Datasets:

findzebra
/

corpus

Dataset card Data Studio Files Files and versions Community

Split (1)

train · 30.7k rows

text stringlengths 297 230k	title stringlengths 4 145	cui stringlengths 4 10	idx int64 0 30.7k	source stringclasses 6 values	source_url stringlengths 33 155	retrieved_date timestamp[s]	classification_map stringlengths 2 1.45k
A number sign (#) is used with this entry because X-linked lissencephaly with ambiguous genitalia (LISX2, XLAG), as well as hydranencephaly and abnormal genitalia, can be caused by mutation in the ARX gene (300382). See also Proud syndrome (300004), an allelic disorder with an overlapping phenotype. Early infantile epileptic encephalopathy-1 (EIEE1; 308350) and 2 other forms of X-linked mental retardation (see 309510 and 300419) are allelic disorders without brain malformations. Description X-linked lissencephaly-2 (LISX2) is a developmental disorder characterized by structural brain anomalies, early-onset intractable seizures, severe psychomotor retardation, and ambiguous genitalia. Males are severely affected and often die within the first days or months of life, whereas females may be unaffected or have a milder phenotype (Bonneau et al., 2002). LISX2 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from hydranencephaly and lissencephaly to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1; 308350) to syndromic (309510) and nonsyndromic (300419) mental retardation (Kato et al., 2004; Wallerstein et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432). Clinical Features Dobyns et al. (1999) recognized 5 children from 4 unrelated families with an almost identical disorder comprising lissencephaly with a posterior-to-anterior gradient and only moderate increase in thickness of the cortex, absent corpus callosum, neonatal-onset epilepsy, hypothalamic dysfunction including deficient temperature regulation, and ambiguous genitalia in genotypic males. All also had mild nonspecific dysmorphic facial changes, such as prominent forehead, low forehead, micrognathia, pinched nasal alae, and wide nasal bridge. Their observation of 5 affected males in one of the families was consistent with an X-linked pattern of inheritance. However, the disorder differed in many respects from the X-linked form of isolated lissencephaly sequence that is associated with mutations in the XLIS, or doublecortin, gene (DCX; 300121). Therefore, Dobyns et al. (1999) proposed that this disorder comprises a novel X-linked malformation syndrome, which they referred to as X-linked lissencephaly with ambiguous genitalia. Ogata et al. (2000) reported an additional infant with this condition. The infant had lissencephaly, agenesis of the corpus callosum, intractable epilepsy of neonatal onset, hypothalamic dysfunction including temperature instability, ambiguous genitalia, and a 46,XY karyotype. The infant died at 6 weeks of age and an autopsy showed ventricular septal defect, patent ductus arteriosus (see 607411), mild left lung hypoplasia, megacolon, and small dysgenetic testes, in addition to the brain anomalies. The nonconsanguineous parents had 2 previous pregnancies, both recorded as males, in whom fetal ultrasound studies showed a hydrocephalic appearance. The first resulted in a neonate at 32 weeks of gestation who died of respiratory failure shortly after birth. The second was terminated at 18 weeks of gestation. Although no autopsy was performed on the earlier-born fetuses and information on them was limited, they supported X-linked inheritance of this condition. Bonneau et al. (2002) reported 3 affected boys from 3 unrelated families. The children were all born of nonconsanguineous parents and exhibited tonic-clonic seizures within the first hours of life with variable hypotonia, in addition to having micropenis and undescended testes. Two were described as having craniofacial abnormalities, such as prominent forehead and micrognathia. Brain MRI of all 3 infants showed absence of the corpus callosum, lissencephaly consisting of frontal pachygyria and posterior agyria, abnormally thick cortex, enlarged ventricles, and poorly delineated basal ganglia. Neuropathologic examination showed abnormal lamination of the neocortex with areas of disorganization, gliosis, and numerous pyramidal neurons. Examination of 5 female members of the families, including 2 mothers, revealed absence or partial absence of the corpus callosum, even without clinical symptoms. These findings suggested a semidominant X-linked mode of inheritance. Bonneau et al. (2002) concluded that XLAG is a distinct entity, possibly resulting from a disturbance of key neuronal developmental events. Kitamura et al. (2002) summarized the clinical features of XLAG. All affected individuals with this disorder had been genotypic males, and had severe congenital or postnatal microcephaly, lissencephaly, agenesis of the corpus callosum, neonatal-onset intractable epilepsy, poor temperature regulation, chronic diarrhea, and ambiguous or underdeveloped genitalia. XLAG differs considerably from classic lissencephaly (see 300067), as the resultant cortical thickness is only 6-7 mm in XLAG, rather than 15-20 mm seen in classic lissencephaly associated with mutation in PAFAH1B1 (601545) or DCX (300121). In addition, the cerebral white matter of individuals with XLAG appears immature compared to that associated with classic lissencephaly. ### Carrier Females Marsh et al. (2009) reviewed 25 heterozygous female carriers of known ARX mutations and found that 8 (35%) had significant developmental abnormalities. Twenty-three of the 25 were relatives of a male with an ARX mutation, including 14 mothers and 9 other female relatives. Six of the females had been reported by Bonneau et al. (2002) and 4 had been reported by Proud et al. (1992), ascertained based on the identification of a male relative with XLAG or Proud syndrome (300004), respectively. Clinical features of the affected females were variable, but included agenesis of the corpus callosum, delayed motor development, attention-deficit hyperactivity disorder, learning disabilities, and seizures. None had infantile spasms. Only 3 (33%) of the 9 female relatives other than mothers had completely normal development. Marsh et al. (2009) noted an ascertainment bias: the first reports of human ARX mutations described asymptomatic mothers as healthy carriers of the mutations, which fits well with their having lived to adulthood and having high reproductive fitness. In contrast, other female relatives tended to be more severely affected. The data of Marsh et al. (2009) did not show clear evidence for skewing of X inactivation in either symptomatic or asymptomatic females, but the number of females tested was too low to draw firm conclusions. Marsh et al. (2009) also found that about half of female mice with targeted disruption of the Arx gene developed seizures, further indicating that some female carriers may be affected. Molecular Genetics Kitamura et al. (2002) identified loss-of-function mutations in the ARX gene (300382) in individuals affected with XLAG and in some female relatives. Kitamura et al. (2002) suggested that this may have been the first incidence in which phenotypic analysis of the knockout mice was used to identify a gene associated with an X-linked human brain malformation. In 20 patients with brain and genital malformations, Kato et al. (2004) identified 13 novel and 2 recurrent mutations in the ARX gene. Most of the patients had XLAG, but 2 had hydranencephaly and abnormal genitalia (see, e.g., 300382.0016) and 3 males from 1 family had Proud syndrome (300382.0015). Two of the families had been reported by Bonneau et al. (2002), and were found to have the same mutation (E78X; 300382.0020). Genotype/Phenotype Correlations In a review of 29 males with ARX mutations, Kato et al. (2004) found that those with premature termination or nonsense mutations had brain malformation syndromes, including XLAG and Proud syndrome, whereas those with expansion of the polyalanine tract (300382.0001 and 300382.0002) had epileptic encephalopathy (308350) or mental retardation (309510; 300419) without brain malformations. Missense mutations were equally divided between the 2 groups, but the more severe phenotypes correlated with mutations in highly conserved regions. Animal Model Kitamura et al. (2002) demonstrated that male embryonic mice with mutations in the Arx gene developed with small brains due to suppressed proliferation and regional deficiencies in the forebrain. These mice also showed aberrant migration and differentiation of interneurons containing gamma-aminobutyric acid (GABAergic interneurons) in the ganglionic eminence and neocortex as well as abnormal testicular differentiation. These characteristics recapitulated some of the clinical features of XLAG in humans. INHERITANCE \- X-linked HEAD & NECK Head \- Large anterior fontanelle \- High forehead Face \- Micrognathia \- Long philtrum Ears \- Low-set ears Eyes \- Thin optic nerves \- Duane anomaly (reported in 1 female) Nose \- Wide nasal bridge \- Prominent nasal root \- Pinched nasal alae Mouth \- Thin upper lip \- Long upper lip \- High-arched palate ABDOMEN Gastrointestinal \- Poor feeding \- Diarrhea, chronic GENITOURINARY External Genitalia (Male) \- Ambiguous genitalia \- Small testes \- Underdeveloped scrotal folds \- Small penis NEUROLOGIC Central Nervous System \- Psychomotor retardation, profound \- No development \- Seizures, intractable, neonatal \- Hypotonia \- Spasticity, distal \- Hyperreflexia \- Learning difficulties in affected females \- Lissencephaly, posterior to anterior gradient \- Anterior pachygyria and posterior agyria \- Moderately thickened cortex \- Enlarged ventricles \- Dysplastic basal ganglia \- Agenesis of the corpus callosum \- Neuronal migration defect \- Gliosis of the white matter ENDOCRINE FEATURES \- Hypothalamic dysfunction \- Impaired temperature regulation MISCELLANEOUS \- Early death in males \- Some female carriers are more mildly affected MOLECULAR BASIS \- Caused by mutation in the X-linked aristaless-related homeobox gene (ARX, 300382.0005 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	LISSENCEPHALY, X-LINKED, 2	c1846171	7,400	omim	https://www.omim.org/entry/300215	2019-09-22T16:20:40	{"doid": ["0050453"], "mesh": ["C564563"], "omim": ["300215"], "orphanet": ["452"], "synonyms": ["Alternative titles", "LISSENCEPHALY, X-LINKED, WITH AMBIGUOUS GENITALIA", "XLISG"]}
A form of hereditary cerebral hemorrhage with amyloidosis characterized by an age of onset between 50-70 years of age, recurrent lobar intracerebral hemorrhages and cognitive decline. This subtype is due to a mutation in the APP gene (21q21.2), encoding the beta-amyloid precursor protein. This mutation causes an increased accumulation of amyloid-beta protein in the walls of the arteries and capillaries of the meninges, cerebellar cortex and cerebral cortex, leading to the weakening and eventual rupture of these vessels. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	ABetaL34V amyloidosis	c2931672	7,401	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=324703	2021-01-23T19:00:18	{"mesh": ["C537944"], "omim": ["605714"], "icd-10": ["E85.4+", "I68.0*"], "synonyms": ["ABeta amyloidosis, Piedmont type", "ABetaL34V-related amyloidosis", "HCHWA, Piedmont type", "Hereditary cerebral hemorrhage with amyloidosis, Piedmont type"]}
A form of hereditary cerebral hemorrhage with amyloidosis characterized by an age of onset of 20-30 years, major systemic amyloidosis and recurrent lobar intracerebral hemorrhages. Unlike other forms of hereditary cerebral hemorrhage with amyloidosis, this subtype is due to a mutation in the CST3 gene (20p11.2), encoding the precursor protein cystatin C. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	ACys amyloidosis	c1527338	7,402	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100008	2021-01-23T18:30:24	{"mesh": ["D028243"], "omim": ["105150"], "umls": ["C1527338"], "icd-10": ["E85.4+", "I68.0*"], "synonyms": ["CST3-related amyloidosis", "Cystatin amyloidosis", "HCHWA, Icelandic type", "Hereditary cerebral hemorrhage with amyloidosis, Icelandic type", "Hereditary cystatin C amyloid angiopathy"]}
Acrocallosal syndrome is a rare condition characterized by a brain abnormality called agenesis of the corpus callosum, the presence of extra fingers and toes (polydactyly), and distinctive facial features. The signs and symptoms of this disorder are present at birth, and their severity varies widely among affected individuals. Agenesis of the corpus callosum occurs when the tissue that connects the left and right halves of the brain (the corpus callosum) fails to form normally during the early stages of development before birth. Other brain abnormalities, including the growth of large cysts in brain tissue, have also been reported in people with acrocallosal syndrome. The changes in brain structure associated with this condition lead to delayed development and intellectual disability, which is most often moderate to severe. Some affected individuals also experience seizures. Extra fingers and toes are common in people with acrocallosal syndrome. The extra digits can be on the same side of the hand or foot as the pinky or little toe (postaxial polydactyly) or on the same side as the thumb or great toe (preaxial polydactyly). Some affected individuals also have webbed or fused skin between the fingers or toes (syndactyly). Distinctive facial features that can occur with acrocallosal syndrome include widely spaced eyes (hypertelorism) and a high, prominent forehead. Many affected individuals also have an unusually large head size (macrocephaly). ## Frequency This condition appears to be rare. Only a few dozen cases have been reported in the medical literature. ## Causes Mutations in the KIF7 gene have been found to cause acrocallosal syndrome. Mutations in another gene, GLI3, can also cause features of this disorder. However, the signs and symptoms overlap significantly with those of a similar disorder called Greig cephalopolysyndactyly syndrome (which is also caused by GLI3 gene mutations), so acrocallosal syndrome resulting from GLI3 gene mutations is sometimes considered a severe form of that condition. The proteins produced from the KIF7 and GLI3 genes play critical roles in the normal shaping (patterning) of many tissues and organs before birth. The proteins are part of a chemical signaling pathway called Sonic Hedgehog signaling. This pathway is involved in cell growth, cell specialization, and the patterning of structures such as the brain and limbs. Mutations in either the KIF7 or GLI3 gene are thought to impair Sonic Hedgehog signaling, which has wide-ranging effects on development before birth. The roles of these genes in brain and limb patterning may help explain why mutations lead to agenesis of the corpus callosum, polydactyly, and the other features of acrocallosal syndrome. ### Learn more about the genes associated with Acrocallosal syndrome * GLI3 * KIF7 ## Inheritance Pattern When acrocallosal syndrome is caused by KIF7 gene mutations, it 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. Acrocallosal syndrome (or severe Greig cephalopolysyndactyly syndrome) resulting from GLI3 gene mutations is considered autosomal dominant , which means one copy of the altered gene in each cell is sufficient to cause the disorder. This condition results from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Acrocallosal syndrome	c0796147	7,403	medlineplus	https://medlineplus.gov/genetics/condition/acrocallosal-syndrome/	2021-01-27T08:25:26	{"gard": ["5721"], "mesh": ["D055673"], "omim": ["200990"], "synonyms": []}
## Clinical Features Headington and Astle (1987) described a 14-year-old girl and her mother who had patchy hair loss present from early childhood. When studied in transverse section, biopsy specimens from both women showed marked anagen-telogen transformation that appeared to be irreversible. Preservation of telogen epithelium with absence of inflammation and scarring distinguished familial focal alopecia from pseudopelade (alopecia cicatrisata) and from localized alopecia areata (see 104000). They could find no description of similar cases. 'Anagen' refers to the growth phase of the cycle of activity of the hair follicle. 'Telogen' refers to the resting phase of the cycle of activity of the hair follicle. 'Catagen' refers to the involutional phase of the cycle of activity of the hair follicle. (VAM) Hair \- Patchy hair loss Lab \- Marked irreversible anagen-telogen transformation 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	ALOPECIA, FAMILIAL FOCAL	c1863092	7,404	omim	https://www.omim.org/entry/104110	2019-09-22T15:41:17	{"mesh": ["C566301"], "omim": ["104110"]}
Von Hippel-Lindau syndrome is an inherited disorder characterized by the formation of tumors and fluid-filled sacs (cysts) in many different parts of the body. Tumors may be either noncancerous or cancerous and most frequently appear during young adulthood; however, the signs and symptoms of von Hippel-Lindau syndrome can occur throughout life. Tumors called hemangioblastomas are characteristic of von Hippel-Lindau syndrome. These growths are made of newly formed blood vessels. Although they are typically noncancerous, they can cause serious or life-threatening complications. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination (ataxia). Hemangioblastomas can also occur in the light-sensitive tissue that lines the back of the eye (the retina). These tumors, which are also called retinal angiomas, may cause vision loss. People with von Hippel-Lindau syndrome commonly develop cysts in the kidneys, pancreas, and genital tract. They are also at an increased risk of developing a type of kidney cancer called clear cell renal cell carcinoma and a type of pancreatic cancer called a pancreatic neuroendocrine tumor. Von Hippel-Lindau syndrome is associated with a type of tumor called a pheochromocytoma, which most commonly occurs in the adrenal glands (small hormone-producing glands located on top of each kidney). Pheochromocytomas are usually noncancerous. They may cause no symptoms, but in some cases they are associated with headaches, panic attacks, excess sweating, or dangerously high blood pressure that may not respond to medication. Pheochromocytomas are particularly dangerous in times of stress or trauma, such as when undergoing surgery or in an accident, or during pregnancy. About 10 percent of people with von Hippel-Lindau syndrome develop endolymphatic sac tumors, which are noncancerous tumors in the inner ear. These growths can cause hearing loss in one or both ears, as well as ringing in the ears (tinnitus) and problems with balance. Without treatment, these tumors can cause sudden profound deafness. Noncancerous tumors may also develop in the liver and lungs in people with von Hippel-Lindau syndrome. These tumors do not appear to cause any signs or symptoms. ## Frequency The incidence of von Hippel-Lindau syndrome is estimated to be 1 in 36,000 individuals. ## Causes Mutations in the VHL gene cause von Hippel-Lindau syndrome. The VHL gene is a tumor suppressor gene, which means it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in this gene prevent production of the VHL protein or lead to the production of an abnormal version of the protein. An altered or missing VHL protein cannot effectively regulate cell survival and division. As a result, cells grow and divide uncontrollably to form the tumors and cysts that are characteristic of von Hippel-Lindau syndrome. ### Learn more about the gene associated with Von Hippel-Lindau syndrome * VHL ## Inheritance Pattern Mutations in the VHL gene are inherited in an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors and cysts. Most people with von Hippel-Lindau syndrome inherit an altered copy of the gene from an affected parent. In about 20 percent of cases, however, the altered gene is the result of a new mutation that occurred during the formation of reproductive cells (eggs or sperm) or very early in development. Unlike most autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the VHL gene must be altered to trigger tumor and cyst formation in von Hippel-Lindau syndrome. A mutation in the second copy of the VHL gene occurs during a person's lifetime in certain cells within organs such as the brain, retina, and kidneys. Cells with two altered copies of this gene do not make functional VHL protein, which allows tumors and cysts to develop. Almost everyone who inherits one VHL mutation will eventually acquire a mutation in the second copy of the gene in some cells, leading to the features of von Hippel-Lindau 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	Von Hippel-Lindau syndrome	c0019562	7,405	medlineplus	https://medlineplus.gov/genetics/condition/von-hippel-lindau-syndrome/	2021-01-27T08:24:53	{"gard": ["7855"], "mesh": ["D006623"], "omim": ["193300"], "synonyms": []}
A number sign (#) is used with this entry because autosomal dominant mental retardation-13 (MRD13) is caused by heterozygous mutation in the DYNC1H1 gene (600112) on chromosome 14q32. Description MRD13 is an autosomal dominant form of mental retardation associated with variable neuronal migration defects resulting in cortical malformations. More variable features include early-onset seizures and mild dysmorphic features. Some patients may also show signs of peripheral neuropathy, such as abnormal gait, hyporeflexia, and foot deformities (summary by Willemsen et al., 2012 and Poirier et al., 2013). Clinical Features Vissers et al. (2010) reported a 4-year-old boy with de novo occurrence of moderately severe mental retardation. He showed hypotonia at age 6 months, followed by delayed psychomotor development. Mild dysmorphic features included prominent forehead, plagiocephaly, hypotonic face with downslanting palpebral fissures, and short, broad hands and feet. Brain MRI was reported as normal. His parents were unaffected. Follow-up of the patient at age 6 years by Willemsen et al. (2012) noted that he had hypotonia, hyporeflexia, and broad-based waddling gait with toe walking. Reevaluation of brain MRI showed signs of bilateral cortical malformation with deficient gyration of the frontal lobes and an area suggestive of focal cortical dysplasia. Willemsen et al. (2012) also reported a 51-year-old woman with severe mental retardation and an inability to walk or speak. She had short stature, microcephaly, clubfeet, and small hands and feet with short toes. Craniofacial features included brachycephaly, prominent forehead, hypertelorism, deep-set eyes, wide mouth with everted lower lip, and downturned corners of the mouth. She developed generalized seizures at age 3 years. Other features included kyphoscoliosis, spastic tetraplegia, and swallowing difficulties. Cerebral CT scan at the age 46 years showed enlarged ventricles and clear signs of cortical malformation with wide opercular regions and an abnormal flat cortex with only a few simple and shallow sulci; MRI scan was not possible. Poirier et al. (2013) reported 8 unrelated patients with mental retardation associated with cortical brain malformations on MRI. All but 1 had seizures, most of early onset. Three had microcephaly, 3 were bedridden with spastic tetraplegia, 2 were described as having 'awkwardness' on neurologic examination, and 3 patients had foot deformities consistent with axonal neuropathy. Brain MRI showed predominantly posterior pachygyria, and some patients also had frontal polymicrogyria or nodular heterotopia. Several patients also had other brain abnormalities, including dysmorphic basal ganglia and hypoplasia of the corpus callosum, brainstem, and/or cerebellum. Inheritance The majority of reported patients with MRD13 and neuronal migration defects had de novo mutations in the DYNC1H1 gene, consistent with sporadic occurrence of the disorder. One family with a mild phenotype showed autosomal dominant inheritance (Poirier et al., 2013). Molecular Genetics By family-based exome sequencing of 10 case-parent trios of de novo mental retardation, Vissers et al. (2010) identified a de novo heterozygous mutation in the DYNC1H1 gene (H3822P; 600112.0002) in 1 patient. Willemsen et al. (2012) identified a second de novo heterozygous mutation in the DYNC1H1 gene (E1518K; 600112.0003) in a 51-year-old woman with severe mental retardation since infancy and an inability to walk or speak. Willemsen et al. (2012) noted that DYNC1H1 interacts with LIS1 (601545), haploinsufficiency of which results in the severe neuronal migration disorder lissencephaly-1 (607432), and that Dync1h1 mutant mice show neuronal migration defects (Ori-McKenney and Vallee, 2011), providing evidence of the pathogenicity of the mutations. Willemsen et al. (2012) also noted that their 2 patients showed variable signs consistent with peripheral neuropathy and that some patients with CMT2O (614228) (Weedon et al., 2011) carrying a DYNC1H1 mutation showed learning difficulties, indicating that DYNC1H1 mutations may result in a broad neurologic phenotypic spectrum. Poirier et al. (2013) identified 8 different de novo heterozygous mutations in the DYNC1H1 gene (see, e.g., 600112.0007-600112.0009) in 8 unrelated patients ascertained for evaluation due to malformations of cortical development. Mutations in the first several patients were found by whole-exome sequencing, whereas subsequent patients were identified by direct sequencing of this gene in a larger cohort of affected individuals. In vitro functional expression studies of 2 of the variants showed that the mutant proteins had decreased microtubule binding affinity compared to wildtype. In addition, there was 1 family in which a mother and her 2 children carried a missense variant (K3241T): 1 of the children had mild intellectual disability, but the mother and the other child had normal cognition. All 3 were normocephalic, showed posterior pachygyria, and had focal seizures. No functional studies were performed on the K3241T variant, which occurred at a nonconserved residue. Jamuar et al. (2014) used a customized panel of known and candidate genes associated with brain malformations to apply targeted high-coverage sequencing (depth greater than or equal to 200x) to leukocyte-derived DNA samples from 158 individuals with brain malformations. They found potentially causal mutations in the candidate gene DYNC1H1 in 2 individuals with pachygyria; in a parallel study they had found de novo mutations in DYNC1H1 in 2 other individuals with pachygyria. The 4 individuals had strikingly similar MRI findings, with posterior-predominant pachygyria, thickened cortex in the perisylvian region, and mildly dysmorphic corpus callosum. One of the individuals identified in the report of Jamuar et al. (2014) had onset of seizures at age 5 years and mental and motor retardation. The other had dysarthria and cognitive delay but normal vision, hearing, and head circumference, and no seizures. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Microcephaly (in some patients) \- Prominent forehead (in some patients) Face \- Facial dysmorphism, mild (in some patients) SKELETAL Hands \- Small hands (in some patients) Feet \- Foot deformities (in some patients) NEUROLOGIC Central Nervous System \- Mental retardation (in some patients) \- Seizures, generalized \- Focal seizures \- Spastic tetraplegia (in some patients) \- Abnormal gait \- Pachygyria, usually posterior \- Polymicrogyria, usually frontal (in some patients) \- Nodular heterotopia (in some patients) \- Thin corpus callosum (in some patients) \- Dysmorphic basal ganglia (in some patients) \- Cerebellar hypoplasia (in some patients) \- Brainstem hypoplasia (in some patients) Peripheral Nervous System \- Axonal neuropathy (in some patients) \- Hyporeflexia (in some patients) Behavioral Psychiatric Manifestations \- Autistic features (in some patients) MISCELLANEOUS \- Most patients have de novo mutations \- Dysmorphic features are mild or variable MOLECULAR BASIS \- Caused by mutation in the dynein, cytoplasmic 1, heavy chain 1 gene (DYNC1H1, 600112.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	MENTAL RETARDATION, AUTOSOMAL DOMINANT 13	c3281202	7,406	omim	https://www.omim.org/entry/614563	2019-09-22T15:54:52	{"doid": ["0070043"], "omim": ["614563"], "orphanet": ["178469"], "synonyms": ["Alternative titles", "MENTAL RETARDATION, AUTOSOMAL DOMINANT 13, WITH NEURONAL MIGRATION DEFECTS"]}
A number sign (#) is used with this entry because of evidence that nonsyndromic autosomal recessive deafness-18A (DFNB18A) is caused by homozygous mutation in the gene encoding harmonin (605242) on chromosome 11p15. Mutations in the harmonin gene also cause Usher syndrome type IC (USH1C; 276904). A form of autosomal recessive deafness designated DFNB18B (614945), which also maps to chromosome 11p15, is caused by mutation in the OTOG gene (604487). Clinical Features Jain et al. (1997, 1998) reported a large consanguineous Indian family in which several members had profound, prelingual, nonsyndromic sensorineural deafness. Vestibular function and visual function were normal. Mapping Jain et al. (1997, 1998) studied the linkage of autosomal recessive nonsyndromic sensorineural hearing loss segregating in a large consanguineous Indian family and found that it maps to 11p15.1-p14. They designated the new locus DFNB18. Maximum lod scores of 4.30 and 3.93 at theta = 0.0 were obtained for the polymorphic microsatellite markers D11S1888 and D11S4130. Haplotype analysis localized the gene between D11S1307 and D11S1308, spanning a distance of approximately 4 cM and encompassing the USH1C region. Based on the linkage data, Jain et al. (1997, 1998) postulated that DFNB18 and USH1C are allelic. (Usher syndrome, of which there are many forms, has retinopathy in association with deafness.) A precedent has been set by the demonstration that different mutations in the gene encoding myosin-7A (276903) can cause either USH1B or DFNB2 (600060). The MYO7A gene is located on the long arm of chromosome 11. Molecular Genetics Verpy et al. (2000) identified a PDZ-domain-containing gene on 11p15.1-p14, mutations in which are responsible for USH1C. They proposed that the USH1C gene underlies the DFNB18 form of isolated deafness also. They suggested that the fact that several of the inner ear Ush1c transcripts of the mouse are not present in the eye is consistent with mutations in the USH1C gene underlying a form of isolated deafness. Mutations in connexin-26 (121011) provide another example of syndrome deafness and nonsyndromic deafness being caused by different alleles of the same gene: isolated autosomal recessive deafness (220290), autosomal dominant isolated deafness (601544), and keratoderma with deafness (148350). In the family in which Jain et al. (1998) mapped DFNB18 to 11p, Ahmed et al. (2002) identified a leaky splice site mutation in the harmonin gene (605242.0008), indicating that Usher syndrome type IC and DFNB18 are allelic. Ouyang et al. (2002) indeed demonstrated that mutations in alternatively spliced exons of USH1C cause nonsyndromic recessive deafness DFNB18. They screened 32 Chinese multiplex families with nonsyndromic recessive deafness for USH1C mutations. In 1 family, congenital profound deafness without RP was associated with a C-to-G transversion in the alternatively spliced exon D, predicting an arg608-to-pro (605242.0009) amino acid substitution in the proline-, serine-, and threonine-rich region of harmonin. They also screened 320 deaf probands from other ethnic backgrounds and found 3 who were heterozygous for changes in the alternately spliced exons. None of these mutations were detected in DNA from 200 control subjects with normal hearing, including 110 Chinese. These findings showed that USH1C mutations can also cause nonsyndromic deafness and that some harmonin isoforms are specifically required for inner ear function. Animal Model Johnson et al. (2003) mapped 2 recessive, allelic murine mutations causing circling behavior and deafness to the same region on chromosome 7. The 'deaf circler' (dfcr) mutation is a 12.8-kb intragenic deletion in Ush1c that eliminates 3 constitutive and 5 alternatively spliced exons. The 'deaf circler-2 Jackson' (dfcr-2J) mutation is a 1-bp deletion in an alternatively spliced exon of Ush1c that creates a transcriptional frameshift, changing 38 amino acid codons before introducing a premature stop codon. Both mutations cause congenital deafness and severe balance deficits due to inner ear dysfunction. The stereocilia of cochlear hair cells are disorganized and splayed in mutant mice, with subsequent degeneration of the hair cells and spiral ganglion cells. Harmonin has been shown to bind, by means of its PDZ-domains, with the products of other Usher syndrome genes, including Myo7a, Cdh23 (605516), and Sans (USH1G; 607696). The complexes formed by these protein interactions are thought to be essential for maintaining the integrity of hair cell stereocilia. Inheritance \- Autosomal recessive Ears \- Nonsyndromic sensorineural hearing loss ▲ 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	DEAFNESS, AUTOSOMAL RECESSIVE 18A	c1865870	7,407	omim	https://www.omim.org/entry/602092	2019-09-22T16:13:56	{"doid": ["0110473"], "mesh": ["C566580"], "omim": ["602092"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive non-syndromic neurosensory deafness type DFNB", "Alternative titles", "Autosomal recessive isolated sensorineural deafness type DFNB", "DEAFNESS, AUTOSOMAL RECESSIVE 18", "Autosomal recessive isolated neurosensory deafness type DFNB"], "genereviews": ["NBK1434"]}
## Clinical Features In 2 daughters of Iraqi first-cousin parents, Harbord et al. (1990) observed a progressive neurologic disorder characterized by megalencephaly, spasticity, ataxia, and seizures. Onset of manifestations occurred between ages 2 and 3. Computerized tomography scans showed diffuse hypodensity of the white matter, and brain biopsy in one showed dysmyelination without evidence of demyelination. The electroencephalogram showed posterior discharges and an unusual photoparoxysmal response; the findings of brainstem auditory evoked potentials were consistent with a white matter disorder. The combination of megalencephaly with diffuse white matter hypodensity on brain imaging is found in Alexander disease (203450), Canavan disease (271900), and GM1 gangliosidosis (230500). Brain biopsy showed no Rosenthal fibers typical of Alexander disease or spongy changes characteristic of Canavan disease. Furthermore, no deficiency of aspartoacylase or of beta-galactosidase was found to support the diagnosis of Canavan disease or GM1 gangliosidosis, respectively. Harbord et al. (1990) suggested that the disorder in the sisters was a previously undescribed condition. Radiology \- Diffuse white matter hypodensity on CT scan Neuro \- Spasticity \- Ataxia \- Seizures Inheritance \- Autosomal recessive Misc \- Onset ages 2 to 3 Lab \- Dysmyelination without demyelination on brain biopsy \- Posterior discharges and an unusual photoparoxysmal response on EEG \- Brain stem auditory evoked potentials consistent with white matter disorder HEENT \- Megalencephaly ▲ 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	MEGALENCEPHALY WITH DYSMYELINATION	c1855309	7,408	omim	https://www.omim.org/entry/249240	2019-09-22T16:25:30	{"mesh": ["C565408"], "omim": ["249240"], "synonyms": ["Alternative titles", "MEGALENCEPHALY WITH DIFFUSE WHITE MATTER HYPODENSITY"]}
## Clinical Features Coats disease, also called retinal telangiectasis, is a sporadic disorder characterized by a defect of retinal vascular development that results in vessel leakage, subretinal exudation, and retinal detachment. The disorder was first reported by Coats (1908) in 6 children. Initially, the condition is seen within a sector of the retina and at this stage may be associated with normal vision. However, the consequent retinal detachment often leads to progressive visual loss. In its classic form, Coats disease is almost invariably seen in males and, unlike other forms of retinal telangiectasis, is unilateral (Black et al., 1999). In a review of reported cases of Coats disease and 150 of their own cases, Shields and Shields (2002) found that the mean age of onset of Coats disease was 5 years. Most cases were unilateral (95%) and occurred in males (75%). In most cases, the disease was slowly progressive with increasing exudative retinal detachment. Shields et al. (2007) noted that retinal telangiectasia compatible with Coats disease can be an extramuscular manifestation of facioscapulohumeral dystrophy (FSHD; 158900) but that most affected patients have asymptomatic retinal telangiectasia found at ocular screening after diagnosis of FSHD. They described a young child who had advanced eye findings of unilateral neovascular glaucoma from bilateral retinal telangiectasia 3 years before FSHD became apparent. Smithen et al. (2005) reported 13 patients diagnosed after the age of 35 years (mean age at diagnosis, 50 years). Those diagnosed in adulthood manifested features similar to those diagnosed in childhood: unilateral disease, male predominance, vascular telangiectasis, lipid exudation, macular edema, and areas of capillary nonperfusion with adjacent webs of filigree-like capillaries. Differences in the adult cases included limited area of involvement, slower disease progression, and hemorrhage near larger vascular dilatations. Lim et al. (2005) described a 29-year-old woman with an unusual case of Coats disease in which there was a prominent inflammatory component in addition to the subretinal and retinal lipid crystal deposits and abnormal retinal vasculature characteristic of the disease. The patient had a 9-year history of bilateral uveitis complicated by secondary glaucoma in the right eye. Inflammation in the right eye was only partially controlled by prednisolone and cyclosporine. She developed intractable neovascular glaucoma in the left eye that led to complete loss of vision. Immunochemical staining revealed that the intraluminal inflammatory cells were macrophages and that the perivascular inflammatory infiltrates were composed largely of T lymphocytes. Kase et al. (2013) examined the expression of vascular endothelial growth factor (VEGF; 192240) and VEGF receptor (VEGFR; 191306) in eyes enucleated because of Coats disease. Histologically, the enucleated eyes demonstrated the presence of macrophage infiltration and cholesterol clefts in the subretinal space. There were marked retinal vascular abnormalities, including dilated vessels with hyalinized vessel walls in 6 globes. Exudative retinal detachment was noted in all globes. VEGF immunoreactivity was observed in macrophages infiltrating the subretinal space and in the detached retina including several blood vessels. VEGF-positivity in macrophages was significantly higher in cases containing retinal vessel abnormalities than in those without abnormalities (P less than 0.01). VEGFR immunoreactivity was detected in endothelial cells lining the abnormal retinal vessels, where VEGFR1 (165070) and VEGFR3 (136352) were not expressed. Molecular Genetics Black et al. (1999) presented evidence that Coats disease can be caused by somatic mutation in the NDP gene (300658), which is also mutant in Norrie disease (310600). They reported a woman with a unilateral variant of Coats disease who gave birth to a son affected by Norrie disease. Both carried a missense mutation within the NDP gene (cys96 to trp; 300658.0018) on Xp11.4. Subsequent analysis of the retinas of 9 enucleated eyes from males with Coats disease demonstrated in 1 a somatic mutation in the NDP gene that was not present in nonretinal tissue. This mutation was identical to that identified in the mother and son. Black et al. (1999) suggested that Coats telangiectasis is secondary to somatic mutation in the NDP gene, which results in a deficiency of norrin within the developing retina. This supported observations that the protein is critical for normal retinal vasculogenesis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	COATS DISEASE	c0154832	7,409	omim	https://www.omim.org/entry/300216	2019-09-22T16:20:39	{"doid": ["7765"], "mesh": ["D058456"], "omim": ["300216"], "icd-9": ["362.12"], "icd-10": ["H35.02", "H35.07"], "orphanet": ["190"], "synonyms": ["Alternative titles", "RETINAL TELANGIECTASIS"], "genereviews": ["NBK1331"]}
## Clinical Features Cockshott and Omololu (1958) described a father and his infant daughter with congenital posterior dislocation of the radial head. Neither could extend their elbows below the right angle, whereas pronation and supination were unrestricted. The tendons of insertion of both biceps stood out prominently in the father's antecubital fossae, raising skin webs. Reichenbach et al. (1995) reported on 4 cases of congenital posterior dislocation of radial heads in 3 generations of a family with 3 instances of male-to-male transmission. All affected subjects had mild limitation of extension and a strong restriction of rotation in the elbows. Shun-Shin (1954) observed this disorder associated with antecubital pterygium (178200) in members of 3 generations of a family. Inheritance Abbott (1892) reported 7 cases of congenital anterior dislocation of the radius in 1 family and 2 cases with posterior dislocation. Gunn and Pillay (1964) described congenital posterior dislocation of the head of the radius in a mother and daughter in Malaya. The mother's parents were consanguineous and she had married within a restricted group. A third unrelated patient came from first-cousin parents who were stated to be normal. The authors favored recessive inheritance. The transmission pattern of congenital anterior dislocation of the radius in the family reported by Reichenbach et al. (1995) was consistent with autosomal dominant inheritance. Joints \- Limited elbow extension \- Restricted forearm rotation Limbs \- Congenital radial head posterior dislocation \- Antecubital webbing or pterygium Inheritance \- Autosomal dominant vs. 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	RADIAL HEADS, POSTERIOR DISLOCATION OF	c1867398	7,410	omim	https://www.omim.org/entry/179200	2019-09-22T16:35:21	{"mesh": ["C566728"], "omim": ["179200"]}
The superior and inferior lumbar triangles with a cross section at the level of the superior lumbar triangle Grynfeltt-Lesshaft hernia is a herniation of abdominal contents through the back, specifically through the superior lumbar triangle, which is defined by the quadratus lumborum muscle, twelfth rib, and internal oblique muscle. ## History[edit] Grynfeltt described a hernia through the superior lumbar triangle in 1866 (Grynfeltt, 1866). In 1870, Lesshaft independently reported a similar case (Lesshaft, 1870). ## See also[edit] Petit's hernia ## References[edit] * Grynfeltt, J.: La Hernie Lombaire. Montpellier Med., 16:329, 1866. * Lesshaft, P.: Die Lumbalgegend in Anat. Chirurgischer Hinsicht. Arch. f. Anat. u. Physiol. u. Wissensch., Med. Leipzig, 37:264, 1870. * 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 This surgery 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	Grynfeltt-Lesshaft hernia	None	7,411	wikipedia	https://en.wikipedia.org/wiki/Grynfeltt-Lesshaft_hernia	2021-01-18T18:33:07	{"wikidata": ["Q5612430"]}
Congenital hemorrhagic diathesis due to an excess of a clotting inhibitor has not been fully established. Quick (1957) diagnosed congenital hyperheparinemia in a woman with abnormal bleeding from age 3. Heni and Krauss (1956) described a similar condition in a father and daughter. In both instances the in vitro clotting defect was repaired by protamine sulfate and by toluidine blue, and Quick achieved correction of the defect in vivo as well. Inheritance \- Autosomal dominant Lab \- In vitro clotting defect corrected by protamine sulfate and by toluidine blue Heme \- Congenital hemorrhagic diathesis \- Congenital hyperheparinemia ▲ 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	HYPERHEPARINEMIA	c3203346	7,412	omim	https://www.omim.org/entry/144050	2019-09-22T16:39:58	{"mesh": ["C562723"], "omim": ["144050"], "icd-10": ["D68.32"]}
A number sign (#) is used with this entry because of evidence that acid-labile subunit deficiency (ACLSD) is caused by homozygous or compound heterozygous mutation in the IGFALS gene (601489) on chromosome 16p13. Description Acid-labile subunit deficiency is characterized by severely reduced serum insulin-like growth factor I (IGF1; 147440) and IGF-binding protein-3 (IGFBP3; 146732) concentrations that are incongruent with an associated mild growth retardation (height, -2 to -3 SD before and during puberty). Pubertal delay in boys and insulin insensitivity are common findings (summary by Domene et al., 2011). Clinical Features Domene et al. (2004) described a 17-year-old boy with delayed onset of puberty and slow pubertal progress. Childhood medical history was unremarkable, and psychomotor and neurologic development were normal. He was first referred at 14 years of age for evaluation of growth pubertal delay, at which time his height was 145.2 cm (2.05 SD below the mean) and his weight was 35.9 kg. He was Tanner stage 1 for both sexual development and pubic hair. Both testes were 3 ml in volume. Bone age was 12.5 years. Growth hormone (GH; 139250) responses to provocative tests were normal, but there was marked reduction of both IGF1 and IGFBP3, which remained unchanged after stimulation with growth hormone. The acid-labile subunit was undetectable in the serum before and after growth hormone stimulation. Domene et al. (2007) described a family in which 3 affected sibs had complete acid-labile subunit deficiency. The index case was an adolescent male with delayed growth and pubertal development (Tanner stage 1, -2.00 SD score for height at the age of 15.3 years) and poor response to GH treatment. All 3 sibs had marked reduction of IGF1 and IGFBP3 levels, undetectable serum levels of acid-labile subunit, inability to form ternary complexes, and moderate insulin resistance. All of them attained a normal adult height that was nonetheless lower than that of their unaffected brother. Molecular Genetics In a 17-year-old boy with acid-labile subunit deficiency, Domene et al. (2004) identified a homozygous mutation in the IGFALS gene. In 3 sibs with acid-labile subunit deficiency, Domene et al. (2007) identified compound heterozygous mutations in the IGFALS gene (601489.0002-601489.0003). Domene et al. (2011) stated that 16 unique homozygous or compound heterozygous inactivating mutations of the IGFALS gene had been identified in 21 patients with acid-labile subunit deficiency from 16 different families of various ethnic backgrounds. All of the mutations occurred in exon 2 and included missense mutations, frameshifts with a premature stop codon, in-frame insertions, and nonsense mutations. Thirteen of the mutations produced defects in the leucine-rich repeat region of the protein. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	ACID-LABILE SUBUNIT DEFICIENCY	c4321359	7,413	omim	https://www.omim.org/entry/615961	2019-09-22T15:50:27	{"omim": ["615961"], "orphanet": ["140941"], "synonyms": []}
Paroxysmal exercise-induced dystonia Other namesParoxysmal exertion-induced dyskinesia This condition is inherited in an autosomal dominant manner SpecialtyNeurology Paroxysmal exercise-induced dystonia or PED is a rare neurological disorder characterized by sudden, transient, involuntary movements, often including repetitive twisting motions and painful posturing triggered by exercise or other physical exertion.[1] PED is in the class of paroxysmal dyskinesia which are a group of rare movement disorders characterized by attacks of hyperkinesia with intact consciousness.[2] The term paroxysmal indicates that the episodes are sudden and short lived and usually unpredicted, and return to normal is rapid.[1] The number of reported cases of people with PED is very small leading to difficulty in studying and classifying this disease and most studies are limited to a very small number of test subjects. ## Contents * 1 Symptoms and signs * 2 Causes * 2.1 Familial * 2.2 Sporadic * 3 Diagnosis * 3.1 Related disorders * 4 Treatments * 5 Epidemiology * 6 Research * 7 See also * 8 References * 9 External links ## Symptoms and signs[edit] Episodes are relatively short-lived, lasting anywhere from 5–30 minutes, and in most cases disappear completely after cessation of the physical exercise. Most patients will experience 1 to 5 episodes per month, but some can have attacks daily.[1] The muscles most often affected are usually in the legs and feet (75% of reported cases), but the upper body muscles such as the arms, face, neck, and trunk have also been observed to be affected during the episodes of dystonia.[3] Age of onset is usually sometime in childhood, but can range from 1–30 years old.[4] In one study it was found that the mean age of onset was around 8 years. Similarly in the study, the legs were the most common affected part of the body and the attacks were reported as stiffening and cramps by those affected. During an episode of PED patients find walking nearly impossible.[5] Cerebral spinal fluid analysis showed a two-fold increase of homovanillic acid and 5-hydroxyindoleacetic acid immediately following exercise compared to normal levels. This indicated that increased dopaminergic transmission could contribute to PED and other paroxysmal dyskinesias.[6] Neurological examinations, EEG, and brain imaging are all normal in PED patients.[7] ## Causes[edit] ### Familial[edit] In most cases, PED is familial, but can also be sporadic. In familial cases, pedigrees examined have shown PED to be an autosomal-dominant inheritance trait.[1] PED also has been associated with Parkinson's disease, epilepsy and migraines, although the exact relationship between these is unknown.[8] A suspected contributor to familial PED is a mutation in the GLUT1 gene, SLC2A1, which codes for the transporter GLUT1, a protein responsible for glucose entry across the blood–brain barrier.[5] It is not thought that the mutation causes a complete loss of function of the protein but rather only slightly reduces the transporter's activity.[8] In a study of PED patients, a median cerebrospinal fluid/blood glucose ratio of .52 compared to a normal .60 was found. In addition, reduced glucose uptake by mutated transporters compared with wild-type in Xenopus oocytes confirmed a pathogenic role of these mutations.[5] Another recent study was performed to continue to look at the possible connection between PED and mutations on the SLC2A1 gene which codes for the GLUT1 transporter. While PED can occur in isolation it was also noted that it occurs in association with epilepsy as well. In this study the genetics of a five-generation family with history of PED and epilepsy were evaluated. From the results it was noted that most of the mutations were due to frameshift and missense mutations. When looking at homologous GLUT1 transporters in other species it was noted that serine (position 95), valine (position 140), and asparagine (position 317) were highly conserved and therefore mutations in these residues would most likely be pathogenic. Therefore, these are areas of interest when looking at what could lead to PED.All mutations that were observed appeared to only affect the ability of GLUT1 to transport glucose and not the ability for it to be inserted in the membrane. The observed maximum transport velocity of glucose was reduced anywhere from 3 to 10 fold.[5] A study was performed to determine if the mutation known for the PNKD locus on chromosome 2q33-35 was the cause of PED. In addition, other loci were observed such as the familial hemiplegic migraine (FHM) locus on chromosome 19p, or the familial infantile convulsions and paroxysmal choreoathetosis (ICCA). All three of these suspected regions were found to not contain any mutations, and were therefore ruled out as possible candidates for a cause of PED.[4] ### Sporadic[edit] Sporadic cases may be brought on by minor head injuries and concussions. This was observed in one patient who started experiencing painless dystonia after mild exercise following a concussion.[3] More research still needs to be done to determine how injuries can induce PED, as little is known in this area. Two cases of PED have been associated with insulinomas, after removal of which the symptoms of PED were resolved.[3] ## Diagnosis[edit] Since the age of onset is relatively young of PED it is important to correctly diagnose this disease. The limited cases and limited knowledge of the disease makes this difficult but a few characteristics seem to be consistent. It appears that patients with PED would have normal neurological examinations and MRI but the noticeable characteristic would be in low levels of glucose in the cerebral spinal fluid due to the GLUT1 mutations.[5] ### Related disorders[edit] PED differs from two closely related disorders, for example paroxysmal kinesogenic dyskinesia (PKD) and paroxysmal nonkinesigenic dyskinesia (PNKD), based on what brings on the symptoms, namely prolonged exercise, such as brisk walking or running for at least 10 minutes. This is in contrast to PKD where the symptoms are brought about by sudden movements, and PNKD where the symptoms are spontaneous in nature and prolonged. PED is usually affects muscles on both sides of the body (bilateral), it has also been observed to have unilateral effects.[citation needed] PED has also been shown to be a precursor to Parkinson's disease. In two observed cases, PED preceded any symptoms of Parkinson's Disease by 1.5 and 5 years. Although a rare indicator, PED can be an early sign of the disorder, suggesting they are related.[9] In one case a patient with PED showed evidence of dopamine depletion revealed by a dopamine transporter SPECT scan. This is typical of Parkinson's disease, further showing the linkage between the diseases.[10] A correlation between epilepsy and PED has been observed in several families across multiple generations, demonstrating an autosomal dominant heritability of symptoms. The occurrence of coexistent seizures and PED symptoms are observed mainly during infancy and childhood, with symptoms of PED continuing throughout a lifetime.[11] Epileptic seizures vary in type and have been observed as absence and generalized seizures. Simultaneous seizure and PED attacks are often premeditated by bouts of dizziness. Attacks have been shown to be reduced or prevented with food ingestion, although the reasons for this are unclear. Various evidence shows that the disorders are likely caused by dysfunction in voltage-gated ion channels, which may lead to abnormal excitability in different brain regions, specifically the cerebral cortex and basal ganglia.[12] ## Treatments[edit] As there appeared to be a connection with PED and mutated GLUT1 transporters a possible treatment was looking at changing patients diets. A common treatment for another disorder with a mutated GLUT1 transporter is the ketogenic diet. The diet is a strict 3:1 ratio of fat (3) to protein and carbohydrates (1). This diet is thought to help restore the unbalance created by the decreased amount of glucose in the brain caused by the faulty GLUT1 transporter. This diet was administered to three patients who had been screened and found to have mutation in their SLC2A genes coding for GLUT1 and were experiencing PED symptoms. All three showed benefit from this treatment and a reduction in their PED episodes. They were able to exercise and run long distances for the first time in their lives. No other studies have been performed using this diet as many patients feel the advantages of the diet do not outweigh its disadvantages.[5] As some cases have noted that patients were able to alleviate or lessen their PED attacks with a sugary snack, another diet that was tried on patients was one rich in carbohydrates with additional frequent carbohydrate-containing snacks. Four patients with reported PED symptoms were put on this diet but no observable improvements were noted and in fact one patient even complained of worsening symptoms.[5] Additionally it has been observed that levodopa may reduce some symptoms associated with PED. This may demonstrate that PED is a precursor to Parkinson's disease. Acetazolamide was beneficial to some patients, but also worsened symptoms in others. Additionally, a modified version of the Atkin's diet helped to regulate glucose levels in the cerebrospinal fluid.[8] Patients with PED associated with insulinomas appeared to have symptoms resolved after consuming sugary drinks.[3] Currently, there are no drugs that are particularly useful in completely curing all symptoms.[citation needed] ## Epidemiology[edit] There are very few reported cases of PED, there are approximately 20 reported sporadic cases of PED and 9 PED families but there is some dispute on the exact number of cases.[5] In addition it appears that PED becomes less severe with aging. Prior to onset of a PED episode some patients reported onset of symptoms including sweating, pallor, and hyperventilation. In brain scans it was observed that patients suffering form frequent PEDs there was increased metabolism in the putamen of the brain and decreased metabolism in the frontal lobe.[5] Another study using subtraction single photon emission computed tomographic (SPECT) imaging technique which was coregistered with an MRI on a patient presented with PED symptoms showed increased cerebral perfusion in the primary somatosensory cortex area, and a mild increase in the region of the primary motor cortex and cerebellum.[13] While all these correlations are not fully understand as to what exactly is happening in the brain it provides areas of interest to study further to hopefully understand PED more fully.[citation needed] ## Research[edit] Since paroxysmal exercise-induced dystonia is such a rare disorder it makes it difficult to study the disease and find consistencies. Many of the current studies seem to have contradicting conclusion but this is due to the fact that studies are usually limited to a very small number of test subjects. With such small numbers it is hard to determine what is a trend and what is random when in comes to characterizing the disease. Further study is needed to find better diagnostic techniques and treatments for PED. Patients with PED are living a limited lifestyle since simple tasks like walking and exercise are often impossible.[citation needed] ## See also[edit] * Paroxysmal dyskinesia * Paroxysmal nonkinesogenic dyskinesia ## References[edit] 1. ^ a b c d Poon, Michael. Paroxysmal Dyskinesias. Shrine of Neurology. Nov. 2004 http://www.angelfire.com/retro/michaelpoon168/paroxysmal_dyskinesias.htm Archived 2010-03-06 at the Wayback Machine 2. ^ Blueprints Neurology, 2nd ed. 3. ^ a b c d Tan NC, Tan AK, Sitoh YY, Loh KC, Leow MK, Tjia HT (November 2002). "Paroxysmal exercise-induced dystonia associated with hypoglycaemia induced by an insulinoma". J. Neurol. 249 (11): 1615–6. doi:10.1007/s00415-002-0876-0. PMID 12532934. S2CID 7067562. Archived from the original on 2011-07-14. . 4. ^ a b Münchau A, Valente EM, Shahidi GA, et al. (May 2000). "A new family with paroxysmal exercise induced dystonia and migraine: a clinical and genetic study". J. Neurol. Neurosurg. Psychiatry. 68 (5): 609–14. doi:10.1136/jnnp.68.5.609. PMC 1736900. PMID 10766892. 5. ^ a b c d e f g h i Suls A, Dedeken P, Goffin K, et al. (July 2008). "Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1". Brain. 131 (Pt 7): 1831–44. doi:10.1093/brain/awn113. PMC 2442425. PMID 18577546. 6. ^ Barnett MH, Jarman PR, Heales SJ, Bhatia KP (November 2002). "Further case of paroxysmal exercise-induced dystonia and some insights into pathogenesis". Mov. Disord. 17 (6): 1386–7. doi:10.1002/mds.10291. PMID 12465091. 7. ^ Diagnosis and Treatment of Paroxysmal Dyskinesias Revisited: Paroxysmal Exercise-induced (Exertion-induced) Dyskinesia Medscape Today 2008 London. http://www.medscape.com/viewarticle/581684_5 8. ^ a b c Schneider SA, Paisan-Ruiz C, Garcia-Gorostiaga I, et al. (August 2009). "GLUT1 gene mutations cause sporadic paroxysmal exercise-induced dyskinesias". Mov. Disord. 24 (11): 1684–8. doi:10.1002/mds.22507. PMID 19630075. 9. ^ Bozi M, Bhatia KP (December 2003). "Paroxysmal exercise-induced dystonia as a presenting feature of young-onset Parkinson's disease". Mov. Disord. 18 (12): 1545–7. doi:10.1002/mds.10597. PMID 14673897. 10. ^ Bruno MK, Ravina B, Garraux G, et al. (February 2004). "Exercise-induced dystonia as a preceding symptom of familial Parkinson's disease". Mov. Disord. 19 (2): 228–30. doi:10.1002/mds.10626. PMID 14978684.[dead link] 11. ^ Guerrini R, Bonanni P, Nardocci N, et al. (March 1999). "Autosomal recessive rolandic epilepsy with paroxysmal exercise-induced dystonia and writer's cramp: delineation of the syndrome and gene mapping to chromosome 16p12-11.2". Ann. Neurol. 45 (3): 344–52. doi:10.1002/1531-8249(199903)45:3<344::AID-ANA10>3.0.CO;2-9. PMID 10072049. Archived from the original on 2013-01-05. 12. ^ Kamm C, Mayer P, Sharma M, Niemann G, Gasser T (April 2007). "New family with paroxysmal exercise-induced dystonia and epilepsy". Mov. Disord. 22 (6): 873–7. doi:10.1002/mds.21350. PMID 17290464. 13. ^ Yoon JH, Lee PH, Yoon SN (November 2007). "Subtraction brain SPECT imaging in a patient with paroxysmal exercise-induced dystonia: role of the primary somatosensory cortex". Arch. Neurol. 64 (11): 1652–6. doi:10.1001/archneur.64.11.1652. PMID 17998449. ## External links[edit] Classification D * ICD-10: G24.8 * OMIM: 612126 * MeSH: C564288 External resources * Orphanet: 98811 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Paroxysmal exercise-induced dystonia	c1842534	7,414	wikipedia	https://en.wikipedia.org/wiki/Paroxysmal_exercise-induced_dystonia	2021-01-18T18:37:47	{"gard": ["10541"], "mesh": ["C564288"], "umls": ["C1842534"], "orphanet": ["98811"], "wikidata": ["Q7139585"]}
