable seizures, myopathic fascies with craniofacial dysmorphism (trigonocephaly/progressive microcephaly, low anterior hairline, arched eyebrows, hypotelorism, strabismus, small nose, prominent philtrum, thin upper lip, high-arched palate, micrognathia, malocclusion), severe, congenital flexion joint contractures and elevated serum creatine kinase levels. Scoliosis, optic atrophy, mild hepatomegaly, and hypoplastic genitalia may also be associated. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Congenital muscular dystrophy with intellectual disability and severe epilepsy	c3554385	29,089	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=329178	2021-01-23T18:50:19	{"gard": ["12416"], "omim": ["615042"], "icd-10": ["E77.8"], "synonyms": ["CDG syndrome type Iu", "CDG-Iu", "CDG1U", "CMD with intellectual disability and severe epilepsy", "Carbohydrate deficient glycoprotein syndrome type Iu", "Congenital disorder of glycosylation type 1u", "Congenital disorder of glycosylation type Iu", "DPM2-CDG"]}
A number sign (#) is used with this entry because of evidence that complex cortical dysplasia with other brain malformations-7 (CDCBM7) is caused by heterozygous mutation in the TUBB2B gene (612850) on chromosome 6p25. Description Complex cortical dysplasia with other brain malformations-7 is an autosomal dominant, clinically heterogeneous disorder showing a wide spectrum of abnormalities of cortical brain development. The most severely affected patients are fetuses with microlissencephaly, absence of the cortical plate, agenesis of the corpus callosum, and severely hypoplastic brainstem and cerebellum. Other patients have lissencephaly, polymicrogyria, cortical dysplasia, or neuronal heterotopia. Those with less severe malformations can survive, but usually have some degree of neurologic impairment, such as mental retardation, seizures, and movement abnormalities (summary by Chang et al., 2006; Fallet-Bianco et al., 2014). For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039). Clinical Features Caraballo et al. (2000) reported a mother and son with unilateral right focal polymicrogyria. Both had cognitive impairment (IQ of 85 and 80, respectively) and congenital contralateral hemiparesis. The son also had focal seizures. Brain imaging of both patients showed right frontoparietal cortical dysplasia consistent with polymicrogyria. Autosomal dominant inheritance was suggested. Chang et al. (2006) reported 4 unrelated families in which 2 members of each family had unilateral right-sided polymicrogyria. Common clinical features included developmental delay, variable cognitive defects, contralateral (left) hemiparesis, and focal seizures. In 1 family, both affected sibs also had left hemianopia. Three families had 2 affected sibs born of nonconsanguineous unaffected parents; the fourth family that was previously reported by Caraballo et al. (2000) had affected mother and son. Familial occurrence strongly suggested a germline genetic etiology, although the pattern of inheritance was unclear. Chang et al. (2006) noted that features typically seen in DiGeorge /velocardiofacial syndrome (DGS, 188400; VCFS, 192430) were not present in their patients. Jaglin et al. (2009) reported 4 patients with asymmetric polymicrogyria. All had microcephaly, and 3 had severe neuromotor impairment with mental retardation. Three also had seizures. Brain imaging studies showed asymmetric polymicrogyria predominantly in the frontal, temporal, and parietal lobes, with dysmorphic caudate, cerebellar atrophy, and abnormalities of the corpus callosum and brainstem. Guerrini et al. (2012) reported 3 unrelated children with polymicrogyria. All had delayed psychomotor development, microcephaly, and mental retardation. Two had oromotor dyspraxia, 2 had hypotonia, and 1 had seizures. Brain MRI revealed diffuse polymicrogyria in 2 patients, more severe in the perisylvian region in 1 and with an irregular cortex resembling cobblestone cortex in the other. MRI of the third patient showed pachygyria with cortical thickening and irregular folding in the postrolandic and parietoposterior temporal regions. One patient had a small pons and another had a thin corpus callosum. The cerebellum was normal in all 3 patients. Fallet-Bianco et al. (2014) reported 6 unrelated fetuses with CDCBM7. Two of the fetuses (individuals 13 and 19) had a more severe phenotype of microlissencephaly, with microcephaly, enlarged germinal zone, complete agenesis of the corpus callosum, severe cerebellar hypoplasia/dysplasia, and pontine hypoplasia with focal overmigration. Another fetus (14) was classified as having lissencephaly, with a thick 4-layered cortex, heterotopia, complete agenesis of the corpus callosum, and mild pontocerebellar hypoplasia. The last 3 fetuses (16, 15, and 12) had polymicrogyria with cortical dysplasia, including heterotopia in 2 and agenesis of the olfactory bulb in 1, complete agenesis of the corpus callosum in 2, and mild cerebellar hypoplasia in all. These 6 fetuses were part of a cohort of 26 fetuses with malformations of cortical development associated with mutations in various tubulin genes. All of the fetuses carried heterozygous missense mutations in the TUBB2B gene (see, e.g., 612850.0001 and 612850.0008). Functional studies of the variants and studies of patient cells were not performed. Laquerriere et al. (2016) reported a 15-week-old fetus with CDCBM7 manifest as microlissencephaly. Postmortem examination showed microcephaly, smooth brain surface, a 2-layered cortex, absent olfactory tracts, and hypoplastic brainstem and cerebellum. ### Clinical Variability Cederquist et al. (2012) found a heterozygous missense mutation in the TUBB2B gene (E421K; 612850.0007) in a mother and her 2 daughters with polymicrogyria, intellectual disability, and congenital fibrosis of the extraocular muscles (CFEOM). The family had originally been reported by Flaherty et al. (2001). The daughters were noted to have ptosis and limitation of eye movements shortly after birth. Both girls showed delayed psychomotor development with moderate intellectual disability. Ophthalmic examination confirmed CFEOM with limited eye movements. Brain MRI of both girls showed polymicrogyric cortical dysplasia with dilation of the left lateral ventricle, hypoplasia of the left caudate body, and fusion of an enlarged caudate head with the underlying putamen. There was also thinning of the extraocular muscles. The mother had low intellectual functioning and limited extraocular movements. Her brain MRI showed mild bilateral polymicrogyria with asymmetry of the ventricles and basal ganglia, similar to her daughters. All 3 patients had a thinned corpus callosum. Cytogenetics Robin et al. (2006) reviewed clinical data including brain imaging on 21 patients from their subject database and 11 patients from the literature, all with polymicrogyria associated with deletion 22q11.2 (DGS/VCFS). The authors found that the cortical malformation consisted of perisylvian polymicrogyria of variable severity and frequent asymmetry with a striking predisposition for the right hemisphere (p = 0.008). Molecular Genetics In 4 unrelated patients and a fetus with asymmetric polymicrogyria, Jaglin et al. (2009) identified 5 different heterozygous mutations in the TUBB2B gene (see, e.g., 612850.0001-612850.0003). In vitro studies of some of the mutant proteins showed impaired formation of functional alpha/beta tubulin heterodimers and impaired incorporation into well-defined microtubules. The patients showed some phenotypic variability, but most had neuromotor impairment, mental retardation, and seizures. Brain imaging studies showed asymmetric polymicrogyria predominantly in the frontal, temporal, and parietal lobes, with dysmorphic caudate, cerebellar atrophy, and abnormalities of the corpus callosum and brainstem. In 3 (2.3%) of 128 unrelated children with polymicrogyria, Guerrini et al. (2012) identified 3 different heterozygous mutations in the TUBB2B gene (612850.0004-612850.0006). De novo occurrence of the mutation was proven in 2 patients and suspected in 1. The mutations were predicted to interfere with normal function of microtubules. In a fetus with microlissencephaly, Laquerriere et al. (2016) identified a de novo heterozygous missense mutation in the TUBB2B gene (C239F; 612850.0008). In vitro functional expression studies showed that the mutant protein caused impairment of the tubulin heterodimerization process. Cellular transfection of the mutant protein showed that it incorporated into microtubules, but there were high levels of unpolymerized cytosolic tubulin heterodimers, indicating that it incorporated poorly into the cytoskeleton. The mutation also altered microtubule dynamics, with an accelerated rate of repolymerization compared to controls. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Microcephaly Eyes \- Contralateral hemianopsia (1 family) \- Congenital fibrosis of the extraocular muscles (1 family) \- Limited extraocular movements (1 family) Mouth \- Sialorrhea \- Oromotor dyspraxia NEUROLOGIC Central Nervous System \- Malformations of cortical development, variable \- Polymicrogyria, asymmetric or symmetric \- Pachygyria \- Lissencephaly \- Enlarged granular layer \- Irregular folding of the cortex \- Frontotemporoparietal cortical dysplasia \- Contralateral hemiparesis, congenital \- Seizures \- Delayed motor development \- Cognitive delay \- Learning difficulties \- Mental retardation \- Thin corpus callosum \- Agenesis of the corpus callosum \- Cerebellar hypoplasia (variable) \- Brainstem abnormalities \- Neuronal migration defect MISCELLANEOUS \- Highly variable severity \- May result in death in utero in severe cases MOLECULAR BASIS \- Caused by mutation in the beta-2B tubulin gene (TUBB2B, 612850.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 7	c3552236	29,090	omim	https://www.omim.org/entry/610031	2019-09-22T16:05:13	{"doid": ["0090132"], "omim": ["610031"], "orphanet": ["300573"], "synonyms": ["POLYMICROGYRIA, SYMMETRIC OR ASYMMETRIC", "Alternative titles"], "genereviews": ["NBK1348"]}