Congenital malformation of the cerebellar vermis Dandy–Walker malformation Other namesDandy–Walker syndrome (DWS),[1] Dandy–Walker complex (DWC),[2] Dandy–Walker continuum[3] T2-weighted sagittal MRI of Dandy–Walker variant (DWV) with dysplasia of the pons and cerebellar vermis in an 8-year old SpecialtyMedical genetics SymptomsHydrocephalus: increasing head size, vomiting, excessive sleepiness, irritability, vertical gaze palsy, seizures[4] Associated genetic conditions: congenital heart defects, eye abnormalities, intellectual disability, agenesis of the corpus callosum, skeletal abnormalities, etc.[5] ComplicationsShunt failure (shifting, overdrainage), subdural haematoma, infection[6] TypesDandy–Walker variant (DWV),[7][6] mega cisterna magna(?)[6][8] CausesCiliopathic or chromosomal genetic conditions, often not identified[5] Diagnostic methodMRI, prenatal ultrasound or CT[6] Differential diagnosisBlake's pouch cyst (BPC),[3][8] mega cisterna magna(?),[6][8] posterior fossa arachnoid cyst[6][9] TreatmentCystoperitoneal shunt, ventriculoperitoneal shunt, endoscopic third ventriculostomy (ETV)[6][10] Prognosis15% risk of death, mostly from hydrocephalus or its treatment[6] Frequency1 in 25,000 to 1 in 50,000[5][11] Dandy–Walker malformation (DWM), also known as Dandy–Walker syndrome (DWS), is a rare congenital brain malformation in which the part joining the two hemispheres of the cerebellum (the cerebellar vermis) does not fully form, and the fourth ventricle and space behind the cerebellum (the posterior fossa) are enlarged with cerebrospinal fluid. Most of those affected develop hydrocephalus within the first year of life,[6] which can present as increasing head size, vomiting, excessive sleepiness, irritability, downward deviation of the eyes and seizures.[4] Other, less common symptoms are generally associated with comorbid genetic conditions and can include congenital heart defects, eye abnormalities, intellectual disability, congenital tumours, other brain defects such as agenesis of the corpus callosum, skeletal abnormalities, an occipital encephalocele or underdeveloped genitalia or kidneys.[5] It is sometimes discovered in adolescents or adults due to mental health problems.[5][6] DWM is usually caused by a ciliopathic or chromosomal genetic condition, though the causative condition is only identified in around half of those diagnosed before birth[6] and a third of those diagnosed after birth.[5] The mechanism involves impaired cell migration and division affecting the long period of development of the cerebellar vermis.[6] The mechanism by which hydrocephalus occurs in DWM is not yet fully understood.[6] The condition is diagnosed by MRI or, less commonly, prenatal ultrasound.[6] There are other malformations that can strongly resemble DWM, and disagreement exists around the criteria and classifications used for the malformation.[5][6][12] Treatment for most involves the implantation of a cerebral shunt in infancy. This is usually inserted in the posterior fossa, but a shunt in the lateral ventricles may be used instead or in conjunction. Endoscopic third ventriculostomy (ETV) is a less invasive option for patients older than 1 year. Posterior fossa shunts are most effective (80% of the time) but carry the highest risk of complications, while ETV is least effective but has the least risk of complications.[6] The mortality rate is roughly 15%, mostly due to complications from hydrocephalus or its treatment, which can include subdural haematomas or infection.[6] The prognosis after successful hydrocephalus treatment is usually good but depends on any associated condition and its symptoms.[5][6] Those without hydrocephalus are treated based on any associated symptoms or condition.[13] The prevalence of DWM is estimated at between 1 in 25,000 to 1 in 50,000.[5][11] DWM is the cause of around 4.3% of cases of congenital hydrocephalus[14] and 2.5% of all cases of hydrocephalus.[6] At least 21% of those with DWM have a sibling with the malformation, and at least 16% have a parent with the malformation.[5] The malformation was first described by English surgeon John Bland-Sutton in 1887,[6][15] though it was named by German psychiatrist Clemens Ernst Benda [de] in 1954[1][6] after American neurosurgeons Walter Dandy and Arthur Earl Walker, who described it in 1914 and 1942, respectively.[6][16][17] ## Contents * 1 Signs and symptoms * 1.1 Hydrocephalus * 1.2 Neurological * 1.3 Associated anomalies * 2 Cause * 2.1 Ciliopathic genetic conditions * 2.2 Chromosomal abnormalities * 2.3 External toxins * 3 Pathophysiology * 3.1 Pathophysiology of hydrocephalus * 4 Diagnosis * 4.1 Criteria and classification * 4.2 Methods * 4.3 Differential diagnosis * 4.3.1 Blake's pouch cyst * 4.3.2 Mega cisterna magna * 4.3.3 Posterior fossa arachnoid cyst * 5 Treatment * 5.1 Hydrocephalus/cyst * 5.2 Other * 6 Prognosis * 7 Epidemiology * 8 History * 9 References * 10 Further reading * 11 External links ## Signs and symptoms[edit] ### Hydrocephalus[edit] The most frequent and prominent symptoms of DWM are those associated with hydrocephalus in the postnatal period. Hydrocephalus occurs in an estimated 80% of patients with classic DWM. This usually presents within the first year of life (85% of the time), most often within the first 3 months.[6] Signs of hydrocephalus in infants include increasing head size, vomiting, excessive sleepiness, irritability, downward deviation of the eyes (known as "sunsetting eyes") and seizures.[4] In contrast to classic DWM, only around 30% of those with Dandy–Walker variant (DWV), in which the posterior fossa is not enlarged, have hydrocephalus.[6] ### Neurological[edit] Despite the hypoplastic cerebellar vermis, just over half of individuals with DWM (between 27% and 84%) do not appear to have significant intellectual disability or developmental delay.[5][18] However, many of the genetic conditions associated with DWM can present with developmental delay and other brain anomalies.[5][6] Agenesis of the corpus callosum has been found in between 5% and 17% of those with DWM.[10][19] This does not seem to result in intellectual disability on its own, however.[18] Other brain abnormalities known to be sometimes associated with DWM include grey matter heterotopia, pachygyria (fewer ridges in the brain), lissencephaly (shallower ridges), polymicrogyria, holoprosencephaly and schizencephaly.[6][10] Individuals with these features tend to have developmental delay or seizures. Those without any other central nervous system abnormalities tend to have normal or close-to-normal intellectual development.[6][18] A 2003 review found that moderate-to-severe intellectual disability and non-DWM brain abnormalities were only present in those with the most severe cerebellar vermis malformations (less than two fissures/three lobules in the vermis), and these comprised 16% of their sample. Hydrocephalus also affected all of these patients.[12] In Dandy–Walker variant (DWV) and mega cisterna magna specifically, which are less severe malformations, there appears to be an increased rate of psychotic spectrum disorders such as schizophrenia, bipolar disorder, mania or catatonia.[2][5][20] ### Associated anomalies[edit] A 2017 review found the following associations in patients with DWS (usually from an associated genetic condition or abnormality):[5] * 27% of patients had a congenital heart defect. These included patent ductus arteriosus, coarctation of the aorta, ventricular septal defect and atrial septal defect. In 2.7% of patients, heart failure was reported.[5] * 24% of patients had at least one ocular abnormality. These included cataracts, small eyes (microphthalmia), chorioretinal dysplasia/atrophy, optic nerve dysplasia/atrophy, a small cornea (microcornea) or corneal opacity (leukoma), short-sightedness (myopia) and coloboma (a hole in an eye structure).[5] * 16% of patients were diagnosed with a mental or behavioural disorder, with 6.4% also having a learning disability. 5.3% had either bipolar disorder or a psychotic spectrum disorder, and 2.1% had ADHD. Slightly more of these were found in Dandy–Walker variant (DWV) than in classic DWM, despite DWV being less common, at only around 20% of DWS diagnoses.[5] * Around 12% of patients had cancers or tumours arising from congenital genetic abnormalities. The most common were neurocutaneous melanosis (5.9%), hemangiomas (4.8%, including those with PHACE syndrome) and Wilms' tumour (4.4%). 3.2% of patients had congenital melanocytic nevi, and 2.1% had tongue hamartoma. The melanocytic tumours in these cases are thought to relate to the same genetic errors in the development of the embryonic neural tube that lead to the DWM, since the subsequent embryonic neural crest gives rise to melanocytes, among other cells.[5] * 10% of patients had endocrine or metabolic disorders, and 2.7% had excessive hair growth (hypertrichosis).[5] * 9% of patients (almost all with classic DWM) had musculoskeletal abnormalities, which included scoliosis or kyphoscoliosis and arthrogryposis.[5] * 5.9% of patients had underdeveloped reproductive organs, such as hypoplastic genitalia or undescended testicles (cryptorchidism).[5] * 5.3% of patients had underdeveloped or polycystic kidneys.[5] Occipital encephalocele may occur in DWM.[6] This has generally been found at rates between 6 and 8%.[21][22][19] It has been suggested to occur to compensate for the increased pressure in the posterior fossa during foetal life.[6] Syringomyelia occasionally occurs with DWM, though it is not certain how often.[6][23] One review reported an occurrence of 4.3% in a sample.[7] This may be due to herniation of the bottom of the cyst through the foramen magnum (a similar mechanism to Chiari malformation). Alternatively, it may be a result of hydrocephalus, in which it forms as a "fifth ventricle" due to an enlarged central canal.[6] Rarely, spina bifida has been found with DWM. When it is present, it is usually spina bifida occulta.[24] ## Cause[edit] Fourth ventricle (E) location shown in red, between the cerebellum and the pons (B) DWM is caused by any disruption to embryonic development that affects the formation of the cerebellar vermis. This is usually a genetic mutation that results in impaired cell migration and division. A large number of genetic conditions can result in the anomaly. In a large portion of DWM cases, the condition is identified in the person affected, however in most cases the cause is not identified. At least 21% of those with DWM have a sibling with the malformation, and at least 16% have a parent with the malformation.[5] ### Ciliopathic genetic conditions[edit] Main article: Ciliopathy A genetic condition is identified in around 33% of those diagnosed with DWM after birth.[5] In a 2017 review, 4.3% were found to have PHACE syndrome, a condition involving brain, cardiovascular and eye abnormalities, while 2.3% had Joubert syndrome, a condition involving neurological and sometimes eye and kidney abnormalities. Anywhere from 21% to 81% of those with PHACE syndrome have DWM.[25][26] Other comorbid genetic conditions that were found included oculocerebrocutaneous syndrome, oral-facial-digital syndrome, Coffin–Siris syndrome, Meckel–Gruber syndrome type 7 and Kallmann syndrome, among many others.[5] DWM has also been associated with 3C syndrome, Rubinstein–Taybi syndrome, Marden–Walker syndrome, Sheldon–Hall syndrome, Shah–Waardenburg syndrome, Fryns syndrome,<[27] Walker–Warburg syndrome, Fukuyama congenital muscular dystrophy, Ellis–van Creveld syndrome, Fraser syndrome, Aicardi syndrome, Cornelia de Lange syndrome,<[10] Klippel–Feil syndrome[28][29] and acrocallosal syndrome,[30] among others. Many of these disorders are classified as ciliopathies, genetic disorders that affect the cellular primary cilia, thin cell projections made from microtubules that are believed to be crucial in signalling embryonic cell division and migration.[31] DWM is one of the single largest predictors of a ciliopathic genetic disease.[32] Other genes that have been linked to DWM include ZIC1, ZIC4, FOXC1, FGF17, LAMC1 and NID1.[5] ### Chromosomal abnormalities[edit] In those who are diagnosed with DWM before birth on ultrasound, up to half are found to have a chromosomal abnormality,[6] with the most common being Edwards syndrome (trisomy 18), at roughly 26% of prenatal DWM cases.[27] 6.5% of those diagnosed with DWM after birth also have Edwards syndrome.[5] Other chromosomal abnormalities that can lead to DWM include triploidy, Patau syndrome (trisomy 13), trisomy 9 and partial 3q deletion or duplication.[5][6] The 3q24 region contains the ZIC1 and ZIC4 genes, known to be associated with DWM.[6][27] ### External toxins[edit] Warfarin use during pregnancy has been known to lead to systemic defects in the fetus, including ocular dysgenesis, microcephaly, agenesis of the corpus callosum, skeletal abnormalities and heart defects. In 1985, it was also linked to DWM.[33] ## Pathophysiology[edit] Diagram of the cerebellum, fourth ventricle and pons. The white arrow shows the foramen of Magendie (medial aperture) connecting the fourth ventricle to the cisterna magna (3). This usually remains open in DWM.[6] The cerebellum begins forming at the fifth week of embryonic development. It differentiates at the top of the metencephalon, while the pons (in the brainstem) differentiates at the bottom, separated by the fourth ventricle. The cerebellar hemispheres form from the rhombic lips on the forward surface of the fourth ventricle, which expand and roll over to fuse in the midline to form the cerebellar vermis by the 15th week. If this process does not complete, the cerebellar vermis will not form fully. This long period of development of the cerebellar vermis makes it particularly vulnerable to disruptions.[6] In DWM, the fourth ventricle opens up into and is continuous with almost the entire posterior fossa subarachnoid space.[6] ### Pathophysiology of hydrocephalus[edit] The reason why hydrocephalus occurs in DWM is not yet fully understood. The earliest authors had put it down it to blockage or narrowing of the foramina of Magendie and Luschka, the two apertures in the fourth ventricle that allow cerebrospinal fluid (CSF) to escape into the subarachnoid space of the posterior fossa. However, later studies found that these foramina are usually open in DWM.[6] Hydrocephalus is also usually (80% of the time) not present at birth in those with DWM.[6] The impairment to CSF flow may lie beyond the outlets of the fourth ventricle. Theories of abnormal development or inflammation of the arachnoid mater in the posterior fossa have been put forward.[6] The arachnoid mater contains granulations necessary to return CSF from the subarachnoid spaces to the dural veins and circulation. Excisions of the cyst in DWM have not been able to show whether impaired arachnoid absorption is involved, since the subarachnoid space always takes days to weeks to fill up following excision.[6] Aqueductal stenosis (narrowing of the passage between the third and fourth ventricles) does not seem to be a factor in DWM. It is usually open, and shunts placed in the posterior fossa cyst almost always drain all above ventricles. When it is present, it may be the result of compression from a herniated vermis or cyst or an associated developmental abnormality.[6] It is known that once hydrocephalus has started, the compression by the posterior fossa cyst against the venous passages in the arachnoid mater is involved in the worsening pathology.[6] ## Diagnosis[edit] Dandy–Walker malformation is diagnosed based on the characteristic neuroimaging findings. It can be diagnosed prenatally on ultrasound as early as 14 weeks of gestation, although it is usually diagnosed postnatally by MRI. It is diagnosed within the first year of life 41% of the time, normally due to increasing signs of hydrocephalus,[18] but 28% of the time it is discovered in adolescence or adulthood due to mental health problems, such as psychosis or mood disorder.[5][6] ### Criteria and classification[edit] The precise diagnostic criteria and classification systems of DWM are not agreed upon, and significant dispute exists as to which terms or criteria should be used.[5][6][12] The core criteria of DWM are hypoplasia of the cerebellar vermis and an enlarged fourth ventricle and posterior fossa (the space behind the cerebellum), though the specific degree of hypoplasia or cystic enlargement for diagnosis of DWM is not agreed upon.[7] Additionally, there are several similar conditions which have at various times been grouped with DWM on a continuum by some authors and separated as distinct by others, further complicating diagnosis.[6][8] In 1976, Harwood-Nash and Fitz proposed the term Dandy–Walker variant (DWV) for a malformation in which the posterior fossa is not enlarged but the cerebellar vermis is hypoplastic.[7][6] In 1989, Barkovich et al. proposed the term Dandy–Walker complex (DWC) to include classic DWM and DWV (under type A) plus a third malformation (under type B) in which the cerebellar vermis remains large enough to sit between the fourth ventricle and the cisterna magna beneath it, and instead it is mostly the cisterna magna that is enlarged. In this type, the hypoplasia of the cerebellar vermis does not reach past the horizontal midline of the fourth ventricle, and the posterior fossa is also not as large. The authors noted that this form would previously have been classified as simply mega–cisterna magna.[2][6] In 1999, Calabró et al. first used the phrase Dandy–Walker continuum when referring to proposals that a condition known as Blake's pouch cyst falls under the umbrella of the Dandy–Walker complex proposed by Barkovich.[3] Later authors would put these terms and systems under intense scrutiny and state that they added considerable confusion to the diagnosis of DWM.[5][6][12] However, they remain commonly used.[5] In 2011, Spennato et al. came up with a set of criteria based on Klein et al. (2003) that they considered necessary for diagnosis of DWM:[6] * The lower portion of the cerebellar vermis is absent to varying degrees (three quarters, one half or one quarter missing). * The posterior fossa (the space behind the cerebellum) is enlarged, and its cerebrospinal fluid flow is continuous with that of the fourth ventricle. * The rest of the cerebellar vermis is hypoplastic and is pushed upwards and rotated forwards due to the enlarged posterior fossa. * The cerebellar hemispheres are pushed forwards and to the side by the enlarged posterior fossa. * The angle at the centre of the cerebellar vermis (representing the location of the fastigial nucleus) is large, giving a flattened appearance to the bottom of the vermis, or the fastigial nucleus is absent entirely. * The confluence of sinuses, part of the drainage system located at the far rear of the occipital lobe, is elevated due to the enlarged posterior fossa. (The adjacent cerebellar tentorium is also elevated.) Due to the inconsistency of the presence of hydrocephalus in DWM, Spennato and Klein suggested that it should not be considered a criterion for DWM.[6][12] Klein's criteria differed from Spennato's mainly in that it required no apparent cerebellar hemisphere hypoplasia, but it may also have required the vermis to touch the tentorium or an absence of brainstem abnormalities.[12] ### Methods[edit] DWM can be observed prenatally on ultrasound as early as 14 weeks of gestation,[5] though an MRI scan is the most useful method for diagnosis. MRI can delineate the shape and extent of the malformation as well as assessing additional areas for malformations such as the cerebellar hemispheres, cerebral aqueduct or corpus callosum. Cardiac-gated phase-contrast MRI can observe the flow of cerebrospinal fluid (CSF) during systole and diastole of the heart. In true DWM, this will find a flow from the cerebral aqueduct to the posterior fossa and no flow between the cisterna magna and the space behind the cervical spinal cord.[6] CT may also be used if MRI is unavailable, but it provides less detail.[6] Klein et al. (2003) suggested that a suspected diagnosis based on CT or ultrasound should not be confirmed until an MRI is performed, due to the large number of conditions that can present highly similarly and confound diagnosis.[12] ### Differential diagnosis[edit] DWM has a large number of conditions that can present highly similarly on imaging and confound diagnosis.[6] #### Blake's pouch cyst[edit] Blake's pouch cyst (BPC), or persistent Blake's pouch, is a condition that arises when Blake's pouch, an invagination in the fourth ventricle that ruptures at around 4 months of gestation to form the foramen of Magendie (medial aperture), fails to rupture. This can lead to a dilated fourth ventricle and subsequent hydrocephalus of all four ventricles.[6] In a Blake's pouch cyst, unlike in DWM:[6] * The cerebellum is not hypoplastic, though it may be compressed by the enlarged posterior fossa (mass effect). * The posterior fossa is not enlarged. * The cerebellar tentorium/confluence of sinuses is not raised. * Hydrocephalus, when it occurs, involves all four ventricles. Some authors, however, consider Blake's pouch cyst part of a continuum with DWM (the "Dandy–Walker continuum").[3][8] #### Mega cisterna magna[edit] Mega cisterna magna is a condition in which the cisterna magna, the subarachnoid cistern below the fourth ventricle, is enlarged. It has been proposed to be due to a delayed rupture of Blake's pouch rather than a failed rupture.[9] In mega cisterna magna, unlike in DWM:[9] * The cerebellum is not usually hypoplastic. * The fourth ventricle is of relatively normal shape. * Hydrocephalus is uncommon. There is debate as to whether this malformation is distinct from DWM or forms part of the "Dandy–Walker continuum".[6][8] #### Posterior fossa arachnoid cyst[edit] Main article: Arachnoid cyst An arachnoid cyst is a collection of cerebrospinal fluid (CSF) in the arachnoid mater. 10% of these occur in the posterior fossa.[9] In a posterior fossa arachnoid cyst, unlike in DWM:[6][9] * The cyst is clearly localised in a specific location separate from the fourth ventricle outlets. * The cerebellum is not hypoplastic, though it may be compressed by the cyst (mass effect). * The CSF flow in the cyst is not continuous with that of the fourth ventricle. * Hydrocephalus, if it occurs, is due to the cyst pressing on the cerebellum and compressing the cerebral aqueduct or fourth ventricle outlets. ## Treatment[edit] The main immediate goal of treatment is the control of hydrocephalus and the enlarged posterior fossa cyst, as these can lead to increased intracranial pressure and brain damage. A minority of those affected do not develop hydrocephalus and are treated based on any associated symptoms or condition.[13] ### Hydrocephalus/cyst[edit] For hydrocephalus or the posterior fossa cyst, shunts are the mainstay of treatment. However, those with DWM have a higher rate of shunt-related complications than other patients with hydrocephalus (mainly due to the unconventional anatomy).[6] One explanation for a failure of a shunt to reduce intracranial pressure in DWM has been that the cyst may herniate into the foramen magnum and form a scarring adhesion at the cervical junction, preventing it from shrinking again. If this occurs, a suboccipital decompression with duraplasty may be attempted.[6] In DWM, it is not agreed whether a shunt should be placed in the fourth ventricle (a cystoperitoneal shunt, or CP shunt), the lateral ventricles (a ventriculoperitoneal shunt, or VP shunt) or both, due to conflicting studies on whether the cerebral aqueduct is affected by the malformation. However, a CP shunt almost always drains both the fourth and lateral ventricles in DWM, and according to strict definitions of the malformation, the aqueduct should be assumed open,[6] though imaging is important to confirm this.[10] Many authors therefore recommend the CP shunt as the logical option. However, it is associated with a high rate of complications, including shifting and overdrainage. Overdrainage can lead to subdural haematomas, a tethered spinal cord, due to scarring, or downward herniation of the cerebral hemispheres. Spennato et al. therefore recommend a flow-regulating or anti-syphon valve. On the other hand, VP shunts have a lower rate of complications than CP shunts and are recommended initially by some. However, they are less effective in DWM, and the elevated position of the tentorium should be considered before installing a VP shunt.[6] In patients older than 1 year, endoscopic third ventriculostomy (ETV) may be considered as the first-line treatment. This less invasive procedure creates an artificial hole in the third ventricle to allow CSF to bypass any obstruction. It cannot be used on those with brain abnormalities such as agenesis of the corpus callosum, due to the risk of CSF escaping to other brain areas. A compressed brainstem is not a contraindication, however. ETV has a more modest success rate than shunts, as the hole often closes over. It is more likely to fail in younger patients (below 1 year), and its effects on the developing brain are not yet known.[6] Cysts posterior to the cerebellum, presenting in children younger than 5 years, have been labeled developmental retrocerebellar cysts under a new classification in relation to the proposed neuroendoscopic management.[34] Previously, craniotomy of the posterior fossa and excision of the cystic membrane was used, which was often unsuccessful in preventing cyst reformation and carried a degree of mortality. This may still be reserved for patients with repeated shunt failures/infections.[6][10] ### Other[edit] Treatments for any other symptoms are generally focussed on the specific condition involved and may include supported education, physical therapy or other services. Genetic counselling may be offered to parents for future conceptions.[13] ## Prognosis[edit] The prognosis is first and foremost dependent on the early and successful treatment of hydrocephalus, if present. The other significant factor affecting prognosis is the presence of a comorbid genetic condition or brain anomaly.[5][6] Mortality rates from DWM are roughly 15%.[6] In a study of Dandy–Walker variant (DWV), a mortality rate of 12.5% was observed.[7] The most common cause of death is complications from hydrocephalus or its treatment.[6][18] Untreated hydrocephalus can lead to increased intracranial pressure and brain damage. Shunts used to treat DWM have a moderate-to-good success rate, but they have a higher-than-average failure rate, which can result in failure to reduce the intracranial pressure or infection, such as meningitis. Complications from overdrainage such as subdural haematomas are also possible and can lead to mortality.[6][35] Shunts in the fourth ventricle (cystoperitoneal shunts, or CP shunts) have a generally high rate of successful cyst and ventricle size reduction, especially in the cyst (at least 80%). With a shunt in the lateral ventricles (ventriculoperitoneal shunt, or VP shunt), studies have generally found a roughly 50% successful cyst size reduction rate, with successful ventricle size reduction roughly two thirds of the time.[6] Other systemic or genetic conditions are often present with DWM, and each have their own significant effect on prognosis.[6] ## Epidemiology[edit] The prevalence of DWM is estimated at between 1 in 25,000 to 1 in 50,000.[5][11] DWM is the cause of around 4.3% of cases of congenital hydrocephalus[14] and 2.5% of all cases of hydrocephalus.[6] A 2017 review found that most patients (65%) were diagnosed with either "Dandy–Walker malformation" or "Dandy–Walker syndrome", while 20% were diagnosed with "Dandy–Walker variant" and 1.1% with "mega cisterna magna".[5] ## History[edit] The malformation was first described in 1887 by English surgeon John Bland-Sutton as hypoplasia of the cerebellar vermis, an enlarged posterior fossa and hydrocephalus.[6][15] In 1914, American neurosurgeon Walter Dandy and American paediatrician Kenneth Blackfan described the malformation as partial or complete absence of the cerebellar vermis, an enlarged fourth ventricle and hydrocephalus.[6][16] In 1942, American physician John K. Taggart and Canadian–American neurosurgeon Arthur Earl Walker detailed the phenomenon extensively, ascribing the potential cause as underdevelopment of the foramina of Luschka and Magendie,[17] now no longer believed to be significant.[6] The term Dandy–Walker syndrome (DWS) was introduced by German psychiatrist Clemens Ernst Benda [de] in 1954; he also used the term Dandy–Walker malformation once.[1][6] In 1976, Harwood-Nash and Fitz proposed the term Dandy–Walker variant (DWV) for a malformation in which the posterior fossa is not enlarged but the cerebellar vermis is hypoplastic.[7][6] In 1989, Barkovich et al. proposed the term Dandy–Walker complex (DWC) to include classic DWM and DWV (under type A) plus a third malformation (under type B) in which the cerebellar vermis remains large enough to sit between the fourth ventricle and the cisterna magna, and instead it is mostly the cisterna magna that is enlarged (sometimes diagnosed as "mega cisterna magna"). In 1999, Calabró et al. first used the phrase Dandy–Walker continuum when referring to proposals that a condition known as Blake's pouch cyst falls under the umbrella of the Dandy–Walker complex proposed by Barkovich.[3] These additional terms are mostly discouraged by modern authors due to additional confusion and complexity to the diagnosis of DWM.[5][6][12] ## References[edit] 1. ^ a b c Benda, Clemens E. (1954-01-01). "The Dandy-Walker Syndrome or The So-Called Atresia of the Foramen Magendie". Journal of Neuropathology & Experimental Neurology. 13 (1): 14–29. doi:10.1093/jnen/13.1.14. ISSN 0022-3069. PMID 13118372. 2. ^ a b c Barkovich, A. J.; Kjos, B. O.; Norman, D.; Edwards, M. S. (December 1989). "Revised classification of posterior fossa cysts and cystlike malformations based on the results of multiplanar MR imaging". AJR. American Journal of Roentgenology. 153 (6): 1289–1300. doi:10.2214/ajr.153.6.1289. ISSN 0361-803X. PMID 2816648. 3. ^ a b c d e Calabrò, F.; Arcuri, T.; Jinkins, J. R. (2000-04-01). "Blake's pouch cyst: an entity within the Dandy-Walker continuum". Neuroradiology. 42 (4): 290–295. doi:10.1007/s002340050888. ISSN 1432-1920. PMID 10872175. S2CID 10545199. 4. ^ a b c "Hydrocephalus Fact Sheet \| National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov. Retrieved 2019-12-31. 5. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak Stambolliu, Emelina; Ioakeim-Ioannidou, Myrsini; Kontokostas, Kimonas; Dakoutrou, Maria; Kousoulis, Antonis A. (2017-09-01). "The Most Common Comorbidities in Dandy-Walker Syndrome Patients: A Systematic Review of Case Reports" (PDF). Journal of Child Neurology. 32 (10): 886–902. doi:10.1177/0883073817712589. ISSN 0883-0738. PMID 28635420. S2CID 20046766. 6. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl bm bn bo bp bq br bs bt bu bv bw bx by Spennato, Pietro; Mirone, Giuseppe; Nastro, Anna; Buonocore, Maria Consiglio; Ruggiero, Claudio; Trischitta, Vincenzo; Aliberti, Ferdinando; Cinalli, Giuseppe (October 2011). "Hydrocephalus in Dandy-Walker malformation". Child's Nervous System. 27 (10): 1665–1681. doi:10.1007/s00381-011-1544-4. ISSN 1433-0350. PMID 21928031. S2CID 25063114. 7. ^ a b c d e f Sasaki-Adams, Deanna; Elbabaa, Samer K.; Jewells, Valerie; Carter, Lori; Campbell, Jeffrey W.; Ritter, Ann M. (September 2008). "The Dandy-Walker variant: a case series of 24 pediatric patients and evaluation of associated anomalies, incidence of hydrocephalus, and developmental outcomes". Journal of Neurosurgery. Pediatrics. 2 (3): 194–199. doi:10.3171/PED/2008/2/9/194. ISSN 1933-0707. PMID 18759601. S2CID 16364934. 8. ^ a b c d e f Azab, Waleed A.; Shohoud, Sherien A.; Elmansoury, Tamer M.; Salaheddin, Waleed; Nasim, Khurram; Parwez, Aslam (2014-07-24). "Blake's pouch cyst". Surgical Neurology International. 5: 112. doi:10.4103/2152-7806.137533. ISSN 2229-5097. PMC 4123264. PMID 25101207. 9. ^ a b c d e Bosemani, Thangamadhan; Orman, Gunes; Boltshauser, Eugen; Tekes, Aylin; Huisman, Thierry A. G. M.; Poretti, Andrea (2015-01-01). "Congenital Abnormalities of the Posterior Fossa". RadioGraphics. 35 (1): 200–220. doi:10.1148/rg.351140038. ISSN 0271-5333. PMID 25590398. 10. ^ a b c d e f Kollias, S. S.; Ball, W. S.; Prenger, E. C. (November 1993). "Cystic malformations of the posterior fossa: differential diagnosis clarified through embryologic analysis". Radiographics. 13 (6): 1211–1231. doi:10.1148/radiographics.13.6.8031352. ISSN 0271-5333. PMID 8031352. 11. ^ a b c "Orphanet: Isolated Dandy Walker malformation". www.orpha.net. Retrieved 2019-12-30. 12. ^ a b c d e f g h Klein, O.; Pierre-Kahn, A.; Boddaert, N.; Parisot, D.; Brunelle, F. (August 2003). "Dandy-Walker malformation: prenatal diagnosis and prognosis". Child's Nervous System. 19 (7–8): 484–489. doi:10.1007/s00381-003-0782-5. ISSN 0256-7040. PMID 12879343. S2CID 40944958. 13. ^ a b c "Dandy Walker Malformation". NORD (National Organization for Rare Disorders). Retrieved 2020-01-06. 14. ^ a b Lumenta, Christianto B.; Skotarczak, Ulrich (1995-03-01). "Long-term follow-up in 233 patients with congenital hydrocephalus". Child's Nervous System. 11 (3): 173–175. doi:10.1007/BF00570260. ISSN 1433-0350. PMID 7773979. S2CID 22265554. 15. ^ a b Sutton, J. Bland (1886-10-01). "The Lateral Recesses of the Fourth Ventricle; Their Relation to Certain Cysts and Tumours of the Cerebellum, and to Occipital Meningocele". Brain. 9 (3): 352–361. doi:10.1093/brain/9.3.352. ISSN 0006-8950. 16. ^ a b Dandy, Walter E.; Blackfan, Kenneth D. (1914-12-01). "AN EXPERIMENTAL, CLINICAL AND PATHOLOGICAL STUDY: Part 1.—Experimental Studies". American Journal of Diseases of Children. VIII (6): 406–482. doi:10.1001/archpedi.1914.02180010416002. ISSN 0096-8994. 17. ^ a b Taggart, John K.; Walker, A. Earl (1942-10-01). "Congenital Atresia of the Foramens of Luschka and Magendie". Archives of Neurology & Psychiatry. 48 (4): 583–612. doi:10.1001/archneurpsyc.1942.02290100083008. ISSN 0096-6754. 18. ^ a b c d e Bindal, Ajay K.; Storrs, Bruce B.; McLone, David G. (1990). "Management of the Dandy-Walker Syndrome". Pediatric Neurosurgery. 16 (3): 163–169. doi:10.1159/000120518. ISSN 1016-2291. PMID 2134009. 19. ^ a b Kumar, Raj; Jain, Manoj; Chhabra, Devendra (2001-05-01). "Dandy-Walker syndrome: different modalities of treatment and outcome in 42 cases". Child's Nervous System. 17 (6): 348–352. doi:10.1007/s003810000425. ISSN 1433-0350. PMID 11417415. S2CID 23789193. 20. ^ Pandurangi, Swapna; Pandurangi, Aditya; Matkar, Abhay; Shetty, Nithin; Patil, Preetam (January 2014). "Psychiatric Manifestations Associated With Mega Cisterna Magna". The Journal of Neuropsychiatry and Clinical Neurosciences. 26 (2): 169–171. doi:10.1176/appi.neuropsych.13040097. ISSN 0895-0172. PMID 24763763. 21. ^ Bindal, A. K.; Storrs, B. B.; McLone, D. G. (1990–1991). "Management of the Dandy-Walker syndrome". Pediatric Neurosurgery. 16 (3): 163–169. doi:10.1159/000120518. ISSN 1016-2291. PMID 2134009. 22. ^ Forzano, F.; Mansour, S.; Ierullo, A.; Homfray, T.; Thilaganathan, B. (2007). "Posterior fossa malformation in fetuses: a report of 56 further cases and a review of the literature". Prenatal Diagnosis. 27 (6): 495–501. doi:10.1002/pd.1722. ISSN 1097-0223. PMID 17367101. S2CID 21270692. 23. ^ Hammond, Christopher J.; Chitnavis, Bhupal; Penny, Christopher C.; Strong, Anthony J. (2002-01-01). "Dandy-Walker Complex and Syringomyelia in an Adult: Case Report and Discussion". Neurosurgery. 50 (1): 191–194. doi:10.1097/00006123-200201000-00028. ISSN 0148-396X. PMID 11844250. S2CID 45057003. 24. ^ Golden, Jeffrey A.; Rorke, Lucy B.; Bruce, Derek A. (1987). "Dandy-Walker Syndrome and Associated Anomalies". Pediatric Neurosurgery. 13 (1): 38–44. doi:10.1159/000120299. ISSN 1016-2291. PMID 3684814. 25. ^ Metry DW, Dowd CF, Barkovich AJ, Frieden IJ (July 2001). "The many faces of PHACE syndrome". J. Pediatr. 139 (1): 117–23. doi:10.1067/mpd.2001.114880. PMID 11445804. 26. ^ Poetke, M.; Frommeld, T.; Berlien, H. P. (December 2002). "PHACE syndrome: new views on diagnostic criteria". European Journal of Pediatric Surgery. 12 (6): 366–374. doi:10.1055/s-2002-36849. ISSN 0939-7248. PMID 12548487. 27. ^ a b c Imataka, George; Yamanouchi, Hideo; Arisaka, Osamu (2007). "Dandy–Walker syndrome and chromosomal abnormalities". Congenital Anomalies. 47 (4): 113–118. doi:10.1111/j.1741-4520.2007.00158.x. ISSN 1741-4520. PMID 17988252. S2CID 32024323. 28. ^ Pascual-Castroviejo, I.; Velez, A.; Pascual-Pascual, S. I.; Roche, M. C.; Villarejo, F. (1991-04-01). "Dandy-Walker malformation: analysis of 38 cases". Child's Nervous System. 7 (2): 88–97. doi:10.1007/BF00247863. ISSN 1433-0350. PMID 1863935. S2CID 2733281. 29. ^ Asai, Akio; Hoffman, Harold J.; Hendrick, Bruce; Humphreys, Robin P. (1989). "Dandy-Walker Syndrome: Experience at the Hospital for Sick Children, Toronto". Pediatric Neurosurgery. 15 (2): 66–73. doi:10.1159/000120445. ISSN 1423-0305. PMID 2635298. 30. ^ "OMIM Entry - # 200990 - ACROCALLOSAL SYNDROME; ACLS". www.omim.org. Retrieved 2020-01-06. 31. ^ Baker, Kate; Beales, Philip L. (2009). "Making sense of cilia in disease: The human ciliopathies". American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 151C (4): 281–295. doi:10.1002/ajmg.c.30231. ISSN 1552-4876. PMID 19876933. S2CID 7442991. 32. ^ Badano JL, Mitsuma N, Beales PL, Katsanis N (2006). "The ciliopathies: an emerging class of human genetic disorders". Annu Rev Genom Hum Genet. 7: 125–48. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. S2CID 40223129. 33. ^ Kaplan, Lawrence C. (1985). "Congenital Dandy Walker malformation associated with first trimester warfarin: A case report and literature review". Teratology. 32 (3): 333–337. doi:10.1002/tera.1420320302. ISSN 1096-9926. PMID 4082063. 34. ^ Dhandapani, S; Sahoo, SK (Dec 2019). "Developmental Retrocerebellar Cysts: A New Classification for Neuroendoscopic Management and Systematic Review". World Neurosurg. 132: e654–e664. doi:10.1016/j.wneu.2019.08.052. PMID 31442641. 35. ^ Yüceer N, Mertol T, Arda N (2007). "Surgical treatment of 13 pediatric patients with Dandy–Walker syndrome". Pediatr Neurosurg. 43 (5): 358–63. doi:10.1159/000106383. PMID 17785999. S2CID 2289323. This article incorporates public domain material from the United States Government document: "Dandy-Walker Syndrome Information Page". ## Further reading[edit] * Metry Phaces article in the Journal of Pediatrics, July 2001 * E-medicine webpage definition * Dandy–Walker Malformation article from Pan Arab Journal of Neurosurgery ## External links[edit] Classification D * ICD-10: Q03.1 * ICD-9-CM: 742.3 * OMIM: 220200 * MeSH: D003616 * DiseasesDB: 3449 External resources * eMedicine: radio/206 * 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	Dandy–Walker malformation	c0010964	7,415	wikipedia	https://en.wikipedia.org/wiki/Dandy%E2%80%93Walker_malformation	2021-01-18T19:02:03	{"gard": ["6242"], "mesh": ["D003616"], "umls": ["C0010964"], "icd-9": ["742.3"], "orphanet": ["217"], "wikidata": ["Q733493"]}
A number sign (#) is used with this entry because of evidence that hereditary sensory neuropathy type IF (HSN1F) is caused by heterozygous mutation in the ATL3 gene (609369) on chromosome 11q13. Description Hereditary sensory neuropathy type IF is an autosomal dominant sensory neuropathy affecting the lower limbs. Distal sensory impairment becomes apparent during the second or third decade of life, resulting in painless ulceration of the feet with poor healing, which can progress to osteomyelitis, bone destruction, and amputation. There is no autonomic involvement, spasticity, or cognitive impairment (summary by Kornak et al., 2014). For a discussion of genetic heterogeneity of HSN, see HSAN1A (162400). Clinical Features Kornak et al. (2014) reported a 4-generation German family in which 8 individuals had sensory neuropathy. Four living affected individuals were studied in detail. The patients first noticed abnormal calluses on the feet and valgus deformity of the great toes between ages 14 and 33 years. Thereafter, the patients developed painless chronic ulcerations and fractures of the distal lower limbs, with delayed healing and occasional bone destruction. Radiographs showed osteomyelitis and acroosteolysis. The most severely affected individual had to have amputation below the knees. Sensory nerve conduction studies indicated an axonal sensory neuropathy. Motor nerve conduction was normal, consistent with lack of muscle atrophy or pes cavus. The upper limbs were not affected, and autonomic function was normal. All had normal psychomotor development; spasticity was not present. Two sisters from a 3-generation Spanish family had a similar disorder. They developed bilateral hyperkeratosis and plantar ulcers at ages 14 and 16 years, respectively. They had distal sensory impairment of the lower limbs, affecting touch, pain, and temperature. Muscle strength was normal, although tendon reflexes were diminished and absent at the ankles. Electrophysiologic studies showed a sensory axonal neuropathy in the lower extremities. Radiographs of both patients showed bone destruction of some toes, necessitating amputation. The mother and maternal grandmother reportedly had similar features. Inheritance The transmission pattern of HSN1F in the families reported by Kornak et al. (2014) was consistent with autosomal dominant inheritance. Molecular Genetics In affected members of a German family with autosomal dominant hereditary sensory neuropathy, Kornak et al. (2014) identified a heterozygous missense mutation in the ATL3 gene (Y192C; 609369.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Screening of the ATL3 gene in 115 probands with various types of sensory neuropathy identified the same heterozygous Y192C substitution in 3 affected members of a Spanish family with a similar phenotype. Haplotype analysis suggested a founder effect. In vitro functional expression studies in COS-7 cells showed that the Y192C mutation caused mislocalization of the protein and had a dominant-negative disruptive effect on the regular structure of the endoplasmic reticulum. The findings contributed to the concept that pathogenic alterations in membrane-shaping proteins contribute to axonal degeneration. INHERITANCE \- Autosomal dominant SKELETAL Feet \- Hallux valgus \- Foot arthropathy \- Bony destruction \- Acroosteolysis \- Osteomyelitis \- Chronic ulceration due to sensory neuropathy \- Impaired bone healing SKIN, NAILS, & HAIR Skin \- Ulcers, distal, painless, due to sensory neuropathy \- Foot calluses \- Hyperkeratosis \- Plantar ulcers NEUROLOGIC Peripheral Nervous System \- Distal sensory impairment to pain, temperature, and touch, lower limbs \- Sensory axonal neuropathy \- Hyporeflexia of the lower limbs \- Absent ankle jerks MISCELLANEOUS \- Onset in first or second decade \- Two unrelated families have been reported (last curated February 2014) MOLECULAR BASIS \- Caused by mutation in the atlastin GTPase 3 gene (ATL3, 609369.0001 ) ▲ 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	NEUROPATHY, HEREDITARY SENSORY, TYPE IF	c0020071	7,416	omim	https://www.omim.org/entry/615632	2019-09-22T15:51:22	{"doid": ["0070154"], "mesh": ["D009477"], "omim": ["615632"], "orphanet": ["36386"], "synonyms": ["Alternative titles", "HSN IF"]}
A form of lissencephaly with cerebellar hypoplasia characterized by pronounced microcephaly (at least ± 3 SD), intellectual disability, spastic diplegia and moderate to severe cerebellar hypoplasia involving both vermis and hemispheres. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Lissencephaly with cerebellar hypoplasia type D	c4274991	7,417	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100014	2021-01-23T17:36:48	{"icd-10": ["Q04.3"]}
This article is about the kind of muscle injury. For other uses, see Strain (disambiguation). Not to be confused with Sprain. Strain Other namesMuscle strain, pulled muscle, torn muscle Two images of the same strain to the hamstring and associated bruising. One of the pictures was shot through a mirror. SpecialtyEmergency medicine 3D Medical Animation Depicting Strain A strain is an acute or chronic soft tissue injury that occurs to a muscle, tendon, or both. The equivalent injury to a ligament is a sprain.[1] Generally, the muscle or tendon overstretches and partially tears, under more physical stress than it can withstand, often from a sudden increase in duration, intensity, or frequency of an activity. Strains most commonly occur in the foot, leg, or back. Immediate treatment typically includes five steps abbreviated as P.R.I.C.E.: protection, rest, ice, compression, elevation. ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Risk factors * 3 Treatment * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] Typical signs and symptoms of a strain include pain, functional loss of the involved structure, muscle weakness, contusion, and localized inflammation.[2] A strain can range from mildly annoying to very painful, depending on the extent of injury.[1] ## Cause[edit] A strain can occur as a result of improper body mechanics with any activity (e.g., contact sports, lifting heavy objects) that can induce mechanical trauma or injury. Generally, the muscle or tendon overstretches and is placed under more physical stress than it can withstand.[1] Strains commonly result in a partial or complete tear of a tendon or muscle, or they can be severe in the form of a complete tendon rupture. Strains most commonly occur in the foot, leg, or back.[3] Acute strains are more closely associated with recent mechanical trauma or injury. Chronic strains typically result from repetitive movement of the muscles and tendons over a long period of time.[1] Degrees of Injury (as classified by the American College of Sports Medicine):[4] * First degree (mildest) – little tissue tearing; mild tenderness; pain with full range of motion. * Second degree – torn muscle or tendon tissues; painful, limited motion; possibly some swelling or depression at the spot of the injury. * Third degree (most severe) – limited or no movement; severe acute pain, though sometimes painless straight after the initial injury To establish a uniform definition amongst healthcare providers, in 2012 a Consensus Statement on suggested new terminology and classification of muscle injuries was published.[5] The classification suggestion were: The major difference suggested was the use of "indirect" muscle injury verse "grade 1" to provide a subclassifications when advanced images were negative. Indirect Muscle Injury FUNCTIONAL (Negative MSK US & MRI)[6] * Type 1: Overexertion-related Muscle Disorder * Type 1a: Fatigue induced * Type 1b: DOMS • Type 2: Neuromuscular muscle disorder * * Type 2a: Spine-Related * Type 2b: Muscle-Related STRUCTURAL MUSCLE INJURY (Positive MSK US & MRI)[6] • Type 3: Partial Muscle Tear • Type 4: (Sub) total tear DIRECT MUSCLE INJURY • Bump or Cut: Contact-related ### Risk factors[edit] Although strains are not restricted to athletes and can happen while doing everyday tasks, people who play sports are more at risk for developing a strain. It is common for an injury to develop when there is a sudden increase in duration, intensity, or frequency of an activity.[3] ## Treatment[edit] The first-line treatment for a muscular strain in the acute phase include five steps commonly known as P.R.I.C.E.[7][8] * Protection: Apply soft padding to minimize impact with objects. * Rest: Rest is necessary to accelerate healing and reduce the potential for re-injury. * Ice: Apply ice to induce vasoconstriction, which will reduce blood flow to the site of injury. Never ice for more than 20 minutes at a time. * Compression: Wrap the strained area with a soft-wrapped bandage to reduce further diapedesis and promote lymphatic drainage. * Elevation: Keep the strained area as close to the level of the heart as is possible in order to promote venous blood return to the systemic circulation. Immediate treatment is usually an adjunctive therapy of NSAIDs and Cold compression therapy. Cold compression therapy acts to reduce swelling and pain by reducing leukocyte extravasation into the injured area.[9][10] NSAIDs such as Ibuprofen/paracetamol work to reduce the immediate inflammation by inhibiting Cox-1 and Cox-2 enzymes, which are the enzymes responsible for converting arachidonic acid into prostaglandin. However, NSAIDs, including aspirin and ibuprofen, affect platelet function (this is why they are known as "blood thinners") and should not be taken during the period when tissue is bleeding because they will tend to increase blood flow, inhibit clotting, and thereby increase bleeding and swelling. After the bleeding has stopped, NSAIDs can be used with some effectiveness to reduce inflammation and pain.[11] A new treatment for acute strains is the use of platelet rich plasma (PRP) injections which have been shown to accelerate recovery from non-surgical muscular injuries.[12] It is recommended that the person injured should consult a medical provider if the injury is accompanied by severe pain, if the limb cannot be used, or if there is noticeable tenderness over an isolated spot. These can be signs of a broken or fractured bone, a sprain, or a complete muscle tear.[13] ## See also[edit] * Achilles tendon rupture * Pulled hamstring * Repetitive strain injury ## References[edit] 1. ^ a b c d "Sprains and Strains: In-Depth". National Institutes of Health. January 2015. Retrieved 5 December 2020. 2. ^ Brumitt, Jason; Cuddeford, Tyler (November 2015). "Current Concepts of Muscle and Tendon Adaptation to Strength and Conditioning". International Journal of Sports Physical Therapy. 10 (6): 748–759. ISSN 2159-2896. PMC 4637912. PMID 26618057. 3. ^ a b Mulcahey, Mary K. (June 2020). "Sprains, Strains and Other Soft-Tissue Injuries". OrthoInfo. American Academy of Orthopaedic Surgeons. Retrieved 5 December 2020. 4. ^ Millar, A. Lynn (2011). "Sprains, Strains and Tears". American College of Sports Medicine. Retrieved 5 December 2020. 5. ^ Mueller-Wohlfahrt, Hans-Wilhelm; Haensel, Lutz; Mithoefer, Kai; Ekstrand, Jan; English, Bryan; McNally, Steven; Orchard, John; Dijk, C. Niek van; Kerkhoffs, Gino M.; Schamasch, Patrick; Blottner, Dieter; Swaerd, Leif; Goedhart, Edwin; Ueblacker, Peter (1 October 2012). "Terminology and classification of muscle injuries in sport: The Munich consensus statement". Br J Sports Med. 47 (6): bjsports–2012–091448. doi:10.1136/bjsports-2012-091448. ISSN 0306-3674. PMC 3607100. PMID 23080315. 6. ^ a b Stoller, David W. (2007). Magnetic Resonance Imaging in Orthopaedics and Sports Medicine. Lippincott Williams & Wilkins. ISBN 9780781773577. 7. ^ MedicalMnemonics.com: 235 8. ^ Järvinen, T.A.H.; et al. (April 2007). "Muscle injuries: optimising recovery". Best Practice and Research in Clinical Rheumatology. 21 (2): 317–331. doi:10.1016/j.berh.2006.12.004. PMID 17512485. 9. ^ Prentice, William E. (2014). "Tissue Response to Injury" (PDF). Principles of Athletic Training. ISBN 0078022649. Archived from the original (PDF) on 2017-10-31. 10. ^ "Clinical Studies on Cold and Compression Therapy" (PDF). Endomed, Inc. December 2007. Retrieved 5 December 2020. 11. ^ Day, Richard O.; Graham, Garry G. (1 December 2004). "The Vascular Effects of COX-2 selective inhibitors". Australian Prescriber. 27 (6): 142–145. doi:10.18773/austprescr.2004.119. 12. ^ Halpern, Brian C.; Chaudhury, Salma; Rodeo, Scott A. (2012-07-01). "The role of platelet-rich plasma in inducing musculoskeletal tissue healing". HSS Journal. 8 (2): 137–145. doi:10.1007/s11420-011-9239-7. ISSN 1556-3316. PMC 3715623. PMID 23874254. 13. ^ Neustaedter, Randy. "Natural Treatment for Injuries". Retrieved 5 December 2020. ## External links[edit] Classification D * ICD-10: M62.6, T14.3 * ICD-9-CM: 848.9 * MeSH: D013180 * v * t * e Dislocations/subluxations, sprains and strains Joints and ligaments Head and neck * Dislocation of jaw * Whiplash Shoulder and upper arm * GH (Dislocated shoulder) * AC (Separated shoulder) * ALPSA lesion * SLAP tear * Bankart lesion Elbow and forearm * Pulled elbow * Gamekeeper's thumb Hip and thigh * Hip dislocation Knee and leg * Tear of meniscus * Anterior cruciate ligament injury * Unhappy triad * Patellar dislocation * Knee dislocation Ankle and foot * Sprained ankle (High ankle sprain) * Turf toe Muscles and tendons Shoulder and upper arm * Rotator cuff tear Hip and thigh * Pulled hamstring Knee and leg * Patellar tendon rupture * Achilles tendon rupture * Shin splints [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Strain (injury)	c0080194	7,418	wikipedia	https://en.wikipedia.org/wiki/Strain_(injury)	2021-01-18T18:31:06	{"mesh": ["D013180"], "umls": ["C0080194"], "icd-9": ["848.9"], "icd-10": ["M62.6", "T14.3"], "wikidata": ["Q576145"]}
Erythromelanosis follicularis faciei et colli SpecialtyDermatology Erythromelanosis follicularis faciei et colli is an erythematous pigmentary disease involving the follicles, characterized by a reddish-brown, sharply demarcated, symmetrical discoloration involving the preauricular and maxillary regions.[1]:775–6 ## See also[edit] * Pigmentatio reticularis faciei et colli * 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. This condition of the skin appendages 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	Erythromelanosis follicularis faciei et colli	c0263577	7,419	wikipedia	https://en.wikipedia.org/wiki/Erythromelanosis_follicularis_faciei_et_colli	2021-01-18T18:39:33	{"umls": ["C0263577"], "wikidata": ["Q5396486"]}
A number sign (#) is used with this entry because of evidence that susceptibility to thyrotoxic periodic paralysis-1 (TTPP1) is conferred by variation in the CACNA1S gene on chromosome 1q32. Description Thyrotoxic periodic paralysis is a sporadic muscle disorder characterized by episodic attacks of weakness associated with hypokalemia in individuals with hyperthyroidism. The paralysis resolves upon treatment of hyperthyroidism. The disorder is most common among males of Asian descent, including Chinese, Japanese, Vietnamese, Filipino, and Koreans, although it occurs less commonly in individuals of Caucasian background. Thyrotoxic periodic paralysis is clinically similar to hereditary hypokalemic periodic paralysis (HOKPP; 170400), but the paralysis in TTPP occurs only in the presence of hyperthyroidism. TTPP can also be precipitated by factors that result in hypokalemia, such as carbohydrate ingestion and rest after exercise (review by Kung, 2006). ### Genetic Heterogeneity of Thyrotoxic Periodic Paralysis See also TTPP2 (613239), conferred by variation in the KCNJ18 gene (613236) on chromosome 17p11, and TTPP3 (614834), mapped to chromosome 17q24. Clinical Features Among 1,366 consecutive Southern Chinese patients with thyrotoxicosis, McFadzean and Yeung (1967) found that 25 had a history of 1 or more attacks of periodic paralysis, and that 23 of the 25 were male. Bernard et al. (1972) reported thyrotoxic periodic paralysis in 5 unrelated Californian males of Japanese, Mexican, and Filipino descent. The patients ranged in age from 18 to 36 years. All presented with a chief complaint of periodic muscle weakness and paralysis in the lower limbs, often occurring at night or in the morning or after a large meal. All were subsequently found to have variable clinical features of hyperthyroidism, including palpitations, hypertension, increased heart rate, nervousness, sweating, and weight loss. However, some of the patients had very mild features of hyperthyroidism. When measured, serum potassium was very low during the episodes. All patients had complete recovery after proper treatment for hyperthyroidism, and most had no significant family history. Bernard et al. (1972) noted that some patients may have subtle or even absent clinical signs of hyperthyroidism, which should be evaluated by laboratory studies. Layzer and Goldfield (1974) observed periodic paralysis in a Japanese-American male who 'abused' thyroid hormone. Ali (1975) reported a 30-year-old man of Scottish descent who presented with weight loss, palpitations, sweating, and heat intolerance over 18 months. He also reported episodic attacks of weakness in the legs that usually occurred after awakening, but could come at any time. He had no weakness between attacks. There was no relevant family history. Physical examination showed thyrotoxicosis, with exophthalmos, an enlarged thyroid gland, and hyperreflexia. During an attack, serum potassium was severely depleted and he had complete flaccid paralysis from the waist down associated with absent reflexes. Proper treatment of the hyperthyroidism resulted in complete clinical recovery with no further episodes of paralysis. Leung (1985) observed thyrotoxicosis and periodic paralysis in 4 adult members of a Chinese family: a mother and 3 children, including 2 males and 1 female. Two had Graves disease (275000) and Hashimoto thyroiditis (140300) as evidenced by the presence of thyroid antibodies and elevated thyroxine levels. The other 2 were not available for study. Kilpatrick et al. (1994) found 6 reports of thyrotoxic hypokalemic periodic paralysis in African Americans and described 4 additional cases, all in males. They concluded that the disorder may be more frequent in blacks than previously suspected and should be considered when patients present with unexplained hypokalemia, muscular weakness, and rhabdomyolysis. Inheritance A specific genetic basis for TTPP is suggested by the fact that although occasional cases occur in Caucasians (e.g., Ali, 1975; Shah et al., 1979), the disorder is seen predominantly in Asians. Hsu (1978) stated that Chinese males with thyrotoxicosis who have HLA types BW22 and BW17 and do not have BW46 are most susceptible to periodic paralysis. Thus, thyrotoxic periodic paralysis may be due to a genetic peculiarity of muscle membranes. Yeung (1981) stated that multiple cases in families had been observed. Molecular Genetics Kung et al. (2004) studied 97 male patients with thyrotoxic periodic paralysis, 77 male patients with Graves disease without thyrotoxic periodic paralysis, and 100 normal male subjects, all Chinese. They detected 12 single-nucleotide polymorphisms (SNPs) in the CACNA1S gene, 3 of which were novel. Significant differences in the SNP genotype distribution between subjects with thyrotoxic periodic paralysis compared with Graves disease controls and normal controls were seen at a 5-prime flanking region SNP (114208.0005) and 2 intronic SNPs (114208.0006, 114208.0007). The authors concluded that because these SNPs lie at or near a thyroid hormone-responsive element (TRE), it is possible that they may affect the binding affinity of the TRE and modulate the stimulation of thyroid hormone on the Cav1.1 gene. ### Associations Pending Confirmation Dias Da Silva et al. (2002) identified an arg83-to-his (R83H; 604433.0001) substitution in the KCNE3 gene in 1 of 15 patients with thyrotoxic hypokalemic periodic paralysis. The patient was a 44-year-old Caucasian man of Portuguese descent who experienced episodic paralysis for 2 years before developing thyrotoxicosis caused by Graves disease (275000). Two of his 3 offspring, all asymptomatic, were found to have the same mutation. However, Sternberg et al. (2003) and Jurkat-Rott and Lehmann-Horn (2004) concluded that the R83H variant does not play a causative role in periodic paralysis and that it is a polymorphism. See 604433.0001 for further discussion. Tang et al. (2004) did not identify the R83H substitution, or any mutations in the KCNE3 gene, among 79 Chinese patients with thyrotoxic hypokalemic periodic paralysis. Population Genetics The overall incidence of TTPP in Chinese and Japanese thyrotoxic patients had been estimated at 1.8 and 1.9%, respectively. In North America, the incidence is much lower, at about 0.1 to 0.2% in thyrotoxic patients. The male to female ratio ranges from 17:1 to 70:1 (review by Kung, 2006). INHERITANCE \- Autosomal dominant GROWTH Weight \- Weight loss due to hyperthyroidism HEAD & NECK Eyes \- Exophthalmos due to hyperthyroidism CARDIOVASCULAR Heart \- Tachycardia due to hyperthyroidism \- Palpitations Vascular \- Hypertension due to hyperthyroidism MUSCLE, SOFT TISSUES \- Muscle paralysis, episodic \- Muscle weakness, episodic \- Lower limbs more often affected \- Proximal muscles more often affected \- Recovery between attacks \- Muscle aches, cramps NEUROLOGIC Central Nervous System \- Tremor due to hyperthyroidism Peripheral Nervous System \- Hypo- or areflexia during attacks METABOLIC FEATURES \- Increased sweating due to hyperthyroidism ENDOCRINE FEATURES \- Goiter \- Enlarged thyroid gland \- Hyperthyroidism LABORATORY ABNORMALITIES \- Hypokalemia during attacks \- Increased thyroid hormone \- Decreased TSH MISCELLANEOUS \- Genetic heterogeneity \- More frequent in males \- Usually occurs in young adulthood \- Muscle weakness occurs only in the presence of hyperthyroidism \- More frequent in individuals of Asian descent \- Complete recovery upon treatment of hyperthyroidism \- Attacks precipitated by hypokalemia, administration of glucose or insulin, heavy carbohydrate consumption, stress, fatigue, rest after exercise \- Attacks may present during or after sleep MOLECULAR BASIS \- Susceptibility conferred by mutation in the voltage-dependent calcium channel, L type, alpha-1S subunit gene (CACNA1S, 114208.0005 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	THYROTOXIC PERIODIC PARALYSIS, SUSCEPTIBILITY TO, 1	c0268446	7,420	omim	https://www.omim.org/entry/188580	2019-09-22T16:32:32	{"omim": ["188580"], "orphanet": ["79102"]}
Chronic sclerosing sialadenitis SpecialtyDentistry Chronic sclerosing sialadenitis is a chronic (long-lasting) inflammatory condition affecting the salivary gland. Relatively rare in occurrence, this condition is benign, but presents as hard, indurated and enlarged masses that are clinically indistinguishable from salivary gland neoplasms or tumors. It is now regarded as a manifestation of IgG4-related disease.[1] Involvement of the submandibular glands is also known as Küttner's tumor, named after Hermann Küttner (1870–1932), a German Oral and Maxillofacial Surgeon, who reported four cases of submandibular gland lesions for the first time in 1896.[2] ## Contents * 1 Presentation * 2 Histological features * 3 Pathogenesis * 4 Diagnosis * 5 Existing treatment * 6 See also * 7 References * 8 External links ## Presentation[edit] The inflammatory lesions in Küttner's tumor may occur on one side (unilateral) or both sides (bilateral), predominantly involving the submandibular gland,[3] but is also known to occur in other major and minor salivary glands,[4] including the parotid gland.[5][6] Overall, salivary gland tumors are relatively rare, with approximately 2.5–3 cases per 100,000 people per year seen in the Western world; however, salivary gland malignancies account for 3–5% of all head and neck cancers.[7] However, salivary tumors show a great deal of morphological diversity, as well as variations in the nature of the lesion (malignant vs. benign): approximately 20% to 25% of parotid tumors, 35% to 40% of submandibular tumors, and more than 90% of sublingual gland tumors are malignant.[8] This situation underscores the diagnostic challenges in respect of Küttner's tumor; despite being benign, this condition mimics the clinical appearance of malignancy in the salivary gland. The swollen masses of Küttner's tumor are generally painful, and patients are advised surgical resection (known as 'sialadenectomy') of a part or whole of the glandular tissue upon suspicion of possible malignancy. It is only upon post-surgical histopathology of the excised mass that the diagnosis of Küttner's tumor is definitively made. ## Histological features[edit] The histopathological features that characterize Küttner's tumor[9] include: * Heavy infiltration of the glandular tissue by lymphocytes (predominantly activated B-cells and helper T-cells) as well as plasma cells (collectively known as 'Lymphoplasmacytic Infiltrate'). * Presence of reactive lymphoid follicles in the infiltrate, marked by a lack of atypical lymphoid cells (this is in sharp contrast to the presentations in lymphoma). * Atrophy and loss of acini (groups of secretory cells found in the salivary glands). * Encasement of the glandular ducts in thick fibrous tissues, as a result of chronic presence of inflammatory infiltrate in that area - a condition known as periductal fibrosis. * Eventual periductal and interlobular (inside the gland) sclerosis (replacement of regular tissue with hard connective tissue). ## Pathogenesis[edit] The cause and pathogenesis of this chronic condition are not very well understood. Several factors have been postulated: * Formation of a hard salivary calculus or sialolith by accumulation of calcium salts in the duct of the salivary gland (a process known as Sialolithiasis). This has been proposed as the most common cause for Küttner's tumor of the submandibular gland, with sialoliths observed in an appreciable proportion of cases.[10][11] However, sialolith involvement may not be found in many cases. * Abnormalities of the salivary gland ducts leading to excessive accumulation or retention of ductal secretions, which can excite chronic inflammations.[6] * Immune, especially autoimmune, cause[12] \- which has gained steam, given the observation that the tissue of the glands is overrun with lymphoid immune cells[13] and fibrous connective tissue, as well as corroboration from markedly similar lesions (with histologic and immunohistochemical findings) seen elsewhere in the body.[14][15] The presence of abundant Immunoglobulin G4 (IgG4) associated with Plasma cells infiltrating into the salivary glands, as well as increased serum IgG4 concentration, has been noted with patients with Küttner's tumor.[16][17][18] This chronic condition is primarily observed in adult (40–70 years) patients. However, Küttner's tumor, with prominent immunopathological features, has been described in an 11-year-old boy in Brazil in 2012.[19] ## Diagnosis[edit] Given the difficulties of a definitive pre-operative diagnosis, the clinical entity of Küttner's tumor has so far remained significantly under-reported and under-recognized. In recent times, armed with a better understanding of the occurrences and observable features of this condition, surgeons are increasingly depending upon pre-operative ultrasonography along with Fine-needle aspiration cytological (FNAC) examinations to make an accurate presumptive diagnosis,[20] and according to one estimate, about 44% of patients undergoing submandibular resection are found to have this condition.[20] In the ultrasonogram, Küttner's tumor is characterized by a diffuse, heterogeneous zone of echo-shadows.[21] The FNAC finds cells greatly reduced in number (called 'paucicellularity') along with scattered tubular ducts against a backdrop of lymphoplasmacytic infiltration and fibrous depositions.[21] There may be a reduced but moderate number of cells and ducts enveloped in fibrous sheaths, as well as fibrous proliferation of the gland's septa.[22] The cytologic findings by themselves may not be specific, and the diagnosis requires adjunct consideration of both the ultrasonogram and clinical presentation. Application of magnetic resonance imaging (MRI) has been tried to non-invasively examine the morphological variations in Küttner's tumor and differentiate them from those seen in malignant tumors;[23] while MRI findings of the affected tissue and the pattern of cellular infiltration may offer some diagnostic clues for this condition, so far the results have been inconclusive.[23] ## Existing treatment[edit] Standard, and most effective, therapy to date is glandular sialadenectomy, which is associated with fairly low operative morbidity; however, in recent times, the administration of steroid (which can shrink the inflammatory lesion and is known to reduce serum IgG4 values) has been considered favorably,[16][17] and may be useful in younger patients or those who refuse surgery. ## See also[edit] * Sialadenitis ## References[edit] 1. ^ John H. Stone; Arezou Khosroshahi; Vikram Deshpande; et al. (October 2012). "Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations". Arthritis & Rheumatism. 64 (10): 3061–3067. doi:10.1002/art.34593. PMC 5963880. PMID 22736240. 2. ^ Küttner, H (1896). "Ueber entzündliche Tumoren der submaxillar-speicheldrüse". Beiträge zur Klinischen Chirurgie. 15: 815–828. hdl:2027/uc1.b3731679. 3. ^ Kiverniti, E; Singh A; Clarke P (2008). "Küttner's tumour: an unusual cause of salivary gland enlargement". Hippokratia. 12 (1): 56–58. PMC 2532958. PMID 18923750. 4. ^ Blanco, Mario; Mesko T; Cura M; Cabello-Inchausti B (2003). "Chronic sclerosing sialadenitis (Kuttner's tumor): unusual presentation with bilateral involvement of major and minor salivary glands". Annals of Diagnostic Pathology. 7 (1): 25–30. doi:10.1053/adpa.2003.50004. PMID 12616471. 5. ^ Beriat, GK; Akmansu SH; Kocatürk S; Ataoğlu O (2010). "Chronic Sclerosing Sialadenitis (Küttner's tumour) of the Parotid Gland". Malaysian Journal of Medical Sciences. 17 (4): 57–61. PMC 3216182. PMID 22135562. 6. ^ a b de Vicente, JC; López-Arranz E; García J; López-Arranz JS (2003). "Chronic sclerosing sialadenitis of the parotid gland". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 96 (1): 77–80. doi:10.1016/s1079-2104(03)00096-9. PMID 12847448. 7. ^ Speight, PM; Barrett AW (2002). "Salivary gland tumours". Oral Diseases. 8 (5): 229–240. doi:10.1034/j.1601-0825.2002.02870.x. PMID 12363107. 8. ^ National Cancer Institute (NCI/NIH) (20 July 2012). "General Information About Salivary Gland Cancer". cancer.gov. Retrieved 15 November 2013. 9. ^ Chan ACL; Chan JKC; Abbondanzo SL (2005). "Chapter 5. Tumours of the Salivary Glands" (PDF). In Leon Barnes; John W. Eveson; Peter Reichart; David Sidransky (eds.). World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours. Lyon, France: WHO/IARC Press. p. 278. ISBN 92-83-22417-5. Retrieved 15 November 2013. 10. ^ Epivatianos, A; Harrison JD; Dimitriou T (2006). "Ultrastructural and histochemical observations on microcalculi in chronic submandibular sialadenitis". Journal of Oral Pathology and Medicine. 16 (10): 514–517. doi:10.1111/j.1600-0714.1987.tb00683.x. PMID 3127566. 11. ^ Chan, JKC (1998). "Kuttner tumor (chronic sclerosing sialadenitis) of the submandibular gland: an underrecognized entity". Advances in Anatomic Pathology. 5 (4): 239–51. doi:10.1097/00125480-199807000-00004. PMID 9859756. 12. ^ Ikeda, M; Ikui A; Tanaka M; Omori H; Tomita H (1994). "Immunohistopathological investigation on unspecific chronic sclerosing sialadenitis of the submandibular gland (Kuttner tumor)". Auris Nasus Larynx. 21 (2): 103–110. doi:10.1016/s0385-8146(12)80028-9. PMID 7993223. 13. ^ Tiemann, M; Teymoortash A; Schrader C; Werner JA; Parwaresch R; Seifert G; Klöppel G (2002). "Chronic sclerosing sialadenitis of the submandibular gland is mainly due to a T lymphocyte immune reaction". Modern Pathology. 15 (8): 845–852. doi:10.1097/01.MP.0000022280.72359.04. PMID 12181270. 14. ^ Tsuneyama, K; Saito K; Ruebner BH; Konishi I; Nakanuma Y; Gershwin ME (2000). "Immunological similarities between primary sclerosing cholangitis and chronic sclerosing sialadenitisreport of the overlapping of these two autoimmune diseases". Digestive Diseases and Sciences. 45 (2): 366–372. doi:10.1023/A:1005429130150. PMID 10711453. 15. ^ Sekine, S; Nagata M; Watanabe T (1999). "Chronic sclerosing sialadenitis of the submandibular gland associated with idiopathic retroperitoneal fibrosis". Pathology International. 49 (7): 663–667. doi:10.1046/j.1440-1827.1999.00926.x. PMID 10504530. 16. ^ a b Kamisawa, T; Nakajima H; Hishima T (2006). "Close correlation between chronic sclerosing sialadenitis and immunoglobulin G4". Internal Medicine Journal. 36 (8): 527–529. doi:10.1111/j.1445-5994.2006.01119.x. PMID 16866659. 17. ^ a b Nagai, K; Andoh K; Ogata A; Aoki N; Nakamura N; Hosaka H; Kurihara R (2010). "A new category for chronic sclerosing sialadenitis as an IgG4 related syndrome". BMJ Case Reports. 2010: bcr1020092412. doi:10.1136/bcr.10.2009.2412. PMC 3028012. PMID 22448185. 18. ^ Cheuk, W; Yuen HK; Chu SY; Chiu EK; Lam LK; Chan JK (2008). "Lymphadenopathy of IgG4-related sclerosing disease". Am J Surg Pathol. 32 (5): 671–681. doi:10.1097/PAS.0b013e318157c068. PMID 18344866. 19. ^ Melo, JC; Kitsko D; Reyes-Múgica M (2012). "Pediatric chronic sclerosing sialadenitis: Küttner tumor". Pediatric and Developmental Pathology. 15 (2): 165–169. doi:10.2350/11-04-1023-OA.1. PMID 21985393. 20. ^ a b Chow, TL; Chan TT; Choi CY; Lam SH (2008). "Kuttner's tumour (chronic sclerosing sialadenitis) of the submandibular gland: a clinical perspective" (PDF). Hong Kong Medical Journal. 14 (1): 46–9. PMID 18239243. Retrieved 15 November 2013. 21. ^ a b Chou, YH; Tiu CM; Li WY; Liu CY; Cheng YC; Chiou HJ; Chiou SY; Wang HK; Hung GS (2005). "Chronic sclerosing sialadenitis of the parotid gland: diagnosis using color Doppler sonography and sonographically guided needle biopsy". Journal of Ultrasound in Medicine. 24 (4): 551–555. doi:10.7863/jum.2005.24.4.551. PMID 15784774. Retrieved 17 November 2013. 22. ^ Cheuk, W; Chan, JKC (2002). "Kuttner Tumor of the Submandibular Gland: Fine-Needle Aspiration Cytologic Findings of Seven Case" (PDF). American Journal of Clinical Pathology. 117 (1): 103–108. doi:10.1309/g9t3-22mh-q7kl-g2dl. PMID 11791589. Retrieved 5 December 2013. 23. ^ a b Abu, A; Motoori K; Yamamoto S; Hanazawa T; Nagai Y; Kaneoya K; Ito H (2008). "MRI of chronic sclerosing sialoadenitis". British Journal of Radiology. 81 (967): 531–536. doi:10.1259/bjr/38960620. PMID 18316344. ## External links[edit] Classification D * ICD-10: Xxx.x * ICD-9-CM: xxx * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Chronic sclerosing sialadenitis	c2826557	7,421	wikipedia	https://en.wikipedia.org/wiki/Chronic_sclerosing_sialadenitis	2021-01-18T18:39:21	{"wikidata": ["Q17083598"]}
The arm of a patient with familial multiple lipomatosis. Familial multiple lipomatosis is a hereditary adipose tissue disorder that is characterized by the formation of multiple lipomas that occur in a particular distribution.[1] The lipomas are well-encapsulated, slow-growing, benign fatty tumors. The distribution is defined as being focused in the trunk of the body and extremities.[2] Familial Multiple Lipomatosis can be identified when multiple lipomas occur in multiple family members that span different generations.[2] Some people may have hundreds of lipomas present.[2] ## Contents * 1 Symptoms * 2 Diagnosis * 2.1 Differential diagnoses * 3 Causes * 4 Treatment * 5 In the media * 6 References ## Symptoms[edit] The source of this disease is from family history, and symptoms most often arise in middle age.[2][3] Newly formed lipomas frequently present themselves as a bead-like lump under the skin, and become rubbery and movable.[3] They may be seen throughout the body and in some areas more than others, however, it does not make an appearance on the head or shoulders of the individual.[2] The size of those bumps may vary and could possibly get in the way of an individual living their life peacefully.[2] There are usually no feelings of discomfort or pain unless a lipoma has been aggravated or is directly on a nerve.[4] Lipomas that sit over bony areas such as the ribs and lower back can cause discomfort when lying down or receiving any kind of pressure. The age at which familial multiple lipomatosis begins to make an appearance on the individual’s body varies; for some it may be as early as 5 years of age.[4] ## Diagnosis[edit] Lipoma ultrasound 110322120428 1206550 Familial multiple lipomatosis is usually diagnosed through a physical exam via palpation, medical history and imaging studies such as ultrasound, CT scan, or magnetic resonance imaging (MRI). A CT scan is an imaging method that uses x-rays to create images of cross sections of the body, while an MRI uses powerful magnets and radio waves to create images of lipomas and surrounding tissues.[3] Both tests are useful to establish the diagnosis of multiple symmetric lipomatosis, although magnetic resonance imaging provides more details and may be used when lipomas are large, deep, or have infiltrated muscle fibers or nerves. In some cases, a biopsy of the lipomas may be necessary to confirm the diagnosis.[3] ### Differential diagnoses[edit] •Liposarcoma •Dercum’s disease •Benign symmetric lipomatosis •Madelung’s disease •Cyst ## Causes[edit] The exact cause of FML is not yet known, but there are several theories of different causes:[5] * Hormonal disorder due to the body's inability to properly metabolize fat * Increase in fat cells (adipocytes) * Enzymatic defect or a change in the surface of the cells that could prevent the breakdown of fat * Poor lymphatic drainage * Defective regulation of mitochondria in brown fat. Brown fat is responsible for causing heat in times of stress or cold. For general callus tissue is stimulated by the sympathetic nervous system and this response is mediated by a substance called norepinephrine. This process occurs in the mitochondria * In most families, the mode of inheritance has not been determined. However, changes (mutations) in mitochondrial DNA that involve the MT-TK gene have been identified in some families who have the disease and other conditions that affect many different body systems. ## Treatment[edit] Lipomas removed from the arm of a patient with familial multiple lipomatosis. The only effective treatments for lipomas caused by familial multiple lipomatosis are liposuction or surgical removal.[6] Steroid injections may also be used to shrink the tumors by causing local fat atrophy.[7] Patients with the condition often seek removal when the lipomas are large, disfiguring, or cause pain.[2] This may be done by a dermatologist or other surgeon. In the majority of cases where one to a few subcutaneous lipomas are being excised, the procedure is done under local anaesthetic and the patient can resume most normal activities immediately afterward.[6] Over-the-counter pain medications are generally sufficient in the following days and long-term scarring is minimal.[6] Regrowth is rare because lipomas are usually well-encapsulated and are therefore removed entirely although more new lipomas may start to grow in the same area.[7] Therapeutic treatments that are recommended for adipose tissue disorders include improving lymphatic flow through exercise and massage, following an anti-inflammatory diet, and reducing non-disordered fat tissue when necessary.[6] Weight loss has not been shown to eliminate lipomas but may help reduce overall inflammation and influence hormone levels.[6] While there is no total cure for FML to stop the growth of new lipomas, most of the growths can remain untreated and rarely cause medical complications.[1][7] ## In the media[edit] * April Wesson / Dr. Pimple Popper Season 2 Episode 1: “Nose No Bounds" on January 3, 2019 * Olivia Buckland / Love Island 2016: After 4 years of building the courage to get it checked, the lump located near the star’s left armpit was discovered to be a lipoma, which was removed before her wedding [8] ## References[edit] 1. ^ a b Leffell, David J.; Braverman, Irwin M. (1986-08-01). "Familial multiple lipomatosis: Report of a case and a review of the literature". Journal of the American Academy of Dermatology. 15 (2): 275–279. doi:10.1016/S0190-9622(86)70166-7. ISSN 0190-9622. 2. ^ a b c d e f g "Familial multiple lipomatosis \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2019-11-22. 3. ^ a b c d "Lipomatosis simétrica múltiple \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2019-11-22. 4. ^ a b "OMIM Entry - % 151900 - LIPOMATOSIS, MULTIPLE". omim.org. Retrieved 2019-11-22. 5. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Familial multiple lipomatosis". www.orpha.net. Retrieved 2019-11-22. 6. ^ a b c d e "Treatment Summary". Fat Disorders Resource Society. Retrieved 2019-11-22. 7. ^ a b c "Lipoma - Diagnosis and treatment - Mayo Clinic". www.mayoclinic.org. Retrieved 2019-11-22. 8. ^ Harvey-Jenner, Catriona (2018-11-12). "11 celebrities who have proudly showed off their scars". Cosmopolitan. Retrieved 2019-11-22. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Familial multiple lipomatosis	c1275273	7,422	wikipedia	https://en.wikipedia.org/wiki/Familial_multiple_lipomatosis	2021-01-18T18:53:19	{"mesh": ["D000071070"], "wikidata": ["Q85760447"]}
Gianotti–Crosti syndrome SpecialtyDermatology Gianotti–Crosti syndrome (/dʒəˈnɒti ˈkrɒsti/), also known as infantile papular acrodermatitis,[1] papular acrodermatitis of childhood,[1] and papulovesicular acrolocated syndrome,[2]:389 is a reaction of the skin to a viral infection.[3] Hepatitis B virus[4] and Epstein–Barr virus are the most frequently reported pathogens. Other viruses implicated are hepatitis A virus, hepatitis C virus, cytomegalovirus,[5] coxsackievirus, adenovirus, enterovirus, rotavirus, rubella virus, HIV, and parainfluenza virus.[6] It is named for Ferdinando Gianotti and Agostino Crosti.[7][8] ## Contents * 1 Presentation * 2 Diagnosis * 2.1 Differential diagnosis * 3 Treatment * 4 See also * 5 References * 6 External links ## Presentation[edit] Gianotti–Crosti syndrome mainly affects infants and young children. Children as young as 1.5 months and up to 12 years of age are reported to be affected.[9] It is generally recognized as a papular or papulovesicular skin rash occurring mainly on the face and distal aspects of the four limbs. Purpura is generally not seen but may develop upon tourniquet test. However, extensive purpura without any hemorrhagic disorder has been reported.[9] The presence of less florid lesions on the trunk does not exclude the diagnosis. Lymphadenopathy and hepatomegaly are sometimes noted. Raised AST and ALT levels with no rise in conjugated and unconjugated bilirubin levels are sometimes detectable, although the absence of such does not exclude the diagnosis. Spontaneous disappearance of the rash usually occurs after 15 to 60 days. ## Diagnosis[edit] The diagnosis of Gianotti–Crosti syndrome is clinical. A validated diagnostic criteria[10][11][12] is as follows: A patient is diagnosed as having Gianotti–Crosti syndrome if: 1. On at least one occasion or clinical encounter, he/she exhibits all the positive clinical features, 2. On all occasions or clinical encounters related to the rash, he/she does not exhibit any of the negative clinical features, 3. None of the differential diagnoses is considered to be more likely than Gianotti–Crosti syndrome on clinical judgment, and 4. If lesional biopsy is performed, the histopathological findings are consistent with Gianotti–Crosti syndrome. The positive clinical features are: * Monomorphous, flat-topped, pink-brown papules or papulovesicles 1-10mm in diameter. * At least three of the following four sites involved – (1) cheeks, (2) buttocks, (3) extensor surfaces of forearms, and (4) extensor surfaces of legs. * Being symmetrical, and * Lasting for at least ten days. The negative clinical features are: * Extensive truncal lesions, and * Scaly lesions. ### Differential diagnosis[edit] The differential diagnoses are: acrodermatitis enteropathica, erythema infectiosum, erythema multiforme, hand-foot-and-mouth disease, Henoch–Schönlein purpura, Kawasaki disease, lichen planus, papular urticaria, papular purpuric gloves and socks syndrome, and scabies. ## Treatment[edit] Gianotti-Crosti disease is a harmless and self-limiting condition, so no treatment may be required.[13] Treatment is mainly focused on controlling itching, symptomatic relief and to avoid any further complications. For symptomatic relief from itching, oral antihistamines or any soothing lotions like calamine lotion or zinc oxide may be used. If there are any associated conditions like streptococcal infections, antibiotics may be required.[10][11][12][13] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1228. ISBN 1-4160-2999-0. 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 3. ^ "Gianotti-crosti syndrome, papulovesicular acrodermatitis. DermNet NZ". 4. ^ Michitaka K, Horiike N, Chen Y, et al. (August 2004). "Gianotti-Crosti syndrome caused by acute hepatitis B virus genotype D infection". Internal Medicine (Tokyo, Japan). 43 (8): 696–9. doi:10.2169/internalmedicine.43.696. PMID 15468968. 5. ^ Haki M, Tsuchida M, Kotsuji M, et al. (October 1997). "Gianotti-Crosti syndrome associated with cytomegalovirus antigenemia after bone marrow transplantation". Bone Marrow Transplantation. 20 (8): 691–3. doi:10.1038/sj.bmt.1700945. PMID 9383234. 6. ^ Chandrasekaran M, Mukherjee S (September 2007). "Gianotti Crosti syndrome". Indian Pediatrics. 44 (9): 695. PMID 17921560. 7. ^ synd/4051 at Who Named It? 8. ^ CROSTI A, GIANOTTI F (November 1957). "[Eruptive dermatosis of probable viral origin situated on the acra.]". Dermatologica (in French). 115 (5): 671–7. PMID 13500859. 9. ^ a b Sarma, N; Sarkar UK (Jan–Mar 2013). "Hemorrhagic Gianotti-Crosti Syndrome in a One and Half Month old Infant: An Extremely Unusual Presentation". Indian J Dermatol. 58 (1): 65–67. doi:10.4103/0019-5154.105313. PMC 3555378. 10. ^ a b Chuh, AA (September 2001). "Diagnostic criteria for Gianotti-Crosti syndrome: a prospective case-control study for validity assessment". Cutis; cutaneous medicine for the practitioner. 68 (3): 207–13. PMID 11579787. 11. ^ a b Chuh, Antonio; Lee, Albert; Zawar, Vijay (1 September 2004). "The Diagnostic Criteria of Gianotti-Crosti Syndrome: Are They Applicable to Children in India?". Pediatric Dermatology. 21 (5): 542–547. doi:10.1111/j.0736-8046.2004.21503.x. PMID 15461758. 12. ^ a b Chuh, Antonio; Zawar, Vijay; Law, Michelle; Sciallis, Gabriel (2 January 2012). "Gianotti-Crosti syndrome, pityriasis rosea, asymmetrical periflexural exanthem, unilateral mediothoracic exanthem, eruptive pseudoangiomatosis and papular-purpuric gloves and socks syndrome: a brief review and arguments for diagnostic criteria". Infectious Disease Reports. 4 (1): 12. doi:10.4081/idr.2012.e12. PMC 3892651. PMID 24470919. 13. ^ a b "Gianotti-crosti syndrome. Dermatalk". ## External links[edit] Classification D * ICD-10: L44.4 (ILDS L44.400) * ICD-9-CM: 057.8 * MeSH: D000169 * DiseasesDB: 32236 External resources * eMedicine: derm/165 * v * t * e Skin infections, symptoms and signs related to viruses DNA virus Herpesviridae Alpha HSV * Herpes simplex * Herpetic whitlow * Herpes gladiatorum * Herpes simplex keratitis * Herpetic sycosis * Neonatal herpes simplex * Herpes genitalis * Herpes labialis * Eczema herpeticum * Herpetiform esophagitis Herpes B virus * B virus infection VZV * Chickenpox * Herpes zoster * Herpes zoster oticus * Ophthalmic zoster * Disseminated herpes zoster * Zoster-associated pain * Modified varicella-like syndrome Beta * Human herpesvirus 6/Roseolovirus * Exanthema subitum * Roseola vaccinia * Cytomegalic inclusion disease Gamma * KSHV * Kaposi's sarcoma Poxviridae Ortho * Variola * Smallpox * Alastrim * MoxV * Monkeypox * CPXV * Cowpox * VV * Vaccinia * Generalized vaccinia * Eczema vaccinatum * Progressive vaccinia * Buffalopox Para * Farmyard pox: Milker's nodule * Bovine papular stomatitis * Pseudocowpox * Orf * Sealpox Other * Yatapoxvirus: Tanapox * Yaba monkey tumor virus * MCV * Molluscum contagiosum Papillomaviridae HPV * Wart/plantar wart * Heck's disease * Genital wart * giant * Laryngeal papillomatosis * Butcher's wart * Bowenoid papulosis * Epidermodysplasia verruciformis * Verruca plana * Pigmented wart * Verrucae palmares et plantares * BPV * Equine sarcoid Parvoviridae * Parvovirus B19 * Erythema infectiosum * Reticulocytopenia * Papular purpuric gloves and socks syndrome Polyomaviridae * Merkel cell polyomavirus * Merkel cell carcinoma RNA virus Paramyxoviridae * MeV * Measles Togaviridae * Rubella virus * Rubella * Congenital rubella syndrome ("German measles" ) * Alphavirus infection * Chikungunya fever Picornaviridae * CAV * Hand, foot, and mouth disease * Herpangina * FMDV * Foot-and-mouth disease * Boston exanthem disease Ungrouped * Asymmetric periflexural exanthem of childhood * Post-vaccination follicular eruption * Lipschütz ulcer * Eruptive pseudoangiomatosis * Viral-associated trichodysplasia * Gianotti–Crosti syndrome * v * t * e Papulosquamous disorders Psoriasis Pustular * Generalized pustular psoriasis (Impetigo herpetiformis) * Acropustulosis/Pustulosis palmaris et plantaris (Pustular bacterid) * Annular pustular psoriasis * Localized pustular psoriasis Other * Guttate psoriasis * Psoriatic arthritis * Psoriatic erythroderma * Drug-induced psoriasis * Inverse psoriasis * Napkin psoriasis * Seborrheic-like psoriasis Parapsoriasis * Pityriasis lichenoides (Pityriasis lichenoides et varioliformis acuta, Pityriasis lichenoides chronica) * Lymphomatoid papulosis * Small plaque parapsoriasis (Digitate dermatosis, Xanthoerythrodermia perstans) * Large plaque parapsoriasis (Retiform parapsoriasis) Other pityriasis * Pityriasis rosea * Pityriasis rubra pilaris * Pityriasis rotunda * Pityriasis amiantacea Other lichenoid Lichen planus * configuration * Annular * Linear * morphology * Hypertrophic * Atrophic * Bullous * Ulcerative * Actinic * Pigmented * site * Mucosal * Nails * Peno-ginival * Vulvovaginal * overlap synromes * with lichen sclerosus * with lupus erythematosis * other: * Hepatitis-associated lichen planus * Lichen planus pemphigoides Other * Lichen nitidus * Lichen striatus * Lichen ruber moniliformis * Gianotti–Crosti syndrome * Erythema dyschromicum perstans * Idiopathic eruptive macular pigmentation * Keratosis lichenoides chronica * Kraurosis vulvae * Lichen sclerosus * Lichenoid dermatitis * Lichenoid reaction of graft-versus-host disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Gianotti–Crosti syndrome	None	7,423	wikipedia	https://en.wikipedia.org/wiki/Gianotti%E2%80%93Crosti_syndrome	2021-01-18T19:00:53	{"gard": ["6499"], "icd-9": ["057.8"], "icd-10": ["L44.4"], "wikidata": ["Q475972"]}
## Clinical Features The Wildervanck syndrome consists of congenital perceptive deafness, Klippel-Feil anomaly (see 118100), and abducens palsy with retractio bulbi (Duane syndrome). The disorder is limited, or almost completely limited, to females, raising the question of sex-linked dominance with lethality in the hemizygous male. This syndrome (at least profound childhood deafness and Klippel-Feil malformation) may be responsible for at least 1% of deafness among females. The deafness is perceptive and has been shown by radiologic studies to be due to a bony malformation of the inner ear. Kirkham (1969) described a family which was affected through 5 generations with perceptive deafness and in which 2 members had Duane syndrome. Konigsmark and Gorlin (1976) favored multifactorial inheritance. Wildervanck (1978) gave an extensive review of the subject and concluded that polygenic inheritance with limitation to females is most likely. Balci et al. (2002) reported a child with Wildervanck syndrome with the following findings on MRI: diastematomyelia of the lower medulla and cervical cord accompanied by vermian hypoplasia, tonsillar herniation, and resulting triventricular hydrocephalus. The authors suggested that children with Wildervanck syndrome should be investigated for craniospinal abnormalities by MRI. Abu-Amero et al. (2014) described a male with Wildervanck syndrome who had a microdeletion in the X chromosome. The patient had bilateral type 1 Duane retraction syndrome, type 1 Klippel-Feil anomaly causing almost complete fusion of the cervical vertebral bodies, and bilateral deafness with inner ear malformations involving the cochlea, vestibules, and semicircular canals. Neuroimaging revealed malformations of the lower brainstem and cervical spinal cord with incomplete diastematomyelia, as reported by Balci et al. (2002). In addition, the patient had ventricular septal defect and an atrial septal defect requiring surgery at age 2.5 years. Cytogenetics In a male patient with Wildervanck syndrome, Abu-Amero et al. (2014) detected an approximately 3-kb deletion in chromosome Xq26.3 (chrX:137,779,548-137,782,146, NCBI35) using array CGH. The deletion encompassed the FGF13 gene (300070). The deletion was not present in the patient's mother or in 1 of 8 unaffected sibs. The father was deceased but was reported to have been free of phenotypic features seen in the son. INHERITANCE \- Isolated cases HEAD & NECK Face \- Facial asymmetry Ears \- Sensorineural, conductive, or mixed hearing loss \- Ear anomalies \- Preauricular tags Eyes \- Pseudopapilledema \- Duane syndrome (abducens palsy with retracted globe) Neck \- Klippel-Feil anomaly (fused cervical vertebrae) \- Short, webbed neck MISCELLANEOUS \- Most patients are female ▲ 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	WILDERVANCK SYNDROME	c0265239	7,424	omim	https://www.omim.org/entry/314600	2019-09-22T16:17:04	{"mesh": ["C535326"], "omim": ["314600"], "orphanet": ["3456"], "synonyms": ["Alternative titles", "CERVICOOCULOACOUSTIC SYNDROME"]}
"Trich" redirects here. For the hair-pulling disorder, see Trichotillomania. Not to be confused with Trichinosis or Trichuriasis. Trichomoniasis Other namesTrich[1] Micrograph showing a positive result for trichomoniasis. A trichomonas organism is seen on the top-right of the image. SpecialtyGynecology SymptomsItching in the genital area, bad smelling thin vaginal discharge, burning with urination, pain with sex[1][2] Usual onset5 to 28 days after exposure[1] CausesTrichomonas vaginalis (typically sexually transmitted)[2][1] Diagnostic methodFinding the parasite in vaginal fluid, microbial culture, testing for the parasites DNA[1] PreventionNot having sex, using condoms, not douching[1] MedicationAntibiotics (metronidazole or tinidazole)[1] Frequency122 million (2015)[3] Trichomoniasis (trich) is an infectious disease caused by the parasite Trichomonas vaginalis.[2] About 70% of women and men do not have symptoms when infected.[2] When symptoms do occur they typically begin 5 to 28 days after exposure.[1] Symptoms can include itching in the genital area, a bad smelling thin vaginal discharge, burning with urination, and pain with sex.[1][2] Having trichomoniasis increases the risk of getting HIV/AIDS.[1] It may also cause complications during pregnancy.[1] Trichomoniasis is a sexually transmitted infection (STI) which is most often spread through vaginal, oral, or anal sex.[1] It can also spread through genital touching.[1] People who are infected may spread the disease even when symptoms are not present.[2] Diagnosis is by finding the parasite in the vaginal fluid using a microscope, culturing the vagina or urine, or testing for the parasite's DNA.[1] If present other STIs should be tested for.[1] Methods of prevention include not having sex, using condoms, not douching, and being tested for STIs before having sex with a new partner.[1] Trichomoniasis can be cured with antibiotics, either metronidazole or tinidazole.[1] Sexual partners should also be treated.[1] About 20% of people get infected again within three months of treatment.[2] There were about 122 million new cases of trichomoniasis in 2015.[3] In the United States, there are about 2 million women affected.[1] It occurs more often in women than men.[1] Trichomonas vaginalis was first identified in 1836 by Alfred Donné.[4] It was first recognized as causing this disease in 1916.[5] ## Contents * 1 Signs and symptoms * 1.1 Complications * 2 Causes * 2.1 Genetic sequence * 3 Diagnosis * 4 Prevention * 4.1 Screening * 5 Treatment * 6 Epidemiology * 7 References * 8 External links ## Signs and symptoms[edit] Play media Trichomonas vaginalis as seen by phase contrast microscopy Most people infected with Trichomonas vaginalis do not have any symptoms and can be undetected for years.[6] Symptoms experienced include pain, burning or itching in the penis, urethra (urethritis), or vagina (vaginitis). Discomfort for both sexes may increase during intercourse and urination. For women there may also be a yellow-green, itchy, frothy, foul-smelling ("fishy" smell) vaginal discharge. In rare cases, lower abdominal pain can occur. Symptoms usually appear within 5 to 28 days of exposure.[7] Sometimes trichomoniasis can be confused with chlamydia because the symptoms are similar.[8] ### Complications[edit] Trichomoniasis is linked to two serious complications. * Trichomoniasis is associated with increased risk of transmission and infection of HIV.[9][10] * Trichomoniasis may cause a woman to deliver a low-birth-weight or premature infant.[9] * The role of Trichomonas infection in causing cervical cancer is unclear, although trichomonas infection may be associated with co-infection with high-risk strains of HPV.[11] * T. vaginalis infection in males has been found to cause asymptomatic urethritis and prostatitis. In the prostate, it may create chronic inflammation that may eventually lead to prostate cancer.[12][13] ## Causes[edit] Lifecycle of Trichomonas The human genital tract is the only reservoir for this species. Trichomonas is transmitted through sexual or genital contact.[14] The single-celled protozoan produces mechanical stress on host cells and then ingests cell fragments after cell death.[15] ### Genetic sequence[edit] A draft sequence of the Trichomonas genome was published on January 12, 2007 in the journal Science confirming that the genome has at least 26,000 genes, a similar number to the human genome. An additional ~35,000 unconfirmed genes, including thousands that are part of potentially transposable elements, brings the gene content to well over 60,000.[16] ## Diagnosis[edit] There are three main ways to test for trichomoniasis. * The first is known as saline microscopy. This is the most commonly used method and requires an endocervical, vaginal, or penile swab specimen for examination under a microscope.[17] The presence of one or multiple trichomonads constitutes a positive result. This method is cheap but has a low sensitivity (60-70%) often due to an inadequate sample, resulting in false negatives.[18][19] * The second diagnostic method is culture, which has historically been the "gold standard" in infectious disease diagnosis. Trichomonas vaginalis culture tests are relatively cheap; however, sensitivity is still somewhat low (70-89%).[20] * The third method includes the nucleic acid amplification tests (NAATs) which are more sensitive.[20] These tests are more costly than microscopy and culture, and are highly sensitive (80-90%).[21] ## Prevention[edit] Use of male condoms or female condoms may help prevent the spread of trichomoniasis,[22] although careful studies have never been done that focus on how to prevent this infection. Infection with trichomoniasis through water is unlikely because Trichomonas vaginalis dies in water after 45–60 minutes, in thermal water after 30 minutes to 3 hours and in diluted urine after 5–6 hours.[23] Currently there are no routine standard screening requirements for the general U.S. population receiving family planning or STI testing.[24][25] The Centers for Disease Control and Prevention (CDC) recommends trichomoniasis testing for females with vaginal discharge[26] and can be considered for females at higher risk for infection or of HIV-positive serostatus.[24] The advent of new, highly specific and sensitive trichomoniasis tests present opportunities for new screening protocols for both men and women.[24][27] Careful planning, discussion, and research are required to determine the cost-efficiency and most beneficial use of these new tests for the diagnosis and treatment of trichomoniasis in the U.S., which can lead to better prevention efforts.[24][27] A number of strategies have been found to improve follow-up for STI testing including email and text messaging as reminders of appointments.[28] ### Screening[edit] Evidence from a randomized controlled trials for screening pregnant women who do not have symptoms for infection with trichomoniasis and treating women who test positive for the infection have not consistently shown a reduced risk of preterm birth.[29][30] Further studies are needed to verify this result and determine the best method of screening. In the US, screening of pregnant women without any symptoms is only recommended in those with HIV as trichomonas infection is associated with increased risk of transmitting HIV to the fetus.[31] ## Treatment[edit] Treatment for both pregnant and non-pregnant women is usually with metronidazole,[32] by mouth once.[31] Caution should be used in pregnancy, especially in the first trimester.[33] Sexual partners, even if they have no symptoms, should also be treated.[23] Single oral dose of nitroimidazole is sufficient to kill the parasites.[34] For 95-97% of cases, infection is resolved after one dose of metronidazole.[26][35] Studies suggest that 4-5% of trichomonas cases are resistant to metronidazole, which may account for some “repeat” cases.[33][9] Without treatment, trichomoniasis can persist for months to years in women, and is thought to improve without treatment in men.[9] Women living with HIV infection have better cure rates if treated for 7 days rather than with one dose.[31][36] Topical treatments are less effective than oral antibiotics due to Skene's gland and other genitourinary structures acting as a reservoir.[37] ## Epidemiology[edit] There were about 58 million cases of trichomoniasis in 2013.[38] It is more common in women (2.7%) than males (1.4%).[39] It is the most common non-viral STI in the U.S., with an estimated 3.7 million prevalent cases and 1.1 million new cases per year.[40][41] It is estimated that 3% of the general U.S. population is infected,[21][42] and 7.5-32% of moderate-to-high risk (including incarcerated) populations.[43][44][45][46][47][48][49][50][excessive citations] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t "Trichomoniasis". Office on Women's Health. August 31, 2015. Archived from the original on 27 March 2016. Retrieved 21 March 2016. 2. ^ a b c d e f g "Trichomoniasis - CDC Fact Sheet". CDC. November 17, 2015. Archived from the original on 19 February 2013. Retrieved 21 March 2016. 3. ^ a b Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, Carter A, et al. (GBD 2015 Disease and Injury Incidence and Prevalence Collaborators) (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282. 4. ^ Wiser, Mark (2010). Protozoa and Human Disease. Garland Science. p. 60. ISBN 9781136738166. Archived from the original on 2016-04-02. 