For a general discussion of ovarian cancer, see 167000. Mapping Sekine et al. (2001) performed genomewide linkage analysis in 58 Japanese patients and 9 unaffected members among 28 familial ovarian cancer families with no mutation in BRCA1 (113705) or BRCA2 (600185). Mean age at diagnosis was 49.7 years. Chromosome 3p25-p22 showed a suggestive score for linkage (lod = 3.49 and NPL = 2.77 at D3S3611) based on a multipoint analysis. Additionally, based on a 2-point analysis using dense markers, this 3p25-p22 region showed a P value of less than 0.05 at 10 markers and suggestive evidence for linkage at 2 markers within 19 cM (NPL = 2.60 and 2.49 at D3S1597 and D3S3611, respectively). The frequency of loss of heterozygosity at 4 markers in this region was greater than 50% only in tumor tissues from patients with no mutation in BRCA1 or BRCA2, not in those with a BRCA1 mutation. The authors proposed that a novel tumor suppressor gene may be located in this region of chromosome 3. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	OVARIAN CANCER, SUSCEPTIBILITY TO, 1	c2675601	29,091	omim	https://www.omim.org/entry/607893	2019-09-22T16:08:31	{"omim": ["607893"]}
Fucosidosis is a lysosomal storage disease 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, and the skills they do acquire often deteriorate over time. In severe cases, symptoms appear in infancy; in milder cases, symptoms begin at age 1 or 2. Fucosidosis is caused by mutations in the FUCA1 gene. This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The only currently available treatment is bone marrow transplant, the results of which have been variable and need further study. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Fucosidosis	c0016788	29,092	gard	https://rarediseases.info.nih.gov/diseases/6473/fucosidosis	2021-01-18T18:00:24	{"mesh": ["D005645"], "omim": ["230000"], "umls": ["C0016788"], "orphanet": ["349"], "synonyms": ["Alpha-l-fucosidase deficiency", "Lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues"]}
"Broken tooth" redirects here. For the Macau gangster, see Wan Kuok-koi. Dental trauma A broken upper front tooth. The layers of tissue that make up the tooth are clearly visible, with the pink pulp standing out against the paler dentine and tooth enamel. SpecialtyOral and maxillofacial surgery Dental trauma refers to trauma (injury) to the teeth and/or periodontium (gums, periodontal ligament, alveolar bone), and nearby soft tissues such as the lips, tongue, etc. The study of dental trauma is called dental traumatology.[1] ## Contents * 1 Types * 1.1 Dental injuries * 1.2 Periodontal injuries * 1.3 Injuries to supporting bone * 1.4 Soft tissue laceration * 1.5 Primary teeth * 1.6 Permanent teeth * 1.6.1 Dental Injuries[2] * 1.6.2 Periodontal Injuries[2] * 2 Risk factors * 3 Prevention * 4 Management * 4.1 Splinting * 5 Complications * 5.1 Pulpal necrosis * 5.2 Root resorption * 5.3 Pulpal obliteration * 5.4 Damage to the successor teeth * 6 Epidemiology * 7 See also * 8 References * 9 External links ## Types[edit] Root fracture Simple mandible fracture ### Dental injuries[edit] Dental injuries include:[2][3] * Enamel infraction * Enamel fracture * Enamel-dentine fracture * Enamel-dentine fracture involving pulp exposure * Root fracture of tooth ### Periodontal injuries[edit] * Concussion (bruising) * Subluxation of the tooth (tooth knocked loose) * Luxation of the tooth (displaced) * Extrusive * Intrusive * Lateral * Avulsion of the tooth[4] (tooth knocked out) ### Injuries to supporting bone[edit] 3D CT of mandible fracture. This injury involves the alveolar bone and may extend beyond the alveolus.[5][6] There are 5 different types of alveolar fractures: * Communicated fracture of the socket wall * Fracture of the socket wall * Dentoalveolar fracture (segmental) * Fracture of the maxilla : Le Fort fracture, zygomatic fracture, orbital blowout * Fracture of the mandible Trauma injuries involving the alveolus can be complicated as it does not happen in isolation, very often presents along with other types of tooth tissue injuries. Signs of dentoalveolar fracture: * Change to occlusion * Multiple teeth moving together as a segment and are normally displaced * Bruising of attached gingivae * Gingivae across the fracture line often lacerated Investigation : Require more than one radiographic view to identify the fracture line. Treatment : Reposition displaced teeth under local anaesthetic and stabilise the mobile segment with a splint for 4 weeks, suture any soft tissue lacerations. ### Soft tissue laceration[edit] Facial nerve branches. Facial nerve should be examined for any potential damage when buccal mucosa is involved. Soft tissues injuries are presented commonly in association with dental trauma. Areas normally affected are lips, buccal mucosa, gingivae, frenum and tongue. The most common injuries are lips and gingivae. For lips, important to rule out presence of foreign objects in wounds and lacerations through careful examination. A radiograph can be taken to identify any potential foreign objects.[5][6] Gingivae lacerations that are small normally heals spontaneously and do not require any intervention. However, this can be one of the clinical presentation of an alveolar fracture. Gingivae bleeding especially around the margins may suggest injury to the periodontal ligament of the tooth. The facial nerve and parotid duct should be examined for any potential damage when the buccal mucosa is involved. Deep tissue wounds should be repaired in layers with sutures that are resorbable. ### Primary teeth[edit] Trauma to primary teeth occurs most commonly at the age of 2 to 3 years, during the development of motor coordination.[7] When primary teeth are injured, the resulting treatment prioritises the safety of the adult tooth,[7] and should avoid any risk of damaging the permanent successors.[8] This is because the root apex of an injured primary tooth lies near the tooth germ of the adult tooth.[8] Therefore, a displaced primary tooth will be removed if it is found to have encroached upon the developing adult tooth germ.[8] If this happens, parents should be advised of possible complications such as enamel hypoplasia, hypocalcification, crown/root dilaceration, or disruptions in tooth eruption sequence.[9] Potential sequelae can involve pulpal necrosis, pulp obliteration and root resorption.