5. ^ Pearson, Richard D. (2001). Principles and Practice of Clinical Parasitology. Chichester: John Wiley & Sons. p. 243. ISBN 9780470851722. Archived from the original on 2016-04-02. 6. ^ "STD Facts - Trichomoniasis". cdc.gov. Archived from the original on 2013-02-19. 7. ^ Trichomoniasis symptoms Archived 2013-02-19 at the Wayback Machine. cdc.gov 8. ^ "Can Trichomoniasis Be Confused With Chlamydia?". mylabbox.com. 6 March 2019. Retrieved 18 July 2019. 9. ^ a b c d Secor WE, Meites E, Starr MC, Workowski KA (May 2014). "Neglected parasitic infections in the United States: trichomoniasis". The American Journal of Tropical Medicine and Hygiene. 90 (5): 800–804. doi:10.4269/ajtmh.13-0723. PMC 4015567. PMID 24808247. 10. ^ Kissinger P, Adamski A (September 2013). "Trichomoniasis and HIV interactions: a review". Sexually Transmitted Infections. 89 (6): 426–33. doi:10.1136/sextrans-2012-051005. PMC 3748151. PMID 23605851. 11. ^ Donders GG, Depuydt CE, Bogers JP, Vereecken AJ (30 December 2013). "Association of Trichomonas vaginalis and cytological abnormalities of the cervix in low risk women". PLOS ONE. 8 (12): e86266. Bibcode:2013PLoSO...886266D. doi:10.1371/journal.pone.0086266. PMC 3875579. PMID 24386492. 12. ^ Caini S, Gandini S, Dudas M, Bremer V, Severi E, Gherasim A (August 2014). "Sexually transmitted infections and prostate cancer risk: a systematic review and meta-analysis". Cancer Epidemiology. 38 (4): 329–38. doi:10.1016/j.canep.2014.06.002. PMID 24986642. 13. ^ Stark JR, Judson G, Alderete JF, Mundodi V, Kucknoor AS, Giovannucci EL, et al. (October 2009). "Prospective study of Trichomonas vaginalis infection and prostate cancer incidence and mortality: Physicians' Health Study". Journal of the National Cancer Institute. 101 (20): 1406–11. doi:10.1093/jnci/djp306. PMC 2765259. PMID 19741211. 14. ^ "Trichomoniasis - CDC Fact Sheet". Archived from the original on 19 February 2013. Retrieved 12 January 2011. 15. ^ Midlej V, Benchimol M (January 2010). "Trichomonas vaginalis kills and eats--evidence for phagocytic activity as a cytopathic effect". Parasitology. 137 (1): 65–76. doi:10.1017/S0031182009991041. PMID 19723359. 16. ^ Scientists crack the genome of the parasite causing trichomoniasis Archived 2009-01-04 at the Wayback Machine. Physorg.com. Jan. 12, 2007. 17. ^ Epstein, Aaron; Roy, Subir (2010). "Chapter 50: Vulvovaginitis". In Goodwin, T. Murphy (ed.). Management of Common Problems in Obstetrics and Gynecology (5th ed.). Wiley-Blackwell. p. 228. ISBN 978-1405169165. Archived from the original on 2017-02-15. "In 80% of cases, the diagnosis of trichomoniasis is confirmed by microscopic examination of saline wet mount, with the observation of motile trichominondas; their shape is "football-like" with moving flagella." 18. ^ Fouts AC, Kraus SJ (February 1980). "Trichomonas vaginalis: reevaluation of its clinical presentation and laboratory diagnosis". The Journal of Infectious Diseases. 141 (2): 137–143. doi:10.1093/infdis/141.2.137. PMID 6965976. 19. ^ Schwebke JR, Burgess D (October 2004). "Trichomoniasis". Clinical Microbiology Reviews. 17 (4): 794–803, table of contents. doi:10.1128/cmr.17.4.794-803.2004. PMC 523559. PMID 15489349. 20. ^ a b Nye MB, Schwebke JR, Body BA (February 2009). "Comparison of APTIMA Trichomonas vaginalis transcription-mediated amplification to wet mount microscopy, culture, and polymerase chain reaction for diagnosis of trichomoniasis in men and women". American Journal of Obstetrics and Gynecology. 200 (2): 188.e1–7. doi:10.1016/j.ajog.2008.10.005. PMID 19185101. 21. ^ a b Ginocchio CC, Chapin K, Smith JS, Aslanzadeh J, Snook J, Hill CS, Gaydos CA (August 2012). "Prevalence of Trichomonas vaginalis and coinfection with Chlamydia trachomatis and Neisseria gonorrhoeae in the United States as determined by the Aptima Trichomonas vaginalis nucleic acid amplification assay". Journal of Clinical Microbiology. 50 (8): 2601–8. doi:10.1128/JCM.00748-12. PMC 3421522. PMID 22622447. 22. ^ Vaginitis/Trichomoniasis :Reduce your risk Archived 2008-03-16 at the Wayback Machine, American Social Health Association. Retrieved March 12, 2008. 23. ^ a b Rob, Lukáš; Martan, Alois; Citterbart, Karel; et al. (2008). Gynekologie (in Czech) (2nd ed.). Prague: Galen. p. 136. ISBN 978-80-7262-501-7. 24. ^ a b c d Munson E (January 2014). "Point: new trichs for "old" dogs: prospects for expansion of Trichomonas vaginalis screening". Clinical Chemistry. 60 (1): 151–4. doi:10.1373/clinchem.2013.210021. PMID 24043491. 25. ^ Wendel KA, Workowski KA (April 2007). "Trichomoniasis: challenges to appropriate management". Clinical Infectious Diseases. 44 Suppl 3 (Suppl 3): S123-9. doi:10.1086/511425. PMID 17342665. 26. ^ a b Workowski KA, Berman S (December 2010). "Sexually transmitted diseases treatment guidelines, 2010". MMWR. Recommendations and Reports. 59 (RR-12): 1–110. PMID 21160459. 27. ^ a b Smith LV, Sorvillo F, Kuo T (May 2013). "Implications of Trichomonas vaginalis nucleic acid amplification testing on medical training and practice". Journal of Clinical Microbiology. 51 (5): 1650. doi:10.1128/JCM.00188-13. PMC 3647919. PMID 23592856. 28. ^ Desai M, Woodhall SC, Nardone A, Burns F, Mercey D, Gilson R (August 2015). "Active recall to increase HIV and STI testing: a systematic review". Sexually Transmitted Infections. 91 (5): 314–23. doi:10.1136/sextrans-2014-051930. PMID 25759476: Access provided by the University of Pittsburgh Library System 29. ^ Klebanoff MA, Carey JC, Hauth JC, Hillier SL, Nugent RP, Thom EA, et al. (August 2001). "Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection". The New England Journal of Medicine. 345 (7): 487–93. doi:10.1056/NEJMoa003329. PMID 11519502. 30. ^ McGregor, James A.; French, Janice I.; Parker, Ruth; Draper, Deborah; Patterson, Elisa; Jones, Ward; Thorsgard, Kyja; McFee, John (1995). "Prevention of premature birth by screening and treatment for common genital tract infections: Results of a prospective controlled evaluation". American Journal of Obstetrics and Gynecology. 173 (1): 157–167. doi:10.1016/0002-9378(95)90184-1. PMID 7631673. 31. ^ a b c Workowski KA, Bolan GA (June 2015). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and Reports. 64 (RR-03): 1–137. PMC 5885289. PMID 26042815. 32. ^ Vaginitis/Trichomoniasis :Treatment for trichomoniasis Archived 2008-04-01 at the Wayback Machine, American Social Health Association. Retrieved March 12, 2008. 33. ^ a b Cudmore SL, Delgaty KL, Hayward-McClelland SF, Petrin DP, Garber GE (October 2004). "Treatment of infections caused by metronidazole-resistant Trichomonas vaginalis". Clinical Microbiology Reviews. 17 (4): 783–93, table of contents. doi:10.1128/CMR.17.4.783-793.2004. PMC 523556. PMID 15489348. 34. ^ Forna F, Gülmezoglu AM (2003-04-22). Cochrane Infectious Diseases Group (ed.). "Interventions for treating trichomoniasis in women". The Cochrane Database of Systematic Reviews (2): CD000218. doi:10.1002/14651858.CD000218. PMC 6532670. PMID 12804391. 35. ^ Niccolai LM, Kopicko JJ, Kassie A, Petros H, Clark RA, Kissinger P (May 2000). "Incidence and predictors of reinfection with Trichomonas vaginalis in HIV-infected women". Sexually Transmitted Diseases. 27 (5): 284–8. doi:10.1097/00007435-200005000-00009. PMID 10821602. S2CID 37556873. 36. ^ Kissinger P, Mena L, Levison J, Clark RA, Gatski M, Henderson H, et al. (December 2010). "A randomized treatment trial: single versus 7-day dose of metronidazole for the treatment of Trichomonas vaginalis among HIV-infected women". Journal of Acquired Immune Deficiency Syndromes. 55 (5): 565–71. doi:10.1097/qai.0b013e3181eda955. PMC 3058179. PMID 21423852. 37. ^ Petrin D, Delgaty K, Bhatt R, Garber G (April 1998). "Clinical and microbiological aspects of Trichomonas vaginalis". Clinical Microbiology Reviews. 11 (2): 300–17. doi:10.1128/CMR.11.2.300. PMC 106834. PMID 9564565. 38. ^ Vos T, et al. (GBD Study 2013 Collaborators) (August 2015). "Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 386 (9995): 743–800. doi:10.1016/s0140-6736(15)60692-4. PMC 4561509. PMID 26063472. 39. ^ Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. (December 2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2163–96. doi:10.1016/S0140-6736(12)61729-2. PMC 6350784. PMID 23245607. 40. ^ Centers for Disease Control and Prevention, National Center for HIV/AIDS, Viral Hepatitis, and TB. Division of STD Prevention. Trichomoniasis - CDC Fact Sheet. 2012. 41. ^ Satterwhite CL, Torrone E, Meites E, Dunne EF, Mahajan R, Ocfemia MC, et al. (March 2013). "Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008". Sexually Transmitted Diseases. 40 (3): 187–93. doi:10.1097/OLQ.0b013e318286bb53. PMID 23403598. S2CID 25094427. 42. ^ Sutton M, Sternberg M, Koumans EH, McQuillan G, Berman S, Markowitz L (November 2007). "The prevalence of Trichomonas vaginalis infection among reproductive-age women in the United States, 2001-2004". Clinical Infectious Diseases. 45 (10): 1319–26. doi:10.1086/522532. PMID 17968828. 43. ^ Rogers SM, Turner CF, Hobbs M, Miller WC, Tan S, Roman AM, et al. (2014). "Epidemiology of undiagnosed trichomoniasis in a probability sample of urban young adults". PLOS ONE. 9 (3): e90548. Bibcode:2014PLoSO...990548R. doi:10.1371/journal.pone.0090548. PMC 3953116. PMID 24626058. 44. ^ Javanbakht M, Stirland A, Stahlman S, Smith LV, Chien M, Torres R, Guerry S (October 2013). "Prevalence and factors associated with Trichomonas vaginalis infection among high-risk women in Los Angeles". Sexually Transmitted Diseases. 40 (10): 804–7. doi:10.1097/OLQ.0000000000000026. PMC 4188531. PMID 24275733. 45. ^ Helms DJ, Mosure DJ, Metcalf CA, Douglas JM, Malotte CK, Paul SM, Peterman TA (May 2008). "Risk factors for prevalent and incident Trichomonas vaginalis among women attending three sexually transmitted disease clinics". Sexually Transmitted Diseases. 35 (5): 484–8. CiteSeerX 10.1.1.530.128. doi:10.1097/OLQ.0b013e3181644b9c. PMID 18360314. S2CID 31156646. 46. ^ Swartzendruber A, Sales JM, Brown JL, Diclemente RJ, Rose ES (April 2014). "Correlates of incident Trichomonas vaginalis infections among African American female adolescents". Sexually Transmitted Diseases. 41 (4): 240–5. doi:10.1097/OLQ.0000000000000094. PMC 4313569. PMID 24622635. 47. ^ Muzny CA, Rivers CA, Austin EL, Schwebke JR (September 2013). "Trichomonas vaginalis infection among women receiving gynaecological care at an Alabama HIV Clinic". Sexually Transmitted Infections. 89 (6): 514–8. doi:10.1136/sextrans-2012-050889. PMID 23449600. S2CID 29645466. 48. ^ Munson E, Kramme T, Napierala M, Munson KL, Miller C, Hryciuk JE (December 2012). "Female epidemiology of transcription-mediated amplification-based Trichomonas vaginalis detection in a metropolitan setting with a high prevalence of sexually transmitted infection". Journal of Clinical Microbiology. 50 (12): 3927–31. doi:10.1128/JCM.02078-12. PMC 3503002. PMID 23015673. 49. ^ Freeman AH, Katz KA, Pandori MW, Rauch LM, Kohn RP, Liska S, et al. (March 2010). "Prevalence and correlates of Trichomonas vaginalis among incarcerated persons assessed using a highly sensitive molecular assay". Sexually Transmitted Diseases. 37 (3): 165–8. doi:10.1097/OLQ.0b013e3181bcd3fc. PMID 20023598. 50. ^ Nijhawan AE, DeLong AK, Celentano DD, Klein RS, Sobel JD, Jamieson DJ, Cu-Uvin S (December 2011). "The association between Trichomonas infection and incarceration in HIV-seropositive and at-risk HIV-seronegative women". Sexually Transmitted Diseases. 38 (12): 1094–100. doi:10.1097/OLQ.0b013e31822ea147. PMC 3767476. PMID 22082718. ## External links[edit] Classification D * ICD-10: A59 * ICD-9-CM: 131,007.3 * MeSH: D014246 * DiseasesDB: 13334 External resources * MedlinePlus: 001331 * eMedicine: med/2308 emerg/613 * Trichomoniasis at Centers for Disease Control and Prevention * Vaginitis/Vaginal infection fact sheet from the National Institute of Allergies and Infections. The first version of this article was taken from this public domain resource. * eMedicine Health Trichomoniasis * v * t * e Sexually transmitted infections (STI) Bacterial * Chancroid (Haemophilus ducreyi) * Chlamydia, lymphogranuloma venereum (Chlamydia trachomatis) * Donovanosis (Klebsiella granulomatis) * Gonorrhea (Neisseria gonorrhoeae) * Mycoplasma hominis infection (Mycoplasma hominis) * Syphilis (Treponema pallidum) * Ureaplasma infection (Ureaplasma urealyticum) Protozoal * Trichomoniasis (Trichomonas vaginalis) Parasitic * Crab louse * Scabies Viral * AIDS (HIV-1/HIV-2) * Cancer * cervical * vulvar * penile * anal * Human papillomavirus (HPV) * Genital warts (condyloma) * Hepatitis B (Hepatitis B virus) * Herpes simplex * HSV-1 & HSV-2 * Molluscum contagiosum (MCV) General inflammation female Cervicitis Pelvic inflammatory disease (PID) male Epididymitis Prostatitis either Proctitis Urethritis/Non-gonococcal urethritis (NGU) * v * t * e Parasitic disease caused by Excavata protozoa Discicristata Trypanosomatida Trypanosomiasis * T. brucei * African trypanosomiasis * T. cruzi * Chagas disease Leishmaniasis * Leishmania major / L. mexicana / L. aethiopica / L. tropica * Cutaneous leishmaniasis * L. braziliensis * Mucocutaneous leishmaniasis * L. donovani / infantum * Visceral leishmaniasis Schizopyrenida * Naegleria fowleri * Primary amoebic meningoencephalitis Trichozoa Diplomonadida * Giardia lamblia (Giardiasis) Trichomonadida * Trichomonas vaginalis * Trichomoniasis * Dientamoeba fragilis * Dientamoebiasis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Trichomoniasis	c0040921	7,425	wikipedia	https://en.wikipedia.org/wiki/Trichomoniasis	2021-01-18T18:56:50	{"mesh": ["D014245"], "umls": ["C0040921"], "wikidata": ["Q745865"]}
toxic effects of thallium Thallium poisoning Other namesThallium Toxicity Thallium SpecialtyToxicology Thallium poisoning is poisoning due to thallium and its compounds which are often highly toxic.[1] Contact with skin is dangerous, and adequate ventilation should be provided when melting this metal.[2] Many thallium(I) compounds are highly soluble in water and are readily absorbed through the skin.[citation needed] Exposure to them should not exceed 0.1 mg per m2 of skin in an 8 hour time-weighted average (40 hour work-week). Thallium is a suspected human carcinogen.[2] Part of the reason for thallium's high toxicity is that, when present in aqueous solution as the univalent thallium(I) ion (Tl+), it exhibits some similarities with essential alkali metal cations, particularly potassium (due to similar ionic radii). It can thus enter the body via potassium uptake pathways.[3] Other aspects of thallium's chemistry differ strongly from that of the alkali metals, such as its high affinity for sulfur ligands. Thus, this substitution disrupts many cellular processes by interfering with the function of proteins that incorporate cysteine, an amino acid containing sulfur.[4] Thallium's toxicity has led to its use (now discontinued in many countries) as a rat and ant poison.[1] Among the distinctive effects of thallium poisoning are peripheral nerve damage (victims may experience a sensation of “walking on hot coals”) and hair loss (which led to its initial use as a depilatory, before its toxicity was properly appreciated). However, hair-loss generally only occurs with low doses; with high doses, the thallium kills before this can take effect.[5] Thallium was once an effective murder weapon, before its effects became understood and an antidote (Prussian blue) discovered.[6] It has been called the "poisoner's poison" since it is colorless, odorless, and tasteless; its slow-acting, painful and wide-ranging symptoms are often suggestive of a host of other illnesses and conditions.[7] ## Contents * 1 Cause * 1.1 Bioconcentration * 1.2 Thallium compounds * 2 Diagnosis * 3 Treatment * 4 Notable cases * 4.1 Australia's "Thallium Craze" * 4.2 Others * 4.3 In fiction * 5 References * 6 External links ## Cause[edit] ### Bioconcentration[edit] According to the United States Environmental Protection Agency (EPA), thallium release to the environment was reported in Texas and Ohio. This may indicate bioconcentration in aquatic ecosystems.[8] ### Thallium compounds[edit] The odorless and tasteless thallium sulfate was also used as rat poison and ant killer. Since 1975, this use in the United States and many other countries is prohibited due to safety concerns.[9] ## Diagnosis[edit] Thallium may be quantitated in blood or urine as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths. Normal background blood and urine concentrations in healthy persons are usually less than 1 μg/litre, but they are often in the 1–10 mg/litre range (1,000–10,000 times higher) in survivors of acute intoxication.[10][11] ## Treatment[edit] There are two main methods of removing both radioactive and stable isotopes of thallium from humans. First known was to use Prussian blue, which is a solid ion exchange material, which absorbs thallium. Up to 20 g per day of Prussian blue is fed by mouth to the person, and it passes through their digestive system and comes out in the stool. Hemodialysis and hemoperfusion are also used to remove thallium from the blood stream. At later stage of the treatment additional potassium is used to mobilize thallium from the tissue.[12][13] ## Notable cases[edit] There are numerous recorded cases of fatal thallium poisoning.[14] Because of its use for murder, thallium has gained the nicknames "The Poisoner's Poison" and "Inheritance Powder" (alongside arsenic). ### Australia's "Thallium Craze"[edit] In Australia, in the early 1950s, there was a notable spate of cases of murder or attempted murder by thallium poisoning. At this time, due to the chronic rat infestation problems in overcrowded inner-city suburbs (notably in Sydney), and thallium's effectiveness as a rat poison, it was still readily available over the counter in New South Wales, where thallium sulphate was marketed as a commercial rat bait, under the brand "Thall-rat". * In September 1952, Yvonne Gladys Fletcher, a housewife and mother of two from the inner Sydney suburb of Newtown, was charged and tried for the murders of both her first husband, Desmond Butler (who died in 1948) and her abusive second husband, Bertrand "Bluey" Fletcher, a rat bait layer, from whom Yvonne had obtained the thallium poison that she used to kill him earlier that year. Suspicions were raised after it became obvious to friends and neighbours that Bluey Fletcher was suffering from the same fatal illness that had killed Yvonne's first husband. A police investigation led to the exhumation and testing of Desmond Butler's remains, which showed clear evidence of thallium, and this led to Yvonne being convicted of Butler's murder. She was sentenced to death, but this was subsequently commuted to life imprisonment after the NSW Government abolished the death penalty; she was eventually released in 1964. At the time of the trial, it was reported that this was the first known case in Australia of a person being convicted of murder by administering thallium.[15][16] The Fletcher case is also notable for the fact that one of the arresting officers was Sydney detective Fred Krahe, who later became notorious for his suspected close involvement with elements of Sydney's organised crime scene and his alleged involvement in the disappearance of social activist Juanita Nielsen. * A month later, in October 1952, Bathurst grandmother Ruby Norton was tried for the murder of her daughter's fiancé Allen Williams, who died of thallium poisoning at Cowra Hospital in July 1952. Despite allegations that Norton hated all the men in her family and Williams was an unwanted son-in-law, Norton was acquitted.[16] * In 1953, Sydney woman Veronica Monty, 45, was tried for the attempted murder of her son-in-law, noted Balmain and Australian rugby league player Bob Lulham, who was treated for thallium poisoning in 1952. After separating from her husband, Monty had moved in with her daughter Judy and Judy's husband, Bob Lulham. The sensational trial revealed that Lulham and Monty had an "intimate relationship" while Lulham's wife was at Sunday mass. Monty was found not guilty; Judy Lulham divorced her husband as a result of the revelations about his affair, and Monty killed herself with thallium in 1955.[16] * In July 1953, Sydney woman Beryl Hague was tried for "maliciously administering thallium and endangering her husband's life". Hague confessed to buying Thall-rat from a corner shop and putting it in her husband's tea, because she wanted to "give him a headache to repay the many headaches he had given me" in violent disputes[16] * In 1953, Australian Caroline Grills was sentenced to life in prison after three family members and a close family friend died. Authorities found thallium in tea that she had given to two additional family members. Grills spent the rest of her life in Sydney's Long Bay Gaol, where fellow inmates dubbed her "Aunt Thally".[16][17][18] The Australian TV documentary Recipe for Murder, released in 2011, examined three of the most sensational and widely reported Australian thallium poisonings, the Fletcher, Monty, and Grills cases. ### Others[edit] * Félix-Roland Moumié, a Cameroonian leader, was assassinated with thallium in Geneva on 3 November 1960 by a former agent of the SDECE (French secret service) probably at the request of Cameroonian authorities. * In 1971, thallium was the main poison that Graham Frederick Young used to poison around 70 people in the English village of Bovingdon, Hertfordshire, of whom three died.[19] * From 1976 to late 1979, thallium was used as a chemical warfare agent, most notably by a unit of the British South Africa Police (BSAP) attached to the Selous Scouts during the Rhodesian Bush War.[20] * In 1977, a 19 month-old girl living in Qatar fell ill due to thallium poisoning (from pesticides used by her parents). While doctors were unable to identify the cause, a nurse named Marsha Maitland managed to do it from the description of the symptoms given in The Pale Horse.[21] * In summer 1981 the East German secret service "Stasi" poisoned dissident Wolfgang Welsch, who had previously been expelled to West Germany, during his holiday in Israel. He barely survived.[22] * In 1985, spiritual leader Rajneesh was allegedly poisoned with small doses of poison, by Reagan Administration and Church, as per accounts of his followers. He died after 5 years in 1990. * In 1987, in Kiev, a woman named Tamara Ivanutina was arrested along with her older sister and parents. They were found guilty of 40 cases of poisoning (13 of them lethal) with Clerici solution obtained from an acquaintance working at a geology institute. Tamara (guilty of nine deaths, including four children) was executed in one of the three documented cases of women receiving the capital punishment in post-Stalin Soviet Union. Her relatives received prison terms, the parents dying in jail.[23] * In 1988, members of the Carr family from Alturas, Polk County, Florida, fell ill from what appeared to be thallium poisoning. Peggy Carr, the mother, died slowly and painfully from the poison. Her son and stepson were critically ill but eventually recovered. The Carrs' neighbor, chemist George J. Trepal, was convicted of murdering Mrs. Carr and attempting to murder her family, and sentenced to death. The thallium was slipped into bottles of Coca-Cola at the Carr and Trepal homes.[24] * Thallium was the poison of choice for Saddam Hussein to use on dissidents, which even allowed for them to emigrate before dying.[25] * In 1995, Zhu Ling was the victim of an unsolved attempted thallium poisoning in Beijing, China. In 1994, Zhu Ling was a sophomore studying physical chemistry at Tsinghua University in Beijing. She began to show strange and debilitating symptoms at the end of 1994, when she reported experiencing acute stomach pain and extensive hair loss. Ultimately she was diagnosed on Usenet with poisoning by thallium. To this day, there is still speculation among Chinese expatriates overseas as to the poisoner's identity. The only suspect of the police investigation, Sun Wei, is a member of a family with high-level political connections, which may have been used to halt and suppress the results of the investigation. Sun Wei was Zhu Ling's classmate and roommate in Tsinghua University from 1992–1997. Tsinghua University also said she was the only student who had access to thallium compounds at the school. The investigation's results have never been released to Zhu Ling's parents or the general public. However, Tsinghua University declined to issue Sun Wei's B.S. certificate and refused to provide her with the documentation needed to get a passport or visa in 1997. In 2018 the victim's hair has been examined by the University of Maryland geologist Richard Ash using laser ablation ICP-MS mass spectrometry.[26] He was able to confirm the timeline and pattern of poisoning.[27][28] * In 1999, Norwegian Terje Wiik was sentenced to 21 years imprisonment for poisoning his girlfriend with thallium.[29] * In June 2004, 25 Russian soldiers earned Honorable Mentions in the Darwin Awards after becoming ill from thallium exposure when they found a can of mysterious white powder in a rubbish dump on their base at Khabarovsk in the Russian Far East. Oblivious to the danger of misusing an unidentified white powder from a military dump site, the conscripts added it to tobacco, and used it as a substitute for talcum powder on their feet.[30] * In 2005, a 17 year-old girl in Izunokuni, Shizuoka, Japan admitted to attempting to murder her mother by lacing her tea with thallium, causing a national scandal.[31] * In February 2007, two Americans, Marina and Yana Kovalevsky, a mother and daughter, visiting Russia were hospitalized for thallium poisoning. Both had emigrated from the Soviet Union to the United States in 1991 and had made several trips to Russia since then.[32] * In January 2008, 10 members of two families associated with an Iraqi soccer club, including several children, were poisoned by cake contaminated with thallium.[33] Four died, including two children. * In 2011, a chemist at Bristol-Myers Squibb in New Jersey, Li Tianle, was charged with the murder of her husband. According to an investigation by the Middlesex County Prosecutor's Office, Li Tianle was able to obtain a chemical containing thallium and fed it to her husband.[34] Li was a chemistry student at Beijing University at the time of the highly publicized thallium poisoning of Zhu Ling in 1995 at neighboring Tsinghua University.[35] * In 2012 a chemistry postgraduate student at the University of Southampton, UK, was found to be suffering from the effects of thallium and arsenic poisoning after presenting with neurological symptoms.[36] The student underwent an intensive course of treatment and, although he has shown improvement, faces an uncertain long-term prognosis for the recovery of full locomotion. Urine screening revealed elevated thallium levels in a small number of other members of the chemistry department, though none were at toxic levels. The source of the poisoning remains unknown, and although police investigations were fruitless, foul play is strongly suspected.[citation needed] * In 2018, authorities charged Yukai Yang, a student at Lehigh University, with the attempted murder of his roommate, Juwan Royal. Yang allegedly poisoned Royal with thallium and possibly other chemicals. Royal experienced vomiting, pain and numbness in his lower extremities, and a long-lasting burning sensation on his tongue.[37] ### In fiction[edit] * Ngaio Marsh used thallium acetate in her 1947 detective novel, Final Curtain. It was being used legitimately for scalp problems in a group of school children just after World War II, housed in a private estate. A relative living there used it in place of the heart medicine intended for the owner. * Agatha Christie, who worked as an apothecary's assistant, used thallium in 1961 as the agent of murder in her detective fiction novel The Pale Horse – the first clue to the murder method coming from the hair loss of the victims. This novel is notable as being credited with having saved at least two lives after readers recognised the symptoms of thallium poisoning that Christie described.[38] The Pale Horse was found among possessions of convicted thallium poisoner George Trepal's wife, the orthopedic surgeon Dr. Diana Carr (see above), who was herself considered a suspect in the Peggy Carr (no relation) murder for a time. * In Nigel Williams' 1990 novel The Wimbledon Poisoner, Henry Far uses thallium to baste a roast chicken in a failed attempt to murder his wife. * Thallium figures prominently in the 1995 film The Young Poisoner's Handbook, a dark comedy loosely based on the life of Graham Frederick Young. * In Big Nothing, Josie is the Wyoming Widow; a murderer who befriended men and killed them with whiskey laced with highly concentrated thallium. * In the 2010 episode "Whatever It Takes" of House, a character uses thallium to poison a patient to mimic the effects of polio, then appear to cure it with ultra-high doses of vitamin C. * In the NCIS episode "Dead Man Walking" (2007), thallium-laced cigars are used to murder a Naval officer. * "Page Turner", a 2008 episode of CSI: NY, has radioactive thallium poisoning as its central theme.[39] * In the 2010 film Edge of Darkness, thallium is used to poison both the main character and his daughter. * In the 2015 James Bond film Spectre, the organisation of the same name used thallium to poison Mr. White by lacing his mobile phone with it. * In Season 3 of Royal Pains, the mysterious German billionaire Boris Kuester von Jurgens-Ratenicz was poisoned by thallium added to his pool's water. * In Drop Dead Diva episode "Ashes to Ashes", thallium was used to murder a client's husband, affecting the client when she ate the cremation remains. * In the 2016 TVB drama Two Steps From Heaven, thallium was used to poison Bosco Wong's character. * In S6:E10 of the Father Brown Series, Hercule Flambeau's wife poisons Father Brown with thallium in order to induce Flambeau to exchange a religious relic for her giving Brown the antidote. Guessing the substance his wife used, Flambeau gives Brown clues as to the antidote, Prussian Blue. * In the short story "Just a Taste" in the collection The Horrors Hiding in Plain Sight (2018) by Rebecca Rowland, the main character, Sadie Sorenson, poisons her farmhand as well as her three children using rat poison containing thallium. The story takes place in the mid-twentieth century and use of the chemical as a rodenticide ceased in 1965.[40] * In S6:E9 of Elementary, entitled "Nobody Lives Forever" (2018), a biology professor studying how to prolong life spans is poisoned with thallium. As he dies, he falls onto a shelf containing his lab rats, which escape and eventually eat part of his body. Some dead rats are found inside him, suggesting to the detectives that the cause of death was poisoning. ## References[edit] 1. ^ a b Thallium Toxicity at eMedicine 2. ^ a b "Biology of Thallium". Web Elements. Retrieved 11 November 2008. 3. ^ Zheng, Wei. "A homogenous thallium flux assay for high throughput screen of potassium channels" (PDF). Aurora Biomed. Archived from the original (PDF) on 21 October 2014. 4. ^ Mandzyuk, Bogdan. "Eliminating thallium poisoning". 5. ^ Blum. The Poisoner's Handbook. p. 256.[full citation needed] 6. ^ Douglas, K.T.; Bunni, M.A.; Baindur, S.R. (1990). "Thallium in biochemistry". International Journal of Biochemistry. 22 (5): 429–438. doi:10.1016/0020-711X(90)90254-Z. PMID 2189755. 7. ^ Nutt, Amy Ellis; Epstein, Sue (13 February 2011). "A 15 year-old case yields a timely clue in deadly thallium poisoning". The Star-Ledger. 8. ^ "Thallium". Environmental Protection Agency. Technical drinking water and health contaminant-specific fact sheets. Archived from the original on 27 April 1999. 9. ^ "Chemical fact sheet — Thallium". Spectrum Laboratories. April 2001. Retrieved 2 February 2008. 10. ^ Zhao, Guohua; Ding, Meiping; Zhang, Baorong; Lv, Wen; Yin, Houmin; Zhang, Liang; Ying, Zhilin; Zhang, Qiong (2008). "Clinical Manifestations and Management of Acute Thallium Poisoning". European Neurology. 60 (6): 292–297. doi:10.1159/000157883. PMID 18824857. S2CID 31118790. 11. ^ Baselt, Randall Clint (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1522–1524. 12. ^ Prussian blue fact sheet Archived 2013-10-20 at the Wayback Machine from the Centers for Disease Control and Prevention 13. ^ Malbrain, M. L.; Lambrecht, G. L.; Zandijk, E.; Demedts, P. A.; Neels, H. M.; Lambert, W.; de Leenheer, A. P.; Lins, R. L.; Daelemans, R. (1997). "Treatment of Severe Thallium Intoxication". Clinical Toxicology. 35 (1): 97–100. doi:10.3109/15563659709001173. PMID 9022660. 14. ^ http://www.nj.com/news/index.ssf/2011/02/thallium_is_favored_method_of.html 15. ^ "[no title cited]". Sydney Morning Herald. 24 September 1952. Retrieved 31 January 2013.[full citation needed] 16. ^ a b c d e Donnelly, Marea (23 May 2011). "Post-war days of thallium and old lace". Daily Telegraph. Australia. Retrieved 31 January 2013. 17. ^ "What is thallium?". BBC News. 19 November 2006. Retrieved 21 November 2006. 18. ^ Donnelly, Marea (23 May 2011). "Post-war days of thallium and old lace". Daily Telegraph. Australia. 19. ^ Cavanagh, J.B. (1991). "What have we learnt from Graham Frederick Young? Reflections on the mechanism of thallium neurotoxicity". Neuropathology and Applied Neurobiology. 17 (1): 3–9. doi:10.1111/j.1365-2990.1991.tb00687.x. PMID 2057049. S2CID 25539855. 20. ^ Cross, Glenn (2017). Dirty War: Rhodesia and chemical-biological warfare, 1975-1980. Solihull, UK: Helion & Company. 21. ^ Emsley, John (28 April 2005). The Elements of Murder: A history of poison. ISBN 9780191517358 – via Google Books.[full citation needed] 22. ^ "Giftmord Thallium hat Arsen abgeloest". Morgen Post (in German). Germany. Print archive article 102972391.[full citation needed]}} 23. ^ "Tamara Ivanyutina and her family of serial killers". Bizarrepedia. 24. ^ "The Case of Trepal, George (w/m)". The Commission on Capital Cases. State of Florida. Archived from the original on 16 February 2008. Retrieved 29 November 2007. 25. ^ "Slow-acting killer that was Saddam's favourite instrument of vengeance". timesonline.co.uk. London, UK: The Times.[full citation needed] 26. ^ Ash, Richard David; He, Min (2018). "Details of a thallium poisoning case revealed by single hair analysis using laser ablation inductively coupled plasma mass spectrometry". Forensic Science International. 292: 224–231. doi:10.1016/j.forsciint.2018.10.002. ISSN 0379-0738. PMID 30343235. 27. ^ "Mass spectrometry sheds new light on thallium poisoning cold case". sciencedaily.com. 13 December 2018. Retrieved 25 December 2018. 28. ^ Ouellette, Jennifer (25 December 2018). "Study brings us one step closer to solving 1994 thallium poisoning case". Ars Technica. Retrieved 26 December 2018. 29. ^ "21 år for Terje Wiik". Dagbladet.no (in Norwegian). 11 February 2000. Retrieved 1 July 2018. 30. ^ "White Russians". DarwinAwards.com. 2004. 31. ^ "Ruling on Japan poison-diary girl". BBC News. 1 May 2006. 32. ^ "Embassy confirms hospitalization of two Americans for thallium poisoning". Foxnews.com. 7 March 2007. Retrieved 7 March 2007. 33. ^ Centers for Disease Control Prevention (CDC) (19 September 2008). "Thallium Poisoning from Eating Contaminated Cake – Iraq, 2008". MMWR Morb Mortal Wkly Rep. 57 (37): 1015–1018. PMID 18802411. 34. ^ "Death by poison N.J. police charge woman in death of her husband". NBC New York. 8 February 2011. 35. ^ "A 15 year-old case yields a timely clue in deadly thallium poisoning". NJ.com. News. 13 February 2011. 36. ^ "Southampton University labs shut after student poisoning". BBC News. 14 September 2012. Retrieved 8 June 2017. 37. ^ Yates, Riley. "Former Lehigh University student charged with trying to poison his roommate". The Morning Call. Retrieved 21 December 2018.[full citation needed] 38. ^ Aronson, Jeff (2007). "When I use a word: Colourful metals". British Medical Journal. 334 (7586): 205. doi:10.1136/bmj.39091.708981.BE. PMC 1781989. 39. ^ Huntley, Kristine. "CSI: New York – 'Page Turner'". csifiles.com. Retrieved 2 May 2014. 40. ^ Riyaz, R.; Pandalai, S.L.; Schwartz, M.; Kazzi, Z.N. (4 August 2012). "A fatal case of thallium toxicity: Challenges in management". Journal of Medical Toxicology. 9 (1): 75–78. doi:10.1007/s13181-012-0251-1. PMC 3576490. PMID 22865288. ## External links[edit] Classification D * ICD-10: T60.4 * ICD-9-CM: 985.8 * DiseasesDB: 13009 Look up thallium in Wiktionary, the free dictionary. Wikimedia Commons has media related to Thallium. * "Thallium, elemental". National Institutes of Health. NLM hazardous substances databank. U.S. Department of Health and Human Services. * Curley, Robert. "Cyril Wecht, Thallium". crimelibrary.com. Archived from the original on 17 April 2008. * "ToxFAQs". Centers for Disease Control. ATSDR. U.S. Department of Health and Human Services. * "Two Iraqi children die from Thallium poisoning". The Guardian. reports. 9 February 2008. * v * t * e * Poisoning * Toxicity * Overdose History of poison Inorganic Metals Toxic metals * Beryllium * Cadmium * Lead * Mercury * Nickel * Silver * Thallium * Tin Dietary minerals * Chromium * Cobalt * Copper * Iron * Manganese * Zinc Metalloids * Arsenic Nonmetals * Sulfuric acid * Selenium * Chlorine * Fluoride Organic Phosphorus * Pesticides * Aluminium phosphide * Organophosphates Nitrogen * Cyanide * Nicotine * Nitrogen dioxide poisoning CHO * alcohol * Ethanol * Ethylene glycol * Methanol * Carbon monoxide * Oxygen * Toluene Pharmaceutical Drug overdoses Nervous * Anticholinesterase * Aspirin * Barbiturates * Benzodiazepines * Cocaine * Lithium * Opioids * Paracetamol * Tricyclic antidepressants Cardiovascular * Digoxin * Dipyridamole Vitamin poisoning * Vitamin A * Vitamin D * Vitamin E * Megavitamin-B6 syndrome Biological1 Fish / seafood * Ciguatera * Haff disease * Ichthyoallyeinotoxism * Scombroid * Shellfish poisoning * Amnesic * Diarrhetic * Neurotoxic * Paralytic Other vertebrates * amphibian venom * Batrachotoxin * Bombesin * Bufotenin * Physalaemin * birds / quail * Coturnism * snake venom * Alpha-Bungarotoxin * Ancrod * Batroxobin Arthropods * Arthropod bites and stings * bee sting / bee venom * Apamin * Melittin * scorpion venom * Charybdotoxin * spider venom * Latrotoxin / Latrodectism * Loxoscelism * tick paralysis Plants / fungi * Cinchonism * Ergotism * Lathyrism * Locoism * Mushrooms * Strychnine 1 including venoms, toxins, foodborne illnesses. * Category * Commons * WikiProject [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Thallium poisoning	c0238452	7,426	wikipedia	https://en.wikipedia.org/wiki/Thallium_poisoning	2021-01-18T19:05:58	{"icd-9": ["985.8"], "icd-10": ["T60.4"], "wikidata": ["Q374832"]}
Oculocerebrorenal syndrome Other namesLowe syndrome Oculocerebrorenal syndrome is X-linked recessive. SpecialtyObstetrics and gynaecology, urology, neurology, medical genetics, endocrinology SymptomsCataracts[1] CausesMutations in OCRL gene[1] Diagnostic methodMRI, urinalysis[2] TreatmentPhysical therapy, clomipramine[3] Oculocerebrorenal syndrome (also called Lowe syndrome) is a rare X-linked recessive disorder characterized by congenital cataracts, hypotonia, intellectual disability, proximal tubular acidosis, aminoaciduria and low-molecular-weight proteinuria. Lowe syndrome can be considered a cause of Fanconi syndrome (bicarbonaturia, renal tubular acidosis, potassium loss and sodium loss[4]).[5][6] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 History * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] Boys with Lowe syndrome are born with cataracts in both eyes; glaucoma is present in about half of the individuals with Lowe syndrome, though usually not at birth. While not present at birth, kidney problems develop in many affected boys at about one year of age.[1] Renal pathology is characterized by an abnormal loss of certain substances into the urine, including bicarbonate, sodium, potassium, amino acids, organic acids, albumin, calcium and L-carnitine. This problem is known as Fanconi-type renal tubular dysfunction.[medical citation needed] ## Genetics[edit] Fibroblasts This syndrome is caused by mutations in the OCRL gene which encodes an inositol polyphosphate-5-phosphatase. At least one mechanism by which these mutations cause this syndrome is by loss of its Rab-binding domain.[7][8] This protein is associated with the primary cilia of the retinal pigment epithelial cells, fibroblasts and kidney tubular cells. This suggests that this syndrome is due to dysfunction of the cilia in these cells.[8] About 120 mutations are associated with this condition and OCRL gene which is associated with oculocerebrorenal syndrome[9] ## Diagnosis[edit] Diagnosis of oculocerebrorenal syndrome can be done via genetic testing[10] Among the different investigations that can de done are:[2] * Urinalysis * MRI * Blood test ## Treatment[edit] Potassium citrate In terms of treatment of oculocerebrorenal syndrome for those individuals who are affected by this condition includes the following:[3] * Glaucoma control (via medication) * Nasogastric tube feeding * Physical therapy * Clomipramine * Potassium citrate ## Epidemiology[edit] Because oculocerebrorenal syndrome is an X-linked recessive condition, the disease develops mostly in men with very rare occurrences in women, while women are carriers of the disease; it has an estimated prevalence of 1 in 500,000 people.[11] ## History[edit] It was first described in 1952 by American paediatrician Charles Upton Lowe (August 24, 1921 – February 9, 2012)[12][13] and colleagues at the Massachusetts General Hospital in Boston.[14] Because of the three major organ systems involved (eyes, brain and kidney), it is known as oculocerebrorenal syndrome.[1] ## See also[edit] * List of congenital disorders ## References[edit] 1. ^ a b c d "Oculocerebrorenal Syndrome: Background, Pathophysiology, Epidemiology". 2016-06-01. Cite journal requires `\|journal=` (help) 2. ^ a b "Lowe's (Oculo-Cerebro-Renal) Syndrome \| Doctor \| Patient". Patient. Retrieved 21 December 2016. 3. ^ a b RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Oculocerebrorenal syndrome of Lowe". www.orpha.net. Retrieved 21 December 2016. 4. ^ "Fanconi syndrome: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2016-12-21. 5. ^ Lewis, Richard Alan; Nussbaum, Robert L.; Brewer, Eileen D. (1993-01-01). "Lowe Syndrome". In Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora J.H.; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). GeneReviews. Seattle (WA): University of Washington, Seattle. PMID 20301653.update 2012 6. ^ "OMIM Entry - # 309000 - LOWE OCULOCEREBRORENAL SYNDROME; OCRL". omim.org. Retrieved 21 December 2016. 7. ^ Hagemann, Nina; Hou, Xiaomin; Goody, Roger S.; Itzen, Aymelt; Erdmann, Kai S. (2017-06-01). "Crystal structure of the Rab binding domain of OCRL1 in complex with Rab8 and functional implications of the OCRL1/Rab8 module for Lowe syndrome". Small GTPases. 3 (2): 107–110. doi:10.4161/sgtp.19380. ISSN 2154-1256. PMID 22790198. 8. ^ a b Reference, Genetics Home. "Lowe syndrome". Genetics Home Reference. Retrieved 21 December 2016. 9. ^ Reference, Genetics Home. "OCRL gene". Genetics Home Reference. Retrieved 21 December 2016. 10. ^ "Lowe syndrome - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Retrieved 21 December 2016. 11. ^ Loi M (2006). "Lowe Syndrome". Orphanet Journal of Rare Diseases. 1: 16. doi:10.1186/1750-1172-1-16. PMC 1526415. PMID 16722554. 12. ^ Kelly, Evelyn B. (2013). Encyclopedia of human genetics and disease. Santa Barbara, Calif.: Greenwood. ISBN 9780313387142. Retrieved 21 December 2016. 13. ^ Loring, David W.; Bowden, Stephen (2015). INS Dictionary of Neuropsychology and Clinical Neurosciences. Oxford University Press, Incorporated. ISBN 9780195366457. Retrieved 21 December 2016. 14. ^ Lowe CU, Terrey M, MacLachlan EA (1952). "Organic-aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation; a clinical entity". American Journal of Diseases of Children. 83 (2): 164–84. doi:10.1001/archpedi.1952.02040060030004. PMID 14884753. ## Further reading[edit] * Bökenkamp, Arend; Ludwig, Michael (1 January 2016). "The oculocerebrorenal syndrome of Lowe: an update". Pediatric Nephrology (Berlin, Germany). 31 (12): 2201–2212. doi:10.1007/s00467-016-3343-3. ISSN 0931-041X. PMC 5118406. PMID 27011217. ## External links[edit] Classification D * ICD-10: E72.0 * ICD-9-CM: 270.8 * OMIM: 309000 * MeSH: D009800 * DiseasesDB: 29146 External resources * eMedicine: oph/516 * GeneReviews: Lowe Syndrome * Orphanet: 534 Scholia has a topic profile for Oculocerebrorenal syndrome. * 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 * t * e X-linked disorders X-linked recessive Immune * Chronic granulomatous disease (CYBB) * Wiskott–Aldrich syndrome * X-linked severe combined immunodeficiency * X-linked agammaglobulinemia * Hyper-IgM syndrome type 1 * IPEX * X-linked lymphoproliferative disease * Properdin deficiency Hematologic * Haemophilia A * Haemophilia B * X-linked sideroblastic anemia Endocrine * Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy * KAL1 Kallmann syndrome * X-linked adrenal hypoplasia congenita Metabolic * Amino acid: Ornithine transcarbamylase deficiency * Oculocerebrorenal syndrome * Dyslipidemia: Adrenoleukodystrophy * Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency * Pyruvate dehydrogenase deficiency * Danon disease/glycogen storage disease Type IIb * Lipid storage disorder: Fabry's disease * Mucopolysaccharidosis: Hunter syndrome * Purine–pyrimidine metabolism: Lesch–Nyhan syndrome * Mineral: Menkes disease/Occipital horn syndrome Nervous system * X-linked intellectual disability: Coffin–Lowry syndrome * MASA syndrome * Alpha-thalassemia mental retardation syndrome * Siderius X-linked mental retardation syndrome * Eye disorders: Color blindness (red and green, but not blue) * Ocular albinism (1) * Norrie disease * Choroideremia * Other: Charcot–Marie–Tooth disease (CMTX2-3) * Pelizaeus–Merzbacher disease * SMAX2 Skin and related tissue * Dyskeratosis congenita * Hypohidrotic ectodermal dysplasia (EDA) * X-linked ichthyosis * X-linked endothelial corneal dystrophy Neuromuscular * Becker's muscular dystrophy/Duchenne * Centronuclear myopathy (MTM1) * Conradi–Hünermann syndrome * Emery–Dreifuss muscular dystrophy 1 Urologic * Alport syndrome * Dent's disease * X-linked nephrogenic diabetes insipidus Bone/tooth * AMELX Amelogenesis imperfecta No primary system * Barth syndrome * McLeod syndrome * Smith–Fineman–Myers syndrome * Simpson–Golabi–Behmel syndrome * Mohr–Tranebjærg syndrome * Nasodigitoacoustic syndrome X-linked dominant * X-linked hypophosphatemia * Focal dermal hypoplasia * Fragile X syndrome * Aicardi syndrome * Incontinentia pigmenti * Rett syndrome * CHILD syndrome * Lujan–Fryns syndrome * Orofaciodigital syndrome 1 * Craniofrontonasal dysplasia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Oculocerebrorenal syndrome	c2713392	7,427	wikipedia	https://en.wikipedia.org/wiki/Oculocerebrorenal_syndrome	2021-01-18T18:42:53	{"gard": ["3295"], "mesh": ["D009800"], "umls": ["C2713392"], "icd-9": ["270.8"], "orphanet": ["534"], "wikidata": ["Q1200839"]}
Axillary nerve dysfunction Axillary nerve(green arrow) SpecialtyNeurology Axillary nerve dysfunction is any disorder caused by damage to the axillary nerve.[1] The axillary nerve is a branch of the brachial plexus that innervates the deltoid and teres minor muscles. This nerve can be injured or damaged in a variety of ways - penetrating injury such as knife or gunshot wounds, surgical trauma, stretch injury (common after motor cycle accidents), and various metabolic or rheumatic conditions that may cause focal disruption of the blood supply to the nerve. The exact cause of the axillary nerve dysfunction cannot be identified with electromyography, but the way that the nerve has responded to the injury, and whether or not the nerve is healing, can. ## References[edit] 1. ^ "Axillary nerve dysfunction". MedlinePlus. Retrieved 16 June 2015. ## External links[edit] Classification D External resources * MedlinePlus: 000689 * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Axillary nerve dysfunction	None	7,428	wikipedia	https://en.wikipedia.org/wiki/Axillary_nerve_dysfunction	2021-01-18T18:58:54	{"wikidata": ["Q4830469"]}
A rare genetic syndrome with limb malformations as a major feature characterized by preaxial polydactyly of the hands and feet with variable phenotypic expressivity in combination with hypertrichosis extending from the posterior hairline to the middle of the back. Reported limb malformations include triphalangeal thumbs, duplicated thumbs, preaxial extra ray, and syndactyly between digits I and II in the hands, and large or duplicated hallux and syndactyly between toes I and II in the feet. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome	None	7,429	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=476119	2021-01-23T17:04:24	{}
Colon polyps Polyp of sigmoid colon as revealed by colonoscopy. Approximately 1 cm in diameter. The polyp was removed by snare cautery. SpecialtyGastroenterology A colorectal polyp is a polyp (fleshy growth) occurring on the lining of the colon or rectum.[1] Untreated colorectal polyps can develop into colorectal cancer.[2] Colorectal polyps are often classified by their behaviour (i.e. benign vs. malignant) or cause (e.g. as a consequence of inflammatory bowel disease). They may be benign (e.g. hyperplastic polyp), pre-malignant (e.g. tubular adenoma) or malignant (e.g. colorectal adenocarcinoma). ## Contents * 1 Signs and symptoms * 2 Structure * 3 Genetics * 3.1 Familial adenomatous polyposis * 3.2 Hereditary nonpolyposis colorectal cancer (Lynch Syndrome) * 3.3 Peutz–Jeghers syndrome * 3.4 Juvenile polyposis syndrome * 4 Types * 4.1 Comparison table * 4.2 Hyperplastic polyp * 4.3 Neoplastic polyp * 4.3.1 Adenomas * 4.4 Hamartomatous polyp * 4.5 Inflammatory polyp * 5 Diagnosis * 5.1 Gallery * 5.2 NICE classification * 6 Prevention * 7 Treatment * 8 References * 9 External links ## Signs and symptoms[edit] Colorectal polyps are not usually associated with symptoms.[2] When they occur, symptoms include bloody stools; changes in frequency or consistency of stools (such as a week or more of constipation or diarrhoea);[3] and fatigue arising from blood loss.[2] Anemia arising from iron deficiency can also present due to chronic blood loss, even in the absence of bloody stools.[3][4] Another symptom may be an increased mucous production especially those involving villous adenomas.[4] Copious production of mucous causes loss of potassium that can occasionally result in symptomatic hypokalemia.[4] Occasionally, if a polyp is big enough to cause a bowel obstruction, there may be nausea, vomiting and severe constipation.[3] ## Structure[edit] Polyps are either pedunculated (attached to the intestinal wall by a stalk) or sessile (grow directly from the wall).[5][6]:1342 In addition to the gross appearance categorization, they are further divided by their histologic appearance as tubular adenoma which are tubular glands, villous adenoma which are long finger like projections on the surface, and tubulovillous adenoma which has features of both.[6]:1342 ## Genetics[edit] Hereditary syndromes causing increased colorectal polyp formation include: * Familial adenomatous polyposis (FAP) * Hereditary nonpolyposis colorectal cancer * Peutz–Jeghers syndrome * Juvenile polyposis syndrome Several genes have been associated with polyposis, such as GREM1, MSH3, MLH3, NTHL1, RNF43 and RPS20.[7] ### Familial adenomatous polyposis[edit] Main article: Familial adenomatous polyposis Familial adenomatous polyposis (FAP) is a form of hereditary cancer syndrome involving the APC gene located on chromosome q521.[8] The syndrome was first described in 1863 by Virchow on a 15-year-old boy with multiple polyps in his colon.[8] The syndrome involves development of multiple polyps at an early age and those left untreated will all eventually develop cancer.[8] The gene is expressed 100% in those with the mutation and it is autosomal dominant.[8] 10% to 20% of patients have negative family history and acquire the syndrome from spontaneous germline mutation.[8] The average age of newly diagnosed patient is 29 and the average age of newly discovered colorectal cancer is 39.[8] It is recommended that those affected undergo colorectal cancer screening at younger age with treatment and prevention are surgical with removal of affected tissues.[8] ### Hereditary nonpolyposis colorectal cancer (Lynch Syndrome)[edit] Main article: Hereditary nonpolyposis colorectal cancer Hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch syndrome) is an hereditary colorectal cancer syndrome.[8] It is the most common hereditary form of colorectal cancer in the United States and accounts for about 3% of all cases of cancer.[8] It was first recognized by Alder S. Warthin in 1885 at the University of Michigan.[8] It was later further studied by Henry Lynch who recognized an autosomal dominant transmission pattern with those affected having relatively early onset of cancer (mean age 44 years), greater occurrence of proximal lesions, mostly mucinous or poorly differentiated adenocarcinoma, greater number of synchronous and metachronous cancer cells, and good outcome after surgical intervention.[8] The Amsterdam Criteria was initially used to define Lynch syndrome before the underlying genetic mechanism had been worked out.[8] The Criteria required that the patient has three family members all first-degree relatives with colorectal cancer that involves at least two generations with at least one affected person being younger than 50 years of age when the diagnosis was made.[8] The Amsterdam Criteria is too restrictive and was later expanded to include cancers of endometrial, ovarian, gastric, pancreatic, small intestinal, ureteral, and renal pelvic origin.[8] The increased risk of cancer seen in patients with by the syndrome is associated with dysfunction of DNA repair mechanism.[8] Molecular biologists have linked the syndrome to specific genes such as hMSH2, hMSH1, hMSH6, and hPMS2.[8] ### Peutz–Jeghers syndrome[edit] Main article: Peutz–Jeghers syndrome Peutz–Jeghers syndrome is an autosomal dominant syndrome that presents with hamartomatous polyps, which are disorganized growth of tissues of the intestinal tract, and hyperpigmentation of the interlining of the mouth, lips and fingers.[8] The syndrome was first noted in 1896 by Hutchinson, and later separately described by Peutz, and then again in 1940 by Jeghers.[8] The syndrome is associated with malfunction of serine-threonine kinase 11 or STK 11 gene, and has a 2% to 10% increase in risk of developing cancer of the intestinal tract.[8] The syndrome also causes increased risk of extraintestinal cancer such as that involving breast, ovary, cervix, fallopian tubes, thyroid, lung, gallbladder, bile ducts, pancreas, and testicles.[8] The polyps often bleeds and may cause obstruction that would require surgery.[8] Any polyps larger than 1.5 cm needs removal and patients should be monitored closely and screen every 2 years for malignancy.[8] ### Juvenile polyposis syndrome[edit] Main article: Juvenile polyposis syndrome Juvenile polyposis syndrome is an autosomal dominant syndrome characterized by increased risk of cancer of intestinal tract and extraintestinal cancer.[8] It often presents with bleeding and obstruction of the intestinal tract along with low serum albumin due to protein loss in the intestine.[8] The syndrome is linked to malfunction of SMAD4 a tumor suppression gene that is seen in 50% of cases.[8] Individuals with multiple juvenile polyps have at least 10% chance of developing malignancy and should undergo abdominal colectomy with ileorectal anastomosis, and close monitoring via endoscopy of rectum.[8] For individuals with few juvenile polyps, patients should undergo endoscopic polypectomy.[8] ## Types[edit] Incidences and malignancy risks of various types of colorectal polyps. Colorectal polyps can broadly be classified as follows: * hyperplastic, * neoplastic (adenomatous & malignant), * hamartomatous and, * inflammatory. ### Comparison table[edit] Colorectal polyps Type Risk of containing malignant cells Histopathology Image Hyperplastic polyp 0% No dysplasia.[9] * Mucin-rich type: Serrated (“saw tooth”) appearance, containing glands with star-shaped lumina.[10] Crypts that are elongated but straight, narrow and hyperchromatic at the base. All crypts reach to the muscularis mucosae.[10] * Goblet cell-rich type: Elongated, fat crypts and little to no serration. Filled with goblet cells, extending to surface, which commonly has a tufted appearance.[10] Tubular adenoma 2% at 1.5 cm[11] Low to high grade dysplasia[12] Over 75% of volume has tubular appearance.[13] Tubulovillous adenoma 20% to 25%[14] 25%-75% villous[13] Villous adenoma 15%[15] to 40%[14] Over 75% villous[13] Sessile serrated adenoma (SSA)[16] * Basal dilation of the crypts * Basal crypt serration * Crypts that run horizontal to the basement membrane (horizontal crypts) * Crypt branching. Colorectal adenocarcinoma 100% * In carcinoma in situ (Tis): cancer cells invading into the lamina propria, and may involve but not penetrate the muscularis mucosae. Can be classified as "high-grade dysplasia", because prognosis and management are essentially the same.[9] * Invasive adenocarcinoma: Extending through the muscularis mucosae into the submucosa and beyond.[9] ### Hyperplastic polyp[edit] Main article: Hyperplastic polyp Most hyperplastic polyps are found in the distal colon and rectum.[17] They have no malignant potential,[17] which means that they are no more likely than normal tissue to eventually become a cancer. Hyperplastic polyps on the right side of the colon do exhibit a malignant potential. This occurs through multiple mutations that affect the DNA-mismatch-repair pathways. As a consequence, DNA mutations during replication are not repaired. This leads to microsatellite instability, which can eventually lead to malignant transformation in polyps on the right side of the colon.[citation needed] ### Neoplastic polyp[edit] A neoplasm is a tissue whose cells have lost normal differentiation. They can be either benign growths or malignant growths. The malignant growths can either have primary or secondary causes. Adenomatous polyps are considered precursors to cancer and cancer becomes invasive once malignant cells cross the muscularis mucosa and invade the cells below.[8] Any cellular changes seen above the lamina propria are considered non-invasive and are labeled atypia or dysplasia. Any invasive carcinoma that has penetrated the muscularis mocos has the potential for lymph node metastasis and local recurrence which will require more aggressive and extensive resection.[8] The Haggitt's criteria is used for classification of polyps containing cancer and is based on the depth of penetration.[8] The Haggitt's criteria has level 0 through level 4, with all invasive carcinoma of sessile polyp variant by definition being classified as level 4.[8] * Level 0: Cancer does not penetrate through the muscularis mucosa.[8] * Level 1: Cancer penetrates through the muscularis mucosa and invades the submucosa below but is limited to the head of the polyp.[8] * Level 2: Cancer invades through with involvement of the neck of polyp.[8] * Level 3: Cancer invades through with involvement of any parts of the stalk.[8] * Level 4: Cancer invades through the submucosa below the stalk of the polyp but above the muscularis propria of the bowel wall.[8] #### Adenomas[edit] Main article: Colorectal adenoma Neoplastic polyps of the bowel are often benign hence called adenomas. An adenoma is a tumor of glandular tissue, that has not (yet) gained the properties of a cancer.[citation needed] The common adenomas of the colon (colorectal adenoma) are the tubular, tubulovillous, villous, and sessile serrated (SSA).[17] A large majority (65% to 80%) are of the benign tubular type with 10% to 25% being tubulovillous, and villous being the most rare at 5% to 10%.[8] As is evident from their name, sessile serrated and traditional serrated adenomas (TSAs) have a serrated appearance and can be difficult to distinguish microscopically from hyperplastic polyps.[17] Making this distinction is important, however, since SSAs and TSAs have the potential to become cancers,[18] while hyperplastic polyps do not.[17] The villous subdivision is associated with the highest malignant potential because they generally have the largest surface area. (This is because the villi are projections into the lumen and hence have a bigger surface area.) However, villous adenomas are no more likely than tubular or tubulovillous adenomas to become cancerous if their sizes are all the same.[17] ### Hamartomatous polyp[edit] Hamartomatous polyps are tumours, like growths found in organs as a result of faulty development. They are normally made up of a mixture of tissues. They contain mucus-filled glands, with retention cysts, abundant connective tissue, and a chronic cellular infiltration of eosinophils.[19] They grow at the normal rate of the host tissue and rarely cause problems such as compression. A common example of a hamartomatous lesion is a strawberry naevus. Hamartomatous polyps are often found by chance; occurring in syndromes such as Peutz–Jegher syndrome or Juvenile polyposis syndrome. Peutz–Jeghers syndrome is associated with polyps of the GI tract and also increased pigmentation around the lips, genitalia, buccal mucosa feet and hands. People are often diagnosed with Peutz-Jegher after presenting at around the age of 9 with an intussusception. The polyps themselves carry little malignant potential but because of potential coexisting adenomas there is a 15% chance of colonic malignancy. Juvenile polyps are hamartomatous polyps which often become evident before twenty years of age, but can also be seen in adults. They are usually solitary polyps found in the rectum which most commonly present with rectal bleeding. Juvenile polyposis syndrome is characterised by the presence of more than five polyps in the colon or rectum, or numerous juvenile polyps throughout the gastrointestinal tract, or any number of juvenile polyps in any person with a family history of juvenile polyposis. People with juvenile polyposis have an increased risk of colon cancer.[18] ### Inflammatory polyp[edit] These are polyps which are associated with inflammatory conditions such as ulcerative colitis and Crohn's disease.[citation needed] ## Diagnosis[edit] Colorectal polyps can be detected using a faecal occult blood test, flexible sigmoidoscopy, colonoscopy, virtual colonoscopy, digital rectal examination, barium enema or a pill camera.[3][failed verification] Malignant potential is associated with * degree of dysplasia * Type of polyp (e.g. villous adenoma): * Tubular Adenoma: 5% risk of cancer * Tubulovillous adenoma: 20% risk of cancer * Villous adenoma: 40% risk of cancer * Size of polyp: * <1 cm =<1% risk of cancer[20] * 1–2 cm=10% risk of cancer[20] * >2 cm=50% risk of cancer[20] Normally an adenoma which is greater than 0.5 cm is treated. ### Gallery[edit] * Microvesicular hyperplastic polyp. H&E stain. * Microvesicular hyperplastic polyp. H&E stain. * Traditional serrated adenoma. H&E stain. * Gross appearance of a colectomy specimen containing two colorectal polyps and one invasive colorectal carcinoma * Micrograph of a tubular adenoma, the most common type of dysplastic polyp in the colon. * Micrograph of a sessile serrated adenoma. H&E stain. * Micrograph of a Peutz–Jeghers colonic polyp – a type of hamartomatous polyp. H&E stain. * Micrograph of a tubular adenoma – dysplastic epithelium (dark purple) on left of image; normal epithelium (blue) on right. H&E stain. * Micrograph of a villous adenoma. These polyps are considered to have a high risk of malignant transformation. H&E stain. * Paris classification of colorectal neoplasms.[21] ### NICE classification[edit] In colonoscopy, colorectal polyps can be classified by NICE (Narrow-band imaging International Colorectal Endoscopic):[22] Type 1 Type 2 Type 3 Color Same or lighter than background Browner than background Browner or darkly browner than background, sometimes patchy whiter areas Vessels None, or isolated lacy vessels coursing across the lesion Brown vessels surrounding white structures Area of disrupted or missing vessels Surface Pattern Homogenous, or dark or white spots of uniform size Oval, tubular or branched white structures surrounded by brown vessels Amorphous or absent surface pattern Most likely pathology Hyperplasia Adenoma Deep submucosal invasive cancer Treatment Follow up Mucosal or submucosal polypectomy Surgical operation ## Prevention[edit] Diet and lifestyle are believed to play a large role in whether colorectal polyps form. Studies show there to be a protective link between consumption of cooked green vegetables, brown rice, legumes, and dried fruit and decreased incidence of colorectal polyps.[23] ## Treatment[edit] Polyps can be removed during a colonoscopy or sigmoidoscopy using a wire loop that cuts the stalk of the polyp and cauterises it to prevent bleeding.[3][failed verification] Many "defiant" polyps—large, flat, and otherwise laterally spreading adenomas—may be removed endoscopically by a technique called endoscopic mucosal resection (EMR), which involves injection of fluid underneath the lesion to lift it and thus facilitate endoscopic resection. Saline water may be used to generate lift, though some injectable solutions such as SIC 8000 may be more effective.[24] Minimally invasive surgery is indicated for polyps that are too large or in unfavorable locations, such as the appendix, that cannot be removed endoscopically.[25] These techniques may be employed as an alternative to the more invasive colectomy.[26] ## References[edit] 1. ^ Marks, Jay W.; Anand, Bhupinder. "Colon Polyps: Symptoms, Causes, Cancer Risk, Treatment, and Prevention". Colon polyps center. MedicineNet. Retrieved 18 Jan 2020. 2. ^ a b c Phillips, Michael M.; Zieve, David; Conaway, Brenda (September 25, 2019). "Colorectal polyps". Medical Encyclopedia. MedlinePlus. Retrieved 18 Jan 2020. 3. ^ a b c d e "Colon polyps". Mayo Clinic. Mayo Foundation for Medical Education and Research. Retrieved 18 Jan 2020. 4. ^ a b c Quick CR, Reed JB, Harper SJ, Saeb-Parsy K, Burkitt HG (2014). Essential Surgery: Problems, Diagnosis and Management. Edinburgh: Elsevier. ISBN 9780702054839. OCLC 842350865.[page needed] 5. ^ Classen, Meinhard; Tytgat, G.N.J.; Lightdale, Charles J. (2002). Gastroenterological Endoscopy. Thieme. p. 303. ISBN 1-58890-013-4. 6. ^ a b Townsend CM, Beauchamp RD, Evers BM, Mattox KL, eds. (2015). Sabiston Textbook of Surgery E-Book (19th ed.). Philadelphia, Pennsylvania: Elsevier Saunders. ISBN 978-1-4377-1560-6 – via Google Books (Preview). 7. ^ Valle L, de Voer RM, Goldberg Y, Sjursen W, Försti A, Ruiz-Ponte C, Caldés T, Garré P, Olsen MF, Nordling M, Castellvi-Bel S, Hemminmki K (October 2019). "Update on genetic predisposition to colorectal cancer and polyposis". Molecular Aspects of Medicine. Elsevier. 69: 10–26. doi:10.1016/j.mam.2019.03.001. PMID 30862463. 8. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak Najjia N. Mahmoud, Joshua I.S. Bleier, Cary B. Aarons, E. Carter Paulson, Skandan Shanmugan and Robert D. Fry (2017). Sabiston Textbook of Surgery. Elsevier.CS1 maint: multiple names: authors list (link)[page needed] 9. ^ a b c Finlay A Macrae. "Overview of colon polyps". UpToDate. This topic last updated: Dec 10, 2018. 10. ^ a b c Robert V Rouse (2010-01-31). "Hyperplastic Polyp of the Colon and Rectum". Stanford University School of Medicine. Last updated 6/2/2015 11. ^ Minhhuyen Nguyen. "Polyps of the Colon and Rectum". MSD Manual. Last full review/revision June 2019 12. ^ Robert V Rouse. "Adenoma of the Colon and Rectum". Original posting/last update : 1/31/10, 1/19/14 13. ^ a b c Bosman, F. T. (2010). WHO classification of tumours of the digestive system. Lyon: International Agency for Research on Cancer. ISBN 978-92-832-2432-7. OCLC 688585784. 14. ^ a b Amersi, Farin; Agustin, Michelle; Ko, Clifford Y (2005). "Colorectal Cancer: Epidemiology, Risk Factors, and Health Services". Clinics in Colon and Rectal Surgery. 18 (3): 133–140. doi:10.1055/s-2005-916274. ISSN 1531-0043. PMC 2780097. PMID 20011296. 15. ^ Alnoor Ramji. "Villous Adenoma Follow-up". Medscape. Updated: Oct 24, 2016 16. ^ Rosty, C; Hewett, D. G.; Brown, I. S.; Leggett, B. A.; Whitehall, V. L. (2013). "Serrated polyps of the large intestine: Current understanding of diagnosis, pathogenesis, and clinical management". Journal of Gastroenterology. 48 (3): 287–302. doi:10.1007/s00535-012-0720-y. PMC 3698429. PMID 23208018. 17. ^ a b c d e f Kumar, Vinay (2010). "17—Polyps". Robbins and Cotran pathologic basis of disease (8th ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 978-1-4160-3121-5. 18. ^ a b Stoler, Mark A.; Mills, Stacey E.; Carter, Darryl; Joel K. Greenson; Reuter, Victor E. (2009). Sternberg's Diagnostic Surgical Pathology. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-7942-5.[page needed] 19. ^ Calva, Daniel; Howe, James R (2008). "Hamartomatous Polyposis Syndromes". Surgical Clinics of North America. 88 (4): 779–817, vii. doi:10.1016/j.suc.2008.05.002. PMC 2659506. PMID 18672141. 20. ^ a b c Summers, Ronald M (2010). "Polyp Size Measurement at CT Colonography: What Do We Know and What Do We Need to Know?". Radiology. 255 (3): 707–20. doi:10.1148/radiol.10090877. PMC 2875919. PMID 20501711. 21. ^ Luis Bujanda Fernández de Piérola, Joaquin Cubiella Fernández, Fernando Múgica Aguinaga, Lander Hijona Muruamendiaraz and Carol Julyssa Cobián Malaver (2013). "Malignant Colorectal Polyps: Diagnosis, Treatment and Prognosis". Colonoscopy and Colorectal Cancer Screening: Future Directions. doi:10.5772/52697. ISBN 9789535109495.CS1 maint: multiple names: authors list (link) Creative Commons Attribution 3.0 License 22. ^ Hattori, Santa (2014). "Narrow-band imaging observation of colorectal lesions using NICE classification to avoid discarding significant lesions". World Journal of Gastrointestinal Endoscopy. 6 (12): 600. doi:10.4253/wjge.v6.i12.600. ISSN 1948-5190. 23. ^ Tantamango, Yessenia M; Knutsen, Synnove F; Beeson, W Lawrence; Fraser, Gary; Sabate, Joan (2011). "Foods and Food Groups Associated with the Incidence of Colorectal Polyps: The Adventist Health Study". Nutrition and Cancer. 63 (4): 565–72. doi:10.1080/01635581.2011.551988. PMC 3427008. PMID 21547850. 24. ^ Hoff, RT; Lakha, A (1 February 2020). "Rectal Tubulovillous Adenoma". The Journal of the American Osteopathic Association. 120 (2): 121. doi:10.7556/jaoa.2020.024. PMID 31985762. 25. ^ [1], Fisichella M. Laparoscopic Cecal Wedge Resection Appendectomy. J Med Ins. 2016;2016(207) doi:https://jomi.com/article/207 26. ^ "How I Do It" – Removing large or sessile colonic polyps. Archived 2008-04-11 at the Wayback Machine Brian Saunders; St. Mark’s Academic Institute; Harrow, Middlesex, UK. Retrieved April 9, 2008. ## External links[edit] * Villous Adenoma – Medscape Classification D * ICD-10: K63.5 & various * MeSH: D003111 External resources * MedlinePlus: 000266 * eMedicine: med/414 * v * t * e Digestive system neoplasia GI tract Upper Esophagus * Squamous cell carcinoma * Adenocarcinoma Stomach * Gastric carcinoma * Signet ring cell carcinoma * Gastric lymphoma * MALT lymphoma * Linitis plastica Lower Small intestine * Duodenal cancer * Adenocarcinoma Appendix * Carcinoid * Pseudomyxoma peritonei Colon/rectum * Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers Cronkhite–Canada * Polyposis syndromes: Juvenile * MUTYH-associated * Familial adenomatous/Gardner's * Polymerase proofreading-associated * Serrated polyposis * Neoplasm: Adenocarcinoma * Familial adenomatous polyposis * Hereditary nonpolyposis colorectal cancer Anus * Squamous cell carcinoma Upper and/or lower * Gastrointestinal stromal tumor * Krukenberg tumor (metastatic) Accessory Liver * malignant: Hepatocellular carcinoma * Fibrolamellar * Hepatoblastoma * benign: Hepatocellular adenoma * Cavernous hemangioma * hyperplasia: Focal nodular hyperplasia * Nodular regenerative hyperplasia Biliary tract * bile duct: Cholangiocarcinoma * Klatskin tumor * gallbladder: Gallbladder cancer Pancreas * exocrine pancreas: Adenocarcinoma * Pancreatic ductal carcinoma * cystic neoplasms: Serous microcystic adenoma * Intraductal papillary mucinous neoplasm * Mucinous cystic neoplasm * Solid pseudopapillary neoplasm * Pancreatoblastoma Peritoneum * Primary peritoneal carcinoma * Peritoneal mesothelioma * Desmoplastic small round cell tumor [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Colorectal polyp	c0009376	7,430	wikipedia	https://en.wikipedia.org/wiki/Colorectal_polyp	2021-01-18T18:47:10	{"mesh": ["D003111"], "umls": ["C0009376"], "icd-10": ["K63.5"], "wikidata": ["Q1209892"]}
TANGO2-related metabolic encephalopathy and arrhythmias is a disease that can cause episodes of metabolic crises and abnormal heart rhythms (arrhythmia). A metabolic crisis is caused by having low blood sugar (hypoglycemia) and the buildup of toxic products in the blood. A metabolic crisis can occur in any person with a metabolic disorder, and they are more likely to occur after a person has gone long periods without eating or during an illness. Most people with TANGO2-related metabolic encephalopathy and arrhythmias present with symptoms of a breakdown of muscle tissue (rhabdomyolysis). This can cause kidney damage and symptoms include fatigue, muscle weakness, and having a dark color of the urine. Other symptoms of TANGO2-related metabolic encephalopathy and arrhythmias include developmental delay, intellectual disability, seizures, hearing loss, low thyroid function (hypothyroidism) and trouble coordinating movements (ataxia). Signs and symptoms of the disease are most likely to first occur during infancy or early childhood. The disease is most common in people who are of Caucasian or Hispanic/Latino descent. TANGO2-related metabolic encephalopathy and arrhythmias is caused by a genetic change (mutation or pathogenic variant) in the TANGO2 gene. The disease is inherited in an autosomal recessive manner. The disease may be suspected in people who have a metabolic crisis, episodes of rhabdomyolysis, and arrhythmias. The diagnosis can be confirmed with genetic testing. Treatment of the disease is focused on avoiding metabolic crisis by avoiding fasting or illness. If a metabolic crisis does occur, it is important to have a plan in place so that proper treatment can occur. Other symptoms of the disease may be managed with therapies and medications. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	TANGO2-Related Metabolic Encephalopathy and Arrhythmias	c4225171	7,431	gard	https://rarediseases.info.nih.gov/diseases/13423/tango2-related-metabolic-encephalopathy-and-arrhythmias	2021-01-18T17:57:25	{"omim": ["616878"], "orphanet": ["480864"], "synonyms": ["TANGO2 related disease", "Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration", "Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome", "TANGO2"]}
A number sign (#) is used with this entry because Charcot-Marie-Tooth disease type 4B2 is caused by mutation in the SBF2 gene (607697). Description Autosomal recessive Charcot-Marie-Tooth disease type 4B is a demyelinating hereditary motor and sensory neuropathy characterized by abnormal folding of myelin sheaths. CMT4B1 (601382) is a clinically similar disorder caused by mutation in the MTMR2 gene (603557) on 11q22. For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating CMT, see CMT4A (214400). Clinical Features Gambardella et al. (1998) reported 2 sibs in a family from a small village in southern Italy who had early-onset CMT with focally folded myelin sheaths. The patients developed symptoms at 2 and 10 years of age, respectively. Both had progressive distal lower limb weakness and atrophy, followed by involvement of the upper limbs. There was distal sensory loss, areflexia, and bilateral pes equinovarus. Both patients also had unilateral sensorineural hearing loss, suggesting cranial nerve involvement. Sural nerve biopsy showed segmental demyelination and redundant loops and folds of the myelin sheath. Gambardella et al. (1998) suggested autosomal recessive inheritance. Linkage analysis excluded the CMT4B1 locus on chromosome 11q23. Senderek et al. (2003) reported a consanguineous Turkish family in which 4 patients were affected with a severe sensorimotor neuropathy characterized by focally folded myelin sheaths on nerve biopsy. Disease onset was around age 5 years and was characterized by distal muscle weakness and atrophy, foot deformities such as pes cavus and hammertoes, steppage gait, and areflexia in the lower limbs. Motor nerve conduction velocities (NCVs) were severely reduced (e.g., 16.5 m/s, 18.5 m/s). Sural nerve biopsies showed severe loss of myelinated fibers with focally folded myelin protrusions. ### CMT4B2 With Early-Onset Glaucoma Kiwaki et al. (2000) reported a consanguineous family from southern Japan in which 3 members had hereditary motor and sensory neuropathy with myelin folding accompanied by juvenile-onset open-angle glaucoma. All 3 patients had early childhood onset of neuropathy, markedly slowed NCVs of less than 20 m/s, aberrantly excessive myelin folding complexes with segmental de- and remyelination on nerve biopsy, increased CSF protein, and juvenile-onset glaucoma. Azzedine et al. (2003) reported 2 consanguineous families from Tunisia and Morocco with a demyelinating sensorimotor neuropathy and early-onset glaucoma. Mean age at onset was 8 years. Motor nerve conduction velocities were severely reduced, and nerve biopsies showed myelin outfoldings. In the index patient of each family, visual impairment was precocious and severe, leading to a loss of vision. Ophthalmologic examination showed congenital glaucoma with a buphthalmos, a megalocornea, and increased intraocular pressure. Other affected members of both families had increased intraocular pressure. Mapping In 2 Tunisian families with a CMT4B phenotype, Ben Othmane et al. (1999) excluded linkage to the CMT4B1 locus, thus demonstrating genetic heterogeneity. Using homozygosity mapping and linkage analysis in the largest Tunisian pedigree, they mapped the disorder to chromosome 11p15. A maximum 2-point lod score of 6.05 was obtained with marker D11S1329. Recombination events refined the CMT4B2 locus region to a 5.6-cM interval between markers D11S1331 and D11S4194. The second Tunisian CMT4B family was also excluded from linkage to the 11p15 locus, demonstrating the existence of at least a third locus for the CMT4B phenotype. Linkage analysis of both families affected with CMT4B2 with early-onset glaucoma reported by Azzedine et al. (2003) yielded a maximum lod score of 6.25 at D11S4149. Haplotype reconstruction in both families placed the candidate interval in a 4.6-cM region flanked by markers D11S1760 and D11S4194. Molecular Genetics In all 4 affected individuals of a Turkish family with CMT4B2, Senderek et al. (2003) identified a homozygous in-frame deletion of exons 11 and 12 of the SBF2 gene (607697.0001). In 2 Italian sibs with CMT4B2 reported by Gambardella et al. (1998), Conforti et al. (2004) identified a homozygous splice site mutation in the SBF2 gene (607697.0005). ### CMT4B2 With Early-Onset Glaucoma In 2 families with CMT4B2 with early-onset glaucoma, Azzedine et al. (2003) identified 2 homozygous nonsense mutations in the SBF2 gene (607697.0002-607697.0003). The mutations segregated with the disease in both pedigrees. Hirano et al. (2004) identified a homozygous nonsense mutation in the SBF2 gene (607697.0004) in 3 affected members of a family with CMT4B2 with early-onset glaucoma reported by Kiwaki et al. (2000). Hirano et al. (2004) noted that CMT4B2 patients with truncating mutations in the SBF2 gene developed early-onset glaucoma. Animal Model Tersar et al. (2007) generated Sbf2-null mice as a mouse model of CMT4B2 and found that Sbf2-null mice progressively developed myelin outfoldings and infoldings in motor and sensory peripheral nerves concomitant with decreased motor performance. The number and complexity of myelin misfoldings increased with age, associated with axonal degeneration, and decreased compound motor action potential amplitude. There was mild impairment of nerve conduction velocities. There was not a significant alteration in myelin thickness or axon diameter. Loss of Sbf2 did not affect the levels of its binding partner Mtmr2 in peripheral nerves. Robinson et al. (2008) found that mice with targeted disruption of the Sbf2 gene developed a peripheral neuropathy characterized by reduced nerve conduction velocity, myelin outfoldings and infoldings, and progressive dysmyelination, similar to that observed in CMT4B2. Although myelin infoldings and outfoldings were most prominent at the paranode, morphologic analysis indicated that the ultrastructure of the node of Ranvier and paranode was intact in Sbf2-deficient nerve fibers. Mtmr2 levels were decreased by approximately 50% in Sbf2-deficient sciatic nerves, suggesting a regulatory relationship between the 2 proteins. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Sensorineural hearing loss (described in 1 family) Eyes \- Glaucoma, open-angle, early-onset (occurs in patients with nonsense or truncating mutations in the SBF2 gene) \- Glaucoma may precede development of neuropathy SKELETAL Spine \- Kyphoscoliosis may be present Hands \- Claw hand deformities (in severe cases) Feet \- Pes cavus \- Talipes equinus \- Hammertoes \- Foot deformities NEUROLOGIC Peripheral Nervous System \- Distal limb muscle weakness due to peripheral neuropathy \- Distal limb muscle atrophy due to peripheral neuropathy \- Difficulty walking \- 'Steppage' gait \- Foot drop \- Severe distal sensory impairment \- Hyporeflexia \- Areflexia \- CSF protein content increased or at upper limit of normal \- Decreased motor nerve conduction velocity (NCV) (15-30 m/s) \- 'Onion bulb' formations on nerve biopsy \- Segmental demyelination/remyelination on nerve biopsy \- Decreased number of large and small myelinated fibers \- Thin myelin sheaths \- Abnormal myelin folding consisting of globular masses of irregular myelin thickening MISCELLANEOUS \- Onset in first or second decade (range 4 to 13 years) \- Onset in feet and legs (peroneal distribution) \- Upper limb involvement usually occurs later \- Patients with glaucoma have nonsense or truncating SBF2 mutations ( 607697.0002 ) \- Genetic heterogeneity (see CMT4B1, 601382 ) MOLECULAR BASIS \- Caused by mutation in the set-binding factor-2 gene (SBF2, 607697.0001 ) ▲ 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	CHARCOT-MARIE-TOOTH DISEASE, TYPE 4B2	c1858278	7,432	omim	https://www.omim.org/entry/604563	2019-09-22T16:11:52	{"doid": ["0110190"], "mesh": ["C535421"], "omim": ["604563"], "orphanet": ["99956"], "synonyms": ["Alternative titles", "CHARCOT-MARIE-TOOTH DISEASE, WITH FOCALLY FOLDED MYELIN SHEATHS, AUTOSOMAL RECESSIVE, TYPE 4B2", "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 4B2"]}
Inflammatory skin disease with redness and scaling Erythroderma Other namesExfoliative dermatitis, Dermatitis exfoliativa Red skin syndrome SpecialtyDermatology Erythroderma is an inflammatory skin disease with redness and scaling that affects nearly the entire cutaneous surface.[1][2] This term applies when 90% or more of the skin is affected. In ICD-10, a distinction is made between "exfoliative dermatitis" at L26, and "erythroderma" at L53.9. ## Contents * 1 Causes * 2 Treatment * 3 Epidemiology * 4 History * 5 References * 6 External links ## Causes[edit] Erythroderma is generalized exfoliative dermatitis, which involves 90% or more of the patient's skin.[3] The most common cause of erythroderma is exacerbation of an underlying skin disease, such as psoriasis, contact dermatitis, seborrheic dermatitis, lichen planus, pityriasis rubra pilaris or a drug reaction, such as the use of topical steroids.[4] Primary erythroderma is less frequent and is usually seen in cases of cutaneous T-cell lymphoma, in particular in Sézary's disease.[5] The most common causes of exfoliative dermatitis are best remembered by the mnemonic device ID-SCALP.[3] The causes and their frequencies are as follows: * Idiopathic - 30% * Drug allergy - 28% * Seborrheic dermatitis - 2% * Contact dermatitis - 3% * Atopic dermatitis - 10% * Lymphoma and leukemia - 14% * Psoriasis - 8% ## Treatment[edit] The treatment for erythroderma depends on the primary cause. Topical steroids and use of a sauna suit are often used to treat exfoliative dermatitis regardless of the cause. Retinoids and immunosuppressive drugs can be used when it is caused by psoriasis or pityriasis rubra pilaris.[2] A sedative antihistamine may be a useful adjunct for pruritic patients, since it helps patients to sleep at night, thus limiting nocturnal scratching and excoriations. Antimicrobial agents often are used if an infection is suspected to be precipitating or complicating exfoliative dermatitis. Other drugs specifically indicated for management of underlying cause of exfoliative dermatitis may be necessary.[3] ## Epidemiology[edit] The incidence of erythroderma is estimated to be 1-2 in 100,000.[6] While erythroderma can occur at any age, it is most common in older, male adults. ## History[edit] The classification of exfoliative dermatitis into Wilson-Brocq (chronic relapsing), Hebra or pityriasis rubra (progressive), and Savill (self-limited) types may have had historical value, but it currently lacks pathophysiologic or clinical utility.[1] ## References[edit] 1. ^ a b Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. p. 436. ISBN 0-07-138076-0. 2. ^ a b James, William D.; Elston, Dirk M.; Treat, James R.; Rosenbach, Misha A.; Neuhaus, Isaac M. (2020). "Pityriasis Rosea, Pityriasis Rubra Pilaris, and Other Papulosquamous and Hyperkeratotic Diseases". Andrews' Diseases of the Skin: Clinical Dermatology (13th ed.). Edinburgh. pp. 205–214. ISBN 9780323547536. 3. ^ a b c Umar, Sanusi H. (5 December 2020). "Erythroderma (Generalized Exfoliative Dermatitis): Background, Pathophysiology, Etiology". eMedicine. Medscape. Retrieved 15 January 2021. 4. ^ Fukaya, Mototsugu (2000). Withdrawal from corticosteroids in patients with atopic dermatitis. www.tclinic.jp. Archived from the original on December 23, 2014.CS1 maint: unfit URL (link) 5. ^ "Dermatology: An Illustrated Colour Text - David J. Gawkrodger - Google Books". web.archive.org. June 16, 2013. 6. ^ Sigurdsson, V (November 2001). "The incidence of erythroderma: a survey among all dermatologists in The Netherlands". Journal of the American Academy of Dermatology. 45 (5): 675–678. doi:10.1067/mjd.2001.116224. PMID 11606915. ## External links[edit] Classification D * ICD-10: L26, L53.9 * ICD-9-CM: 695.9 * MeSH: D003873 * DiseasesDB: 29735 * SNOMED CT: 55012006 External resources * MedlinePlus: 001610 * eMedicine: derm/142 * 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 * v * t * e Papulosquamous disorders Psoriasis Pustular * Generalized pustular psoriasis (Impetigo herpetiformis) * Acropustulosis/Pustulosis palmaris et plantaris (Pustular bacterid) * Annular pustular psoriasis * Localized pustular psoriasis Other * Guttate psoriasis * Psoriatic arthritis * Psoriatic erythroderma * Drug-induced psoriasis * Inverse psoriasis * Napkin psoriasis * Seborrheic-like psoriasis Parapsoriasis * Pityriasis lichenoides (Pityriasis lichenoides et varioliformis acuta, Pityriasis lichenoides chronica) * Lymphomatoid papulosis * Small plaque parapsoriasis (Digitate dermatosis, Xanthoerythrodermia perstans) * Large plaque parapsoriasis (Retiform parapsoriasis) Other pityriasis * Pityriasis rosea * Pityriasis rubra pilaris * Pityriasis rotunda * Pityriasis amiantacea Other lichenoid Lichen planus * configuration * Annular * Linear * morphology * Hypertrophic * Atrophic * Bullous * Ulcerative * Actinic * Pigmented * site * Mucosal * Nails * Peno-ginival * Vulvovaginal * overlap synromes * with lichen sclerosus * with lupus erythematosis * other: * Hepatitis-associated lichen planus * Lichen planus pemphigoides Other * Lichen nitidus * Lichen striatus * Lichen ruber moniliformis * Gianotti–Crosti syndrome * Erythema dyschromicum perstans * Idiopathic eruptive macular pigmentation * Keratosis lichenoides chronica * Kraurosis vulvae * Lichen sclerosus * Lichenoid dermatitis * Lichenoid reaction of graft-versus-host disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Erythroderma	c0011606	7,433	wikipedia	https://en.wikipedia.org/wiki/Erythroderma	2021-01-18T18:40:10	{"gard": ["6393"], "mesh": ["D003873"], "umls": ["C0011606"], "icd-9": ["695.9"], "icd-10": ["L26"], "wikidata": ["Q1363741"]}
A rare syndrome characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and low urinary calcium excretion. ## Epidemiology Gitelman syndrome (GS) prevalence is estimated at 1 to 10 per 40,000 and potentially higher in Asia. GS is arguably the most frequent inherited tubulopathy. ## Clinical description GS presents mainly in adolescents and adults but also encountered in children, as early as in the neonatal period. The diagnosis may be incidental, due to blood tests obtained for unrelated reasons. Clinical symptoms may include salt craving, thirst and nocturia, transient periods of muscle weakness and tetany, sometimes accompanied by abdominal pain. Paresthesias, especially in the face, may occur. Remarkably, some patients are completely asymptomatic. In adulthood, chondrocalcinosis may appear, which can be associated with inflammation over the affected joints. Blood pressure is typically lower than that in the general population, although reports of hypertension in adult patients exist. Sudden cardiac arrest has been described in case reports and long QT syndrome may be present. In general, growth is normal but can be delayed. ## Etiology GS is caused by biallelic inactivating mutations in the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter NCC expressed in the apical membrane of cells lining the distal convoluted tubule. At present, more than 350 different NCC mutations throughout the whole protein have been identified. ## Diagnostic methods Diagnosis is based on the clinical symptoms and biochemical abnormalities (chronic hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalciuria) and can be confirmed by genetic testing. ## Differential diagnosis Bartter syndrome (especially type III, caused by mutation in CLCNKB) can be clinically indistinguishable from GS. Mutation in the HNF1B can mimic the electrolyte abnormalities (particularly hypomagnesemia) encountered in GS. Biochemical abnormalities are identical in EAST/SESAME syndrome, but the extra renal features allow it to be distinguished from GS. Chronic thiazide use can cause an acquired GS-like clinical picture. ## Antenatal diagnosis Antenatal diagnosis for GS is technically feasible but not advised because of the good prognosis in the majority of patients. ## Genetic counseling Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy. ## Management and treatment The management of GS should be individualized and at least annual follow-up in a nephrology clinic to monitor potential complications and evolution is advocated. It is recommended to encourage patients to follow their propensity for salt consumption. Lifelong supplementation of salt, potassium (KCl) or magnesium supplementation (magnesium-oxide and magnesium-sulfate) should be considered. Many symptoms are improved by supplementation, but there is no evidence correlating the severity of biochemical abnormalities with the severity of symptoms. Cardiac work-up should be offered to screen for risk factors for cardiac arrhythmias. All GS patients are encouraged to maintain a high sodium and high potassium diet. ## Prognosis To date, there is no evidence that GS affects life expectancy. * 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	Gitelman syndrome	c0268450	7,434	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=358	2021-01-23T18:39:01	{"gard": ["8547"], "mesh": ["D053579"], "omim": ["263800"], "umls": ["C0268450"], "icd-10": ["N15.8"], "synonyms": ["Primary renal tubular hypokalemic hypomagnesemia with hypocalciuria"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive familial adenomatous polyposis-2 (FAP2) is caused by homozygous or compound heterozygous mutation in the MUTYH (MYH) gene (604933) on chromosome 1p34. Description Autosomal recessive colorectal adenomatous polyposis is a disorder characterized by adult-onset of multiple colorectal adenomas and adenomatous polyposis. Affected individuals have a significantly increased risk of colorectal cancer (summary by Sieber et al., 2003). Cheadle and Sampson (2003) reviewed the molecular pathology and biochemistry of MYH colonic polyposis. For a discussion of genetic heterogeneity of FAP, see 175100. Clinical Features Autosomal recessive FAP is characterized by multiple colorectal adenomas and a high risk of colorectal cancer (summary by Sampson et al., 2003). ### Clinical Variability A combination of pilomatricomas (132600) and adenomatous polyposis coli as an autosomal recessive trait has been reported with mutation in the MYH gene (604933.0008) (Baglioni et al., 2005). Barnetson et al. (2007) reported a patient with endometrial adenocarcinoma (see 608089) and sebaceous carcinoma of the face who was compound heterozygous for 2 common mutations in the MUTYH gene (Y165C; 604933.0001 and G382D; 604933.0002). Colonic adenomas were not reported, but a paternal aunt reportedly had colorectal cancer in her thirties. Barnetson et al. (2007) noted that the phenotype associated with biallelic MUTYH mutations may include extracolonic manifestations, including endometrial cancer and sebaceous carcinoma, as seen in other inherited colorectal cancer syndromes such as Muir-Torre syndrome (158320) and Lynch syndrome (120435). Inheritance Among 614 families recorded in 6 regional registers of polyposis in the UK, Sampson et al. (2003) identified 111 with neither dominant transmission nor evidence of APC mutation. Molecular genetic analysis showed that 25 had biallelic mutations of the MYH gene. The data showed that MYH polyposis can be transmitted as an autosomal recessive trait, requiring a change in genetic counseling, testing, and surveillance. Sampson et al. (2003) recommended that genetic analysis of MYH be offered to patients with a phenotype resembling FAP or attenuated FAP when no clear evidence of vertical transmission is recorded. Further studies were considered necessary to clarify the risk of colorectal cancer for MYH heterozygous individuals. Molecular Genetics Al-Tassan et al. (2002) studied a British family in which 3 sibs had multiple colorectal adenomas and carcinoma. There was no clear pathogenic change in the APC gene. Analysis of the MYH gene showed that the sibs were compound heterozygous for nonconservative missense variants (604933.0001-604933.0002). Jones et al. (2002) and Sieber et al. (2003) also identified biallelic MYH mutations in patients with multiple colorectal adenomas. Rouleau et al. (2011) reported a 45-year-old French man who was found to have 25 colorectal adenomas on colonoscopy. He had no family history of the disorder. Analysis of the APC gene was negative, and molecular analysis identified compound heterozygosity for mutations in the MUTYH gene: a missense mutation (604933.0002) and a large rearrangement resulting in the deletion of exons 3 to 16 (604933.0009). INHERITANCE \- Autosomal recessive ABDOMEN Gastrointestinal \- Multiple colonic adenomatous polyps \- Multiple colorectal polyps NEOPLASIA \- Increased risk of colorectal carcinoma MISCELLANEOUS \- Age at diagnosis ranges from the teens to the 60s MOLECULAR BASIS \- Caused by mutation in the MutY DNA glycosylase gene (MUTYH, 604933.0001 ) ▲ 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	FAMILIAL ADENOMATOUS POLYPOSIS 2	c2674616	7,435	omim	https://www.omim.org/entry/608456	2019-09-22T16:07:52	{"doid": ["0080410"], "mesh": ["C538265"], "omim": ["608456"], "orphanet": ["220460", "247798"], "synonyms": ["Alternative titles", "COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE", "ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE"], "genereviews": ["NBK107219"]}
A number sign (#) is used with this entry because malonyl-CoA decarboxylase deficiency is caused by homozygous or compound heterozygous mutation in the MLYCD gene (606761) on chromosome 16q23. Description Malonyl-CoA decarboxylase deficiency is an uncommon inherited metabolic disease. The characteristic phenotype is variable, but may include developmental delay in early childhood, seizures, hypotonia, diarrhea, vomiting, metabolic acidosis, hypoglycemia, ketosis, abnormal urinary compounds, lactic acidemia, and hypertrophic cardiomyopathy (Sweetman and Williams, 2001). Clinical Features Brown et al. (1984) described deficiency of malonyl-CoA decarboxylase in a 5-year-old boy who had been studied for short stature, abdominal pain, chronic constipation, episodic vomiting, and metabolic acidosis. Abnormal amounts of malonic, methylmalonic, and succinic acids were found in his urine. The parents were first cousins, and a sib had died at 3.5 months of age. The mitochondrial malonyl-CoA decarboxylase was very deficient and both parents had an intermediate level of activity. Haan et al. (1986) reported a second boy with more severe malonyl-CoA decarboxylase deficiency who presented in a quite different way from the previous patient and whose urine contained, in addition to the above-mentioned organic acids, adipic, glutaric, and suberic acids. The child was mildly mentally retarded and presented with vomiting, seizures, hypoglycemia, and mild metabolic acidosis during a urinary tract infection. Mitochondrial malonyl-CoA decarboxylase activity in fibroblasts was 4% of normal; in both parents it was about half normal. MacPhee et al. (1993) described 2 patients, a son of second-cousin Irish parents and a girl, the daughter of first-cousin Scottish parents. They were investigated during episodes of vomiting and febrile convulsions associated with concomitant developmental delay. Malonicaciduria and grossly reduced malonyl-CoA decarboxylase activity were demonstrated. FitzPatrick et al. (1999) provided an analysis of the 7 reported cases of MCD deficiency. The condition was present in early childhood and was associated with malonicaciduria, methylmalonicaciduria, and developmental delay in all 7, seizure disorder and hypoglycemia in 4, and cardiomyopathy in 2. De Wit et al. (2006) reported a 4.5-year-old girl, born of consanguineous Moroccan parents, with MCD deficiency. Family history revealed 2 neonatal deaths and several miscarriages. The patient had feeding problems, failure to thrive, and severe developmental delay with no language development. Diagnosis occurred at age 2 years when metabolic screening showed compensated metabolic acidosis, hyperammonemia, increased malonic acid, and other abnormalities. Skin fibroblasts showed complete MCD deficiency. Cardiac exam was normal. The patient also had a very poor appetite. Brain MRI showed generalized atrophy, major white matter loss, thickened cortex with pachygyria, and periventricular nodular heterotopia. These findings were consistent with a malformation of cortical development. A review of the literature found that some previously reported patients also had brain imaging abnormalities, such as frontotemporal atrophy and white matter changes. Inheritance The cases reported by Brown et al. (1984), Haan et al. (1986), and MacPhee et al. (1993) supported autosomal recessive inheritance. Clinical Management Haan et al. (1986) showed in one case that a high-fat, low-carbohydrate diet led to symptomatic hypoglycemia, moderate acidosis, and urinary excretion of the organic acids. They pointed to this experience as evidence that methyl-CoA decarboxylase has an important function in the mitochondrion in preventing accumulation of malonyl-CoA, which has complex metabolic effects. MacPhee et al. (1993) described 2 patients with the deficiency and agreed with Brown et al. (1984) and Haan et al. (1986) that a low-fat, high-carbohydrate diet would lead to near normalization of the urinary organic acid excretion with no further hypoglycemic episodes. Hospital admission was recommended during periods of infection as well as during febrile illness as the harmful effects of the disorder became apparent. Molecular Genetics Gao et al. (1999) identified a 4-bp deletion at the 3-prime end of exon 2 of the MLYCD gene (606761.0003) in homozygosity in a patient with malonyl-CoA decarboxylase deficiency. By RT-PCR analysis of fibroblast RNA from 2 consanguineous Scottish patients with MCD deficiency reported by MacPhee et al. (1993), FitzPatrick et al. (1999) identified homozygous mutations in the MCD gene (606761.0002-606761.0003). Sacksteder et al. (1999) identified a 2-bp deletion (606761.0004) in a patient with severe malonicaciduria. By genomic sequencing of the MLYCD gene, Wightman et al. (2003) succeeded in identifying 16 of 18 pathogenic alleles in 9 unrelated patients with malonyl-CoA decarboxylase deficiency. (see, e.g., 606761.0005-606761.0007). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy ABDOMEN Gastrointestinal \- Diarrhea \- Vomiting \- Abdominal pain \- Chronic constipation MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Developmental delay in early childhood \- Seizures \- Frontotemporal atrophy \- White matter changes on brain imaging (less common) \- Pachygyria (less common) \- Nodular heterotopia (less common) METABOLIC FEATURES \- Metabolic acidosis LABORATORY ABNORMALITIES \- Hypoglycemia \- Ketosis \- Abnormal urinary compounds \- Lactic acidemia \- Mitochondrial malonyl-CoA decarboxylase activity in fibroblasts is very low (as low as 4%) MISCELLANEOUS \- Symptoms may be precipitated by infection MOLECULAR BASIS \- Caused by mutation in the malonyl-CoA decarboxylase gene (MLYCD, 606761.0001 ) ▲ 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	MALONYL-CoA DECARBOXYLASE DEFICIENCY	c0342793	7,436	omim	https://www.omim.org/entry/248360	2019-09-22T16:25:41	{"mesh": ["C535702"], "omim": ["248360"], "orphanet": ["943"]}
Glucose-6-phosphate dehydrogenase deficiency is a genetic disorder that occurs almost exclusively in males. This condition mainly affects red blood cells, which carry oxygen from the lungs to tissues throughout the body. In affected individuals, a defect in an enzyme called glucose-6-phosphate dehydrogenase causes red blood cells to break down prematurely. This destruction of red blood cells is called hemolysis. The most common medical problem associated with glucose-6-phosphate dehydrogenase deficiency is hemolytic anemia, which occurs when red blood cells are destroyed faster than the body can replace them. This type of anemia leads to paleness, yellowing of the skin and whites of the eyes (jaundice), dark urine, fatigue, shortness of breath, and a rapid heart rate. In people with glucose-6-phosphate dehydrogenase deficiency, hemolytic anemia is most often triggered by bacterial or viral infections or by certain drugs (such as some antibiotics and medications used to treat malaria). Hemolytic anemia can also occur after eating fava beans or inhaling pollen from fava plants (a reaction called favism). Glucose-6-phosphate dehydrogenase deficiency is also a significant cause of mild to severe jaundice in newborns. Many people with this disorder, however, never experience any signs or symptoms and are unaware that they have the condition. ## Frequency An estimated 400 million people worldwide have glucose-6-phosphate dehydrogenase deficiency. This condition occurs most frequently in certain parts of Africa, Asia, the Mediterranean, and the Middle East. It affects about 1 in 10 African American males in the United States. ## Causes Glucose-6-phosphate dehydrogenase deficiency results from mutations in the G6PD gene. This gene provides instructions for making an enzyme called glucose-6-phosphate dehydrogenase. This enzyme is involved in the normal processing of carbohydrates. It also protects red blood cells from the effects of potentially harmful molecules called reactive oxygen species, which are byproducts of normal cellular functions. Chemical reactions involving glucose-6-phosphate dehydrogenase produce compounds that prevent reactive oxygen species from building up to toxic levels within red blood cells. If mutations in the G6PD gene reduce the amount of glucose-6-phosphate dehydrogenase or alter its structure, this enzyme can no longer play its protective role. As a result, reactive oxygen species can accumulate and damage red blood cells. Factors such as infections, certain drugs, or ingesting fava beans can increase the levels of reactive oxygen species, causing red blood cells to be destroyed faster than the body can replace them. A reduction in the number of red blood cells causes the signs and symptoms of hemolytic anemia. Researchers believe that people who have a G6PD mutation may be partially protected against malaria, an infectious disease carried by a certain type of mosquito. A reduction in the amount of functional glucose-6-phosphate dehydrogenase appears to make it more difficult for this parasite to invade red blood cells. Glucose-6-phosphate dehydrogenase deficiency occurs most frequently in areas of the world where malaria is common. ### Learn more about the gene associated with Glucose-6-phosphate dehydrogenase deficiency * G6PD ## Inheritance Pattern Glucose-6-phosphate dehydrogenase is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. Males have only one X chromosome and females have two copies of the X chromosome. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In females, who have two copies of the X chromosome, one altered copy of the G6PD gene in each cell can lead to less severe features of the condition or may cause no signs or symptoms at all. However, many females with one altered copy of this gene have glucose-6-phosphate dehydrogenase deficiency similar to affected males because the X chromosome with the normal copy of the G6PD gene is turned off through a process called X-inactivation . Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, such that each X chromosome is active in about half of the body cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation. Research shows that females with glucose-6-phosphate dehydrogenase deficiency caused by mutation of the G6PD gene often have skewed X-inactivation, which results in the inactivation of the X chromosome with the normal copy of the G6PD gene in most cells of the body. This skewed X-inactivation causes the chromosome with the mutated G6PD gene to be expressed in more than half of cells. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Glucose-6-phosphate dehydrogenase deficiency	c4016516	7,437	medlineplus	https://medlineplus.gov/genetics/condition/glucose-6-phosphate-dehydrogenase-deficiency/	2021-01-27T08:25:50	{"gard": ["6520"], "omim": ["305900"], "synonyms": []}
Chancroid is a bacterial infection that is spread through sexual contact. It is caused by a type of bacteria called Haemophilus ducreyi. Chancroid is characterized by a small bump on the genital which becomes a painful ulcer. Men may have just one ulcer, but women often develop four or more. About half of the people who are infected with a chancroid will develop enlarged inguinal lymph nodes, the nodes located in the fold between the leg and the lower abdomen. In some cases, the nodes will break through the skin and cause draining abscesses. The swollen lymph nodes and abscesses are often called buboes. Chancroid infections can be treated with antibiotics, including azithromycin, ceftriaxone, ciprofloxacin, and erythromycin. Large lymph node swellings need to be drained, either with a needle or local surgery. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Chancroid	c0007947	7,438	gard	https://rarediseases.info.nih.gov/diseases/9522/chancroid	2021-01-18T18:01:32	{"mesh": ["D002602"], "umls": ["C0007947"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that Adie pupil is a characteristic of Charcot-Marie-Tooth disease type 2J (607736), which is caused by mutation in the MPZ gene (159440). Adie (1932) described a stationary, benign disorder characterized by tonic, sluggishly reacting pupil and hypoactive or absent tendon reflexes. De Rudolf (1936) described the disorder in mother and daughter, McKinney and Frocht (1940) in father and son, and Mylius (1938) in sibs. The pupil (Laties and Scheie, 1965) is excessively sensitive to mecholyl (methacholine). In familial dysautonomia, a recessive (see 223900), the pupil is also mecholyl-sensitive and tendon reflexes are absent. An autopsied case was reported by Harriman and Garland (1968), who found neuronal degeneration in the ciliary ganglion. Selective degeneration of neurons in dorsal root ganglia may have been the basis for areflexia. From electrophysiologic studies carried out in 11 patients with Adie syndrome, Miyasaki et al. (1988) concluded that the hyporeflexia in this condition is due to the loss of large spindle afferents or the reduced effectiveness of their monosynaptic connections to motoneurons. Triggs et al. (2006) described Adie pupil in a family with Charcot-Marie-Tooth disease type 2J. They noted that when diminished deep tendon reflexes are associated with a tonic pupil, the condition is designated Holmes-Adie syndrome. Misc \- Stationary, harmless disorder Eyes \- Sluggish pupillary response \- Mecholyl-sensitive pupil Neuro \- Hyporeflexia 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	ADIE PUPIL	c0001519	7,439	omim	https://www.omim.org/entry/103100	2019-09-22T16:45:17	{"doid": ["11549"], "mesh": ["D000270"], "omim": ["103100"], "icd-9": ["379.46"], "icd-10": ["H57.05"], "orphanet": ["454718"], "synonyms": ["Alternative titles", "ADIE SYNDROME", "POORLY REACTING PUPILS"]}