[10] Necrosis is the most common complication and an assessment is generally made based on the colour supplemented with radiograph monitoring. A change in colour may mean that the tooth is still vital but if this persists it is likely to be non-vital. ### Permanent teeth[edit] #### Dental Injuries[2][edit] Dental Injury Clinical Findings Radiographic Findings Treatment Follow-up 1) Enamel Infraction A crack in enamel with no loss of tooth structure Tooth is not tender No abnormalities Generally no treatment needed Discolouration of prominent cracks can be prevented by etching and sealing with resin No follow-up required 2) Enamel Fracture Fracture involving enamel only Tooth not tender with normal mobility and pulpal response Loss of enamel May need lip or cheek x-ray to locate tooth fragments or other materials If available, tooth fragment can be bonded back onto the tooth If not available, tooth can be restored with composite resin 6–8 weeks: clinical and radiographic examination 1 year: clinical and radiographic examination 3) Enamel-dentine Fracture Fracture involving both enamel and dentine without pulp exposure Tooth not tender with normal mobility and pulpal response Loss of enamel and dentine May need lip or cheek x-ray to locate tooth fragments or other materials If available, tooth fragment can be bonded back onto the tooth If not available, tooth can be restored with composite resin If dentine is within 0.5mm of the pulp, calcium hydroxide placed and covered with glass ionomer 6–8 weeks: clinical and radiographic examination 1 year: clinical and radiographic examination 4)Enamel-dentine-pulp Fracture Fracture involving enamel and dentine with pulp exposure Tooth not tender with normal mobility Exposed pulp will be sensitive to stimuli Loss of enamel and dentine May need lip or cheek x-ray to locate tooth fragments or other materials In developing teeth, preserve pulp vitality by pulp capping or partial pulpotomy using calcium hydroxide In mature teeth, root canal treatment is usually performed 6–8 weeks: clinical and radiographic examination 1 year: clinical and radiographic examination 5)Crown-root fracture without Pulp Involvement Fracture involving enamel, dentine and cementum without pulp exposure Fracture extends below the gum margin Tender tooth with mobile crown fragment Fracture line extending down the root may not be visible Emergency: aim is to stabilise the loose fragment by splinting it to adjacent teeth Non-emergency: removal of loose fragment (following gingivectomy, surgery or via orthodontics), root canal treatment and restoration with post-retained crown In extreme cases (such as a vertical fracture), tooth may need to be extracted 6–8 weeks: clinical and radiographic examination 1 year: clinical and radiographic examination 6) Crown-root fracture with Pulp Involvement Fracture involving enamel, dentine and cementum with pulp exposure Tender tooth with mobile crown fragment Fracture line extending down the root may not be visible Emergency: aim is to stabilise the loose fragment by splinting it to adjacent teeth In developing teeth, preserve pulp vitality by pulp capping or partial pulpotomy using calcium hydroxide In mature teeth, root canal treatment is usually performed Non-emergency: removal of loose fragment (following gingivectomy, surgery or via orthodontics), root canal treatment and restoration with post-retained crown In extreme cases (such as a vertical fracture), tooth may need to be extracted 6–8 weeks: clinical and radiographic examination 1 year: clinical and radiographic examination 7) Root Fracture Mobile or displaced crown segment Tender tooth that may be bleeding from the gum Tooth may be discoloured (red or grey) Fracture line involving the root will be seen as well as the direction If displaced, reposition tooth and check the position with an x-ray Flexible splint used to stabilise tooth for at least 4 weeks and then reassess tooth stability Monitor healing for at least 1 year to assess the status of the pulp Root canal treatment will be needed if pulp necrosis develops (this occurs in ~20% of root fractures²) 4 weeks: splint removal, clinical and radiographic examination 6–8 weeks: clinical and radiographic examination 4 months: splint removal in cervical third fractures, clinical and radiographic examination 6 months: clinical and radiographic examination 1 year: clinical and radiographic examination 5 years: clinical and radiographic examination #### Periodontal Injuries[2][edit] Periodontal Injury Clinical Findings Radiographic Findings Treatment Follow-up 1) Concussion Tender tooth with no displacement and normal mobility No abnormalities No treatment required 4 weeks: clinical and radiographic examination 6–8 weeks: clinical and radiographic examination 1 year: clinical and radiographic examination 2) Subluxation Tender tooth with no displacement but increased mobility May be bleeding from the gum No abnormalities Usually no treatment required Can use a flexible splint to stabilise the tooth for up to 2 weeks 2 weeks: splint removal, clinical and radiographic examination 4 weeks: clinical and radiographic examination 6–8 weeks: clinical and radiographic examination 6 months: clinical and radiographic examination 1 year: clinical and radiographic examination 3) Extrusion Tooth looks longer and is very mobile Periodontal ligament space is increased apically Tooth is repositioned gently in the socket Tooth stabilised with a flexible splint for 2 weeks Signs and symptoms of pulp necrosis indicates the need for root canal treatment to prevent root resorption 2 weeks: splint removal, clinical and radiographic examination 4 weeks: clinical and radiographic examination 6–8 weeks: clinical and radiographic examination 6 months: clinical and radiographic examination 1 year: clinical and radiographic examination yearly 5 years: clinical and radiographic examination 4) Lateral Luxation Tooth is displaced, most commonly towards roof of mouth/tongue or the lip Tooth will be immobile Tapping on the tooth will give a high-pitched, metallic (ankylotic) sound Alveolar process fracture Periodontal ligament space is widened Reposition the tooth using fingers or forceps to remove its “bony lock” and gently reposition it in the socket Tooth stabilised with a flexible splint for 4 weeks Signs and symptoms of pulp necrosis indicates the need for root canal treatment to prevent root resorption 2 weeks: clinical and radiographic examination 4 weeks: splint removal, clinical and radiographic examination 6–8 weeks: clinical and radiographic examination 6 months: clinical and radiographic examination 1 year: clinical and radiographic examination Yearly for 5 years: clinical and radiographic examination 5) Intrusion Tooth is displaced into the alveolar bone Tapping on the tooth will give a high-pitched, metallic (ankylotic) sound Absence of periodontal ligament space from part or entirety of the root Cemento-enamel junction appears more apically for the traumatised tooth If incomplete root formation: allow time for tooth to naturally erupt but if no movement after a few weeks then start orthodontic repositioning intruded >7mm: surgical or orthodontic repositioning stabilise with flexible splint for 4 weeks after repositioning If complete root formation: intruded <3mm: allow time for natural eruption but if no movement after 2–4 weeks then reposition surgically or orthodontically intruded 3-7mm: surgical or orthodontic repositioning intruded >7mm: surgical repositioning likelihood of pulpal necrosis in these teeth so root canal therapy with temporary calcium hydroxide filling in first instance and start root canal treatment 2–3 weeks after repositioning stabilise with flexible splint for 4 weeks after repositioning 2 weeks: clinical and radiographic examination 4 weeks: splint removal, clinical and radiographic examination 6–8 weeks: clinical and radiographic examination 6 months: clinical and radiographic examination 1 year: clinical and radiographic examination Yearly for 5 years: clinical and radiographic examination 6) Avulsion Tooth completely removed from socket Radiograph required to ensure that missing tooth is not intruded For information on first aid procedures for avulsed teeth, see “Management” section of this page Treatment will depend on whether the tooth has an open or closed apex and how long the tooth has been out of the mouth prior to dental clinic arrival (see Dental Trauma Guide for full treatment details) 4 weeks: splint removal, clinical and radiographic examination 3 months: clinical and radiographic examination 6 months: clinical and radiographic examination 1 year: clinical and radiographic examination yearly ## Risk factors[edit] * Age, especially young children[8][9][11] 1. Primary dentition stage (2–3 years old, when children's motor function is developing and start learning how to walk/ run) 2. Mixed dentition stage (8–10 years old) 3. Permanent dentition stage (13–15 years old) * Male > Female [11][12] * Season (Many trauma incidents occur more in summer compared to winter)[13] * Sports, especially contact sports such as football, hockey, rugby, basketball and skating [14] * Piercing in tongue and lips[15] * Military training[16][17] * Acute changes in the barometric pressure, i.e. dental barotrauma,[18] which can affect scuba divers[19] and aviators[20] * Class II malocclusion with increased overjet and Class II skeletal relationship [21][22] and incompetent lips[23] are the significant risk factors ## Prevention[edit] Prevention in general is relatively difficult as it's nearly impossible to stop accidents from happening, especially in children who are quite active. Regular use of a gum shield during sports and other high-risk activities (such as military training) is the most effective prevention for dental trauma.