This article is about theileriosis caused by Theileria parva in cattle. For diseases caused by other Theileria species, see Theileriosis (disambiguation). Kinete stage of Theileria parva in the transmitting tick Rhipicephalus appendiculatus Brisket -edema-in theileriosis by Mitun Sarkar East Coast fever, also known as theileriosis, is a disease of cattle which occurs in Africa and is caused by the protozoan parasite Theileria parva. The primary vector which spreads T. parva between cattle is a tick, Rhipicephalus appendiculatus.[1] East Coast fever is of major economic importance to livestock farmers in Africa,[2] killing at least one million cattle each year.[3] The disease occurs in Burundi, Democratic Republic of Congo, Kenya, Malawi, Mozambique, Rwanda, South Sudan, Tanzania, Uganda, Zimbabwe, Zambia.[3] In 2003, East Coast fever was introduced to Comoros by cattle imported from Tanzania.[4] It has been eradicated in South Africa.[3] A more acute form of East Coast fever called corridor disease occurs when buffalo-derived T. parva is transmitted to cattle.[3] Another form, called January disease, only occurs over the winter months in Zimbabwe due to the tick lifecycle.[citation needed] Native cattle are often resistant to the parasite, but not without symptoms. They are hosts to the parasite, but do not suffer as severely as foreign cattle.[5][6] ## Contents * 1 Clinical signs and diagnosis * 2 Treatment and control * 3 History * 4 References ## Clinical signs and diagnosis[edit] Mortality can be up to 100%, with death occurring around 18–30 days after the initial attachment of infected ticks, because the incubation required is around 10–25 days, and the parasite spreads quickly and is rather aggressive.[citation needed] Clinical signs include fever and enlarged lymph nodes near the tick bites. Smears and stains can also be done to check for the parasite. Schizonts (meronts, or segmentors) can be found in infected lymphocytes. Pathology includes anorexia, dyspnea, corneal opacity, nasal discharge, frothy nasal discharge, diarrhea, pulmonary edema, leukopenia, and anemia. Endemic cattle given medication sometimes recover to varying degrees, or death follows due to blocked capillaries and parasites infecting the central nervous system.[7] Cattle in endemic areas which survive infection become carriers.[citation needed] For diagnosis, post mortem findings are characteristic and mainly include damage to the lymphoid and respiratory systems.[citation needed] ## Treatment and control[edit] One study using the medicinal plant Peganum harmala showed it to have a lifesaving effect on cattle infected with East Coast fever.[8] The classical treatment with tetracyclines (1970–1990) cannot provide efficiency more than 50%.[citation needed] Since the early 1990s, buparvaquone is used in bovine theileriosis with remarkable results (90 to 98% recovery).[citation needed] Other than the buparvaquones, other chemotherapeutic options are the parvaquones, e.g. Clexon.[9] Halofuginone lactate[10] has also been shown to have an 80.5% efficacy against Theirelia parva parva infections. The ultimate factor that causes death is pulmonary edema. In May 2010, a vaccine to protect cattle against East Coast fever reportedly had been approved and registered by the governments of Kenya, Malawi and Tanzania.[11] This consists of cryopreserved sporozoites from crushed ticks, but it is expensive and can cause disease.[citation needed] Control of the disease relies on control of ticks of domestic animals. This is a major concern in tropical countries with large livestock populations, especially in the endemic area. Pesticides (acaricides) are applied in dipping baths or spray races, and cattle breeds with good ability to acquire immune resistance to the vector ticks are used.[citation needed] ## History[edit] This disease was first reported in southern Africa, south of the Zambezi river, in 1902.[12] It became known as East Coast fever after it was determined that the disease had originated in cattle imported from the East Coast of Africa.[12] ## References[edit] 1. ^ Olwoch JM, Reyers B, Engelbrecht FA, Erasmus BF (2008). "Climate change and the tick-borne disease, Theileriosis (East Coast fever) in sub-Saharan Africa". Journal of Arid Environments. 72 (2): 108–20. doi:10.1016/j.jaridenv.2007.04.003. 2. ^ "Protecting Africa's cattle with a live vaccine: An East Coast fever impact narrative". ILRI Research Brief. No. 24. International Livestock Research Institute. September 2014. Retrieved 2018-05-06. 3. ^ a b c d Nene, V; Kiara, H; Lacasta, A; Pelle, R; Svitek, N; Steinaa, L (June 2016). "The biology of Theileria parva and control of East Coast fever - Current status and future trends". Ticks and Tick-borne Diseases. 7 (4): 549–64. doi:10.1016/j.ttbdis.2016.02.001. PMID 26972687. 4. ^ Gachohi, J; Skilton, R; Hansen, F; Ngumi, P; Kitala, P (7 September 2012). "Epidemiology of East Coast fever (Theileria parva infection) in Kenya: past, present and the future". Parasites & Vectors. 5: 194. doi:10.1186/1756-3305-5-194. PMC 3465218. PMID 22958352. 5. ^ Norval RA, Perry BD, Young AS (1992). The Epidemiology of Theileriosis in Africa. London: Academic Press. ISBN 978-0-12-521740-8. 6. ^ International Livestock Research Institute 7. ^ Morrison WI, Goddeeris BM, Brown WC, Baldwin CL, Teale AJ (February 1989). "Theileria parva in cattle: characterization of infected lymphocytes and the immune responses they provoke". Vet Immunol Immunopathol. 20 (3): 213–37. doi:10.1016/0165-2427(89)90003-2. PMID 2497579. 8. ^ Derakhshanfar A, Mirzaei M (March 2008). "Effect of Peganum harmala (wild rue) extract on experimental ovine malignant theileriosis: pathological and parasitological findings". Onderstepoort J Vet Res. 75 (1): 67–72. doi:10.4102/ojvr.v75i1.90. PMID 18575066. 9. ^ ILRI. "Treatment of East coast Fever using Clexon in Uganda". Archived from the original on 2011-09-28. Retrieved 2011-05-26. 10. ^ PubMed (June 1987). "Clinical Trial of Halofuginone Lactate for the Treatment of East Coast Fever in Kenya". Vet. Rec. 120 (24): 575–7. doi:10.1136/vr.120.24.575. PMID 3303642. 11. ^ "Cattle disease vaccine launched 30 years after invention". 2010-05-07. SciDev.net (7 May 2010). 12. ^ a b Norval, R.A.I.; Perry, B.D.; Young, A.S. (1992). "Chapter 1.1 The epidemiology of East Coast fever. Introduction". The epidemiology of theileriosis in Africa. London: Academic Press. pp. 2–3. ISBN 9780125217408. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	East Coast fever	c0039753	7,440	wikipedia	https://en.wikipedia.org/wiki/East_Coast_fever	2021-01-18T18:56:03	{"mesh": ["D013801"], "umls": ["C0039753"], "wikidata": ["Q481392"]}
Binge drinking 1912 U.S. Happy New Year postcard SpecialtyPsychiatry Binge drinking, or heavy episodic drinking, is a modern epithet for drinking alcoholic beverages with an intention of becoming intoxicated by heavy consumption of alcohol over a short period of time, but definitions (see below) vary considerably.[1] Binge drinking is a style of drinking that is popular in several countries worldwide, and overlaps somewhat with social drinking since it is often done in groups. The degree of intoxication, however, varies between and within various cultures that engage in this practice. A binge on alcohol can occur over hours, last up to several days, or in the event of extended abuse, even weeks. Due to the long term effects of alcohol abuse, binge drinking is considered to be a major public health issue.[2] Binge drinking is more common in males, during adolescence and young adulthood. Heavy regular binge drinking is associated with adverse effects on neurologic, cardiac, gastrointestinal, hematologic, immune, musculoskeletal organ systems as well as increasing the risk of alcohol induced psychiatric disorders.[3][4] A US-based review of the literature found that up to one-third of adolescents binge-drink, with 6% reaching the threshold of having an alcohol-related substance use disorder.[5] Approximately one in 25 women binge-drinks during pregnancy, which can lead to fetal alcohol syndrome and fetal alcohol spectrum disorders.[6] Binge drinking during adolescence is associated with traffic accidents and other types of accidents, violent behavior as well as suicide. The more often a child or adolescent binge drinks and the younger they are the more likely that they will develop an alcohol use disorder including alcoholism. A large number of adolescents who binge-drink also consume other psychotropic substances.[7] Frequent binge drinking can lead to brain damage faster and more severely than chronic drinking (alcoholism). The neurotoxic insults are due to very large amounts of glutamate which are released and over-stimulate the brain as a binge finishes. This results in excitotoxicity, a process which damages or kills neurons (brain cells).[8] Each binge drinking episode immediately insults the brain; repeat episodes result in accumulating harm. The developing adolescent brain is thought to be particularly susceptible to the neurotoxic effects of binge drinking, with some evidence of brain damage occurring from drinking more than 10 or 11 drinks once or twice per month.[9] With prolonged abstinence neurogenesis occurs which can potentially reverse the damage from alcohol abuse.[10] ## Contents * 1 Definitions * 2 Health effects * 2.1 Adolescence and young adulthood * 2.2 Central nervous system * 2.3 Pregnancy * 2.4 Sudden death * 2.5 Urinary system * 2.6 Acute hazards * 2.7 Cardiovascular system * 3 Cause * 4 Pathophysiology * 5 Diagnosis * 6 Prevention * 6.1 Reduction * 7 Treatment * 8 Epidemiology * 9 Society and culture * 10 Sex differences * 11 See also * 12 Notes * 13 References * 14 External links ## Definitions[edit] Stolle, Sack and Thomasius define binge drinking as episodic excessive drinking.[7] There is currently no worldwide consensus on how many drinks constitute a "binge", but in the United States, the term has been described in academic research to mean consuming five or more standard drinks (male), or four or more drinks (female),[11] over a two-hour period.[12] In 2015, the US Centers for Disease Control and Prevention, citing the National Institute on Alcohol Abuse and Alcoholism, defines binge drinking as "a pattern of drinking that brings a person’s blood alcohol concentration (BAC) to 0.08 grams percent or above. This typically happens when men consume five or more drinks, and when women consume four or more drinks, in about two hours."[13] and estimated that about 16% of American adults met these binge drinking criteria four times per month. One 2001 definition from the publication Psychology of Addictive Behavior states that five drinks for men and four drinks for women must be consumed on one occasion at least once in a two-week period for it to be classed as binge drinking.[14] This is colloquially known[by whom?] as the "5/4 definition", and depending on the source, the timeframe can vary. In the United Kingdom, binge drinking is defined by one academic publication as drinking more than twice the daily limit, that is, drinking eight units or more for men or six units or more for women (roughly equivalent to five or four American standard drinks, respectively).[15] In Australia, binge drinking is also known as risky single occasion drinking (RSOD)[16] and can be classified by the drinking of seven or more standard drinks (by males) and five or more standard drinks (by females) within a single day.[17] When BEACH (Bettering the Evaluation and Care of Health) conducted a study which gathered information of people over the age of 18, it defined binge drinkers as those who consumed six or more standard drinks on one occasion whether that be weekly or monthly.[18] The above definitions are limited in that they do not take into account the time period over which the drinking occurs or the body mass of the person drinking. A person could be defined as a binge drinker even if he or she never becomes intoxicated. The term, however, has succeeded in drawing public awareness to the problem of excess drinking.[citation needed]. Other, less common definitions rely on blood alcohol concentration (BAC). For example, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines the term "binge drinking" as a pattern of drinking that brings a person's blood alcohol concentration (BAC) to 0.08 grams percent or above.[19] Whatever the numerical definition used, heavy drinking or rapid consumption over a short period of time with the intention of becoming intoxicated is often implied when the term is used colloquially, since four or five drinks consumed over the course of a whole day and as an accompaniment to meals will not have the same effects as the same amount consumed over a couple of hours on an empty stomach.[20] An alternative colloquial term for binge drinking, "going on a bender", formerly implied a drinking spree of several days.[21] ## Health effects[edit] See also: Long-term effects of alcohol consumption Acute intoxication, such as binge drinking and alcoholism, are known potent risk factors for suicide.[22] Binge drinking is also associated with an increased risk of unplanned and unprotected sex, unplanned pregnancies, and an increased risk of HIV infection. 10% of women and 19% of men have reported being assaulted as a result of alcohol. Males who drink more than 35 units of alcohol per week report being physically hurt as a result of alcohol, and 15% report physically hurting others as a result of their drinking. Almost 16% of binge drinkers report being taken advantage of sexually, and 8% report taking advantage of another person sexually as a result of alcohol within a one-year period. Heavy drinkers cause approximately 183,000 rapes and sexual assaults, 197,000 robberies, 661,000 aggravated assaults, and 1.7 million simple assaults each year.[23] Binge drinking has been associated with high odds of divorce, spousal abuse, and poor job performance.[24] Binge drinking can cause adverse effects on the body including effects on blood homeostasis and its circadian variation, cardiac rhythm, ischaemic heart disease, blood pressure, white blood cell activity, female reproductive hormone levels as well as adverse effects on the fetus. There is also evidence from animal studies that binge drinking causes brain damage.[25] Binge drinking has been associated with lower abdominal pain in women.[26] Ketoacidosis can occur in individuals who chronically abuse alcohol and have a recent history of binge drinking.[27] Alcohol affects brain development quite significantly especially during adolescence when the brain is still developing. The main lobes that are involved in decision making and complex thought processes are undergoing their final development phase during adolescence and binge drinking can negatively stunt the growth of these frontal lobes.[28] ### Adolescence and young adulthood[edit] A young man lying comatose after a binge drinking session The high levels of binge drinking among young people and the adverse consequences that include increased risk of alcoholism as an adult and liver disease make binge drinking a major public health issue.[2] Recent research has found that young college binge drinkers who drink four or more drinks on more than three occasions in the past two weeks are statistically 19 times more likely to develop alcoholism than non-binge drinkers, though the direction of causality remains unclear.[29] This is particularly interesting as drinking for the sole purpose of getting drunk, remains a major health and social problem on college campuses across the United States.[30] Heavy and regular binge drinking during adolescence is associated with an increased risk of alcoholism. Approximately 40% of alcoholics report heavy drinking during adolescence.[31] Repeated episodes of excessive drinking, especially at an early age, are thought to cause a profound increase in the risk of developing an alcohol-related disorder (ICD-10, harmful use/dependence syndrome). Heavy drinking is also closely associated with depression. Those with severe depression have higher rates of alcohol abuse than those with low depression. [32] College students who are depressed are more susceptible to use alcohol than college students who are not depressed.[33] In a study conducted at Harvard University, it was found that about 32% of students surveyed were diagnosable for alcohol abuse and about 6% were diagnosed as alcohol dependent.[34] Binge drinking is also becoming an increasing problem in Australian adolescents, the Australian School Students Alcohol and Drug survey conducted by the National Cancer Council discovered that around 33% of students between years 7 and 11 consumed alcohol in the week leading up to the survey, they also found that 10% of the students participated in binge drinking at a consumption level which is considered dangerous to adults. When the survey results were separated into age groups the findings were that 13% of 15-year-old's and 22% of 17-year-old's had alcohol consumption levels above the daily maximum suggested to adults and that 20% of 17-year-old's had a consumption level of alcohol considered risky to adults.[35] Other risk factors that influence the development of alcohol abuse or alcoholism include social and genetic factors. Several researchers have found that starting drinking before the age of 15 is associated with a fourfold increased risk for developing alcoholism compared to people that delay drinking until age 20 or later. It has been estimated by some that if the age at which people started drinking could be delayed to age 20, there would be a 50% reduction in the number of cases of alcohol use disorder.[7] However, it is unclear whether this is a causal relationship, or a function of confounding familial (and other) factors associated with both age at first drink and propensity for alcoholism.[36] The main cause of death among adolescents as a result of binge drinking is road traffic accidents; a third of all fatal road traffic accidents among 15- to 20-year-olds are associated with drinking alcohol. Cyclists and pedestrians are likely to have less spatial awareness and concentration while travelling after binge drinking and, also, it is more common that adolescents that binge-drink drive drunk or are the passenger of a drunk driver. It has been found that 50% of all head injuries in adolescents in the US are associated with alcohol consumption. Violence and suicide combine to become the third-most-common cause of death associated with binge drinking among adolescents. The suicide risk in adolescents is more than four times higher among binge drinkers than non-binge drinking adolescents.[7] Earlier sexual activity, increased changing of sexual partners, higher rate of unwanted (teenage) pregnancy, higher rate of sexually transmitted diseases, infertility, and alcohol-related damage to the fetus during pregnancy is associated with binge drinking. Female binge drinkers are three times more likely to be victims of sexual assault; 50% of adolescent girls reporting sexual assault were under the influence of alcohol or another psychotropic substance at the time.[7] Adolescents who regularly participated in binge drinking for several years show a smaller hippocampus brain region, in particular those who began drinking in early adolescence. Heavy binge drinking is associated with neurocognitive deficits of frontal lobe processing and impaired working memory as well as delayed auditory and verbal memory deficits. Animal studies suggest that the neurodegenerative effects of alcohol abuse during adolescence can be permanent.[7] Research in humans, which utilised sophisticated brain scanning technology suggests that in adolescent teenagers, drinking more than four or five drinks once or twice a month results in subtle damage to the teenagers developing brain tissue, in particular the white matter.[9] However, this research is primarily cross-sectional and done with fairly small sample sizes, making causality less certain. Several studies have been conducted to discover if there is a link between binge drinking in adolescent years and becoming a chronic alcohol consumer when they transition into adulthood. A particular study conducted by the National Longitudinal Survey of Youth found that harmful drinking during adolescent years was significantly associated with the continuance of dangerous levels of alcohol consumption into adulthood years.[37][38] Binge drinking is a way for young adolescents to rely alcohol as a way to cope with certain stress or depression.[39] ### Central nervous system[edit] See also: Alcohol withdrawal syndrome § Kindling, and Kindling (substance withdrawal) Heavy binge drinkers tend to have delayed auditory and verbal memory and deficits in executive planning function and episodic memory, which are similar to deficits seen in Korsakoff's syndrome. Impairments in spatial working memory and pattern recognition tasks also have been found in heavy binge drinkers. Impulse control is also impaired in binge drinkers, especially female binge drinkers. Additionally, immediate and delayed recall of verbal and visual information is impaired; conversely, semantic organizational ability is better in binge drinkers compared to non-binge drinkers. Studies in adolescents have shown that regular binge drinking may cause long-lasting cognitive impairments, though the threshold needed to produce significant effects remains unclear. Cognitive impairment in adults is also unclear, as one study found no association between binge drinking and cognitive impairment.[29] Binge drinking is believed to increase impulsivity due to altered functioning of prefrontal–subcortical and orbitofrontal circuits. Binge drinking and alcoholics who have undergone multiple detoxifications is associated with an inability to interpret facial expressions properly; this is believed to be due to kindling of the amygdala with resultant distortion of neurotransmission. Adolescents, females and young adults are most sensitive to the neuropsychological effects of binge drinking. Adolescence, in particular early adolescence, is a developmental stage that is particularly vulnerable to the neurotoxic and neurocognitive adverse effects of binge drinking due to it being a time of significant brain development.[15] Binge drinking regimes are associated with causing an imbalance between inhibitory and excitatory amino acids and changes in monoamines release in the central nervous system, which increases neurotoxicity and may result in cognitive impairments, psychological problems and in long-term heavy binge drinkers may cause irreversible brain damage in both adolescents and adults.[40][41] While several rat studies indicate that alcohol is more toxic during adolescence than adulthood, some researchers believe that it remains unclear whether this is also the case in humans. Though heavy binge drinking adolescent humans show impaired brain activity during memory tests and underdeveloped brain structures compared to adolescents who did not binge-drink, they argue that these findings are similar to adult alcoholics who did not abuse alcohol during adolescence.[42] Extrapolation from animal studies to humans is notoriously difficult,[43] and a review by the group Choose Responsibility concluded that alcohol's long-term damage to cognitive processes was the same regardless of whether heavy drinking commenced during adolescence or later.[42] ### Pregnancy[edit] Binge drinking is a more important factor rather than average alcohol intake, with regard to the severity of alcohol induced damage to the fetus. Alcohol has definite long-term adverse effects on the fetus, in particular impaired attentional skills and may lead to psychiatric disorders when the child grows up.[44] In a 2005 study in the US, approximately one in five non-pregnant women binge-drank and one in 25 pregnant women binge-drank.[6] Binge drinking during pregnancy is associated with fetal alcohol syndrome, alcohol-related birth defects as well as alcohol-related neurodevelopmental disorders. The affected children after birth can suffer mental retardation and problems with learning, memory, attention, problem solving and problems with mental health and social interactions. Deformities in facial features, skeletal and body organs as well as a smaller head circumference are also sometimes present in these children.[45][46] Studies in sheep indicate that fetal neurotoxicity induced by alcohol may be due to acidaemia and hypercapnia.[47] Binge drinking three or more times during pregnancy has been associated with an increased risk of stillbirth.[40] ### Sudden death[edit] Binge drinking is also associated with strokes and sudden death.[48] Binge drinking increases the risk of stroke by 10 times.[1] In countries where binge drinking is commonplace, rates of sudden death on the weekend in young adults and middle aged people increase significantly.[49] The withdrawal phase after an episode of binge drinking is particularly associated with ischaemic stroke as well as subarachnoid haemorrhage and intracerebral haemorrhage in younger men. In individuals with an underlying cardiac disorder a binge on alcohol increases the risk of silent myocardial ischaemia as well as angina.[50] Binge drinking has negative effects on metabolism, lipid profile, blood coagulation and fibrinolysis, blood pressure and vascular tone and is associated with embolic stroke and acute myocardial infarction. Due to these risks experts believe that it is extremely important to warn people of the risks of binge drinking.[51] Binge-drinking by people otherwise considered to be light drinkers is associated with an increased risk of cardiovascular problems and mortality.[52] Binge drinking increases cardiovascular toxicity due to its adverse effects on the electrical conduction system of the heart and the process of atherothrombosis.[53] Excessive alcohol consumption is responsible for an average of 80,000 deaths in the U.S. each year1 and $223.5 billion in economic costs in 2006.2 More than half of these deaths and three-quarters of the economic costs are due to binge drinking1 and 2 (≥4 drinks for women; ≥5 drinks for men, per occasion).[54] ### Urinary system[edit] The bladder may rupture if overfilled and not emptied.[55] This can occur in the case of binge drinkers having consumed very large quantities, but are not aware, due to stupor, of the need to urinate. This condition is very rare in women, but it does occur. Symptoms include localized pain and uraemia (poisoning due to reabsorbed waste). The recovery rate is high, with most fatalities due to septic blood poisoning. A person is more likely to urinate while passed out before the bladder ruptures, as alcohol relaxes the muscles that normally control their bladder.[56] ### Acute hazards[edit] The most common risk of consuming massive quantities of alcohol in a short period of time is a dangerously high blood alcohol level. The result is called alcohol poisoning (overdose), which can be fatal. Choking on (or inhalation of) vomit is also a potential cause of death, as are injuries from falls, fights, motor vehicle and bicycle accidents. Nine percent of college students who binge drink drive after binge drinking.[57] Another common risk is a blackout (alcohol-related amnesia), which can cause shame, guilt, embarrassment, harm to personal relationships, injury or death, and is also associated with the loss of personal belongings.[58] ### Cardiovascular system[edit] A recent study conducted on an American College tested to discover if excessive binge drinking would have an effect on the cardiovascular system. From the results they received they found alterations in the binge drinker's macrocirculation and microcirculation functions which may be sign of a risk in cardiovascular disease. The study suggests that binge drinkers with a past history of strong binge drinking should be screened regularly.[59] ## Cause[edit] Culture as well as peer pressure play an important role in driving binge drinking.[3] In adults, binge drinking is more common in people who have never been married and score a grade B or less in education.[29] The reasons for binge drinking by children and adolescents in Europe include:[7] * It's really fun (76%) * I feel more sociable (65%) * I feel happy/relaxed (51% each) * I forget my problems (41%) Other causes include feeling more grown-up and fitting in with peers and to increase the chance of sexual encounters. Some also drink to alleviate stress or anxiety.[7] Semi-structured interview were carried out with 64 14- to 17-year-olds who had an experience of binge drinking. These interviews found that motivations included social facilitation which was ease in social situations, individual benefits such as getting a 'buzz' and influences of peer pressure and social norms.[60] Risk factors for binge drinking among adolescents include: low socioeconomic status, large amount of disposable (pocket) money, sensation and novelty seeking, low self-control, delinquency and having delinquent friends. Other risk factors include: using alcohol as a coping strategy for emotional problems (more common in adolescent girls), excessive drinking among peers, poor relationship with parents, alcohol abuse by parents. Genetic conditions combined with a background of negative environmental factors increase the harmful use of alcohol.[7] Additionally the risk-taking behavior associated with adolescence promotes binge drinking.[61] ## Pathophysiology[edit] William Hogarth, 1731 Binge drinking has the propensity to result in brain damage faster as well as more severely than chronic drinking (alcoholism), due to the neurotoxic effects of the repeated rebound withdrawal effects. During the repeated alcohol free stages associated with binge drinking, a larger amount of glutamate is released than occurs during withdrawal from chronic alcohol abuse; additionally this extreme release of glutamate happens on a repeated basis in binge drinkers leading to excitotoxicity. The tolerance that occurs during chronic ('non-stop') drinking delays alcohol-related brain damage compared to binge drinking, which induced immediate and repeated insults to the brain.[8] Impairments in impulse control in binge drinkers, which is more prominent in female binge drinkers, is due to dysfunction of the frontal lobe. The findings in humans have been largely concordant with animal studies. Such animal studies find that heavy and regular binge drinking causes neurodegeneration in corticolimbic brain regions areas that are involved in learning and spatial memory, such as the olfactory bulb, piriform cortex, perirhinal cortex, entorhinal cortex, and the hippocampal dentate gyrus. A study in rats found that a heavy two-day drinking binge caused extensive neurodegeneration in the entorhinal cortex with resultant learning deficits. While brain damage from binge drinking is known to occur as a result of binge drinking patterns, it is unclear how long drinking sessions last and how regular binge drinking is done to cause brain damage in humans. One study found that humans who drank at least 100 drinks (male) or 80 drinks (female) per month (concentrated to 21 occasions or less per month) throughout a three-year period had impaired decision making skills compared to non-binge drinkers. Repeated acute withdrawal from alcohol, which occurs in heavy binge drinkers, has been shown in several studies to be associated with cognitive deficits as a result of neural kindling; neural kindling due to repeated withdrawals is believed to be the mechanism of cognitive damage in both binge drinkers and alcoholics. Neuronal kindling also leads to each subsequent acute withdrawal episode being more severe than previous withdrawal episodes.[29] Blackouts, a form of amnesia that occurs in binge drinkers may be due to suppressed hippocampus function with rebound NMDA (glutamate) activity combined with excessive glucocorticoid release induced by the stress of repeated intoxication followed by acute withdrawal/abstinence is the proposed mechanism of neural kindling leading to neurotoxicity of structures involved in learning and memory within the brain of binge drinkers.[29] Frontal lobe processing may become impaired as a result of binge drinking with resultant neurocognitive deficits and impaired working memory.[29] A drunken man, 1804 Alcohol suppresses brain function during intoxication; but upon withdrawal rebound effects occur in the glutamate/NMDA system and with excess glutamate activity glucocorticoid release; due to the repeated intoxication, followed by acute withdrawal, a neurotoxic effect that damages the central nervous system develops, leading to persisting impairments in verbal and nonverbal cognitive abilities as well as impairment of spatial orientation. Due to developmental processes occurring during adolescence including myelinization and restructuring of the synapses, adolescents are thought to be more vulnerable to the neurotoxic effects of alcohol.[7] Age and genetic factors influence the risk of developing alcohol-related neurotoxicity.[61] Adolescence, especially early adolescence (i.e. before age 15), is a critical and delicate developmental stage when specialised neuronal and synaptic systems mature. This critical developmental stage is where lifelong adult traits e.g., talents, reasoning and complex skills mature; however alcohol and in particular binge drinking may disrupt and interfere with this developmental process. Adolescence is also a period of development characterised by a high level of novel seeking, thrill seeking and risk taking behaviour and thus alcohol and other drug experimentation and abuse is common.[62] An adolescent rat study found that a short exposure to high levels of alcohol resulted in long-lasting changes to functional brain activity with corresponding abnormalities in EEG brain waves that persisted into adulthood, including persisting disturbances in sleep EEG with a reduction in slow wave sleep. These EEG findings are similar to premature aging. According to one review of the literature, if the developmental stage of adolescence is similar to the developmental stage of the fetus with regard to sensitivity to the neurotoxic effects of alcohol, and if long-lasting or permanent damage to the brain occurs similar to what animal studies suggest, then this represents a major public health issue due to the high levels of alcohol use by adolescents.[63] Indeed, alcohol can affect the remodeling and functional changes in synaptic plasticity and neuronal connectivity in different brain regions that occurs during adolescence (see this related article). ## Diagnosis[edit] An alcohol use disorder may develop when a person continues to drink heavily despite recurrent social, interpersonal, and/or legal problems. Behaviorally, frequent binge drinking is usually involved, but not everyone who engages in binge drinking develops an alcohol use disorder.[64] For the purpose of identifying an alcohol use disorder when assessing binge drinking, using a time frame of the past 6 months eliminates false negatives. For example, it has been found that using a narrow two week window for assessment of binge drinking habits leads to 30% of heavy regular binge drinkers wrongly being classed as not having an alcohol use disorder.[29] However, the same researchers also note that recall bias is somewhat enhanced when longer timeframes are used.[29] ## Prevention[edit] Binge drinking is considered harmful, regardless of a person's age, and there have been calls for healthcare professionals to give increased attention to their patients’ drinking habits, especially binge drinking.[65] Some researchers believe that raising the legal drinking age and screening brief interventions by healthcare providers are the most effective means of reducing morbidity and mortality rates associated with binge drinking.[66] Programs in the United States have thought of numerous ways to help prevent binge drinking. The Centers for Disease Control and Prevention suggests increasing the cost of alcohol or the excise taxes, restricting the number of stores who may obtain a license to sell liquor (reducing "outlet density"), and implementing stricter law enforcement of underage drinking laws.[19] There are also a number of individual counseling approaches, such as motivational interviewing and cognitive behavioral approaches, that have been shown to reduce drinking among heavy drinking college students.[67] In 2006, the Wisconsin Initiative to Promote Healthy Lifestyles implemented a program that helps primary care physicians identify and address binge drinking problems in patients.[68] In August 2008, a group of college presidents calling itself the Amethyst Initiative asserted that lowering the legal drinking age to 18 (presumably) was one way to curb the "culture of dangerous binge drinking" among college students.[69] This idea is currently the subject of controversy. Proponents[70][71] argue that the 21 law forces drinking underground and makes it more dangerous than it has to be, while opponents[72] have claimed that lowering the age would only make the situation worse. Despite health warnings, most Australian women drink at least one night a week. But experts are warning they are not only damaging their bodies but are also at risk of attracting sexual predators.[73] ### Reduction[edit] Research shows ways to reduce binge drinking or engage in dangerous drinking. Some computer-based intervention appear to reduce binge drinking,[74] an example of which is "rethinking drinking".[75] Understanding consumer personality and how people view others is important. People were shown ads talking of the harmful effects of binge drinking. People who valued close friends as a sense of who they are, were less likely to want to binge drink after seeing an ad featuring them and a close friend. People who were loners or who did not see close friends important to their sense of who they were reacted better to ads featuring an individual. A similar pattern was shown for ads showing a person driving at dangerous speeds. This suggests ads showing potential harm to citizens from binge drinking or dangerous driving are less effective than ads highlighting a person's close friends.[76] In 2009 the Australian Government Department of Health and Ageing spent $53.5 million Australian Dollars on National Binge Drinking Strategy to target young Australians. This campaign titled "Don't Turn a Night Out Into a Nightmare" was delivered to the public over many mass media platforms to show the harms and consequences of risky single occasion drinking (RSOD) as binge drinking is defined in Australia. Evidence as to the effectiveness of these types of campaigns is mixed. Research needs to be completed to ensure that the effectiveness of the messages are resulting in a positive shift in the behaviours of the target audience.[16] ## Treatment[edit] Due to the risks especially in adolescents, of cognitive impairments and possible irreversible brain damage associated with binge drinking, urgent action has been recommended.[40] There is some evidence that interventions by employers such as, health and lifestyle checks, psychosocial skills training and peer referral, can reduce the level of binge drinking.[77] In the US brief motivational interventions have shown some benefit in reducing future binge drinking.[7] Adolescents who misuse alcohol can benefit from interventions aimed at risk reduction. For more severe cases an intervention involving parents, guardians, or a psychotherapist is recommended.[78] An effective strategy of intervention for adolescents whose binge drinking leads to admission to hospital, e.g. for alcohol poisoning or injury, is manualised brief interventions at the hospital in one to four counseling sessions each lasting 30 to 60 minutes conducted by trained staff. Evaluation of personal pattern of drinking and associated risks and an emphasis on personal responsibility in a non-condescending manner is recommended during the intervention; discussing and informing and educating the adolescent of possible negative short and long-term consequences of drinking is recommended. The setting of goals and rules to achieve those goals is also recommended during intervention with problem binge drinking adolescents.[7] Motivational enhancement therapy also shows promise as a treatment.[79] Increasing public information and awareness regarding the risks of binge drinking, conducting interviews in emergency departments of young people suspected of harmful drinking patterns and trying to persuade them to accept individual counseling in youth addiction counseling services are effective strategies for reducing the harm of binge drinking. Encouraging recreational and adventurous training activities such as climbing or driving can be used alternative "natural buzzes" to alcohol misuse. Additionally, the provision of educational content about the risks of binge drinking and a risk assessment are beneficial during intervention with young binge drinkers and a referral in the case of an alcohol use disorder for specialised help.[7] According to the NIAAA definition of "heavy drinkers", men may be at risk for alcohol-related problems if their alcohol consumption exceeds 14 standard drinks per week or four drinks per day, and women may be at risk if they have more than seven standard drinks per week or three drinks per day. Despite this risk, a 2014 report in the National Survey on Drug Use and Health found that only 10% of either "heavy drinkers" or "binge drinkers" also met the criteria for alcohol dependence, while only 1.3% of non-binge drinkers met this criteria.[80] An inference drawn in this study is that evidence-based policy strategies and clinical preventive services may effectively reduce binge drinking without requiring addiction treatment in most cases. ## Epidemiology[edit] Main article: Epidemiology of binge drinking Binge drinking is more common in men than it is in women. Among students in the US, approximately 50% of men and 39% of women binge drink.[81] Racial differences exist among binge drinking with Hispanics followed by Caucasians having the highest level of binge drinking. Caucasians have been found to be nearly twice as likely to binge drink than blacks.[82] It is a common pattern among Native Americans.[83] Among the Australian youth population, 31% of males and 14% of women aged 15–17 years engage in risky alcohol consumption.[84] Binge drinking can prompt police action for public intoxication and disturbing the peace. Individuals of African descent have a lower level of binge drinking followed by those of Asian descent. In the case of Asians their low level of binge drinking may be due to the presence of the aldehyde dehydrogenase gene (ALDH2, Chromosome 12) in many (but by no means the vast majority) that results in poor metabolism of alcohol, which leads to severe adverse effects such as facial flushing.[29] Men are more likely to binge drink (up to 81% of alcohol binges are done by men) than women and men are also more likely to develop alcohol dependence than women. People who are homozygous for the ALDH2 gene are less likely to binge-drink due to severe adverse effects that occur even with moderate amounts of alcohol consumption. College students have been found to be more likely to binge drink than their same age peers who were not enrolled in college. This effect is more prevalent in women than in men.[85] Other factors that have been found to correlate with higher levels of binge drinking include low religiosity, marijuana use, living with roommates, and cigarette use.[86] ## Society and culture[edit] See also: List of deaths through alcohol Binge drinking costs the UK economy approximately £20 billion a year; 17 million working days are estimated to be lost due to hangovers and drink-related illness each year.[87] The cost of binge drinking to employers is estimated to be £6.4 billion and the cost per year of alcohol harm is estimated to cost the National Health Service £2.7 billion.[40] Urgent action has been recommended to understand the binge drinking culture and its aetiology and pathogenesis and urgent action has been called for to educate people with regard to the dangers of binge drinking.[40] The Centers for Disease Control and Prevention (CDC) released a study in October 2011 that showed that in the United States binge drinking costs society $223 billion a year, which amounts to $2 per drink. These costs include health care costs for alcohol-related issues, including liver cirrhosis, loss of work productivity, property damage due to drunk driving, and expenditures related to criminal acts.[88] Overall, 11.9% of binge drinkers drove during or within two hours of their most recent binge drinking episode. Those drinking in licensed establishments (bars, clubs, and restaurants) accounted for 54.3% of these driving episodes. Significant independent risk factors for driving after binge drinking included male gender (AOR=1.75); being aged 35–54 or ≥55 years compared to 18–34 years (AOR=1.58 and 2.37, respectively); and drinking in bars or clubs compared to drinking in the respondent's home (AOR=7.81). Drivers who drank most of their alcohol in licensed establishments consumed an average of 8.1 drinks, and 25.7% of them consumed ≥10 drinks.[89] ## Sex differences[edit] Women become intoxicated more quickly than men, and experience a higher blood alcohol level. This difference in effect occurs even when a woman's body weight and consumption of alcohol are the same as that of a man.[90][91] Because of these discrepancies, college-age women tend to experience the consequences of binge drinking before their male counterparts.[92] There is no known safe level of alcohol consumption either when trying to get pregnant or during pregnancy.[93] With alcohol abuse remaining highly stigmatized—particularly in the case of pregnant women—some advocate for treatment programs to focus on a non-judgmental stance, on personal empowerment, and on offering contraceptives to women engaging in sex, in order to prevent fetal alcohol spectrum disorder.[94] ## See also[edit] * 0-0-1-3 \- U.S. Air Force program for binge drinking prevention * Alcarelle ## Notes[edit] 1. ^ a b Renaud, SC. (2001). "Diet and stroke". J Nutr Health Aging. 5 (3): 167–72. PMID 11458287. 2. ^ a b Mathurin, P.; Deltenre, P. (May 2009). "Effect of binge drinking on the liver: an alarming public health issue?". Gut. 58 (5): 613–7. doi:10.1136/gut.2007.145573. PMID 19174416. S2CID 43370272. 3. ^ a b Standridge, JB.; Zylstra, RG.; Adams, SM. (Jul 2004). "Alcohol consumption: an overview of benefits and risks". South Med J. 97 (7): 664–72. doi:10.1097/00007611-200407000-00012. PMID 15301124. S2CID 26801239. 4. ^ Kuntsche, E.; Rehm, J.; Gmel, G. (Jul 2004). "Characteristics of binge drinkers in Europe". Soc Sci Med. 59 (1): 113–27. doi:10.1016/j.socscimed.2003.10.009. PMID 15087148. 5. ^ Clark, DB.; Bukstein, O.; Cornelius, J. (2002). "Alcohol use disorders in adolescents: epidemiology, diagnosis, psychosocial interventions, and pharmacological treatment". Paediatr Drugs. 4 (8): 493–502. doi:10.2165/00128072-200204080-00002. PMID 12126453. S2CID 30900197. 6. ^ a b Floyd, RL.; O'Connor, MJ.; Sokol, RJ.; Bertrand, J.; Cordero, JF. (Nov 2005). "Recognition and prevention of fetal alcohol syndrome". Obstet Gynecol. 106 (5 Pt 1): 1059–64. CiteSeerX 10.1.1.537.7292. doi:10.1097/01.AOG.0000181822.91205.6f. PMID 16260526. 7. ^ a b c d e f g h i j k l m Compare: Stolle, M.; Sack, PM.; Thomasius, R. (May 2009). "Binge drinking in childhood and adolescence: epidemiology, consequences, and interventions". Dtsch Arztebl Int. 106 (19): 323–8. doi:10.3238/arztebl.2009.0323. PMC 2689602. PMID 19547732. "Excessive episodic consumption of alcohol is usually referred to these days as 'binge drinking.'" 8. ^ a b Ward RJ, Lallemand F, de Witte P (2009). "Biochemical and neurotransmitter changes implicated in alcohol-induced brain damage in chronic or 'binge drinking' alcohol abuse". Alcohol Alcohol. 44 (2): 128–35. CiteSeerX 10.1.1.695.779. doi:10.1093/alcalc/agn100. PMID 19155229. 9. ^ a b Michelle Trudeau (January 25, 2010). "Teen Drinking May Cause Irreversible Brain Damage". USA: National Public Radio. Archived from the original on October 20, 2017. 10. ^ Crews FT, Boettiger CA (September 2009). "Impulsivity, frontal lobes and risk for addiction". Pharmacol. Biochem. Behav. 93 (3): 237–47. doi:10.1016/j.pbb.2009.04.018. PMC 2730661. PMID 19410598. 11. ^ Foxcroft, David R.; Moreira, Maria Teresa; Almeida Santimano, Nerissa M. L.; Smith, Lesley A. (2015-12-29). "Social norms information for alcohol misuse in university and college students". The Cochrane Database of Systematic Reviews (12): CD006748. doi:10.1002/14651858.CD006748.pub4. hdl:10284/8115. ISSN 1469-493X. PMID 26711838. 12. ^ "College Alcohol Study". Hsph.harvard.edu. 2004-06-25. Archived from the original on 2010-02-27. Retrieved 2010-03-15. 13. ^ Fact Sheets - Binge Drinking Archived 2013-05-12 at the Wayback Machine CDC.gov, last updated October 16, 2015; URL accessed 17 Mar 2017 14. ^ Dejong W (December 2001). "Finding common ground for effective campus-based prevention". Psychol Addict Behav. 15 (4): 292–6. doi:10.1037/0893-164x.15.4.292. PMID 11767259. 15. ^ a b Stephens, DN.; Duka, T. (Oct 2008). "Review. Cognitive and emotional consequences of binge drinking: role of amygdala and prefrontal cortex". Philos Trans R Soc Lond B Biol Sci. 363 (1507): 3169–79. doi:10.1098/rstb.2008.0097. PMC 2607328. PMID 18640918. 16. ^ a b van Gemert, Caroline (2011). "The Australian national binge drinking campaign: campaign recognition among young people at a music festival who report risky drinking". BMC Public Health. 11: 482. doi:10.1186/1471-2458-11-482. PMC 3148999. PMID 21689457. 17. ^ Kubacki, Krzysztof (2011). "College binge drinking: a new approach". Journal of Consumer Marketing. 28 (3): 225–233. doi:10.1108/07363761111127644. 18. ^ Charles, Janice; Valenti, Lisa; Miller, Greame (August 2011). "Binge Drinking" (PDF). Focus. 40 (8): 569. PMID 21814649. Archived from the original (PDF) on 2019-12-05. Retrieved 2019-12-05. 19. ^ a b "Alcohol & Public Health: Fact Sheets - Binge Drinking". Centers for Disease Control and Prevention. 7 November 2012. Archived from the original on 12 May 2013. Retrieved 7 June 2013. 20. ^ "Binge drinking". British Medical Association. March 2005. Archived from the original on 3 April 2005. Retrieved 7 June 2013. 21. ^ Compare: Watson, Stephanie (2011-09-01). "The History of Binge Drinking". Binge Drinking. Essential Issues Set. 3. ABDO Publishing Company (published 2011). p. 22. ISBN 9781617878503. Retrieved 2016-07-02. "Bender is a word people use to describe binge drinking. [Ca 1945] binge drinking was considered to be a period of drinking that went on for several days. Usually, a person who went on a binge or a bender was an alcoholic [...]." 22. ^ O'Connell, H; Lawlor, BA (October–December 2005). "Recent alcohol intake and suicidality--a neuropsychological perspective" (PDF). Irish Journal of Medical Science. 174 (4): 51–4. doi:10.1007/BF03168983. PMID 16445162. S2CID 11707884. 23. ^ Dasgupta, Amitava (2011). The Science of Drinking: How Alcohol Affects Your Body and Mind. Rowman & Littlefield Publishers. 24. ^ Dawson, Deborah; Li, Ting-Kai; Grant, Bridget F. (May 1, 2008). "A Prospective Study of Risk Drinking: At risk for what?". Drug and Alcohol Dependence. 95 (1–2): 62–72. doi:10.1016/j.drugalcdep.2007.12.007. PMC 2366117. PMID 18243584. 25. ^ Gill, Jan S (March–April 2002). "Reported levels of alcohol consumption and binge drinking within the UK undergraduate student population over the last 25 years". Alcohol and Alcoholism. 37 (2): 109–20. doi:10.1093/alcalc/37.2.109. PMID 11912065. Archived from the original on 2010-06-09. 26. ^ Dooldeniya, MD; Khafagy, R; Mashaly, H; Browning, AJ; Sundaram, SK; Biyani, CS (Nov 2007). "Lower abdominal pain in women after binge drinking". British Medical Journal (Clinical Research Ed.). 335 (7627): 992–3. doi:10.1136/bmj.39247.454005.BE. PMC 2072017. PMID 17991983. 27. ^ Mihai, B; Lăcătuşu, C; Graur, M (April–June 2008). "Alcoholic ketoacidosis" [Alcoholic ketoacidosis]. Revista Medico-chirurgicală̆ A Societă̆ţ̜ii de Medici ş̧i Naturaliş̧ti Din Iaş̧i (in Romanian and English). 112 (2): 321–6. PMID 19294998. 28. ^ Hayes, Katie. "Talking about binge drinking". Counselling in Practice. Retrieved 2015-04-13. 29. ^ a b c d e f g h i Courtney, KE.; Polich, J. (Jan 2009). "Binge drinking in young adults: Data, definitions, and determinants". Psychol Bull. 135 (1): 142–56. doi:10.1037/a0014414. PMC 2748736. PMID 19210057. 30. ^ Brody, J.E. (2008, September 09). Curbing binge drinking takes group effort. The New York Times, pp. 7. 31. ^ Enoch, MA. (Dec 2006). "Genetic and environmental influences on the development of alcoholism: resilience vs. risk". Ann N Y Acad Sci. 1094 (1): 193–201. Bibcode:2006NYASA1094..193E. doi:10.1196/annals.1376.019. PMID 17347351. 32. ^ Miller, B. E.; Miller, M. N.; Verhegge, R.; Linville, H. H.; Pumariega, A. J. (2002). "Alcohol misuse among college athletes: self-medication for psychiatric symptoms?". Journal of Drug Education. 32 (1): 41–52. doi:10.2190/JDFM-AVAK-G9FV-0MYY. ISSN 0047-2379. PMID 12096556. S2CID 37631050. 33. ^ Geisner, Irene M.; Varvil-Weld, Lindsey; Mittmann, Angela J.; Mallett, Kimberly; Turrisi, Rob (March 2015). "Brief web-based intervention for college students with comorbid risky alcohol use and depressed mood: does it work and for whom?". Addictive Behaviors. 42: 36–43. doi:10.1016/j.addbeh.2014.10.030. ISSN 1873-6327. PMC 4272863. PMID 25462652. 34. ^ Knight, John R; Wechsler, Henry; Kuo, Meichun; Seibring, Mark; Weitzman, Elissa R; Schuckit, Marc A (2015-01-04). "Alcohol abuse and dependence among U.S. college students". Journal of Studies on Alcohol. 63 (3): 263–270. doi:10.15288/jsa.2002.63.263. PMID 12086126. 35. ^ Mogensen, K. (2005). I don't like Mondays. Australian Educator, 48(1), 28-31. Retrieved from http://search.informit.com.au.ipacez.nd.edu.au/fullText;dn=146966;res=AEIPT 36. ^ Schwandt, M.L.; S.G. Lindell; S. Chen; J.D. Higley; S.J. Suomi; M. Heilig; C.S. Barr (Feb 2010). "Alcohol response and consumption in adolescent rhesus macaques". Alcohol. 44 (1): 67–80. doi:10.1016/j.alcohol.2009.09.034. PMC 2818103. PMID 20113875. 37. ^ McCarty C.; Ebel B.; Garrison M.; DiGiuseppe D.; Christakis D.; Rivara F. (2004). "Continuity of Binge and Harmful Drinking From Late Adolescence to Early Adulthood". Pediatrics. 114 (3): 714–719. doi:10.1542/peds.2003-0864-L. PMID 15342844. S2CID 25041948. 38. ^ Mathurin P.; Deltenre P. (2009). "Effect of binge drinking on the liver: an alarming public health issue?". Gut. 58 (1): 613–617. doi:10.1136/gut.2007.145573. PMID 19174416. S2CID 43370272. 39. ^ "Underage Drinking". National Institute on Alcohol Abuse and Alcoholism (NIAAA). 2011-09-14. Retrieved 2020-06-03. 40. ^ a b c d e Ward, RJ.; Lallemand, F.; de Witte, P. (March–April 2009). "Biochemical and neurotransmitter changes implicated in alcohol-induced brain damage in chronic or 'binge drinking' alcohol abuse". Alcohol Alcohol. 44 (2): 128–35. doi:10.1093/alcalc/agn100. PMID 19155229. Archived from the original on 2014-09-24. 41. ^ Crews, FT.; Boettiger, CA. (Sep 2009). "Impulsivity, frontal lobes and risk for addiction". Pharmacol Biochem Behav. 93 (3): 237–47. doi:10.1016/j.pbb.2009.04.018. PMC 2730661. PMID 19410598. 42. ^ a b "Alcohol, Adolescents, and Adults (citations)". Choose Responsibility. Archived from the original on 22 February 2014. Retrieved 7 June 2013. 43. ^ Bracken, Michael B. (2009). "Why animal studies are often poor predictors of human reactions to exposure". Journal of the Royal Society of Medicine. 102 (3): 120–122. doi:10.1258/jrsm.2008.08k033. PMC 2746847. PMID 19297654. 44. ^ Williams, JH.; Ross, L. (Jun 2007). "Consequences of prenatal toxin exposure for mental health in children and adolescents: a systematic review". Eur Child Adolesc Psychiatry. 16 (4): 243–53. doi:10.1007/s00787-006-0596-6. PMID 17200791. S2CID 21142815. 45. ^ May, PA.; Gossage, JP. (2001). "Estimating the prevalence of fetal alcohol syndrome. A summary". Alcohol Res Health. 25 (3): 159–67. PMC 6707173. PMID 11810953. Archived from the original on 2010-06-12. 46. ^ Cook, LJ. (June 2004). "Educating women about the hidden dangers of alcohol". J Psychosoc Nurs Ment Health Serv. 42 (6): 24–31. doi:10.3928/02793695-20040601-09. PMID 15237789. 47. ^ Wood, CE. (Sep 2007). "Maternal binge drinking and fetal neuronal damage". Exp Physiol. 92 (5): 821. doi:10.1113/expphysiol.2007.038448. PMID 17827257. S2CID 29592437. 48. ^ Altura, BM.; Altura, BT. (Oct 1999). "Association of alcohol in brain injury, headaches, and stroke with brain-tissue and serum levels of ionized magnesium: a review of recent findings and mechanisms of action". Alcohol. 19 (2): 119–30. doi:10.1016/S0741-8329(99)00025-7. PMID 10548155. 49. ^ Britton, A.; McKee, M. (May 2000). "The relation between alcohol and cardiovascular disease in Eastern Europe: explaining the paradox". J Epidemiol Community Health. 54 (5): 328–32. doi:10.1136/jech.54.5.328. PMC 1731674. PMID 10814651. 50. ^ Puddey, IB.; Rakic, V.; Dimmitt, SB.; Beilin, LJ. (May 1999). "Influence of pattern of drinking on cardiovascular disease and cardiovascular risk factors--a review". Addiction. 94 (5): 649–63. doi:10.1046/j.1360-0443.1999.9456493.x. PMID 10563030. 51. ^ Biyik, I.; Ergene, O. (January–February 2007). "Alcohol and acute myocardial infarction". J Int Med Res. 35 (1): 46–51. doi:10.1177/147323000703500104. PMID 17408054. 52. ^ O'Keefe, JH.; Bybee, KA.; Lavie, CJ. (Sep 2007). "Alcohol and cardiovascular health: the razor-sharp double-edged sword". J Am Coll Cardiol. 50 (11): 1009–14. doi:10.1016/j.jacc.2007.04.089. PMID 17825708. 53. ^ van de Wiel, A.; de Lange, DW. (Dec 2008). "Cardiovascular risk is more related to drinking pattern than to the type of alcoholic drinks". Neth J Med. 66 (11): 467–73. PMID 19075312. 54. ^ Esser, Melissa (June 2012). "Binge Drinking Intensity : A Comparison of Two Measures". American Journal of Preventive Medicine. 42 (6): 625–629. doi:10.1016/j.amepre.2012.03.001. PMC 4536810. PMID 22608381. 55. ^ Atkins, Lucy (November 20, 2007). "Lucy Atkins on binge-drinking induced 'exploding bladders'". The Guardian. London. Archived from the original on March 12, 2016. 56. ^ "If you thought a hangover was bad ...: A new report says binge drinking has increased to such an extent that cases of 'exploding bladders' are on the rise in the UK." report of article in the British Medical Journal (BMJ) by Lucy Atkins in The Guardian November 20, 2007 57. ^ Hingson, Ralph W; Zha, Wenxing; Weitzman, Elissa R (2015-01-09). "Magnitude of and Trends in Alcohol-Related Mortality and Morbidity Among U.S. College Students Ages 18-24, 1998-2005". Journal of Studies on Alcohol and Drugs, Supplement (s16): 12–20. doi:10.15288/jsads.2009.s16.12. PMC 2701090. PMID 19538908. 58. ^ Sweeney, Donal (2004). The Alcohol Blackout - Walking, Talking, Unconscious, and Lethal. Mnemosyne Press. p. 221. ISBN 978-0974794303. 59. ^ Goslawski M.; Piano M.; Bian J.T.; Church E.; Szczurek M.; Phillips S. (2013). "Binge Drinking Impairs Vascular Function in Young Adults". Journal of the American College of Cardiology. 62 (3): 201–207. doi:10.1016/j.jacc.2013.03.049. PMC 3727916. PMID 23623907. 60. ^ Davies, Sue (2005). "Binge drinking". Research Digest. Retrieved 2015-04-17. 61. ^ a b Bowden, SC.; Crews, FT.; Bates, ME.; Fals-Stewart, W.; Ambrose, ML. (Feb 2001). "Neurotoxicity and neurocognitive impairments with alcohol and drug-use disorders: potential roles in addiction and recovery". Alcohol Clin Exp Res. 25 (2): 317–21. doi:10.1111/j.1530-0277.2001.tb02215.x. PMID 11236849. 62. ^ Crews, F.; He, J.; Hodge, C. (Feb 2007). "Adolescent cortical development: a critical period of vulnerability for addiction". Pharmacol Biochem Behav. 86 (2): 189–99. doi:10.1016/j.pbb.2006.12.001. PMID 17222895. S2CID 6925448. 63. ^ Ehlers, CL.; Criado, JR. (Feb 2010). "Adolescent ethanol exposure: does it produce long-lasting electrophysiological effects?". Alcohol. 44 (1): 27–37. doi:10.1016/j.alcohol.2009.09.033. PMC 2818286. PMID 20113872. 64. ^ Gittings, D. (November 2019). "Terminology surrounding alcohol use". Some Like It Sober. 65. ^ Andréasson, S; Allebeck, P (2005). "Alcohol as medication is no good. More risks than benefits according to a survey of current knowledge" [Alcohol as medication is no good. More risks than benefits according to a survey of current knowledge and understanding]. Läkartidningen (in Swedish and English). 102 (9): 632–7. PMID 15804034. 66. ^ Babor, TF.; Aguirre-Molina, M.; Marlatt, GA.; Clayton, R. (1999). "Managing alcohol problems and risky drinking". Am J Health Promot. 14 (2): 98–103. doi:10.4278/0890-1171-14.2.98. PMID 10724728. S2CID 3267149. 67. ^ "Research about Alcohol and College Drinking Prevention". Collegedrinkingprevention.gov. Archived from the original on 2010-03-10. Retrieved 2010-03-15. 68. ^ "With Support From Collaborative, Primary Care Practices Identify and Address Behavioral Health Issues, Reducing Binge Drinking, Marijuana Use, and Depression Symptoms". Agency for Healthcare Research and Quality. 2013-05-08. Archived from the original on 2016-01-25. Retrieved 2013-05-10. 69. ^ "Bid to reconsider drinking age taps unlikely source" Archived 2017-12-25 at the Wayback Machine, The Wall Street Journal, August 21, 2008 70. ^ http://www.amethystintiative.org Amethyst Intitative Archived November 1, 2012, at the Wayback Machine 71. ^ "Binge Drinking". Choose Responsibility. Archived from the original on 14 May 2013. Retrieved 7 June 2013. 72. ^ Carpenter, C.; Dobkin, C. (Jan 2009). "The Effect of Alcohol Consumption on Mortality: Regression Discontinuity Evidence from the Minimum Drinking Age". American Economic Journal: Applied Economics. 1 (1): 164–82. doi:10.1257/app.1.1.164. PMC 2846371. PMID 20351794. 73. ^ White, Alex (2013-03-27). "Young Women in Binge Drinking Epidemic". Sunday Herald Sun. Archived from the original on 7 May 2016. Retrieved 16 April 2015. 74. ^ Khadjesari, Z; Murray, E; Hewitt, C; Hartley, S; Godfrey, C (February 2011). "Can stand-alone computer-based interventions reduce alcohol consumption? A systematic review". Addiction. 106 (2): 267–82. doi:10.1111/j.1360-0443.2010.03214.x. PMID 21083832. 75. ^ "Featured review". PubMed Health. Archived from the original on 2014-02-19. 76. ^ Martin Brett A. S.; Lee Christina K.C.; Weeks Clinton; Kaya Maria (2013). "How to stop binge drinking and speeding motorists: Effects of relational-interdependent self-construal and self-referencing on attitudes toward social marketing" (PDF). Journal of Consumer Behaviour. 12: 81–90. doi:10.1002/cb.1417. Archived from the original (PDF) on 2015-04-27. Retrieved 2013-04-02. 77. ^ Webb, G.; Shakeshaft, A.; Sanson-Fisher, R.; Havard, A. (Mar 2009). "A systematic review of work-place interventions for alcohol-related problems". Addiction. 104 (3): 365–77. doi:10.1111/j.1360-0443.2008.02472.x. PMID 19207344. 78. ^ Michaud, PA. (Feb 2007). "[Alcohol misuse in adolescents - a challenge for general practitioners]". Ther Umsch. 64 (2): 121–6. doi:10.1024/0040-5930.64.2.121. PMID 17245680. 79. ^ Rhodes KV, Rodgers M, Sommers M, Hanlon A, Crits-Christoph P. The Social Health Intervention Project (SHIP): Protocol for a randomized controlled clinical trial assessing the effectiveness of a brief motivational intervention for problem drinking and intimate partner violence in an urban emergency department. BMC Emergency Medicine, 2014 80. ^ Esser, Marissa B.; Hedden, Sarra L.; Kanny, Dafna; Brewer, Robert D.; Gfroerer, Joseph C.; Naimi, Timothy S. (20 November 2014). "Prevalence of Alcohol Dependence Among US Adult Drinkers, 2009–2011". Preventing Chronic Disease. 11: E206. doi:10.5888/pcd11.140329. PMC 4241371. PMID 25412029. 81. ^ López-Caneda Eduardo; et al. (2013). "Effects of a persistent pinge drinking pattern of alcohol consumption in young people: a follow-up study using event-related potentials" (PDF). Alcohol and Alcoholism. 48 (4): 464–471. doi:10.1093/alcalc/agt046. PMID 23695975. Archived from the original (PDF) on 2014-02-01. 82. ^ Davies, Pamela (2013-01-01). "Binge drinking in college students". SOUTHERN CONNECTICUT STATE UNIVERSITY. Archived from the original on 2016-04-28. Cite journal requires `\|journal=` (help) 83. ^ Anestasia M. Shkilnyk (March 11, 1985). A Poison Stronger than Love: The Destruction of an Ojibwa Community (trade paperback). Yale University Press. p. 21. ISBN 978-0300033250. 84. ^ Howat, Peter (2013). "Booze barns: fuelling hazardous drinking in Australia?". Health Promotion Journal of Australia. 24 (2): 85–6. doi:10.1071/he13068. hdl:20.500.11937/19781. PMID 24168733. Retrieved 9 April 2015. 85. ^ Slutske WS (2005-03-01). "ALcohol use disorders among us college students and their non–college-attending peers". Archives of General Psychiatry. 62 (3): 321–327. doi:10.1001/archpsyc.62.3.321. ISSN 0003-990X. PMID 15753245. 86. ^ Wechsler, H; Dowdall, G W; Davenport, A; Castillo, S (1995). "Correlates of college student binge drinking". American Journal of Public Health. 85 (7): 921–926. doi:10.2105/ajph.85.7.921. PMC 1615519. PMID 7604914. 87. ^ Unit, Strategy (March 2004). "Alcohol Harm Reduction Strategy for England" (PDF). Cabinet Office of the United Kingdom: 9. 88. ^ "CDC Features - Excessive Drinking Costs U.S. $223.5 Billion". www.cdc.gov. 2018-07-13. Archived from the original on 2017-07-17. 89. ^ Naimi, Timothy (October 2009). "Driving After Binge Drinking". American Journal of Preventive Medicine. 37 (4): 314–320. doi:10.1016/j.amepre.2009.06.013. PMID 19765503. 90. ^ Murugiah, Sera (June 2012). "Binge drinking and females at an Australia university". A Discrepancy of Definitions. 31. Retrieved 2015-04-17. 91. ^ Note: This refers to biological sex, not to gender identity. 92. ^ Wechsler, Henry; Dowdall, George W.; Davenport, Andrea; Rimm, Eric B. (July 1995). "A gender-specific measure of binge drinking among college students". American Journal of Public Health. 85 (7): 982–985. doi:10.2105/AJPH.85.7.982. PMC 1615545. PMID 7604925. 93. ^ "Fetal Alcohol Spectrum Disorders (FASDs)". Centers for Disease Control and Prevention. U.S. Department of Health and Human Services. Archived from the original on 28 June 2015. Retrieved 6 January 2017. 94. ^ Stade, Brenda C; Bailey, Carol; Dzendoletas, Darlene; Sgro, Michael; Dowswell, Therese; Bennett, Daniel (2009-04-15). "Psychological and/or educational interventions for reducing alcohol consumption in pregnant women and women planning pregnancy". Cochrane Database of Systematic Reviews (2): CD004228. doi:10.1002/14651858.cd004228.pub2. PMC 4164939. PMID 19370597. ## References[edit] "College Students and Drinking". No. 29 PH 357. National Institute on Alcohol Abuse and Alcoholism. July 1995. * Dowdall, George W. (2009). College Drinking: Reframing a Social Problem. Westport, Conn: Praeger. ISBN 978-0-275-99981-0. * MacLachlan, Malcolm; Smyth, Caroline (2004). Binge Drinking and Youth Culture: Alternative Perspectives. Dublin: Liffey Press. ISBN 978-1-904148-42-5. * Marczinski, Cecile A.; Grant, Estee C.; Grant, Vincent J. (2009). Binge Drinking in Adolescents and College Students. Hauppauge, NY: Nova Science. ISBN 978-1-60692-037-4. * Tan, Andy Soon Leong (2012). "Through the Drinking Glass: an Analysis of the Cultural Meanings of College Drinking". Journal of Youth Studies. 15 (1): 119–142. doi:10.1080/13676261.2011.630997. S2CID 146449952. * Walters, Scott T.; Baer, John S. (2006). Talking with College Students About Alcohol: Motivational Strategies for Reducing Abuse. New York: Guilford Press. ISBN 978-1-59385-222-1. * Wechsler, Henry; Wuethrich, Bernice (2002). Dying to Drink: Confronting Binge Drinking on College Campuses. Emmaus, Pa.: Rodale. ISBN 978-1-57954-583-3. ## External links[edit] Classification D * ICD-10: F10 * ICD-9-CM: 305 * MeSH: D063425 * Global Status Report on Alcohol 2004 by the WHO. * Binge drinking (human behaviour) at the Encyclopædia Britannica * v * t * e Alcohol and health Alcohol use Alcohol-related crimes * Drunk drivers * Alcohol-related traffic crashes in the United States * Driving under the influence (DUI) * Drunk driving in the United States * Public intoxication * Rum-running * Adulterated moonshine/Denatured alcohol * List of methanol poisoning incidents Alcoholism * Alcohol and Native Americans * Alcoholism in adolescence * Alcoholism in family systems * Collaborative Study on the Genetics of Alcoholism * College student alcoholism * Disease theory of alcoholism * High-functioning alcoholic (HFA) * Seeing pink elephants Chemistry * Beer chemistry * Congener * Alcohol congener analysis * Ethanol * Blood alcohol content * Breathalyzer * Fusel alcohol * Wine chemistry Effects * Short-term effects of alcohol consumption * Long-term effects of alcohol * On memory * Subjective response to alcohol Interactions * Aging * Brain * Cancer * breast cancer * Cortisol * Pregnancy * Sleep * Tolerance/intolerance * Weight * Beverage-specific * Beer: Potomania * Red wine: Red wine headache Social issues * Alcohol advertising * on college campuses * Sex * Alcohol myopia * Alcohol abuse among college students * Binge drinking * Epidemiology * Blackout (alcohol-related amnesia) * Blackout Wednesday * Drinking game * list * pregaming * Drinking in public * Drunk dialing * Drunk walking * Drunkorexia * Dry drunk * French paradox * Hair of the dog * Nightcap * Pantsdrunk * Passive drinking * Binge drinking devices * Beer bong * Yard of ale * Routes of administration * Alcohol enema * Alcohol inhalation * Sconcing * Surrogate alcohol * Related issues * Balconing * Suicide History * Dionysian Mysteries * Dipsomania * Gin Craze * List of deaths through alcohol * Rum ration * Speakeasy General * Beer day * Drinking culture * Apéritif and digestif * Hangover remedies * Health effects of wine * Wine and food matching * Long-distance race involving alcohol * List of countries by alcohol consumption per capita * Alcohol consumption by youth in the United States * Nip joint Alcohol control Alcohol law * Administrative license suspension (ALS) * Alcohol packaging warning messages * Drunk driving law by country * DWI court * Field sobriety testing * Hip flask defence * Ignition interlock device * Legal drinking age * Age controversy in US * Underage drinking in US * List of alcohol laws of US Alcohol prohibition * List of countries with alcohol prohibition * Neo-prohibitionism * Temperance movement Sobriety * Alcohol detoxification * Alcohol-free zone * Dry campus * United States open-container laws * Designated driver * Alcohol rehabilitation * Drunk tank * Managed alcohol program * Non-alcoholic drink * List of cocktails * List of mixed drinks * Spritzer * Malt drinks * Teetotalism * Temperance bar * Twelve-step groups * Al-Anon/Alateen * Alcoholics Anonymous (AA): * Adult Children of Alcoholics (ACA) Alcohol limitation * 0-0-1-3 * Alcohol education * Alcohol server training * FRAMES * Dry January * Foundation for Advancing Alcohol Responsibility * Campaigns * Get Your Sexy Back * Liquor license * Low-alcohol drinks * Fermented tea * Low-alcohol beer * Low-alcoholic malt drinks * Small beer * Measurement * Alcoholic spirits measure * Standard drink * Recommended maximum intake of alcoholic beverages Addiction medicine * Disulfiram-like drugs: disulfiram, calcium carbimide, cyanamide. Sulfonic acids: Acamprosate Religion and alcohol * Christian views on alcohol * alcohol in the Bible * Islam and alcohol History * Bratt System Related * Index of alcohol-related articles * Austrian syndrome * Ban on caffeinated alcoholic beverages * Brief intervention * Gateway drug effect * Last call * Mood disorder * Non-alcoholic fatty liver disease * Self-medication * Spins * Sober companion * Sober living houses * Sobering center * Town drunk * 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	Binge drinking	None	7,441	wikipedia	https://en.wikipedia.org/wiki/Binge_drinking	2021-01-18T19:07:46	{"mesh": ["D063425"], "icd-9": ["305"], "icd-10": ["F10"], "wikidata": ["Q1521260"]}
A number sign (#) is used with this entry because autosomal dominant deafness-11 (DFNA11) is caused by heterozygous mutation in the gene encoding myosin VIIA (MYO7A; 276903) on chromosome 11q13. Autosomal recessive nonsyndromic deafness (DFNB2; 600060) and Usher syndrome type IB (276900) are allelic disorders. Description Autosomal dominant deafness-11 is a nonsyndromic form of progressive neurosensory hearing loss with postlingual onset. Some affected individuals have mild vestibular symptoms (summary by Sun et al., 2011). Clinical Features Tamagawa et al. (1996) reported a Japanese family with autosomal dominant nonsyndromic hearing loss. Most affected individuals noticed hearing loss in their first decade of life, after complete speech acquisition, with subsequent gradual progression. All affected individuals had bilateral sensorineural hearing loss without vertigo or associated symptoms. They had symmetric gently sloping or flat audiograms with hearing loss at all frequencies. Most affected individuals between the age of 20 and 60 years had moderate hearing loss. Sun et al. (2011) reported 2 large unrelated Chinese families with autosomal dominant inheritance of postlingual nonsyndromic hearing loss. In 1 family, affected individuals had onset between ages 20 and 47 years of bilateral mild to severe symmetric hearing impairment particularly involving high frequencies. The audiogram was flat or downward sloping. Affected individuals in a second Chinese family had onset between ages 10 and 39 years of bilateral mild to severe symmetric hearing loss affecting mainly low frequencies. The audiogram was flat or ascending. In both families, high-frequency tinnitus occurred at the onset of hearing loss, but there was no vestibular involvement. Electrocochleography in the second family showed no evidence of endolymphatic hydrops. Mapping By linkage and haplotype analysis of a Japanese family with autosomal dominant nonsyndromic hearing loss, Tamagawa et al. (1996) found linkage to a locus, termed DFNA11, on chromosome 11q12.3-q21 between D11S1335 and D11S931. The authors noted that another locus for autosomal recessive nonsyndromic hearing loss, DFNB2 (600060), maps within the 11q12.3-q21 region at 11q13.5. Tamagawa et al. (1996) postulated that DFNB2 may be responsible for both recessive and dominant forms of deafness, or alternatively that several genes responsible for deafness map to the 11q12.3-q21 region. In the family reported by Tamagawa et al. (1996), lod scores of 3.25 at theta = 0 were observed for 5 markers, D11S527, D11S937, D11S918, D11S987, and D11S1314. Some of the alleles segregating with DFNA11 in this family were present in very low frequencies in the normal control population living in the same area. In a review of nonsyndromic hearing impairment, Van Camp et al. (1997) referred to an unpublished family showing linkage of prelingual stable deafness to 11q22-q24. They referred to this autosomal dominant form as DFNA12 (601543). Molecular Genetics In affected members of the Japanese family with autosomal dominant nonsyndromic hearing loss mapping to 11q (Tamagawa et al., 1996), Liu et al. (1997) identified an in-frame 9-bp deletion in exon 22 of the MYO7A gene (276903.0011). The affected family members suffered from postlingual, bilateral, nonsyndromic sensorineural hearing loss, with gradual progression at all frequencies and minor vestibular problems. No evidence was found for retinitis pigmentosa (Tamagawa et al., 2002). Luijendijk et al. (2004) reported a similar family, from Holland, in which affected members were heterozygous for an asn458-to-ile mutation in the MY07A gene (N458I; 276903.0015). Sun et al. (2011) reported 2 Chinese families with autosomal dominant deafness in whom they identified different heterozygous mutations in the MYO7A gene (D218N, 276903.0019 and G671S, 276903.0020, respectively). INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, sensorineural, moderate, postlingual \- Audiogram is gently sloping or flat \- Audiogram may be ascending NEUROLOGIC Central Nervous System \- Vestibular dysfunction, mild \- Vertigo, mild MISCELLANEOUS \- Variable age at onset, ranging from childhood to adult \- Gradual progression of hearing loss \- Allelic disorder to autosomal recessive hearing loss (DFNB2, 600060 ) and Usher syndrome type IB ( 276900 ) MOLECULAR BASIS \- Caused by mutation in the myosin VIIA gene (MYO7A, 276903.0011 ) ▲ 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	DEAFNESS, AUTOSOMAL DOMINANT 11	c1832475	7,442	omim	https://www.omim.org/entry/601317	2019-09-22T16:15:09	{"doid": ["0110543"], "mesh": ["C563353"], "omim": ["601317"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA", "Autosomal dominant non-syndromic sensorineural hearing loss type DFNA"], "genereviews": ["NBK1434"]}
Isolated cleft lip is a fissure type embryopathy extending from the upper lip to the nasal base. ## Epidemiology The annual incidence is 1/4,000 to 1/10,000 births with major variation occurring between geographic locations and ethnic groups. Cleft lip is twice as common in boys as girls and is seen more frequently on the left side. ## Clinical description The cleft is paramedian and located at the level of the philtrum. It presents as a cutaneous, muscular and mucosal interruption from the lip to the nasal base, associated with nostril and nasal septum deformations. Clinical forms range from a simple notch in the upper lip to a complete cleft lip with an opening at the base of the nostril without reaching as far as the gum (alveolar ridge). ## Etiology This embryopathy appears between the 5th and 12th week of pregnancy due to a failure in the fusion of the frontal processes (fronto-nasal process, medial and lateral nasal processes, maxillary process). Cleft lip is an isolated, non-syndromic anomaly in 70% of cases. The remaining 30% of cases are seen in at least 300 syndromes where cleft lip is just one of the featured anomalies. Non-syndromic clefts are possibly caused by a combination of genetic and environmental factors. Factors such as the exposure to teratogenic substances during pregnancy (alcohol, tobacco or drugs) can have an influence on genetic susceptibility. ## Diagnostic methods The diagnosis is clinical. ## Differential diagnosis The presence of associated malformations allows for differentiation between isolated and syndromic forms. ## Antenatal diagnosis Antenatal diagnosis is often possible with a prenatal ultrasound. The case is submitted to a multidisciplinary center for prenatal diagnosis in order to establish if it is an isolated anomaly. ## Management and treatment Management requires multidisciplinary medical and surgical intervention from birth until the end of development. It involves primary surgery sometimes followed by secondary maxillo-facial and plastic surgery. An initial treatment timeline is established during the neonatal period. Secondary management is adapted to the child's age and based on morphological and functional problems that may arise during growth and development. Breathing difficulties can occur due to the nostril anomaly and the deviation of the vomer, of the nasal septum and to the turbinate hypertrophy. Secondary surgery of the nose can be performed to improve appearance and function. ## Prognosis Prognosis is dependent on the quality of initial management and the regular follow-up by an experienced interdisciplinary team until the child is fully grown. Cleft lip can have functional (morphological, respiratory), esthetic and psychological consequences that require management in a specialized health center. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Isolated cleft lip	c0008924	7,443	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=199302	2021-01-23T17:27:32	{"mesh": ["D002971"], "omim": ["119530", "129400", "225060", "600757", "602966", "608371", "608874", "610361", "612858"], "umls": ["C0008924"], "icd-10": ["Q36.0", "Q36.1", "Q36.9"]}
ROHHAD Other namesROHHADNET A photograph of a child who has been diagnosed with ROHHAD Symptomsrapid onset obesity, hypothalamic dysfunction, hypoventilation, autonomic dysfunction, neuroendocrine tumors, behavior problems Usual onset1.5-11 years of age Causesunknown PrognosisLife Limiting Frequency158 cases reported worldwide Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare condition whose etiology is currently unknown.[1] ROHHAD mainly affects the endocrine system and autonomic nervous system, but patients can exhibit a variety of signs. Patients present with both alveolar hypoventilation along with hypothalamic dysfunction, which distinguishes ROHHAD from congenital central hypoventilation syndrome (CCHS).[2] ROHHAD is a rare disease, with only 100 reported cases worldwide thus far.[3] The first sign of ROHHAD is a rapid weight gain between 1.5 and 11 years of age.[4] Typically, hypoventilation, or abnormally slow breathing, presents after the rapid onset obesity.[4] Symptoms of hypothalamic dysfunction and autonomic dysfunction present in a variety of ways, but in order for a diagnosis of ROHHAD they must be present in some form.[3] Approximately 40% of patients will develop neuroendocrine tumors.[1] There is also a possibility of behavioral disorders, but some children with ROHHAD have normal cognitive development and intelligence.[3] Treatment plans for ROHHAD vary depending on each patient's symptoms. There is no cure, so treatment is geared toward managing the symptoms that each patient manifests.[5] ROHHAD is fatal in 50-60% of cases when undiagnosed and untreated, due to cardiopulmonary arrest secondary to untreated hypoventilation.[4] The earlier the disease is diagnosed and treatment starts, the better a child's prognosis is.[5] ## Contents * 1 Signs & symptoms * 1.1 Rapid-onset Obesity * 1.2 Hypothalamic dysfunction * 1.3 Hypoventilation * 1.4 Autonomic Dysfunction * 1.5 Neuroendocrine tumors * 1.6 Behavioral issues * 2 Cause * 3 Pathophysiology * 4 Diagnosis * 5 Prevention * 6 Management * 6.1 Rapid onset obesity treatment * 6.2 Hypothalamic dysfunction treatment * 6.3 Hypoventilation treatment * 6.4 Autonomic dysfunction treatment * 6.5 Neuroendocrine tumor treatment * 7 Prognosis * 8 Research * 9 Epidemiology * 10 History * 11 Society * 12 See also * 13 References ## Signs & symptoms[edit] ### Rapid-onset Obesity[edit] The rapid onset obesity aspect of ROHHAD is usually the first diagnostic indicator of the disease. Patients often present with hyperphagia and rapid weight gain. This rapid weight gain is defined as 20-30 pounds over a 6-12 month period, and typically occurs between the ages of 1.5 and 11.[4] ### Hypothalamic dysfunction[edit] Hypothalamic dysfunction refers to the hypothalamus, which is a structure within the brain which participates in regulating the pituitary gland, autonomic nervous system, and endocrine system.[6] Symptoms related to hypothalamic dysfunction may include abnormal sodium balance (hyponatremia or hypernatremia), high progestin levels, low cortisol levels, delayed or early-onset puberty, and low thyroid hormone.[3] Patients will also often experience a decelerated growth rate throughout childhood.[7] Sodium imbalance within the body can have severe symptoms and be potentially life-threatening if not controlled. Hyponatremia, or low sodium levels, can cause symptoms such as nausea, headache, seizures, or even cause patients to become comatose.[8] Hypernatremia, or high sodium levels in the blood, can cause nausea, muscle weakness, altered mental status, or coma.[9] Irregular temperature regulation and diabetes insipidus are also possible symptoms of hypothalamic dysfunction.[10] ROHHAD patients develop these symptoms at varying ages and in varying numbers, but all patients will develop some symptoms of hypothalamic dysfunction.[3] ### Hypoventilation[edit] Symptoms of hypoventilation and breathing malfunctions typically present after the rapid weight gain. Some patients may initially develop obstructive sleep apnea, which is common in obese children.[3] Obstructive sleep apena is the most common form of sleep apnea, and causes breathing to abruptly stop and begin again during sleep. This is caused by throat muscles relaxing during sleep and blocking the airway, and is typically noticed as patients will snore loudly throughout the night.[11] Every patient diagnosed with ROHHAD develops alveolar hypoventilation, regardless of whether they presented with sleep apnea.[3] Alveolar hypoventilation is a condition in which patients have very low blood oxygen levels and shallow breathing. In healthy patients, when blood oxygen levels are low, the brain sends a signal to breathe and bring more oxygen to the blood. In ROHHAD patients, this reaction does not occur.[12] This condition is usually only present during sleep, however in more severely affected patients shallow breathing may continue throughout the day. Hypoventilation can go unnoticed until cardiopulmonary arrest, which is why ROHHAD has the potential to be a fatal disease.[3] Ventilatory support is required for patients during sleep, however it is only needed during waking hours for those most severely affected (about 50% of patients).[3][10] ### Autonomic Dysfunction[edit] Autonomic dysfunction refers to the autonomic nervous system, which is responsible for regulating internal processes without conscious intervention.[13] This may involve abnormalities in cardiac rhythm, temperature regulation, digestion, and eye movements. Not all ROHHAD patients will experience all of these symptoms, however they will have at least some of these issues.[3] Examples of autonomic dysfunction include hyperthermia, hypothermia, pupillary dysfunction, strabismus, chronic constipation, and chronic diarrhea.[7] ### Neuroendocrine tumors[edit] Approximately 40% of ROHHAD patients will develop tumors originating in the neural crest.[1] These tumors are typically classified as ganglioneuroma or ganglioneuroblastomas.[7] These tumors are not believed to significantly worsen or contribute to the prognosis of ROHHAD.[14] It was suggested that ROHHAD be renamed ROHHADNET in order to include these tumors in the diagnostic criteria, but this has only been adopted for patients who develop these tumors.[3][15] ### Behavioral issues[edit] Some children diagnosed with ROHHAD may also present with behavioral disorders and/or intellectual disability,[16] however this is believed to be a result of low oxygen levels secondary to hypoventilation during childhood development. The later ROHHAD is diagnosed, the greater the risk for behavioral problems due to hypoxia from hypoventilation or during cardiopulmonary arrest.[3] ## Cause[edit] The etiology of ROHHAD is currently unknown, and the condition is diagnosed based on a set of clinical criteria.[1] It is believed that there may be a genetic component to ROHHAD, however there is no widely accepted gene linked to the disease.[3] There has been one ROHHAD patient identified to have a mutation in the retinoic acid-induced 1(RAI1) gene through Whole Exome Sequencing, but there has been no otherwise proven link between the RAI1 gene and ROHHAD.[17] It is believed that ROHHAD originates from a combination of genetic and environmental or immunological factors.[1] As of yet, evidence of its etiology has not been discovered and is not well understood.[1] In 2011, a case of monozygotic twins with divergent ROHHAD phenotypes was reported. One twin was affected with ROHHAD and developed symptoms, while the other twin developed normally. This report questioned the theory that ROHHAD is genetically inherited, and the authors suggest that the disease may have an autoimmune or epigenetic etiology.[18] ## Pathophysiology[edit] The pathophysiology of ROHHAD is not currently known or understood.[1] ## Diagnosis[edit] Rapid obesity is the first symptom to arise between the ages of 1.5 and 11. This is typically followed by hypoventilation, which if left untreated, can result in fatal cardiorespiratory arrest.[4] This is why early diagnosis has proven to be imperative for ROHHAD patients, and it has been suggested that ROHHAD be considered in every isolated case of early rapid-onset obesity.[7] Early diagnosis is also vital in maintaining electrolyte and hormone balances caused by hypothalamic dysfunction in order to promote healthy development and prevent further problems.[14] As the symptoms of ROHHAD are so diverse and the condition is so rare, the disease is often misdiagnosed as Cushing's disease or Congenital Central Hypoventilation Syndrome when it first presents in patients.[7] ## Prevention[edit] As the cause of ROHHAD is unknown, there is no way to prevent onset of the disease.[16] ## Management[edit] There is no known cure for ROHHAD, therefore treatment for the disease involves managing symptoms as they manifest in the patient. As not all ROHHAD patients develop the same symptoms, treatment plans vary between patients. Proper treatment of hypothalamic dysfunction and hypoventilation is the most critical aspect of ROHHAD management, as these symptoms have the greatest ability to cause death or behavioral problems if left uncontrolled.[5] ### Rapid onset obesity treatment[edit] Attempting to control weight through diet and exercise can be exceedingly difficult in patients with ROHHAD due to a number of factors. Encouraging ROHHAD patients to exercise vigorously can be dangerous, as their breathing will not increase with exertion and this can cause hypoxia. Therefore, it is important for ROHHAD patients to exercise at a moderate intensity and for their oxygen levels to be monitored throughout. Typically, the obesity associated with ROHHAD is managed by preventing further weight gain as the child grows.[3] ### Hypothalamic dysfunction treatment[edit] Treatment for hypothalamic dysfunction is tailored to each patient's needs, as there is no set of hypothalamic symptoms that all ROHHAD patients will manifest. All ROHHAD patients should be evaluated by a pediatric endocrinologist in order to determine a treatment plan for hypothalamic dysfunction.[citation needed] Patients may be given human growth hormone to treat stunted growth, or hormone replacement to treat any hormone deficiencies. Often patients are placed on a strict fluid regimen to treat for imbalances such as hyponatremia or hypernatremia.[3] Patients who present with diabetes insipidus may also be treated with desmopressin, a synthetic replacement for anti-diuretic hormone.[19] ### Hypoventilation treatment[edit] Every ROHHAD patient requires some form of ventilatory support, ranging from non-invasive BiPAP machines to tracheostomy procedures. Approximately 50% of ROHHAD patients will require ventilatory support day and night, whereas the other half only require night-time support.[1] A bilevel positive airway pressure machine, or BiPAP, is a ventilator mask worn at night. The BiPAP pushes air into the lungs, therefore breathing for the patient.[20] This is helpful for ROHHAD patients, as hypoventilation causes the mechanism that controls breathing in oxygen to slow and sometimes stop during sleep. A tracheostomy is the result of a surgical procedure to create a hole in the trachea in order to give access to ventilatory tubing. This procedure is performed to create an airway in situations when long term continuous use of a ventilator is needed.[21] ROHHAD patients whose hypoventilation is so severe that they require support during the day and night will often undergo tracheostomies.[10] ### Autonomic dysfunction treatment[edit] Treatment for autonomic dysfunction varies greatly on the severity of the dysfunction and the type. Many patients with ROHHAD experience strabismus, which is a weakness in eye muscle causing a "cross-eyed" effect. This can be treated with glasses, eye muscle exercises, or even surgery.[22] ROHHAD patients also often experience bradycardia, or low heart rate. This may require a cardiac pacemaker be placed in order to regulate heartbeat.[23] Gastrointestinal problems, such as constipation or diarrhea, are often treated on an as-needed basis with laxatives or dietary changes. It is also important that ambient temperatures are monitored in patients who have temperature regulation issues such as hyperthermia or hypothermia.[3] ### Neuroendocrine tumor treatment[edit] Tumors of neural crest origin develop in approximately 40% of patients. These are typically ganglioneuromas or ganglioneuroblastomas. Neural crest tumors have the ability to form in multiple organs tissues throughout the body, typically in the chest or abdomen.[24] It is therefore important for ROHHAD patients to have regular MRI and CT scans to screen for tumor growth.[7] It is believed that these tumors do not significantly affect the prognosis for ROHHAD patients.[14] Neuroendocrine tumors can arise 7–16 years after the initial onset of symptoms, therefore the name ROHHADNET (which includes these tumors) has not been widely accepted as it is believed this name would lead to further misdiagnosis. Treatment for these neuroendocrine tumors requires surgical removal, typically performed by a pediatric oncologist.[3] ## Prognosis[edit] The most dangerous and fatal aspect of ROHHAD is the potential for cardiopulmonary arrest if hypoventilation is not found and treated in a timely manner. Approximately 50 to 60% of ROHHAD patients die due to cardiopulmonary arrest.[4] The earlier symptoms are identified and patients are diagnosed, the more positive their outcomes are.[1] It has been found that children who are diagnosed earlier in life and received treatment for hypoventilation and hypothalamic dysfunction (fluid imbalances, etc.) are less likely to develop behavioral issues or experience sudden cardiorespiratory arrest later in life.[5] ## Research[edit] A group at Ann & Robert H. Lurie Children's Hospital of Chicago has an international repository for patients with ROHHAD, which is available to researchers who are interested in the disease.[25] As of June 2018, there are 3 clinical trials currently recruiting patients with ROHHAD being performed respectively at Lurie Children's Hospital, Sidney Kimmel Cancer Center, and Boston Children's Hospital.[26] ## Epidemiology[edit] There have been at least 158 documented cases of ROHHAD worldwide.[27] ## History[edit] ROHHAD was first described in 1965, and this was believed to be the first reported instance of hypoventilation presenting alongside hypothalamic dysfunction.[2] ROHHAD had often been mistaken for congenital central hypoventilation syndrome, until the distinction was made by Ize-Ludlow et al. in 2007. These conditions are now permanently differentiated from one other, as patients with CCHS have mutations in the PHOX2B gene, whereas ROHHAD patients do not.[28] ## Society[edit] The ROHHAD Association is an organization that aims to increase awareness for ROHHAD and promote research opportunities. They also organized fundraisers and events in order to give to researchers and promote visibility of ROHHAD.[29] ROHHAD Fight Inc is a charity that was created for Marisa, a child who was diagnosed with ROHHAD, with the goal of raising awareness for the condition.[30] ## See also[edit] * Central hypoventilation syndrome * Obesity hypoventilation syndrome * Hypoventilation * Hypothalamus * Rare disease ## References[edit] 1. ^ a b c d e f g h i Ibáñez-Micó, S.; Marcos Oltra, A.M.; De Murcia Lemauviel, S.; Ruiz Pruneda, R.; Martínez Ferrández, C.; Domingo Jiménez, R. (2017-11-01). "Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD syndrome): A case report and literature review". Neurología (English Edition). 32 (9): 616–622. doi:10.1016/j.nrleng.2016.04.003. ISSN 2173-5808. 2. ^ a b FISHMAN, L. S. (1965-08-01). "Primary Alveolar Hypoventilation Syndrome (Ondine's Curse)". American Journal of Diseases of Children. 110 (2): 155–61. doi:10.1001/archpedi.1965.02090030165011. ISSN 0002-922X. PMID 14320765. 3. ^ a b c d e f g h i j k l m n o p q "Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2018-06-03. 4. ^ a b c d e f Reppucci, Diana; Hamilton, Jill; Yeh, E Ann; Katz, Sherri; Al-Saleh, Suhail; Narang, Indra (2016-07-30). "ROHHAD syndrome and evolution of sleep disordered breathing". Orphanet Journal of Rare Diseases. 11 (1): 106. doi:10.1186/s13023-016-0484-1. ISSN 1750-1172. PMC 4967322. PMID 27473663. 5. ^ a b c d Weese-Mayer, Debra E.; Rand, Casey M.; Ize-Ludlow, Diego (August 2013). "Commentary: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): Remember Your ABCs (Airway, Breathing, Circulation)". Journal of the Canadian Academy of Child and Adolescent Psychiatry. 22 (3): 238–239. ISSN 1719-8429. PMC 3749899. PMID 23970914. 6. ^ "hypothalamus \| Definition, Anatomy, & Function". Encyclopedia Britannica. Retrieved 2018-06-03. 7. ^ a b c d e f Bougnères, Pierre; Pantalone, Letitia; Linglart, Agnès; Rothenbühler, Anya; Le Stunff, Catherine (October 2008). "Endocrine Manifestations of the Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neural Tumor Syndrome in Childhood". The Journal of Clinical Endocrinology & Metabolism. 93 (10): 3971–3980. doi:10.1210/jc.2008-0238. ISSN 0021-972X. PMID 18628522. 8. ^ "Hyponatremia - Symptoms and causes". Mayo Clinic. Retrieved 2018-06-08. 9. ^ Reynolds, Rebecca M; Padfield, Paul L; Seckl, Jonathan R (2006-03-25). "Disorders of sodium balance". BMJ : British Medical Journal. 332 (7543): 702–705. doi:10.1136/bmj.332.7543.702. ISSN 0959-8138. PMC 1410848. PMID 16565125. 10. ^ a b c Philadelphia, The Children's Hospital of (2016-08-24). "ROHHAD: Rapid-onset Obesity, Breathing and Behavioral Issues Indicate a Very Sick Patient". www.chop.edu. Retrieved 2018-06-03. 11. ^ "Obstructive sleep apnea - Symptoms and causes". Mayo Clinic. Retrieved 2018-06-06. 12. ^ "Primary alveolar hypoventilation". Scripps Health. 2008-08-28. Retrieved 2018-06-06. 13. ^ "autonomic nervous system \| Divisions & Functions". Encyclopedia Britannica. Retrieved 2018-06-06. 14. ^ a b c Pontual, Loic De; Trochet, Delphine; Caillat-Zucman, Sophie; Shenab, Othman A Abou; Bougneres, Pierre; Crow, Yanick; Cunningham, Steve; Esteva, Blandine; Heberle, Lada Cindro (December 2008). "Delineation of Late Onset Hypoventilation Associated with Hypothalamic Dysfunction Syndrome". Pediatric Research. 64 (6): 689–694. doi:10.1203/PDR.0b013e318187dd0e. ISSN 0031-3998. PMID 18670370. 15. ^ Kocaay, Pınar; Şıklar, Zeynep; Çamtosun, Emine; Kendirli, Tanıl; Berberoğlu, Merih (December 2014). "ROHHAD Syndrome: Reasons for Diagnostic Difficulties in Obesity". Journal of Clinical Research in Pediatric Endocrinology. 6 (4): 254–257. doi:10.4274/jcrpe.1432. ISSN 1308-5727. PMC 4293662. PMID 25541898. 16. ^ a b "ROHHAD \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-06-03. 17. ^ Thaker, Vidhu V.; Esteves, Kristyn M.; Towne, Meghan C.; Brownstein, Catherine A.; James, Philip M.; Crowley, Laura; Hirschhorn, Joel N.; Elsea, Sarah H.; Beggs, Alan H. (May 2015). "Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome". The Journal of Clinical Endocrinology and Metabolism. 100 (5): 1723–1730. doi:10.1210/jc.2014-4215. ISSN 1945-7197. PMC 4422892. PMID 25781356. 18. ^ Patwari, Pallavi P.; Rand, Casey M.; Berry-Kravis, Elizabeth M.; Ize-Ludlow, Diego; Weese-Mayer, Debra E. (2011-09-01). "Monozygotic Twins Discordant for ROHHAD Phenotype". Pediatrics. 128 (3): e711–e715. doi:10.1542/peds.2011-0155. ISSN 0031-4005. PMID 21807698. S2CID 21582413. 19. ^ "Diabetes insipidus - Diagnosis and treatment - Mayo Clinic". www.mayoclinic.org. Retrieved 2018-06-10. 20. ^ "BiPap \| Johns Hopkins Medicine Health Library". www.hopkinsmedicine.org. Retrieved 2018-06-08. 21. ^ "Tracheostomy - Mayo Clinic". www.mayoclinic.org. Retrieved 2018-06-08. 22. ^ "Strabismus — AAPOS". www.aapos.org. Retrieved 2018-06-08. 23. ^ "Bradycardia - Symptoms and causes". Mayo Clinic. Retrieved 2018-06-08. 24. ^ Maguire, Lillias H.; Thomas, Alyssa R.; Goldstein, Allan M. (March 2015). "Tumors of the neural crest: Common themes in development and cancer". Developmental Dynamics. 244 (3): 311–322. doi:10.1002/dvdy.24226. ISSN 1097-0177. PMID 25382669. 25. ^ "ROHHAD Research - ROHHAD Association". ROHHAD Association. Retrieved 2018-06-19. 26. ^ "Search of: ROHHAD - List Results - ClinicalTrials.gov". Retrieved 2018-06-19. 27. ^ Harvengt J, Gernay C, Mastouri M, Farhat N, Lebrethon MC, Seghaye MC, Bours V (July 2020). "ROHHAD(NET) Syndrome: Systematic Review of the Clinical Timeline and Recommendations for Diagnosis and Prognosis". J. Clin. Endocrinol. Metab. 105 (7): 2119–2131. doi:10.1210/clinem/dgaa247. PMID 32407531. 28. ^ Ize-Ludlow, Diego; Gray, Juliette A.; Sperling, Mark A.; Berry-Kravis, Elizabeth M.; Milunsky, Jeff M.; Farooqi, I. Sadaf; Rand, Casey M.; Weese-Mayer, Debra E. (July 2007). "Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood". Pediatrics. 120 (1): e179–188. doi:10.1542/peds.2006-3324. ISSN 1098-4275. PMID 17606542. S2CID 6244907. 29. ^ "About Us - ROHHAD Association". ROHHAD Association. Retrieved 2018-06-19. 30. ^ "Home". www.rohhadfight.org. Retrieved 2018-06-19. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	ROHHAD	c4053506	7,444	wikipedia	https://en.wikipedia.org/wiki/ROHHAD	2021-01-18T18:33:59	{"gard": ["10407"], "umls": ["C4053506"], "orphanet": ["293987"], "wikidata": ["Q4420133"]}