[24][25] They are mainly being fitted on the upper teeth as it has higher risk of dental trauma compared to the lower teeth. Gum shields ideally have to be comfortable for users, retentive, odourless, tasteless and the materials should not be causing any harm to the body.[26] However, studies in various high-risk populations for dental injuries have repeatedly reported low compliance of individuals for the regular using of mouthguard during activities.[27] Moreover, even with regular use, effectiveness of prevention of dental injuries is not complete, and injuries can still occur even when mouthguards are used as users are not always aware of the best makes or size, which inevitably result in a poor fit.[16] Types of gum shield[26][28] * Stock ready-moulded * Not recommended as it does not conform the teeth at all * Poor retention * Poor fit * Higher risk of dislodging during contact sports and airway occlusion which may lead to respiratory distress * Self-moulded/ Boil and bite * Limited range of sizes, which may result in poor fitting * Can be easily remoulded if distorted * Cheap * Custom-made * Made with ethylene vinyl acetate * The most ideal type of gum shield [29] * Good retention * Able to build in multiple layers/ laminations * Expensive One of the most important measures is to impart knowledge and awareness about dental injury to those who are involved in sports environments like boxing and in school children in which they are at high risk of suffering dental trauma through an extensive educational campaign including lectures, leaflets, posters which should be presented in an easy understandable way.[30] ## Management[edit] The management depends on the type of injury involved and whether it is a baby or an adult tooth. If teeth are completely knocked out baby front teeth should not be replaced. The area should be cleaned gently and the child brought to see a dentist. Adult front teeth (which usually erupt at around 6 years of age) can be replaced immediately if clean. See below and the Dental Trauma Guide website for more details. If a tooth is avulsed, make sure it is a permanent tooth (primary teeth should not be replanted, and instead the injury site should be cleaned to allow the adult tooth to begin to erupt). * Reassure the patient and keep them calm. * If the tooth can be found, pick it up by the crown (the white part). Avoid touching the root part. * If the tooth is dirty, wash it briefly (10 seconds) under cold running water but do not scrub the tooth. * Place the tooth back in the socket where it was lost from, taking care to place it the correct way (matching the other tooth) * Encourage the patient to bite on a handkerchief to hold the tooth in position. * If it is not possible to replace the tooth immediately, ideally, the tooth should be placed in Hank's balanced salt solution,[31] if not available, in a glass of milk or a container with the patient's saliva or in the patient's cheek (keeping it between the teeth and the inside of the cheek - note this is not suitable for young children who may swallow the tooth). Transporting the tooth in water is not recommended, as this will damage the delicate cells that make up the tooth's interior. * Seek emergency dental treatment immediately. When the injured teeth are painful while functioning due to damage to the periodontal ligaments (e.g., dental subluxation), a temporary splinting of the injured teeth may relieve the pain and enhance eating ability.[32] Splinting should only be used in certain situations. Splinting in lateral and extrusive luxation had a poorer prognosis than in root fractures.[33] An avulsed permanent tooth should be gently rinsed under tap water and immediately re-planted in its original socket within the alveolar bone and later temporarily splinted by a dentist.[4] Failure to re-plant the avulsed tooth within the first 40 minutes after the injury may result in very poor prognosis for the tooth.[4] Management of injured primary teeth differs from management of permanent teeth; an avulsed primary tooth should not be re-planted (to avoid damage to the permanent dental crypt).[8] This is due to the close proximity of the apex of a primary tooth to the permanent tooth underneath. The permanent dentition can suffer from tooth malformation, impacted teeth and eruption disturbances due to trauma to primary teeth. The priority should always be reducing potential damage to the underlying permanent dentition.[34] For other injuries, it is important to keep the area clean - by using a soft toothbrush and antiseptic mouthwash such as chlorhexidine gluconate. Soft foods and avoidance of contact sports it also recommended in the short term. Dental care should be sought as quickly as possible. ### Splinting[edit] A tooth that has experienced trauma may become loose due to the periodontal ligament becoming damaged or fracture to the root of the tooth. Splinting ensures that the tooth is held in the correct position within the socket, ensuring that no further trauma occurs to enable healing.[35] A splint can either be flexible or rigid. Flexible splints do not completely immobilise the traumatised tooth and still allow for functional movement. Contrastingly, rigid splints completely immobilise the traumatised tooth.[36] The International Association of Dental Traumatology (IADT) guidelines recommend the use of flexible, non-rigid splints for a short duration by stating that both periodontal and pulpal healing is encouraged if the traumatised tooth is allowed slight movement and if the splinting time is not too long.[37][38] ## Complications[edit] Not all sequelae of trauma are immediate and many of them can occur months or years after the initial incident thus required prolonged follow-up. Common complications are pulpal necrosis, pulpal obliteration, root resorption and damage to the successors teeth in primary teeth dental trauma. The most common complication was pulp necrosis (34.2%). 50% of the tooth that have trauma related to avulsion experienced ankylotic root resorption after a median TIC (time elapsed between the traumatic event and the diagnosis of complications) of 1.18 years. Teeth that have multiple traumatic events also showed to have higher chance of pulp necrosis (61.9%) compared to teeth that experienced a single traumatic injury (25.3%) in the studies (1)[39] Image shows a grey discoloured upper right front incisor, usually indicating that the tooth is non-vital ### Pulpal necrosis[edit] Pulp necrosis usually occurs either as ischaemic necrosis (infarction) caused by disruption to the blood supply at the apical foramen or as an infection-related liquefactive necrosis following dental trauma (2). Signs of pulpal necrosis include[40] * Persistent grey colour to tooth that does not fade * Radiographic signs of periapical inflammation * Clinical signs of infection: tenderness, sinus, suppuration, swelling Treatment options will be extraction for the primary tooth. For the permanent tooth, endodontic treatment can be considered. Radiographic signs of periapical inflammation is usually evident in a tooth with necrotic pulp ### Root resorption[edit] Root resorption following traumatic dental injuries, whether located along the root surface or within the root canal appears to be a sequel to wound healing events, where a significant amount of the PDL or pulp has been lost due to the effect of acute trauma.[41] ### Pulpal obliteration[edit] 4-24% of traumatized teeth will have some degrees of pulpal obliteration that is characterized by the loss of pulpal space radiographically and yellow discolouration of the clinical crown. No treatment is needed if it is asymptomatic. Treatment options will be extraction for symptomatic primary tooth. For symptomatic permanent tooth, root canal treatment is often challenging due to pulp chamber is filled with calcified material and the ‘drop off’ sensation of entering a pulp chamber will not occur.[42] ### Damage to the successor teeth[edit] Dental trauma to the primary teeth might cause damage to the permanent teeth. Damage to the permanent teeth especially during development stage might have following consequences:[43] * Crown dilaceration * Odontoma-like malformation * Sequestration of permanent tooth germs * Root dilaceration * Arrest of root formation ## Epidemiology[edit] Dental trauma is most common in younger people, accounting for 17% of injuries to the body in those aged 0–6 years compared to an average of 5% across all ages.[44] It is more frequently observed in males compared to females.[45] Traumatic dental injuries are more common in permanent teeth compared to deciduous teeth and usually involve the front teeth of the upper jaw.[46] "The oral region comprises 1% of the total body area, yet it accounts for 5% of all bodily injuries. In preschool children, oral injuries make up as much as 17% of all bodily injuries. The incidence of traumatic dental injuries is 1%–3%, and the prevalence is steady at 20%–30%.”[47] Almost 30% of the children in pre-school have mostly experienced trauma to primary teeth. Dental injuries involving the permanent teeth happen to almost 25% of children in school and 30% of adults. The incident varies in different countries as well as within the country itself. Dental traumatic accidents depends on one's activity status and also the surrounding environment factor but these are the main predisposing risk factor compared to a person's age and gender.[48] Trauma is the most common cause of loss of permanent incisors in childhood. Dental trauma often lead to the main complication such as pulpal necrosis, and it's nearly impossible to predict the long-term prognosis of the injured tooth and often results in long term restorative problems.[49][50][51] ## See also[edit] * Medicine portal * Dental barotrauma * Cracked tooth syndrome ## References[edit] 1. ^ Textbook and Color Atlas of Traumatic Injuries to the Teeth, Fourth Edition, edited by Andreason J, Andreasen F, and Andersson L, Wiley-Blackwell, Oxford, UK, 2007 2. ^ a b c "Permanent teeth – Dental Trauma Guide". Retrieved 2019-01-20. 3. ^ "Primary teeth – Dental Trauma Guide". Retrieved 2019-01-20. 4. ^ a b c Flores MT, Andersson L, Andreasen JO, Bakland LK, Malmgren B, Barnett F, Bourguignon C, DiAngelis A, Hicks L, Sigurdsson A, Trope M, Tsukiboshi M, von Arx T (June 2007). "Guidelines for the management of traumatic dental injuries. II. Avulsion of permanent teeth". Dental Traumatology. 23 (3): 130–6. doi:10.1111/j.1600-9657.2007.00605.x. PMID 17511833. 5. ^ a b Tagar H, Djemal S (September 2017). "Oral surgery II: Part 1. Acute management of dentoalveolar trauma". British Dental Journal. 223 (6): 407–416. doi:10.1038/sj.bdj.2017.805. PMID 28937097. 6. ^ a b Durham J, Moore UJ, Hill CM, Renton T (December 2017). "Oral surgery II: Part 6. Oral and maxillofacial trauma". British Dental Journal. 223 (12): 877–883. doi:10.1038/sj.bdj.2017.995. PMID 29269898. 7. ^ a b Flores, Marie Therese (2002). "Traumatic injuries in the primary dentition". Dental Traumatology. 18 (6): 287–298. doi:10.1034/j.1600-9657.2002.00153.x. ISSN 1600-4469. PMID 12656861. 8. ^ a b c d e Flores MT, Malmgren B, Andersson L, Andreasen JO, Bakland LK, Barnett F, Bourguignon C, DiAngelis A, Hicks L, Sigurdsson A, Trope M, Tsukiboshi M, von Arx T (August 2007). "Guidelines for the management of traumatic dental injuries. III. Primary teeth". Dental Traumatology. 23 (4): 196–202. doi:10.1111/j.1600-9657.2007.00627.x. PMID 17635351. 9. ^ a b "Guideline on Management of Acute Dental Trauma" (PDF). Council on Clinical Affairs. 2011. 10. ^ Welbury RR, Duggal MS, Hosey MT, eds. (2007). Paediatric Dentistry (Third ed.). Oxford, UK: Oxford University Press. ISBN 978-0071445085. 11. ^ a b Jesus MA, Antunes LA, Risso P, Freire MV, Maia LC (January 2010). "Epidemiologic survey of traumatic dental injuries in children seen at the Federal University of Rio de Janeiro, Brazil". Brazilian Oral Research. 24 (1): 89–94. doi:10.1590/S1806-83242010000100015. PMID 20339720. 12. ^ Ivancic Jokic N, Bakarcic D, Fugosic V, Majstorovic M, Skrinjaric I (February 2009). "Dental trauma in children and young adults visiting a University Dental Clinic". Dental Traumatology. 25 (1): 84–7. doi:10.1111/j.1600-9657.2008.00711.x. PMID 19208016. 13. ^ Perez R, Berkowitz R, McIlveen L, Forrester D (October 1991). "Dental trauma in children: a survey". Endodontics & Dental Traumatology. 7 (5): 212–3. doi:10.1111/j.1600-9657.1991.tb00438.x. PMID 1687388. 14. ^ Young EJ, Macias CR, Stephens L (May 2015). "Common Dental Injury Management in Athletes". Sports Health. 7 (3): 250–5. doi:10.1177/1941738113486077. PMC 4482297. PMID 26131303. 15. ^ Levin L, Zadik Y, Becker T (December 2005). "Oral and dental complications of intra-oral piercing". Dental Traumatology. 21 (6): 341–3. doi:10.1111/j.1600-9657.2005.00395.x. PMID 16262620. 16. ^ a b Zadik Y, Levin L (December 2008). "Orofacial injuries and mouth guard use in elite commando fighters". Military Medicine. 173 (12): 1185–7. doi:10.7205/milmed.173.12.1185. PMID 19149336. 17. ^ Zadik Y, Levin L (February 2009). "Oral and facial trauma among paratroopers in the Israel Defense Forces". Dental Traumatology. 25 (1): 100–2. doi:10.1111/j.1600-9657.2008.00719.x. PMID 19208020. 18. ^ Zadik Y (Jul–Aug 2009). "Dental barotrauma". The International Journal of Prosthodontics. 22 (4): 354–7. PMID 19639071. 19. ^ Zadik Y, Drucker S (September 2011). "Diving dentistry: a review of the dental implications of scuba diving". Australian Dental Journal. 56 (3): 265–71. doi:10.1111/j.1834-7819.2011.01340.x. PMID 21884141. 20. ^ Zadik Y (January 2009). "Aviation dentistry: current concepts and practice". British Dental Journal. 206 (1): 11–6. doi:10.1038/sj.bdj.2008.1121. PMID 19132029. 21. ^ Borzabadi-Farahani A, Borzabadi-Farahani A (December 2011). "The association between orthodontic treatment need and maxillary incisor trauma, a retrospective clinical study". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 112 (6): e75–80. doi:10.1016/j.tripleo.2011.05.024. PMID 21880516. 22. ^ Borzabadi-Farahani A, Borzabadi-Farahani A, Eslamipour F (October 2010). "An investigation into the association between facial profile and maxillary incisor trauma, a clinical non-radiographic study". Dental Traumatology. 26 (5): 403–8. doi:10.1111/j.1600-9657.2010.00920.x. PMID 20831636. 23. ^ Otuyemi OD (June 1994). "Traumatic anterior dental injuries related to incisor overjet and lip competence in 12-year-old Nigerian children". International Journal of Paediatric Dentistry. 4 (2): 81–5. doi:10.1111/j.1365-263X.1994.tb00109.x. PMID 7748855. 24. ^ Zadik Y, Levin L (February 2009). "Does a free-of-charge distribution of boil-and-bite mouthguards to young adult amateur sportsmen affect oral and facial trauma?". Dental Traumatology. 25 (1): 69–72. doi:10.1111/j.1600-9657.2008.00708.x. PMID 19208013. 25. ^ McCrory, Paul (2001-04-01). "Do mouthguards prevent concussion?". British Journal of Sports Medicine. 35 (2): 81–82. doi:10.1136/bjsm.35.2.81. ISSN 0306-3674. PMC 1724314. PMID 11273965. 26. ^ a b Jennings, D C (September 1990). "Injuries sustained by users and non-users of gum shields in local rugby union". British Journal of Sports Medicine. 24 (3): 159–165. doi:10.1136/bjsm.24.3.159. ISSN 0306-3674. PMC 1478784. PMID 2078800. 27. ^ Zadik Y, Jeffet U, Levin L (December 2010). "Prevention of dental trauma in a high-risk military population: the discrepancy between knowledge and willingness to comply". Military Medicine. 175 (12): 1000–3. doi:10.7205/MILMED-D-10-00150. PMID 21265309. 28. ^ Patrick DG, van Noort R, Found MS (May 2005). "Scale of protection and the various types of sports mouthguard". British Journal of Sports Medicine. 39 (5): 278–81. doi:10.1136/bjsm.2004.012658. PMC 1725211. PMID 15849291. 29. ^ Kerr, I. L. (November 1986). "Mouth guards for the prevention of injuries in contact sports". Sports Medicine (Auckland, N.Z.). 3 (6): 415–427. doi:10.2165/00007256-198603060-00003. ISSN 0112-1642. PMID 3538271. 30. ^ Emerich K, Nadolska-Gazda E (July 2013). "Dental trauma, prevention and knowledge concerning dental first-aid among Polish amateur boxers". Journal of Science and Medicine in Sport. 16 (4): 297–301. doi:10.1016/j.jsams.2012.10.002. PMID 23146163. 31. ^ Adnan S, Lone MM, Khan FR, Hussain SM, Nagi SE (April 2018). "Which is the most recommended medium for the storage and transport of avulsed teeth? A systematic review". Dental Traumatology. 34 (2): 59–70. doi:10.1111/edt.12382. PMID 29292570. 32. ^ Flores MT, Andersson L, Andreasen JO, Bakland LK, Malmgren B, Barnett F, Bourguignon C, DiAngelis A, Hicks L, Sigurdsson A, Trope M, Tsukiboshi M, von Arx T (April 2007). "Guidelines for the management of traumatic dental injuries. I. Fractures and luxations of permanent teeth". Dental Traumatology. 23 (2): 66–71. doi:10.1111/j.1600-9657.2007.00592.x. PMID 17367451. 33. ^ Cho WC, Nam OH, Kim MS, Lee HS, Choi SC (May 2018). "A retrospective study of traumatic dental injuries in primary dentition: treatment outcomes of splinting". Acta Odontologica Scandinavica. 76 (4): 253–256. doi:10.1080/00016357.2017.1414956. PMID 29228861. 34. ^ Malmgren B, Andreasen JO, Flores MT, Robertson A, DiAngelis AJ, Andersson L, Cavalleri G, Cohenca N, Day P, Hicks ML, Malmgren O, Moule AJ, Onetto J, Tsukiboshi M (September 2017). "Guidelines for the Management of Traumatic Dental Injuries: 3. Injuries in the Primary Dentition". Pediatric Dentistry. 39 (6): 420–428. doi:10.1111/j.1600-9657.2012.01146.x. PMID 29179384. 35. ^ WELBURY R., DUGGAL M.S. and HOSEY M.T. (2012) Paediatric Dentistry. 4th ed. Chapter 12: Traumatic Injuries to the Teeth. Oxford University Press. Pages 237,238 36. ^ KAHLER B., HU J.Y., MARRIOT-SMITH C.S. and HEITHERSAY G.S. (2016). Splinting of teeth following trauma: a review and a new splinting recommendation. Australian Dental Journal. 61(1): 59-73 37. ^ DIANGELIS A.J., ANDREASEN J.O., EBELESEDER K.A., KENNY D.J., TROPE M., SIGURDSSON A., ANDERSSON L., BOURGUIGNON C., FLORES M.T., HICKS M.L., LENZI A.R., MALMGREN B., MOULE A.J., POHL Y. and TSUKIBOSHI M. (2012). International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: 1. Fractures and luxations of permanent teeth. Dental Traumatology. 28: 2-12. 38. ^ ANDRESSON L., ANDREASEN J.O., DAY P., HEITHERSAY G., TROPE M., DIANGELIS A.J., KENNY D.J., SIGURDSSON A., BOURGUIGNON C., FLORES M.T., HICKS M.L., LENZI A.R., MALMGREN B., MOULE A.J. and TSUKIBOSHI M. (2012). International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: 2. Avulsion of permanent teeth. Dental Traumatology. 28(2): 88-96. 39. ^ Lin S, Pilosof N, Karawani M, Wigler R, Kaufman AY, Teich ST (October 2016). "Occurrence and timing of complications following traumatic dental injuries: A retrospective study in a dental trauma department". Journal of Clinical and Experimental Dentistry. 8 (4): e429–e436. doi:10.4317/jced.53022. PMC 5045691. PMID 27703612. 40. ^ Love RM (May 1997). "Effects of dental trauma on the pulp". Practical Periodontics and Aesthetic Dentistry : PPAD. 9 (4): 427–36, quiz 438. PMID 9550069. 41. ^ Andreasen JO, Andreasen FM (1992). "Root resorption following traumatic dental injuries". Proceedings of the Finnish Dental Society. Suomen Hammaslaakariseuran Toimituksia. 88 Suppl 1: 95–114. PMID 1354871. 42. ^ McCabe PS, Dummer PM (February 2012). "Pulp canal obliteration: an endodontic diagnosis and treatment challenge". International Endodontic Journal. 45 (2): 177–97. doi:10.1111/j.1365-2591.2011.01963.x. PMID 21999441. 43. ^ Mahesh R, Kanimozhi IG, Sivakumar M (May 2014). "Dilaceration and Eruption Disturbances in Permanent Teeth: A Sequelae of Trauma to Their Predecessors-Diagnosis and Treatment Using Cone Beam CT". Journal of Clinical and Diagnostic Research. 8 (5): ZD10–2. doi:10.7860/JCDR/2014/6657.4342. PMC 4080075. PMID 24995254. 44. ^ Zaleckiene V, Peciuliene V, Brukiene V, Drukteinis S (2014). "Traumatic dental injuries: etiology, prevalence and possible outcomes". Stomatologija. 16 (1): 7–14. PMID 24824054. 45. ^ Kania MJ, Keeling SD, McGorray SP, Wheeler TT, King GJ (1996). "Risk factors associated with incisor injury in elementary school children". The Angle Orthodontist. 66 (6): 423–32. doi:10.2319/110109-612.1. PMID 8974178. 46. ^ Granville-Garcia AF, de Menezes VA, de Lira PI (December 2006). "Dental trauma and associated factors in Brazilian preschoolers". Dental Traumatology. 22 (6): 318–22. doi:10.1111/j.1600-9657.2005.00390.x. PMID 17073924. 47. ^ Andersson L (March 2013). "Epidemiology of traumatic dental injuries". Journal of Endodontics. 39 (3 Suppl): S2–5. doi:10.1016/j.joen.2012.11.021. PMID 23439040. 48. ^ Glendor U (December 2008). "Epidemiology of traumatic dental injuries--a 12 year review of the literature". Dental Traumatology. 24 (6): 603–11. doi:10.1111/j.1600-9657.2008.00696.x. PMID 19021651. 49. ^ Marcenes W, al Beiruti N, Tayfour D, Issa S (June 1999). "Epidemiology of traumatic injuries to the permanent incisors of 9-12-year-old schoolchildren in Damascus, Syria". Endodontics & Dental Traumatology. 15 (3): 117–23. doi:10.1111/j.1600-9657.1999.tb00767.x. PMID 10530154. 50. ^ Naidoo S, Sheiham A, Tsakos G (April 2009). "Traumatic dental injuries of permanent incisors in 11- to 13-year-old South African schoolchildren". Dental Traumatology. 25 (2): 224–8. doi:10.1111/j.1600-9657.2008.00749.x. PMID 19290905. 51. ^ Andreasen FM (May 2001). "Pulpal healing following acute dental trauma: clinical and radiographic review". Practical Procedures & Aesthetic Dentistry. 13 (4): 315–22, quiz 324. PMID 11402773. ## External links[edit] * Dental Trauma Guide, an interactive tool for evidence based dental trauma treatment * International Association Of Dental Traumatology * 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Dental trauma	c0242891	29,093	wikipedia	https://en.wikipedia.org/wiki/Dental_trauma	2021-01-18T19:00:19	{"mesh": ["D018677"], "wikidata": ["Q2346266"]}
Craniofaciofrontodigital syndrome is a rare multiple congenital anomalies syndrome characterized by mild intellectual disability, short stature, cardiac anomalies, mild dysmorphic features (macrocephaly, prominent forehead, hypertelorism, exophthalmos), cutis laxa, joint hyperlaxity, wrinkled palms and soles and skeletal anomalies (sella turcica, wide ribs and small vertebral bodies). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Craniofaciofrontodigital syndrome	c2676032	29,094	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363705	2021-01-23T18:56:14	{"mesh": ["C567298"], "omim": ["114620"], "umls": ["C2676032"], "icd-10": ["Q87.0"], "synonyms": ["Cantu craniofaciofrontodigital syndrome"]}
Pruritus ani SpecialtyDermatology Pruritus ani is the irritation of the skin at the exit of the rectum, known as the anus, causing the desire to scratch.[1] The intensity of anal itching increases from moisture,[2] pressure, and rubbing caused by clothing and sitting. At worst, anal itching causes intolerable discomfort that often is accompanied by burning and soreness. It is estimated that up to 5% of the population of the United States experiences this type of discomfort daily. ## Contents * 1 Causes * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 External links ## Causes[edit] If a specific cause for pruritus ani is found it is classified as "secondary pruritus ani". If a specific cause is not found it is classified as "idiopathic pruritus ani".[3] The irritation can be caused by intestinal parasites, anal perspiration, frequent liquid stools, diarrhea, residual stool deposits, or the escape of small amounts of stool as a result of incontinence or flatulence. Another cause is yeast infection or candidiasis. Some diseases increase the possibility of yeast infections, such as diabetes mellitus or HIV infection. Treatment with antibiotics can bring about a disturbance of the natural balance of intestinal flora, and lead to perianal thrush, a yeast infection affecting the anus. Psoriasis also can be present in the anal area and cause irritation. Abnormal passageways (fistulas) from the small intestine or colon to the skin surrounding the anus can form as a result of disease (such as Crohn's disease), acting as channels which may allow leakage of irritating fluids to the anal area. Other problems that can contribute to anal itching include pinworms, hemorrhoids, tears of the anal skin near the mucocutaneous junction (fissures), and skin tags (abnormal local growth of anal skin). Aside from diseases relative to the condition, a common view suggests that the initial cause of the itch may have passed, and that the illness is in fact prolonged by what is known as an itch-scratch-itch cycle.[4][5] It states that scratching the itch encourages the release of inflammatory chemicals, which worsen redness, intensifies itchiness and increases the area covered by dry skin, thereby causing a snowball effect. Some authorities describe “psychogenic pruritus” or "functional itch disorder",[6] where psychological factors may contribute to awareness of itching. Ingestion of pinworm eggs leads to enterobiasis, indicative of severe itching around the anus from migration of gravid females from the bowel. Severe cases of enterobiasis result in hemorrhage and eczema. ## Diagnosis[edit] Diagnosis is usually done with a careful examination of the anus and the patient's history. If the presentation or physical findings are atypical, biopsies can be done.[7] In case of long-lasting symptoms, above all in patients over 50 years of age, a colonoscopy is useful to rule out a colonic polyp or tumor, that can show pruritus ani as first symptom.[8] ## Treatment[edit] The goal of treatment is asymptomatic, intact, dry, clean perianal skin with reversal of morphological changes. For pruritus ani of unknown cause (idiopathic pruritus ani)[3] treatment typically begins with measures to reduce irritation and trauma to the perianal area.[9] Stool softeners can help prevent constipation.[9] If this is not effective topical steroids or injected methylene blue may be tried. Another treatment option that has been met with success in small-scale trials is the application of a very mild (.006) topical capsaicin cream.[10] This strength cream is not typically commercially available and therefore must be diluted by a pharmacist or end-user. If the itchiness is secondary to another condition such as infection or psoriasis these are typically treated.[9] A successful treatment option for chronic idiopathic pruritus ani has been documented using a clean, dry and apply (if necessary) method. The person is instructed to follow this procedure every time the urge to scratch occurs. The treatment makes the assumption that there is an unidentified bacteria in the feces that causes irritation and itching when the feces makes contact with the anal and perianal skin during defecation, flatulation or anal leakage (particularly during sleep). Cleaning the area with warm water, avoiding all soaps and even baby wipes, then drying the area, ideally with a hair dryer to avoid irritation or failing that simply patting gently with a clean, dry, towel. If persons with pruritus ani do not need to scratch after these steps they are instructed to do nothing else. If the urge to scratch is still present they are instructed to apply a topical steroid cream which has antibiotic and antifungal properties. This will address a skin condition which may have become infected. Apply such a cream as directed by your medical professional but usually twice a day for one to two weeks. After this, they must maintain their clean and dry regime and apply an emollient ointment (not cream) to moisturize the skin. This should be applied after each bowel movement and at night. Continue until no longer needed. At any time, persons may use antihistamine treatments orally, to control the itching.[citation needed] ## See also[edit] * Pruritus scroti * Pruritus vulvae * Perianal candidiasis ## 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.[page needed] 2. ^ "Pruritus Ani". American Society of Colon & Rectal Surgeons. 2008. Archived from the original on March 21, 2008. 3. ^ a b Song, Seok-Gyu; Kim, Soung-Ho (2011). "Pruritus Ani". Journal of the Korean Society of Coloproctology. 27 (2): 54–57. doi:10.3393/jksc.2011.27.2.54. PMC 3092075. PMID 21602962. 4. ^ "Itchy skin". NHS. 19 January 2018. 5. ^ Pfenninger JL, Zainea GG (June 2001). "Common anorectal conditions: Part I. Symptoms and complaints". American Family Physician. 63 (12): 2391–8. PMID 11430454. 6. ^ Misery L, Alexandre S, Dutray S, et al. (2007). "Functional itch disorder or psychogenic pruritus: suggested diagnosis criteria from the French psychodermatology group". Acta Dermato-venereologica. 87 (4): 341–4. doi:10.2340/00015555-0266. PMID 17598038. 7. ^ Ansari P (2016). "Pruritus Ani". Clin Colon Rectal Surg. PMID 26929750. 8. ^ Pata, Francesco (2017). "Pruritus ani: the neglected stepchild of Coloproctology" (PDF). Società Italiana di Chirurgia Colo Rettale. 45: 383–395. 9. ^ a b c Markell KW, Billingham RP (February 2010). "Pruritus ani: etiology and management". The Surgical Clinics of North America. 90 (1): 125–35, Table of Contents. doi:10.1016/j.suc.2009.09.007. PMID 20109637. 10. ^ Lysy J, Sistiery-Ittah M, Israelit Y, et al. (September 2003). "Topical capsaicin--a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study". Gut. 52 (9): 1323–6. doi:10.1136/gut.52.9.1323. PMC 1773800. PMID 12912865. ## External links[edit] * Siddiqi, S; Vijay, V; Ward, M; Mahendran, R; Warren, S (2008). "Pruritus Ani". Annals of the Royal College of Surgeons of England. 90 (6): 457–463. doi:10.1308/003588408X317940. PMC 2647235. PMID 18765023. Classification D * ICD-10: L29.0 * ICD-9-CM: 698.0 * MeSH: D011538 * DiseasesDB: 30154 * 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 * 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Pruritus ani	c0033775	29,095	wikipedia	https://en.wikipedia.org/wiki/Pruritus_ani	2021-01-18T18:38:23	{"mesh": ["D011538"], "icd-9": ["698.0"], "icd-10": ["L29.0"], "wikidata": ["Q1633590"]}
Neutrophilic eccrine hidradenitis SpecialtyDermatology Neutrophilic eccrine hidradenitis (NEH) usually is a cutaneous complication of chemotherapy, but it can also occur for other reasons. It consists of fever and non specific skin lesions. It is rare, and self-limited.[1][2] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Fever and a non specific skin eruption – with reddening (erythema) and swelling (oedema) of the skin – are the most common symptoms of NEH. Patients usually present with the skin eruption 1-2 weeks after use of the cytotoxic drug. Sometimes, the skin eruption can be painful. Skin eruptions can be located on the extremities, trunk, and face. Severe lesions are rare, and can mimic cellulitis. Generalised lesions resembling erythema multiforme have been reported.[3] ## Cause[edit] The overwhelming majority of neutrophilic eccrine hidradenitis (NEH) is seen in people with cancer, especially leukaemia, who receive chemotherapy with a cytotoxic drug. These include: Bleomycin, chlorambucil, cyclophosphamide, cytarabine, doxorubicin, lomustine, mitoxantrone, topotecan, and vincristine.[4] NEH was first described in 1982 in a patient with acute myeloid leukaemia (AML) who had received cytarabine as chemotherapy.[5] Cancer itself, infections, and other medicinal drugs also can lead to NEH. NEH has been reported in patients with cancer who have not received any form of chemotherapy (i.e., as a paraneoplastic syndrome), in patients with HIV and/or AIDS, and after the use of paracetamol (acetaminophen). Also the use of targeted agents can lead to NEH, e.g. imatinib, a tyrosine kinase inhibitor.[6][7][8][9] NEH has also been described without any known reason (idiopathic cases), including idiopathic cases in children.[10][11] The exact cause of NEH is unknown. In patients receiving chemotherapy, it has been postulated that a high concentration of the cytotoxic drug in sweat has a direct toxic effect on the eccrine glands.[12] ## Diagnosis[edit] In all cases of suspected NEH, a skin biopsy should be performed, because the clinical symptoms are non specific, but the histopathological findings on the biopsy are specific. The biopsy shows characteristic changes of the eccrine glands, the major sweat glands of the body.[13] In NEH, eccrine gland necrosis, and neutrophils surroundings the eccrine glands, are typical findings on biopsy. If the chemotherapy has recently been administered, chemotherapy induced neutropenia may be present, and, as a result, the neutrophils may be absent. But the other characteristic finding, i.e. eccrine gland necrosis, can still be seen. A vacuolar interface dermatitis also is visible in glands and ducts, along with necrosis of the lining cells. In addition, in patients receiving chemotherapy, keratinocyte atypia can be seen.[14] ## Prevention[edit] A single case report suggested that oral dapsone may be useful for prevention. However, the efficacy of oral dapsone as prevention has not been demonstrated very clearly until now.[15] ## Treatment[edit] NEH is self-limited and usually resolves without treatment. In the overwhelming majority of the cases, spontaneous resolution occurs within 1–2 weeks. However, if the patient developed NEH after chemotherapy, the offending cytotoxic drug has to be discontinued, and the patient must avoid this particular cytotoxic drug in the future, because NEH usually re occurs upon re exposure to the same cytotoxic drug.[16] Despite the fact that NEH is self limited and usually resolves without treatment, some researchers use treatment, mainly systemic corticosteroids, although the efficacy of such a therapy has not been demonstrated in a large randomised controlled clinical trial until now.[17] ## See also[edit] * Skin lesion * List of cutaneous conditions ## 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. :780 2. ^ Neutrophilic eccrine hidradenitis. Bachmeyer C, Aractingi S. Clin Dermatol. 2000 May-Jun;18(3):319-30. 3. ^ Neutrophilic eccrine hidradenitis. Thorisdottir K, Tomecki KJ, Bergfeld WF, Andresen SW. J Am Acad Dermatol. 1993 May;28(5 Pt 1):775-7. 4. ^ Mucocutaneous reactions to chemotherapy. Susser WS, Whitaker-Worth DL, Grant-Kels JM. J Am Acad Dermatol. 1999;40(3):367-98. 5. ^ Neutrophilic eccrine hidradenitis. A distinctive type of neutrophilic dermatosis associated with myelogenous leukemia and chemotherapy. Harrist TJ, Fine JD, Berman RS, Murphy GF, Mihm MC Jr. Arch Dermatol. 1982;118(4):263-6. 6. ^ Unusual manifestations of acute leukemia. Case 2. Leukemia and rash: paraneoplastic or drug-induced? Blank C, Wagner HM, Hohenleutner U, Andreesen R. J Clin Oncol. 2000 Oct 1;18(19):3437-9. 7. ^ Neutrophilic eccrine hidradenitis: a case report and review of the literature. Bailey DL, Barron D, Lucky AW. Pediatr Dermatol. 1989;6(1):33-8. 8. ^ Neutrophilic eccrine hidradenitis: a case report and review of the literature. Margolis DJ, Gross PR. Cutis. 1991;48(3):198-200. 9. ^ Imatinib mesylate and dermatology part 2: a review of the cutaneous side effects of imatinib mesylate. Scheinfeld N. J Drugs Dermatol. 2006 Mar;5(3):228-31. 10. ^ Generalized idiopathic neutrophilic eccrine hidradenitis in childhood. Lee WJ, Kim CH, Chang SE, Lee MW, Choi JH, Moon KC, Koh JK. Int J Dermatol. 2010 Jan;49(1):75-8. 11. ^ Idiopathic palmoplantar eccrine hidradenitis in children. Ben-Amitai D, Hodak E, Landau M, Metzker A, Feinmesser M, David M. Eur J Pediatr. 2001 Mar;160(3):189-91. 12. ^ Neutrophilic eccrine hidradenitis: a distinctive rash associated with cytarabine therapy and acute leukemia. Flynn TC, Harrist TJ, Murphy GF, Loss RW, Moschella SL. J Am Acad Dermatol. 1984;11(4 Pt 1):584-90. 13. ^ Neutrophilic hidradenitis induced by chemotherapy involves eccrine and apocrine glands. Brehler R, Reimann S, Bonsmann G, Metze D. Am J Dermatopathol. 1997;19(1):73-8. 14. ^ Smoller BR, Horn TD. Chemotherapy-induced drug eruptions. In: Dermatopathology in systemic disease. Smoller BR, Horn TD (Eds). Oxford University Press. 2001. 15. ^ Dapsone in prevention of recurrent neutrophilic eccrine hidradenitis. Shear NH, Knowles SR, Shapiro L, Poldre P. J Am Acad Dermatol. 1996;35(5 Pt 2):819-22. 16. ^ Recurrent neutrophilic eccrine hidradenitis. Bernstein EF, Spielvogel RL, Topolsky DL. Br J Dermatol. 1992;127(5):529-33. 17. ^ Neutrophilic eccrine hidradenitis associated with Hodgkin’s disease and chemotherapy. A case report. Beutner KR, Packman CH, Markowitch W. Arch Dermatol. 1986;122(7):809-11. ## External links[edit] Classification D * MeSH: D016575 * SNOMED CT: 238754005 External resources * eMedicine: article/1070937 * 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]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Neutrophilic eccrine hidradenitis	c0162504	29,096	wikipedia	https://en.wikipedia.org/wiki/Neutrophilic_eccrine_hidradenitis	2021-01-18T18:54:57	{"mesh": ["D016575"], "wikidata": ["Q7003148"]}
Immunotactoid or fibrillary glomerulopathy is a term that includes two conditions: immunotactoid glomerulopathy and fibrillary glomerulonephritis, which are uncommon causes of glomerular disease. Most experts feel that fibrillary glomerulonephritis and immunotactoid glomerulopathy are separate disorders but they have many similarities and some experts group these disorders together. Fibrillary glomerulonephritis and immunotactoid glomerulopathy can be distinguished from each other by electron microscopy; the 'fibrils' that characterize fibrillary glomerulonephritis are smaller and randomly oriented as opposed to the larger and organized fibrils of immunotactoid glomerulopathy which also have microtubule formations. Both disorders probably result from deposits derived from immunoglobulins but in most cases the cause is idiopathic (unknown). The signs and symptoms are similar in both diseases and may include blood (hematuria) and protein (proteinuria) in the urine, kidney insufficiency and high blood pressure. Fibrillary glomeurlonephritis is much more common than immunotactoid glomerulopathy. Both fibrillary glomerulonephritis and immunotactoid glomerulopathy have been associated with hepatitis C virus infection and with malignancy and autoimmune disease, but immunotactoid glomerulopathy patients have a greater predisposition to chronic lymphocytic leukemia and B cell lymphomas. All patients should be screened for these conditions. It is also important to rule out another disease known as amyloidosis. When the fibrils are stained with an acid dye known as "Congo red" the results are negative. In amyloidosis the results are positive because the dye is absorbed by the amyloids. Treatment is generally determined by the severity of the kidney problems. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Immunotactoid or fibrillary glomerulopathy	None	29,097	gard	https://rarediseases.info.nih.gov/diseases/12741/immunotactoid-or-fibrillary-glomerulopathy	2021-01-18T17:59:47	{"orphanet": ["91137"], "synonyms": ["Immunotactoid or fibrillary glomerulopathy", "Fibrillary glomerulonephritis and immunotactoid glomerulopathy", "Immunotactoid or fibrillary glomerulonephritis"]}
Leukoencephalopathy-thalamus and brainstem anomalies-high lactate (LTBL) syndrome is a rare, genetic neurological disorder defined by early-onset of neurologic symptoms, biphasic clinical course, unique MRI features (incl. extensive, symmetrical, deep white matter abnormalities), and increased lactate in body fluids. The severe form is characterized by delayed psychomotor development, seizures, early-onset hypotonia, and persistently increased lactate levels. The mild form usually presents with irritability, psychomotor regression after six months of age, and temporary high lactate levels, with overall clinical improvement from the second year onward. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome	c3554079	29,098	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314051	2021-01-23T17:58:16	{"gard": ["12893"], "omim": ["614924"], "icd-10": ["G31.8"], "synonyms": ["COXPD12", "Combined oxidative phosphorylation defect type 12", "LTBL"]}
A rare anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis characterized by necrotizing inflammation of small and medium vessels (capillaries, venules and arterioles), resulting in tissue ischemia. ## Epidemiology The prevalence is estimated between 1/6,400 - 42,000 worldwide with annual incidence between 1/84,000-475,000. There is geographic and/or ethnic variation, with a higher incidence in colder regions and among Caucasians. Childhood-onset disease is characterized by female predominance, and adult-onset by a slight male predominance. ## Clinical description The average age of onset is 45 years but the disease may manifest at any age including childhood. The disease may present with various organ manifestations. Ear, nose and throat symptoms are present in 50-95% (persistent nasal obstruction, destructive sinusitis, crusting and/or hemorrhagic rhinitis, nasal septum deformity, saddle nose deformity, and otitis media), bronchopulmonary symptoms in 60-80% (nodules, alveolar hemorrage, bronchial and/or subglottic stenosis), and renal disease (typically extra-capillary necrotizing glomerulonephritis) in 60-80% of affected individuals. General signs (fever, arthralgia, myalgia, weight loss) are common. Skin lesions (purpura and cutaneous nodules) are observed in 10-50%, peripheral neuropathy (multineuritis) in 25%, central nervous system manifestations (headaches, sensorimotor deficit, hemiplegia and epilepsy) in 10%, and ocular anomalies (scleritis and orbital tumors) in 7-8% of patients. ## Etiology The pathogenesis of GPA is still under study. Genetic susceptibility factors, environmental agents, infectious episodes and anomalies in innate and adaptive immunity seem to play a role in the development of all ANCA-associated vasculitides. Genetic variants appear to correlate with antineutrophil cytoplasmic antibody (ANCA) antigen specificity rather than with clinical phenotype. Thus, cytoplasmic-ANCAs directed to proteinase 3 (PR3-ANCA), found in in 60-80% of GPA cases, are associated with genetic variants in HLA-DP1A and HLA-DP1B (6p21.32) which encode a class II major histocompatibility complex, SERPINA1 (14q32.13) encoding alpha-1 antitrypsin, and PRTN3 (19p13.3) encoding the autoantigen proteinase 3. ## Diagnostic methods Diagnosis relies on clinical findings, imaging studies and biochemical testing, and detection of ANCAs in the serum, principally PR3-ANCAs. Histological analysis of biopsy specimens from affected organs confirms the diagnosis, showing necrotizing vasculitis and granulomatous inflammation. ## Differential diagnosis Differential diagnoses include other ANCA-associated vasculitides such as microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. ## Management and treatment Induction therapy comprises steroid pulses combined with either intravenous Rituximab or Cyclophosphamide. Disease remission is achieved in more than 80% of patients with these protocols. In cases of lacking or insufficient response, plasma exchange can be considered. Azathioprine and Methotrexate are efficacious agents for maintenance immunosuppression whereas Mycophenolate-Mofetil is less effective. Leflunomide is an alternative option for individuals intolerant to Azathioprine or Methotrexate. Anti-TNF antibodies (e.g. Infliximab and Adalimumab) have shown promising results in clinical trials as steroid-sparing agents. ## Prognosis While remission is achieved with treatment in 70-100% of cases, the disease relapses in more than 80% of patients within 10 years. Significant morbidity may emerge both from the disease and its treatment. Ten-year patient survival is around 75%. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Granulomatosis with polyangiitis	c3495801	29,099	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=900	2021-01-23T18:04:34	{"gard": ["7880"], "mesh": ["D014890"], "omim": ["608710"], "umls": ["C0043092", "C3495801"], "icd-10": ["M31.3"], "synonyms": ["GPA"]}

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