A number sign (#) is used with this entry because of evidence that Bartsocas-Papas syndrome (BPS), also known as the lethal type of popliteal pterygium syndrome, is caused by homozygous mutation in the RIPK4 gene (605706) on chromosome 21q22. Biallelic mutation in the RIPK4 gene can also cause CHAND syndrome (CHANDS; 214350), a less severe disorder with overlapping features. Description Bartsocas-Papas syndrome (lethal popliteal pterygium syndrome) is an autosomal recessive disorder characterized by multiple popliteal pterygia, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and syndactyly. Early lethality is common, although survival into childhood and beyond has been reported (summary by Mitchell et al., 2012). A less severe form of popliteal pterygium syndrome (119500) is caused by mutation in the IRF6 gene (607199). Clinical Features Bartsocas and Papas (1972) reported a family in which the parents were third cousins and 4 sibs were severely affected. In addition to marked popliteal pterygium with a cord containing nerves and vessels, synostosis of hand and foot bones with digital hypoplasia and syndactyly occur. Facial clefts, ankyloblepharon and filiform bands between the jaws have been observed. Hall (1984) gave a classification of the lethal pterygium syndromes. In addition to the lethal popliteal pterygium syndrome of Bartsocas and Papas, Hall (1984) recognized 3 lethal multiple pterygium syndromes. Cases of the Bartsocas-Papas syndrome were reported by Hall et al. (1982) and by Di Stefano and Romeo (1974). Papadia et al. (1984) described a case in the offspring of third-cousin parents. Facial cleft and fusion deformity in the hands and feet were also present. Papadia and Longo (1988) insisted that there are numerous nosologic differences between Bartsocas-Papas syndrome and lethal multiple pterygium syndrome (253290), 'so that confusion between them is not possible.' In a Spanish family, Martinez-Frias et al. (1991) described 3 affected sibs and pointed out that all but 1 of the 7 families that have been reported are of Mediterranean origin; 1 case was born to a couple of East Indian ancestry (Hall et al., 1982). The index case in the family of Martinez-Frias et al. (1991) had ankyloblepharon filiforme, absent eyebrows and eyelashes, and hypoplastic nose; bilateral clefts of the upper lip; fusion syndactyly of the hands and feet with bilateral aplasia of the thumb and phalangeal hypoplasia as well as absent nails. Thumb aplasia and fusion syndactyly of the fingers were present also in the proposita reported by Bartsocas and Papas (1972). Giannotti et al. (1992) described an infant who was still alive at the age of 20 months. They pointed to other cases in which the condition had not been neonatally lethal. The clustering of cases among persons of Mediterranean ancestry was again emphasized. Striking synostosis of the hands and feet was illustrated. Massoud et al. (1998) described BPS in 4 sibs in an Arab family. The phenotypically normal parents were unrelated; the father and mother were from Qatar and United Arab Emirates, respectively. The patients showed oral cleft, filiform bands between the jaws, ankyloblepharon, popliteal pterygium, syndactyly of fingers and toes, phalangeal anomalies with synostosis, clubfeet, nail hypoplasia, and genital anomalies. Additional traits included cutis aplasia, widely spaced nipples, low-set umbilicus, and unilateral renal hypoplasia. One of the sibs were stillborn; the other 3 children lived 10 to 17 months. Aslan et al. (2000) described a female infant who presented with pterygia of the inguinal, intercrural, and popliteal areas, flexion contractures and arthrogryposis of some joints, craniofacial anomalies including ectropion, medial canthal web, blepharophimosis, hypoplasia of nose, oral and nasopharyngeal cavities, vocal cords, and tongue, micrognathia, orolabial synechiae secondary to pterygia, low-set ears, alopecia, sad and expressionless face, short neck, asymmetric nipples, anal stenosis, rectal polyp, hypoplastic labia majora, complete syndactyly of all fingers and toes, phalangeal-palmar creases, pes equinovarus, band-like web between feet, and absence of nails. Radiologic examination showed synostosis, absence or hypoplasia of metacarpal, metatarsal, and phalangeal bones of feet and hands, and hypoplasia of pelvic bones and scapulae. Autosomal recessive inheritance was considered likely because 3 sibs were similarly affected and the parents were normal. Teebi (2001) suggested that the disorder in the family reported by Aslan et al. (2000), initially believed to represent a distinct disorder, was the Bartsocas-Papas syndrome because of a strong resemblance to cases that he had reported with Massoud et al. (1998) in an Arab family from Qatar. Kalay et al. (2012) provided follow-up on the consanguineous Turkish family with popliteal pterygium syndrome originally studied by Aslan et al. (2000). Of 6 affected children from 3 sibships, 2 boys and 2 girls died within a week after birth, and 2 female cousins were alive at ages 13 years and 1.5 years. Present in both were alopecia, ankyloblepharon filaforme adnatum, hypoplastic oral cavity and filiform bands between the jaws, limb abnormalities including digital hypoplasia, syndactyly, nail hypoplasia, arthrogryposis, clubfeet, and politeal, axillary, and inguinal pterygia, and hypoplastic labia majora. In addition to classic Bartsocas-Papas syndrome findings, the older girl also had medial canthal webbing, hypoplasia of the iliac wing and scapulae, short stature, anal stenosis, and a rectal polyp. Veenstra-Knol et al. (2003) reported 2 Dutch families with 6 affected children. One of the patients was diagnosed prenatally by ultrasound examination. Previously unreported findings included omphalocele and aplasia of the urethra. Shanske et al. (2004) described a male infant, born of consanguineous Gambian parents, who had large bilateral popliteal pterygia extending from the crurae to the great toes. In addition, he had right-sided cleft lip and palate, abortive left-sided cleft, symblepharon, and synechiae between the upper and lower alveolar ridges. He had normal eyelashes and eyebrows. There was syndactyly of the second, third, and fourth fingers bilaterally, with hypoplasia of the phalanges and fingernails of those digits, and he had bilateral cryptorchidism. He underwent tracheostomy and gastrostomy due to the ankylosed mandible, and the oral synechiae and ocular filiform adhesions were lysed and the cleft lip repaired. A 3-D CT scan of the head demonstrated probable fusion between the left coronoid process and zygoma as well as between the condylar head and the temporomandibular fossa. At 3 years of age, he was developmentally appropriate except for gross physical limitations; his palate remained unrepaired and the jaw was ankylosed. He was evaluated for release of the popliteal pterygia, but because the neurovascular bundles could not be preserved, he underwent bilateral below-the-knee amputations. His mother experienced fetal demise 14 months after the birth of the proband, with delivery of a 33-week gestation female fetus with low-set pinnae, cleft between the eyes, absence of eyebrows and eyelashes, flattened nose, and filiform bands of thickened collagen fibers fusing the eyelids and connecting the lower lip to the maxilla. There were also large pterygia in both popliteal fossae and synostosis of the bones of the second and third fingers of the right hand and of the digits of both feet except for the great toes; no fingernails or toenails were present. Abdalla and Morsy (2011) reported an Egyptian family with Bartsocas-Papas syndrome. The proband was a 3-month-old girl who had striking craniofacial anomalies, including a severely malformed nose with clefting and 2 symmetrical indentations over the nasal root, hypertelorism with major eye anomalies including microphthalmia, small hazy corneas, left ankyloblepharon with filiform bands, multiple right eyelid colobomas, short palpebral fissures with marked upward slanting, and total absence of eyebrows, eyelashes, and scalp hair. No mouth or lips were present, although 2 salivary pits could be identified, and there was a bilateral orofacial cleft extending into the alae nasi and connecting with a bilateral cleft palate. The mandible and maxilla were severely hypoplastic, with a transverse groove over the chin, whereas the ears were relatively large, cupped, and low set. In addition, she had major pterygia of almost all joints, including the shoulders, elbows, wrists, hips, knees, and ankles, but sparing the neck. There was complete syndactyly between all fingers of both hands, flexed fingers, and absent thumbs, and there was adactyly of both feet with dorsiflexion and pes planus. Nails were absent in all fingers and toes. Other anomalies included a very short sternum, widely spaced nipples, low-set umbilicus, and prominent veins over the chest and abdomen, with skin tags over the chest as well as the right palm and right labia minora. She also had ambiguous genitalia with absent clitoris and hypoplastic labia majora, anal stenosis, and sacral dimple. The infant died shortly after examination, and the parents reported a similarly affected older female sib with genital ambiguity who had died in utero after a 26-week gestation complicated by intrauterine growth retardation. In addition, there was a 16-year-old maternal uncle who had mental retardation and ocular, cutaneous, and limb anomalies, including microphthalmia with short and narrow palpebral fissures, sparse lower eyelashes, hypoplastic thumbs, and complete syndactyly. He also had truncal obesity and hypoplastic external genitalia. However, he had no pterygia and displayed multiple cafe-au-lait spots, a feature not previously reported in BPS. Mitchell et al. (2012) studied a 6-year-old boy, the second child of consanguineous parents, who was born with alopecia totalis with only sparse scalp hair, partial ankyloblepharon, oral synechia resulting in partial occlusion of the oral cavity, hypertelorism, cloudy corneas, absent thumbs, finger and toe oligosyndactyly, hypoplastic genitalia, extensive popliteal pterygia, multiple skin tags, and unusual fibrous tethers between the feet and suprapubic region. Intellectual development appeared to be normal. On the basis of these features, a diagnosis of Bartsocas-Papas syndrome was made. Busa et al. (2017) reported a male fetus (patient 1), conceived of consanguineous Moroccan parents, with features of BPS. Autopsy showed a typical facial appearance with absent eyelids, bilateral labio-maxillo-palatal cleft, nasal hypoplasia, and small ears attached to the scalp. There was also a small omphalocele, multiple pterygia of the upper and lower limbs, syndactyly of hands and feet, clubfeet, anal atresia, and absence of external genitalia. Mapping In 2 affected and 10 unaffected members of a consanguineous Turkish family with lethal popliteal pterygium syndrome, originally reported by Aslan et al. (2000), Kalay et al. (2012) performed genomewide homozygosity mapping and observed a single homozygous segment on chromosome 21q22. Within that region, haplotypes between SNP markers rs2838045 and rs225444 were identical in both affected individuals, indicating homozygosity by descent. Microsatellite-marker genotyping in all family members confirmed the 21q22.3 locus, and recombination events narrowed the critical region to an approximately 0.71-Mb interval containing 7 genes and 3 expressed sequence tags. Molecular Genetics In a 6-year-old boy with features consistent with Bartsocas-Papas syndrome who was born of consanguineous parents, Mitchell et al. (2012) performed exome sequencing and identified homozygosity for a nonsense mutation in the RIPK4 gene (S376X; 605706.0001), located within a 9.3-Mb region of homozygosity between SNPs rs1053808 and rs1044998. Both parents were heterozygous for the mutation. Sequencing of RIPK4 in a DNA sample from the 3-year-old boy with Bartsocas-Papas syndrome previously studied by Shanske et al. (2004) revealed homozygosity for a missense mutation (I81N; 605706.0002); although no DNA from his parents was available, the mutation was not found in dbSNP, the 1000 Genomes Database, or in over 4,000 chromosomes from the National Heart, Lung, and Blood Institute Exome Sequencing Project. In a consanguineous Turkish family with lethal popliteal pterygium syndrome mapping to chromosome 21q22.3, originally reported by Aslan et al. (2000), Kalay et al. (2012) analyzed the candidate RIPK4 gene and identified homozygosity for a missense mutation (I121N; 605706.0003) in the 2 surviving affected individuals, whose parents were heterozygous for the mutation. Analysis of another Turkish family with a deceased male infant who had features consistent with Bartsocas-Papas syndrome revealed that the first-cousin parents were both heterozygous for another missense mutation in RIPK4 (DNA was not available from the deceased infant). Kalay et al. (2012) also sequenced the RIPK4 gene in a consanguineous Egyptian family with an affected girl who died at 3.5 months of age, previously described by Abdalla and Morsy (2011), and found that the deceased infant had a homozygous 1-bp insertion in RIPK4 (605706.0004) for which her unaffected parents were heterozygous. Kalay et al. (2012) noted similarities between the Bartsocas-Papas phenotype and the more severe 'cocoon' syndrome (613630) caused by mutation in the CHUK gene (600664), and suggested that RIPK4 and CHUK might function via closely related pathways to promote keratinocyte differentiation and epithelial growth. In a male fetus (patient 1), conceived of consanguineous Moroccan parents, with lethal Bartsocas-Papas syndrome, Busa et al. (2017) identified homozygosity for a single base duplication in the RIPK4 gene (605706.0007). The parents were heterozygous for the mutation. ### Exclusion Studies In a 3-year-old boy with Bartsocas-Papas popliteal pterygium syndrome, Shanske et al. (2004) sequenced exons 3 to 8 and parts of exons 9 and 10 of the IRF6 gene (607199) but found no disease-causing mutations. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation HEAD & NECK Face \- Hypoplastic maxilla (in some patients) \- Hypoplastic mandible (in some patients) \- Facial cleft Ears \- Low-set ears \- Cupped ears (in some patients) Eyes \- Ankyloblepharon filiforme \- Absent eyebrows (in some patients) \- Absent eyelashes (in some patients) \- Hypertelorism (in some patients) \- Cloudy corneas (in some patients) \- Medial canthal webbing (in some patients) \- Microphthalmia (in some patients) \- Eyelid colobomata (in some patients) Nose \- Hypoplastic nose Mouth \- Cleft lip \- Cleft palate \- Filiform bands between mandible and maxilla CHEST Ribs Sternum Clavicles & Scapulae \- Hypoplastic scapulae (in some patients) Breasts \- Asymmetric nipples (in some patients) \- Widely spaced nipples (in some patients) ABDOMEN External Features \- Low-set umbilicus (in some patients) Gastrointestinal \- Anal stenosis GENITOURINARY External Genitalia (Male) \- Hypoplastic genitalia (in some patients) External Genitalia (Female) \- Ambiguous genitalia \- Hypoplastic labia majora \- Absent clitoris (in some patients) Internal Genitalia (Male) \- Cryptorchidism, bilateral (in some patients) SKELETAL Pelvis \- Hypoplasia of iliac wing (in some patients) Hands \- Bony synostosis \- Syndactyly \- Phalangeal hypoplasia \- Thumb aplasia (in some patients) Feet \- Bony synostosis \- Oligosyndactyly of toes SKIN, NAILS, & HAIR Skin \- Popliteal pterygium, bilateral \- Axillary pterygium, bilateral (in some patients) \- Inguinal pterygium, bilateral (in some patients) \- Pterygium of elbow, bilateral (in some patients) \- Pterygium of wrist, bilateral (in some patients) \- Pterygium of bilateral (in some patients) \- Skin tags on chest \- Skin tags on palms (in some patients) \- Skin tags on genitalia (in some patients) Nails \- Absent nails \- Hypoplastic nails Hair \- Alopecia totalis (in some patients) \- Absent eyebrows (in some patients) \- Absent eyelashes (in some patients) MISCELLANEOUS \- Neonatal/infantile death in most patients MOLECULAR BASIS \- Caused by mutation in the receptor-interacting serine-threonine kinase-4 gene (RIPK4, 605706.0001 ) ▲ 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	BARTSOCAS-PAPAS SYNDROME	c1849718	7,445	omim	https://www.omim.org/entry/263650	2019-09-22T16:23:15	{"doid": ["0060055"], "mesh": ["C564874"], "omim": ["263650"], "orphanet": ["1234"], "synonyms": ["Alternative titles", "POPLITEAL PTERYGIUM SYNDROME, LETHAL TYPE", "PTERYGIUM, POPLITEAL, LETHAL TYPE", "MULTIPLE PTERYGIUM SYNDROME, ASLAN TYPE"]}
Pelger–Huët anomaly Other namesPHA[1] blood smear of a patient with myelodysplastic syndrome: red blood cells showing marked poikilocytosis, in part related to post-splenectomy status, and central a hypogranular neutrophil with a pseudo-Pelger-Huet nucleus. Pronunciation * US: /ˈpɛlɡər ˈhuːɛt/ Dutch pronunciation: [ˈpɛlɣər ˈɦuːɛt] SpecialtyMedical genetics Pelger–Huët anomaly is a blood laminopathy associated with the lamin B receptor,[2] wherein several types of white blood cells (neutrophils and eosinophils) have nuclei with unusual shape (being bilobed, peanut or dumbbell-shaped instead of the normal trilobed shape) and unusual structure (coarse and lumpy).[3] Pelger–Huët anomaly has an autosomal dominant pattern of inheritance. It is a genetic disorder with an autosomal dominant inheritance pattern. Heterozygotes are clinically normal, although their neutrophils may be mistaken for immature cells which may cause mistreatment in a clinical setting. Homozygotes tend to have neutrophils with rounded nuclei that do have some functional problems.[citation needed] ## Contents * 1 Congenital Pelger–Huët anomaly * 2 Acquired or pseudo-Pelger–Huët anomaly * 3 References * 4 External links ## Congenital Pelger–Huët anomaly[edit] Is a benign dominantly inherited defect of terminal neutrophil differentiation as a result of mutations in the lamin B receptor gene. The characteristic leukocyte appearance was first reported in 1928 by Karel Pelger (1885-1931), a Dutch Hematologist, who described leukocytes with dumbbell-shaped bilobed nuclei, a reduced number of nuclear segments, and coarse clumping of the nuclear chromatin. In 1931, Gauthier Jean Huet (1879-1970), a Dutch Pediatrician, identified it as an inherited disorder.[4] It is a genetic disorder with an autosomal dominant inheritance pattern.[2][5] Heterozygotes are clinically normal, although their neutrophils may be mistaken for immature cells, which may cause mistreatment in a clinical setting. Homozygotes tend to have neutrophils with rounded nuclei that do have some functional problems. Homozygous individuals inconsistently have skeletal anomalies such as post-axial polydactyly, short metacarpals, short upper limbs, short stature, or hyperkyphosis.[citation needed] Identifying Pelger–Huët anomaly is important to differentiate from bandemia with a left-shifted peripheral blood smear and neutrophilic band forms and from an increase in young neutrophilic forms that can be observed in association with infection.[citation needed] ## Acquired or pseudo-Pelger–Huët anomaly[edit] Anomalies resembling Pelger–Huët anomaly that are acquired rather than congenital have been described as pseudo Pelger–Huët anomaly. These can develop in the course of acute myelogenous leukemia or chronic myelogenous leukemia and in myelodysplastic syndrome. It has also been described in Filovirus disease.[6] In patients with these conditions, the pseudo–Pelger–Huët cells tend to appear late in the disease and often appear after considerable chemotherapy has been administered. The morphologic changes have also been described in myxedema associated with panhypopituitarism, vitamin B12 and folate deficiency, multiple myeloma, enteroviral infections, malaria, muscular dystrophy, leukemoid reaction secondary to metastases to the bone marrow, and drug sensitivity, sulfa and valproate toxicities[7] are examples. In some of these conditions, especially the drug-induced cases, it is important to differentiate between Pelger–Huët anomaly and pseudo-Pelger–Huët to prevent the need for further unnecessary testing for cancer.[citation needed] Peripheral blood smear shows a predominance of neutrophils with bilobed nuclei which are composed of two nuclear masses connected with a thin filament of chromatin. It resembles the pince-nez glasses, so it is often referred to as pince-nez appearance. Usually the congenital form is not associated with thrombocytopenia and leukopenia, so if these features are present more detailed search for myelodysplasia is warranted, as pseudo-Pelger–Huët anomaly can be an early feature of myelodysplasia.[8] ## References[edit] 1. ^ "OMIM Entry - # 169400 - PELGER-HUET ANOMALY; PHA". omim.org. Retrieved 31 October 2019. 2. ^ a b Hoffmann, Katrin; Dreger, Christine K.; Olins, Ada L.; Olins, Donald E.; Shultz, Leonard D.; Lucke, Barbara; Karl, Hartmut; Kaps, Reinhard; Müller, Dietmar; Vayá, Amparo; Aznar, Justo; Ware, Russell E.; Cruz, Norberto Sotelo; Lindner, Tom H.; Herrmann, Harald; Reis, André; Sperling, Karl (2002). "Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger–Huët anomaly)". Nature Genetics. 31 (4): 410–4. doi:10.1038/ng925. PMID 12118250. 3. ^ "Pelger-Huet anomaly". Disease Infosearch. Retrieved 2020-04-27. Creative Commons Attribution 3.0 License 4. ^ Cunningham, John M.; Patnaik, Mrinal M.; Hammerschmidt, Dale E.; Vercellotti, Gregory M. (2009). "Historical perspective and clinical implications of the Pelger-Huet cell". American Journal of Hematology. 84 (2): 116–9. doi:10.1002/ajh.21320. PMID 19021122. 5. ^ Vale, A. M.; Tomaz, L. R.; Sousa, R. S.; Soto-Blanco, B. (2011). "Pelger-Huët anomaly in two related mixed-breed dogs". Journal of Veterinary Diagnostic Investigation. 23 (4): 863–5. doi:10.1177/1040638711407891. PMID 21908340. 6. ^ Gear, JS; Cassel, GA; Gear, AJ; Trappler, B; Clausen, L; Meyers, AM; Kew, MC; Bothwell, TH; Sher, R; Miller, GB; Schneider, J; Koornhof, HJ; Gomperts, ED; Isaäcson, M; Gear, JH (1975). "Outbreake of Marburg virus disease in Johannesburg". British Medical Journal. 4 (5995): 489–93. doi:10.1136/bmj.4.5995.489. PMC 1675587. PMID 811315. 7. ^ Singh, Nishith K.; Nagendra, Sanjai (2008). "Reversible Neutrophil Abnormalities Related to Supratherapeutic Valproic Acid Levels". Mayo Clinic Proceedings. 83 (5): 600. doi:10.4065/83.5.600. PMID 18452694. 8. ^ Pelger-Huet Anomaly at eMedicine ## External links[edit] Classification D * ICD-10: D72.0 * ICD-9-CM: 288.2 * OMIM: 169400 * MeSH: D010381 * DiseasesDB: 29515 External resources * eMedicine: ped/1753 * v * t * e Cytoskeletal defects Microfilaments Myofilament Actin * Hypertrophic cardiomyopathy 11 * Dilated cardiomyopathy 1AA * DFNA20 * Nemaline myopathy 3 Myosin * Elejalde syndrome * Hypertrophic cardiomyopathy 1, 8, 10 * Usher syndrome 1B * Freeman–Sheldon syndrome * DFN A3, 4, 11, 17, 22; B2, 30, 37, 48 * May–Hegglin anomaly Troponin * Hypertrophic cardiomyopathy 7, 2 * Nemaline myopathy 4, 5 Tropomyosin * Hypertrophic cardiomyopathy 3 * Nemaline myopathy 1 Titin * Hypertrophic cardiomyopathy 9 Other * Fibrillin * Marfan syndrome * Weill–Marchesani syndrome * Filamin * FG syndrome 2 * Boomerang dysplasia * Larsen syndrome * Terminal osseous dysplasia with pigmentary defects IF 1/2 * Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1 * Striate palmoplantar keratoderma 3 * Epidermolytic hyperkeratosis * IHCM * KRT2E (Ichthyosis bullosa of Siemens) * KRT3 (Meesmann juvenile epithelial corneal dystrophy) * KRT4 (White sponge nevus) * KRT5 (Epidermolysis bullosa simplex) * KRT8 (Familial cirrhosis) * KRT10 (Epidermolytic hyperkeratosis) * KRT12 (Meesmann juvenile epithelial corneal dystrophy) * KRT13 (White sponge nevus) * KRT14 (Epidermolysis bullosa simplex) * KRT17 (Steatocystoma multiplex) * KRT18 (Familial cirrhosis) * KRT81/KRT83/KRT86 (Monilethrix) * Naegeli–Franceschetti–Jadassohn syndrome * Reticular pigmented anomaly of the flexures 3 * Desmin: Desmin-related myofibrillar myopathy * Dilated cardiomyopathy 1I * GFAP: Alexander disease * Peripherin: Amyotrophic lateral sclerosis 4 * Neurofilament: Parkinson's disease * Charcot–Marie–Tooth disease 1F, 2E * Amyotrophic lateral sclerosis 5 * Laminopathy: LMNA * Mandibuloacral dysplasia * Dunnigan Familial partial lipodystrophy * Emery–Dreifuss muscular dystrophy 2 * Limb-girdle muscular dystrophy 1B * Charcot–Marie–Tooth disease 2B1 * LMNB * Barraquer–Simons syndrome * LEMD3 * Buschke–Ollendorff syndrome * Osteopoikilosis * LBR * Pelger–Huet anomaly * Hydrops-ectopic calcification-moth-eaten skeletal dysplasia Microtubules Kinesin * Charcot–Marie–Tooth disease 2A * Hereditary spastic paraplegia 10 Dynein * Primary ciliary dyskinesia * Short rib-polydactyly syndrome 3 * Asphyxiating thoracic dysplasia 3 Other * Tauopathy * Cavernous venous malformation Membrane * Spectrin: Spinocerebellar ataxia 5 * Hereditary spherocytosis 2, 3 * Hereditary elliptocytosis 2, 3 Ankyrin: Long QT syndrome 4 * Hereditary spherocytosis 1 Catenin * APC * Gardner's syndrome * Familial adenomatous polyposis * plakoglobin (Naxos syndrome) * GAN (Giant axonal neuropathy) Other * desmoplakin: Striate palmoplantar keratoderma 2 * Carvajal syndrome * Arrhythmogenic right ventricular dysplasia 8 * plectin: Epidermolysis bullosa simplex with muscular dystrophy * Epidermolysis bullosa simplex of Ogna * plakophilin: Skin fragility syndrome * Arrhythmogenic right ventricular dysplasia 9 * centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II) Related topics: Cytoskeletal proteins * v * t * e Blood film findings Red blood cells Size * Anisocytosis * Macrocytosis * Microcytosis Shape * Poikilocytosis * Membrane abnormalities * Acanthocyte * Codocyte * Elliptocyte * Hereditary elliptocytosis * Spherocyte * Hereditary spherocytosis * Dacrocyte * Echinocyte * Schistocyte * Degmacyte * Sickle cell/drepanocyte * Sickle cell disease * Stomatocyte * Hereditary stomatocytosis Colour * Anisochromia * Hypochromic anemia * Polychromasia Inclusion bodies * Developmental * Howell–Jolly body * Basophilic stippling * Pappenheimer bodies * Cabot rings * Hemoglobin precipitation * Heinz body Other * Red cell agglutination * Rouleaux White blood cells Lymphocytes * Reactive lymphocyte * Smudge cell * Russell bodies Granulocytes * Hypersegmented neutrophil * Arneth count * Pelger–Huët anomaly * Döhle bodies * Toxic granulation * Toxic vacuolation * Critical green inclusion * Alder–Reilly anomaly * Jordans' anomaly * Birbeck granules * Left shift Other * Auer rod [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Pelger–Huët anomaly	c0030779	7,446	wikipedia	https://en.wikipedia.org/wiki/Pelger%E2%80%93Hu%C3%ABt_anomaly	2021-01-18T18:51:59	{"gard": ["9148"], "mesh": ["D010381"], "umls": ["C0030779", "C4023351"], "icd-9": ["288.2"], "icd-10": ["D72.0"], "wikidata": ["Q975182"]}
Cystic fibrosis-gastritis-megaloblastic anemia, or Lubani-Al Saleh-Teebi syndrome, is a rare genetic disease reported in two siblings of consanguineous Arab parents and is characterized by cystic fibrosis, gastritis associated with Helicobacter pylori, folate deficiency megaloblastic anemia, and intellectual disability. There have been no further descriptions in the literature since 1991. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Cystic fibrosis-gastritis-megaloblastic anemia syndrome	c2931402	7,447	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2575	2021-01-23T17:30:56	{"gard": ["3303"], "mesh": ["C537039"], "omim": ["219721"], "umls": ["C2931402"], "synonyms": ["Lubani-Al Saleh-Teebi syndrome"]}
Pseudohypoparathyroidism (PHP) is a heterogeneous group of endocrine disorders characterized by normal renal function and resistance to the action of parathyroid hormone (PTH), manifesting with hypocalcemia, hyperphosphatemia and elevated PTH levels and that includes the subtypes PHP type 1a (PHP-1a) , PHP type 1b (PHP-1b), PHP type 1c (PHP-1c), PHP type 2 (PHP-2) and pseudopseudohypoparathyroidism (PPHP) (see these terms). ## Epidemiology The exact prevalence is unknown. PHP occurs twice as frequently in females as in males. The estimated prevalence (of PHP-1a, 1b and PPHP) in Italy is 1/150,000. The estimated prevalence in Japan (of PHP-1a and 1b) is 1/295,000. ## Clinical description All forms of PHP can present in infancy, especially if significant hypocalcemia occurs. Symptoms related to low levels of calcium can include: paresthesias, numbness, seizures and tetany (including muscle twitches and hand and foot spasms).Some forms of PHP may remain unnoticed if patients do not have hypocalcemia (or if hypocalcemia is misdiagnosed and treated as ''seizures'') and/or characteristic physical features, which include short stature, rounded face, short neck, centripetal obesity, brachydactyly and soft-tissue and calcifications/ossifications, and are collectively termed Albright hereditary osteodystrophy (AHO; see this term). AHO is observed in patients with PHP-1a, PHP-1c and PPHP but is absent in patients with PHP-1b and PHP-2. Intellectual disability is sometimes observed in patients with AHO features while it is almost always present in PHP-1A and PHP -1C. There have also been reports that olfaction is impaired in PHP-1a but not in PPHP or PHP-1b. Patients with PHP can also present with symptoms of resistance to hormones other than PTH including thyroid-stimulating hormone (TSH) (in PHP1a, PHP1c and sometimes PHP1b), gonadotropins (in PHP1a, PHP1c) and growth-hormone-releasing hormone (GHRH) (in PHP1a). Cataracts, dental problems and intracranial calcifications (bilateral striopallidodentate calcinosis; see this term) represent the long-term complications. ## Etiology PHP-1a, PPHP, and PHP-1b are all due to molecular defects in the same locus of the GNAS (20q13.2-q13.3) gene coding the alpha sub-unit of the stimulatory G protein. Patients inheriting PHP from the mother display all the signs of AHO with multi-hormone resistance, while patients inheriting the disease from the father have AHO without any resistance to hormone action (PPHP). This pattern of inheritance is consistent with a tissue-specific paternal imprinting of the gene causing the disease. Those with the autosomal dominant form of PHP-Ib display an isolated loss of methylationat exon A/B associated with a recurrent 3-kb deletion in the STX16 gene (20q13.32). To date, the genetic anomaly responsible for PHP2 and PHP1c has not yet been identified, although in a few PHP1c patients, GNAS heterozygous mutations have been detected. It has been hypothesized that in most cases, PHP2 may be an acquired defect secondary to vitamin D deficiency. ## Genetic counseling PHP can be sporadic or inherited autosomal dominantly with parental imprinting. In inherited cases, genetic counseling is possible. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Pseudohypoparathyroidism	c0033806	7,448	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97593	2021-01-23T16:54:25	{"gard": ["10758"], "mesh": ["D011547"], "umls": ["C0033806"], "icd-10": ["E20.1"]}
Eruptive pseudoangiomatosis SpecialtyDermatology Eruptive pseudoangiomatosis is a cutaneous condition characterized by the sudden appearance of 2- to 4-mm blanchable red papules.[1]:399 It can appear in children or adults.[2] The papules appear similar to hemangiomas[3] (hence the name). Viruses found in patients include Echovirus 25 and 32, coxsackie B, Epstein-Barr virus, and cytomegalovirus.[4] ## See also[edit] * Boston exanthem disease * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 2. ^ Chaniotakis I, Nomikos K, Gamvroulia C, Zioga A, Stergiopoulou C, Bassukas ID (2007). "Eruptive pseudoangiomatosis: report of an adult case and unifying hypothesis of the pathogenesis of paediatric and adult cases". Dermatology. 215 (1): 59–62. doi:10.1159/000102035. PMID 17587841. S2CID 38222013. 3. ^ Otto Braun-Falco (2000). Dermatology. Springer. pp. 53–. ISBN 978-3-540-59452-9. Retrieved 23 May 2010. 4. ^ Pitarch G, Torrijos A, García-Escrivá D, Martínez-Menchón T (2007). "Eruptive pseudoangiomatosis associated to cytomegalovirus infection". Eur J Dermatol. 17 (5): 455–6. doi:10.1684/ejd.2007.0257 (inactive 2021-01-11). PMID 17673403.CS1 maint: DOI inactive as of January 2021 (link) This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Eruptive pseudoangiomatosis	c2242648	7,449	wikipedia	https://en.wikipedia.org/wiki/Eruptive_pseudoangiomatosis	2021-01-18T19:01:59	{"umls": ["C2242648"], "wikidata": ["Q17120185"]}
A number sign (#) is used with this entry because of evidence that an autosomal dominant form of Bernard-Soulier syndrome can be caused by heterozygous mutations in the gene encoding platelet glycoprotein Ib-alpha (GP1BA; 606672) on chromosome 17p. Homozygous or compound heterozygous mutations in the GP1BA gene cause classic autosomal recessive Bernard-Soulier syndrome (BSSA1; 231200). Clinical Features Miller et al. (1992) reported a 2-generation family in which 5 individuals had a moderate bleeding tendency, thrombocytopenia, and an increased mean platelet volume. The pedigree pattern was consistent with autosomal dominant inheritance. Savoia et al. (2001) reported 6 Italian families with variable manifestations of a mild bleeding diathesis, incidental discovery of thrombocytopenia, or platelet macrocytosis. Some individuals had no symptoms. Mild bleeding tendencies were manifest as epistaxis, gingival bleeding, menorrhagia, easy bruising, or prolonged bleeding after dental surgery. Members of 3 families had bone marrow examination that showed normal numbers of megakaryocytes. Mapping By linkage analysis of 2 large Italian families with autosomal dominant macrothrombocytopenia, Savoia et al. (2001) found linkage to a region on chromosome 17p, in an interval containing the GP1BA gene (606672). Molecular Genetics In a Caucasian family in which 5 members over 2 generations were affected with a mild form of Bernard-Soulier syndrome in an unusual autosomal dominant pattern of inheritance, Miller et al. (1992) identified a heterozygous mutation in the GP1BA gene (L57F; 606672.0004). In affected individuals of 6 Italian families with autosomal dominant inheritance of large platelets, thrombocytopenia, and mild bleeding tendencies, Savoia et al. (2001) identified a heterozygous mutation in the GP1BA gene (A156V; 606672.0006). The patients were originally thought to have Mediterranean macrothrombocytopenia (see 210250). However, the results of Savoia et al. (2001) indicated that a subset of patients diagnosed with so-called Mediterranean macrothrombocytopenia may actually have a heterozygous type of Bernard-Soulier syndrome. INHERITANCE \- Autosomal dominant HEAD & NECK Nose \- Epistaxis Mouth \- Gingival bleeding Teeth \- Prolonged bleeding after dental extraction ABDOMEN Spleen \- Mild splenomegaly GENITOURINARY Internal Genitalia (Female) \- Prolonged menstrual periods SKIN, NAILS, & HAIR Skin \- Petechiae \- Ecchymoses HEMATOLOGY \- Large platelets \- Asymptomatic bleeding tendencies (petechiae, epistaxis, mucosal bleeding) \- Hemolytic anemia \- Erythrocyte stomatocytes \- Absent neutrophil inclusions LABORATORY ABNORMALITIES \- Low-normal platelet count (89-290 x 10(9)/L) \- Mean platelet volume (MPV) 12.6fL \- Normal platelet aggregation studies with ADP, collagen, and ristocetin MOLECULAR BASIS \- Caused by mutation in the glycoprotein Ib, platelet, alpha polypeptide gene (GP1BA, 606672.0006 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	BERNARD-SOULIER SYNDROME, TYPE A2, AUTOSOMAL DOMINANT	c0005129	7,450	omim	https://www.omim.org/entry/153670	2019-09-22T16:38:41	{"doid": ["0111059"], "mesh": ["D001606"], "omim": ["153670"], "orphanet": ["274"]}
Hyperandrogenism Other namesAndrogen excess Testosterone is a type of androgen that is important in the development of hyperandrogenism since high levels of it can cause this condition. Pronunciation * 'hīpər'andrəjənizəm SpecialtyEndocrinology SymptomsAcne, hair loss on scalp, increased body or facial hair, infrequent or absent menstruation[1][2] CausesPolycystic ovary syndrome (PCOS), adrenal hyperplasia, Cushing's disease, cancer[1][3] Diagnostic methodBlood tests, ultrasound[1][4] TreatmentBirth control pills, cyproterone acetate[1] Frequency5% (reproductive age women)[2] Hyperandrogenism is a medical condition characterized by high levels of androgens in females.[4] Symptoms may include acne, seborrhea (inflamed skin), hair loss on the scalp, increased body or facial hair, and infrequent or absent menstruation.[1][2] Complications may include high blood cholesterol.[4] The cause in about 70% of cases is polycystic ovary syndrome (PCOS).[1] Other causes include adrenal hyperplasia, Cushing's disease, certain types of cancers, and certain medications.[1][3][4] Diagnosis often involves blood tests for testosterone, 17-hydroxyprogesterone, and prolactin as well as a pelvic ultrasound.[1][4] Treatment depends on the underlying cause.[4] Symptoms of hyperandrogenism can be improved with birth control pills or antiandrogens such as cyproterone acetate or spironolactone.[1][4] Other measures may include hair removal techniques.[3] It occurs in about 5% of women of reproductive age.[2] The earliest known descriptions of the condition are by Hippocrates in the 5th century BCE.[5][6] In 2011 the International Association of Athletics Federations (now World Athletics), and IOC [7] released statements restricting the eligibility of female athletes with high testosterone, whether through hyperandrogenism, or as a result of a disorder of sex development (DSD). These regulations were referred to by both bodies as hyperandrogenism regulations, and have led to affected DSD athletes being described as having hyperandrogenism.[8][9] ## Contents * 1 Signs and symptoms * 1.1 Women * 1.2 Men * 2 Causes * 2.1 Polycystic ovary syndrome * 2.2 Hyperthecosis and hyperinsulinemia * 2.3 Cushing’s syndrome * 2.4 Congenital adrenal hyperplasia * 2.5 Tumors * 2.5.1 Adrenocortical carcinoma and tumors * 2.5.2 Adenoma of the adrenal gland * 2.5.3 Arrhenoblastoma * 2.5.4 Hilar cell tumor * 2.5.5 Krukenberg tumor * 2.6 Menopause * 2.7 Drug-induced * 2.8 Heredity * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Society and culture * 6.1 Sports * 6.2 Social definition * 6.3 Organizations * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] A woman with hirsutism from increased androgen exposure Hyperandrogenism affects 5-10% of females of reproductive age.[10] Hyperandrogenism can affect both males and females, but is more noticeable in females since elevated levels of androgens in females often facilitates virilization. Because hyperandrogenism is characterized by the elevation of male sex hormone levels, symptoms of hyperandrogenism in men are often negligible. Hyperandrogenism in females is typically diagnosed in late adolescence with a medical evaluation. The medical evaluation tends to consist of a pelvic exam, observation of external symptoms, and a blood test measuring androgen levels.[11] * Hirsutism \- male-pattern hair growth * Alopecia \- balding * Masculine appearance * Hidradenitis suppurativa * Polycystic ovarian syndrome * Oligomenorrhea \- menstrual irregularities * Acne * Obesity * Infertility * Deepening of voice * Oily skin * Seborrhea \- skin inflammation * Libido \- increased sex drive * Type 2 diabetes ### Women[edit] Hyperandrogenism, especially high levels of testosterone, can cause serious adverse effects on women's bodies if left untreated. High testosterone levels have been seen to be associated with obesity, hypertension, amenorrhea (cessation of menstrual cycles), and ovulatory dysfunction, which can lead to infertility. The more prominent signs of hyperandrogenism are hirsutism (unwanted growth of hair especially in the abdominal region and places on the back), acne after adolescence, deepening of voice, and alopecia (balding).[12] Hyperandrogenism has also been seen to cause individuals to have a high tolerance to insulin, which can lead to type two diabetes, and dyslipidemia, such as high cholesterol. These effects have also been seen to have a large psychological impact on the individual, sometimes leading to societal anxiety and depression, especially in adolescent girls and young women. Paired with obesity and hirsutism, it can cause the individual to have low self-esteem, and a poor view of oneself.[11][13] ### Men[edit] Even though hyperandrogenism is not common in men, there have been studies done to look at the effects of high levels of testosterone in males. A study has shown that even though many of the male participants did not have behavior changes[clarification needed] due to the increased levels of testosterone, there were cases where the participants had instances of uncharacteristic aggression. High levels of testosterone in males have not been seen to have a direct impact on their personality, but within those studies, there have been cases of sudden aggression within the male participants.[14] ## Causes[edit] While hyperandrogenism in women is caused by external factors, it can also appear from natural causes. ### Polycystic ovary syndrome[edit] Ultrasound of a polycystic ovary Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by an excess of androgens produced by the ovaries. It is estimated that approximately 90 percent of women with PCOS demonstrate hypersecretion of these hormones.[15] A concrete cause for this condition is currently unknown. Speculations include genetic predisposition, although the gene or genes in particular have yet to be identified.[16] Evidence suggests that the condition may have a hereditary basis. Other possible causes include the effects from an increase in insulin production. Insulin itself has been observed capable of inducing excess testosterone levels in the ovaries.[17] Elevated insulin concentration in the body leads to lower production of sex hormone binding globulin (SHBG), a regulatory glycoprotein that suppresses the function of androgens.[18] High blood levels of insulin also work in conjunction with ovarian sensitivity to insulin to cause hyperandrogenemia, the primary symptom of PCOS. Obese individuals may be more biologically inclined to display PCOS due to markedly higher amounts of insulin in their bodies. This hormonal imbalance can lead to chronic anovulation, in which the ovaries experience difficulty releasing mature eggs. These cases of ovulatory dysfunction are linked to infertility and to menstrual disturbances.[15][19] ### Hyperthecosis and hyperinsulinemia[edit] Hyperthecosis occurs when the cells of the ovarian stroma transition from interstitial cells, which are cells located in between other cells, into luteinized theca cells. Theca cells are located in the ovarian follicles and become luteinized when the ovarian follicle breaks and a new corpus luteum is formed. The dispersal of luteinized theca cells throughout the ovarian stroma, in contrast to PCOS where the luteinized theca cells are only around cystic follicles, causes women with hyperthecosis to have higher testosterone levels and male-attributed characteristics (virilization) than women with PCOS. Excess levels of insulin in the blood, known as hyperinsulinemia, is also a characteristic of hyperthecosis.[20] Hyperthecosis is mostly seen in postmenopausal women and is linked to acne, hirsutism, growth of the clitoris, baldness, and voice deepening.[21] Low levels of insulin can also lead to hyperandrogenism. When the body's insulin levels drop too low, it can force itself to produce too much in an effort to make up for the loss. The result of such an overproduction is a disorder called hyperinsulinemia. An effect of hyperinsulinemia is the body's increased production of androgens in the ovaries.[22] This is all part of HAIR-AN syndrome, a multisystem disorder that involves increased insulin levels that prompt increased androgen levels.[23][24] ### Cushing’s syndrome[edit] Cushing syndrome develops due to long-term exposure to the hormone cortisol. Cushing's syndrome can either be exogenous or endogenous, depending on whether it is caused by an external or internal source, respectively. The intake of glucocorticoids, which are a type of steroid hormone, is a common cause for the development of exogenous Cushing's syndrome. Endogenous Cushing's syndrome can occur when the body produces excessive amounts of cortisol. This occurs when the hypothalamus of the brain transmits corticotropin-releasing hormone (CRH) to the pituitary gland, which in turn secretes adrenocorticotropin hormone (ACTH). ACTH then causes the adrenal glands to release cortisol into the blood. Signs of Cushing's syndrome include muscle weakness, easy bruising, weight gain, male-pattern hair growth (hirsutism), colored stretch marks, and an excessively reddish complexion in the face.[25] Cushing's syndrome has been shown to cause androgen excess, which directly links it to the signs and symptoms seen in hyperandrogenism.[21] ### Congenital adrenal hyperplasia[edit] Congenital adrenal hyperplasia describes a group of autosomal recessive disorders that cause a lack of an enzyme needed for producing cortisol and/or aldosterone, both of which are steroid hormones. Most cases of CAH are due to 21-hydroxylase deficiencies, an enzyme used by the body to produce cortisol and aldosterone. In females, CAH causes uncertainty in the genitals at birth and later on in adolescence excessive pubic hair, enlargement of the clitoris, hirsutism and although it causes rapid growth in childhood adult women with CAH are shorter than average due to early puberty and closure of growth plates. Symptoms in males include early showings of pubic hair, enlargement of the penis, and rapid body and skeletal growth.[26] ### Tumors[edit] #### Adrenocortical carcinoma and tumors[edit] A highly uncommon disease with incidence of 1–2 per million annually. This disease causes cancerous cells to form in the cortex of one or both of the adrenal glands. Adrenocortical tumors produce an additional number of hormones, often leading patients with steroid hormone-producing tumors to develop Cushing's syndrome, Conn syndrome and Hyperandrogenism.[27][citation needed] #### Adenoma of the adrenal gland[edit] Adrenal Adenomas are benign tumors on the adrenal gland. In most cases the tumors display no symptoms and require no treatment. In rare cases, however, some Adrenal Adenomas may become activated, in that they begin to produce hormones in much larger quantities than what adrenal glands tend to produce leading to a number of health complications including Primary aldosteronism and Hyperandrogenism.[28] #### Arrhenoblastoma[edit] An arrhenoblastoma is an uncommon tumor of the ovary. It is often composed of sterol cells, leydig cells or some combination of the two. The tumor can produce male or female hormones in the patient and may cause masculinization. In a prepubescent child, a tumor may cause precocious puberty. Malignant Arrhenoblastoma accounts for 30% of all cases of Arrhenoblastoma, the other 70% being largely benign and curable with surgery.[29] #### Hilar cell tumor[edit] An ovarian, Androgen producing tumor afflicting older women in most cases and often leading to the development of virilization. This tumor tends to occur around the region of the ovary where the blood vessels enter the organ otherwise known as the hilum. This type of tumor tends to be rather small in size and in most cases could be entirely removed and its symptoms reversed through surgery.[30] #### Krukenberg tumor[edit] A quickly developing malignant tumor that is normally found in one of or both ovaries. The tumor is caused by the transcoelomic spread. It primarily grows in the stomach and intestinal regions.[31] ### Menopause[edit] One such cause is the end of ovulation and the beginning of menopause. When the body transitions from ovulation to menopause, it stops releasing estrogen at faster rate than it stops releasing androgens. In some cases, estrogen levels can drop enough that there are substantially higher androgen levels leading to hyperandrogenism. A decrease in sex hormone levels while the free androgen index increases helps to aid this process, as well.[32] ### Drug-induced[edit] Symptoms generally considered hyperandrogenic can also manifest as results of consuming certain drugs. This can happen according to one of five major mechanisms, namely the direct introduction of androgens to the body, the binding of the drug to androgen receptors and subsequent participation in androgenic action (as is the case with anabolic-androgenic steroids), the reduction of sex hormone-binding globulin plasma concentration that leads to a resulting increase in free testosterone, the interference with and alteration of the hypothalamic–pituitary–ovarian (HPO) axis, or the increase in release of adrenal androgens.[33] ### Heredity[edit] Because hyperandrogenism can appear as a symptom of numerous different genetic and medical conditions, it is difficult to make a general statement on whether hyperandrogenic symptoms can be passed from parent to offspring. However, a collection of the conditions with hyperandrogenic symptoms, including polycystic ovary syndrome, have been observed as hereditary in certain cases. One potential cause of polycystic ovary syndrome is maternal hyperandrogenism, where the hormonal irregularities of the mother can affect the development of the child during gestation, resulting in the passing of polycystic ovary syndrome from mother to child.[34] ## Diagnosis[edit] Female patients may show symptoms of hyperandrogenism in their early life, but physicians become more concerned when the patient is in her late teens or older.[11] Hyperandrogenism is most often diagnosed by checking for signs of hirsutism according to a standardized method that scores the range of excess hair growth.[10][11] Checking medical history and a physical examination of symptoms are used for an initial diagnosis.[11] Patient history assessed includes age at thelarche, adrenarche, and menarche; patterns of menstruation; obesity; reproductive history; and the start and advancement of hyperandrogenism symptoms.[11] Patterns of menstruation are examined since irregular patterns may appear with hirsutism.[10] Family history is also assessed for occurrences of hyperandrogenism symptoms or obesity in other family members.[11] A laboratory test can also be done on the patient to evaluate levels of FSH, LH, DHEAS, prolactin, 17OHP, and total and free testosterone in the patient's blood.[11] Abnormally high levels of any of these hormones help in diagnosing hyperandrogenism.[11] ## Prevention[edit] Since risk factors are not known and vary among individuals with hyperandrogenism, there is no sure method to prevent this medical condition.[35] Therefore, more longterm studies are needed first to find a cause for the condition before being able to find a sufficient method of prevention.[35] However, there are a few things that can help avoid long-term medical issues related to hyperandrogenism like PCOS. Getting checked by a medical professional for hyperandrogenism; especially if one has a family history of the condition, irregular periods, or diabetes; can be beneficial.[36] Watching your weight and diet is also important in decreasing your chances, especially in obese females, since continued exercise and maintaining a healthy diet leads to an improved menstrual cycle as well as to decreased insulin levels and androgen concentrations.[35] ## Treatment[edit] Treatment of hyperandrogenism varies with the underlying condition that causes it. As a hormonal symptom of polycystic ovary syndrome, menopause, and other endocrine disorders, it is primarily treated as a symptom of these disorders. Systemically, it is treated with antiandrogens such as cyproterone acetate, flutamide and spironolactone to control the androgen levels in the patient's body. For hyperandrogenism caused by late onset congenital adrenal hyperplasia (LOCAH), treatment is primarily focused on providing the patient with glucocorticoids to combat the low cortisol production and the corresponding increase in androgens caused by the swelling of the Adrenal Glands.[37][38] Oestrogen-based oral contraceptives are used to treat both CAH and PCOS caused hyperandrogenism. These hormonal treatments have been found to reduce the androgen excess and suppress adrenal androgen production and cause a significant decrease in hirsutism.[39][40] Hyperandrogenism is often managed symptomatically. Hirsutism and acne both respond well to the hormonal treatments described above, with 60-100% reporting an improvement in hirsutism.[39] Androgenic alopecia however, does not show a significant improvement with hormonal treatments and requires other treatments, such as hair transplantation.[41] ## Society and culture[edit] Because androgen excess is manifested in noticeable physical features (ex. hirsutism), a certain social stigma is associated with it. ### Sports[edit] Main article: World Athletics Female Eligibility Regulations Caster Semenya, a genetically XY female athlete with 5-alpha reductase deficiency. Following the case of South African athlete Caster Semenya, the International Association of Athletics Federations (IAAF) introduced its hyperandrogenism regulations, which restricted women with high testosterone levels, whether through hyperandrogenism, or having testes and a DSD. These regulations replaced the earlier sex verification rules. Eventually, following a series of legal challenges, the current set of regulations were released on 1 May 2019, now called the Eligibility Regulations for the Female Classification (Athletes with differences of sex development).[42] These regulations only apply to athletes with XY DSDs and testes,[43] and no longer include hyperandrogenism from causes such as PCOS. ### Social definition[edit] Cultural variation can define hyperandrogenism socially—aside from clinical and chemical definitions—to make some hair growth unacceptable even if it is considered clinically normal based on metrics like the Ferriman-Gallwey score. For example, only pubic and axillary hair in North American women is tolerated, while other androgen-dependent hair such as growth on the upper lip, over the linea alba, over the thighs, and any periareolar hair is not.[44] ### Organizations[edit] Professional organizations like the Androgen Excess and PCOS Society exist to promote the research, treatment, diagnosis, and prevention of such disorders along with educating the public and scientific community about them.[45] ## See also[edit] * Hypoandrogenism * Hypergonadism * Hypergonadotropic hypergonadism * Hypogonadism * Hyperestrogenism * Hypoestrogenism * Androgen-dependent condition ## References[edit] 1. ^ a b c d e f g h i Peigné, M; Villers-Capelle, A; Robin, G; Dewailly, D (November 2013). "[Hyperandrogenism in women]". Presse Médicale. 42 (11): 1487–99. doi:10.1016/j.lpm.2013.07.016. PMID 24184282. 2. ^ a b c d Curtis, Michele; Antoniewicz, Leah; Linares, Silvia T. (2014). Glass' Office Gynecology. Lippincott Williams & Wilkins. p. 39. ISBN 9781608318209. 3. ^ a b c Catteau-Jonard, S; Cortet-Rudelli, C; Richard-Proust, C; Dewailly, D (2012). "Hyperandrogenism in adolescent girls". Endocrine Development. 22: 181–93. doi:10.1159/000326688. ISBN 978-3-8055-9336-6. PMID 22846529. 4. ^ a b c d e f g Carlson, Karen J.; Eisenstat, Stephanie A. (2004). The New Harvard Guide to Women's Health. Harvard University Press. p. 286. ISBN 9780674012820. 5. ^ Banker, Manish (2019). Nova IVI Textbook of Infertility & Assisted Reproductive Technology. JP Medical Ltd. p. 237. ISBN 9789388958844. 6. ^ Pathobiology of Human Disease: A Dynamic Encyclopedia of Disease Mechanisms. Elsevier. 2014. p. 1385. ISBN 9780123864574. 7. ^ https://www.olympic.org/news/ioc-addresses-eligibility-of-female-athletes-with-hyperandrogenism 8. ^ https://www.washingtonpost.com/sports/2019/05/01/what-are-issues-behind-cas-ruling-caster-semenya-case/ 9. ^ https://economictimes.indiatimes.com/magazines/panache/whats-with-the-gender-inequality-dutee-chand-talks-about-the-tests-female-athletes-face-before-competing/articleshow/69851149.cms 10. ^ a b c Yildiz, Bulent O. (June 2006). "Diagnosis of hyperandrogenism: clinical criteria". Best Practice & Research Clinical Endocrinology & Metabolism. 20 (2): 167–176. doi:10.1016/j.beem.2006.02.004. ISSN 1521-690X. PMID 16772149. 11. ^ a b c d e f g h i Goodman, Neil (March 2001). "American association of clinical endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of hyperandrogenic disorders". Endocrine Practice. 7 (2): 121. PMID 12940239. 12. ^ Simon, James (22 June 2015). "Androgen". Health Women. National Women's Health Resource Center. Retrieved 14 November 2016. 13. ^ Brettenthaler, Nora; De Geyter, Christian; R. Huber, Peter; Keller, Ulrich (21 April 2004). "Effect of the Insulin Sensitizer Pioglitazone on Insulin Resistance, Hyperandrogenism, and Ovulatory Dysfunction in Women with Polycystic Ovary Syndrome". The Journal of Clinical Endocrinology & Metabolism (published 28 April 2011). 89 (8): 3835–3840. doi:10.1210/jc.2003-031737. PMID 15292314. 14. ^ G. Pope Jr., Harrison; M. Kouri, Elena; I.Hudson, James (5 March 1999). "Effects of Supraphysiologic Doses of Testosterone on Mood and Aggression in Normal Men". Archives of General Psychiatry. 57 (2): 133–40, discussion 155–6. doi:10.1001/archpsyc.57.2.133. PMID 10665615. 15. ^ a b Franks, Stephen. "Polycystic Ovary Syndrome — NEJM." New England Journal of Medicine. N Engl J Med, 28 September 1995. Web. 14 November 2016. 16. ^ "Polycystic Ovary Syndrome (PCOS)." Causes. Mayo Clinic, n.d. Web. 9 November 2016. 17. ^ "Defining PCOS." - The University of Chicago Medicine. The University of Chicago Medical Center, n.d. Web. 10 November 2016. 18. ^ Hammond GL, Bocchinfuso WP (1996). "Sex hormone-binding globulin: gene organization and structure/function analyses". Hormone Research. 45 (3–5): 197–201. doi:10.1159/000184787. PMID 8964583. 19. ^ Burd, Irina, David Zieve, and Isla Ogilvie. "Polycystic Ovary Syndrome: MedlinePlus Medical Encyclopedia." Polycystic Ovary Syndrome: MedlinePlus Medical Encyclopedia. A.D.A.M Inc., n.d. Web. 9 November 2016. 20. ^ Pasquali, Renato (April 2011). "Research in Polycystic Ovary Syndrome Today and Tomorrow". Medscape. Blackwell Publishing. Retrieved 14 November 2016. 21. ^ a b Atmaca, Murat (16 December 2014). "An Interesting Cause of Hyperandrogenemic Hirsutism". Case Reports in Endocrinology. 2014: 987272. doi:10.1155/2014/987272. PMC 4280803. PMID 25580312. 22. ^ Barbieri; Hornstein MD (1988). "Hyperinsulinemia and Ovarian Hyperandrogenism. Cause and Effect". Endocrinology and Metabolism Clinics of North America. 17 (4): 685–703. doi:10.1016/S0889-8529(18)30405-5. PMID 3058472. 23. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. 24. ^ Somani N, Harrison S, Bergfeld WF (2008). "The clinical evaluation of hirsutism". Dermatol Ther. 21 (5): 376–91. doi:10.1111/j.1529-8019.2008.00219.x. PMID 18844715. S2CID 34029116. 25. ^ "Cushing's Syndrome". National Institute of Diabetes and Digestive and Kidney Diseases. April 2012. Retrieved 14 November 2016. 26. ^ Wilson, Thomas (23 June 2016). "Congenital Adrenal Hyperplasia". Medscape. Retrieved 14 November 2016. 27. ^ "Adrenocortical Carcinoma." National Cancer Institute. N.p., n.d. Web. 10 November 2016. 28. ^ "Adenoma of the Adrenal Gland \| Genetic and Rare Diseases Information Center(GARD) – an NCATS Program." U.S National Library of Medicine. U.S. National Library of Medicine, n.d. Web. 10 November 2016. 29. ^ Martin, Elizabeth. Arrhenoblastoma N. Arrhenoblastoma. n.p.: Oxford University Press, 2015. Oxford Reference. Web. 10 November 2016 30. ^ Martin, Elizabeth. "hilar cell tumour." Concise Medical Dictionary. : Oxford University Press, 2015. Oxford Reference. 2015. Date Accessed 10 November 2016 31. ^ Uyeturk, Ummugul, Serife Hulya Arslan, Oznur Bal, Ulku Yalcintas Arslan, and Omur Berna Cakmak Oksuzoglu. "Isolated Ovarian Metastasis of Gastric Cancer: Krukenberg Tumor." Contemporary Oncology. Termedia Publishing House, 19 December 2013. Web. 10 November 2016. 32. ^ "R. H. Fogle, F. Z. Stanczyk, X. Zhang, and R. J. Paulson, "Ovarian androgen production in postmenopausal women"". Journal of Clinical Endocrinology and Metabolism. 92 (8, pp. 3040– 3043, 2007). 33. ^ Neraud, Barbara; Dewailly, Didier. Contemporary Endocrinology: Androgen Excess Disorders in Women: Polycystic Ovary Syndrome and Other Disorders, Second Edition. Edited by: R. Azziz et al. © Humana Press Inc., Totowa, NJ. 34. ^ Puttabyatappa, Muraly; Cardoso, Rodolfo C.; Padmanabhan, Vasantha (5 November 2016). "Puttabyatappa Muraly, Cardoso Rodolfo C., Padmanabhan Vasantha. In Special issue: Impact of maternal metabolism on newborn health". Molecular and Cellular Endocrinology. 435: 29–39. doi:10.1016/j.mce.2015.11.030. PMC 4884168. PMID 26639019. 35. ^ a b c Apter D (1998). "How Possible Is The Prevention Of Polycystic Ovary Syndrome Development In Adolescent Patients With Early Onset Of Hyperandrogenism". Journal of Endocrinological Investigation. 21 (9): 613–617. doi:10.1007/bf03350786. PMID 9856415. S2CID 24263988. 36. ^ Nader S (2013). "Hyperandrogenism during puberty in the development of polycystic ovary syndrome". Fertility and Sterility (Review). 100 (1): 39–42. doi:10.1016/j.fertnstert.2013.03.013. PMID 23642453. 37. ^ Hughes I. A. (1988). "Management of Congenital Adrenal Hyperplasia". Archives of Disease in Childhood. 63 (11): 1399–1404. doi:10.1136/adc.63.11.1399. PMC 1779155. PMID 3060026. 38. ^ Merke D., Bornstein S. R. (2005). "Congenital adrenal hyperplasia". Lancet. 365 (9477): 2125–2136. doi:10.1016/S0140-6736(05)66736-0. PMID 15964450. S2CID 40860427. 39. ^ a b Burkman R.T. Jr (1995). "The Role of Oral Contraceptives in the Treatment of Hyperandrogenic Disorders". Am J Med. 98 (1A): 130S–136S. doi:10.1016/s0002-9343(99)80071-0. PMID 7825633. 40. ^ George Mastorakos; Carolina Koliopoulos; George Creatsas (2002). "Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives". Fertility and Sterility. 77 (5): 919–927. doi:10.1016/s0015-0282(02)02993-x. PMID 12009344. 41. ^ Sinclair R, Wewerinke M, Jolley D (March 2005). "Treatment of female pattern hair loss with oral antiandrogens". Br J Dermatol. 152 (3): 466–73. doi:10.1111/j.1365-2133.2005.06218.x. PMID 15787815. S2CID 26089277. 42. ^ https://www.iaaf.org/download/download?filename=fd2923ad-992f-4e43-9a70-78789d390113.pdf&urlslug=IAAF%20Eligibility%20Regulations%20for%20the%20Female%20Classification%20%5BAthletes%20with%20Differences%20of%20Sex%20Development%5D%20in%20force%20as%20from%208%20May%202019 43. ^ https://www.worldathletics.org/news/press-releases/questions-answers-iaaf-female-eligibility-reg 44. ^ Krishna; R, Usha (1 January 2000). "9. Hyperandrogenism in Adolescence". Adolescent Gynecology (pb). Orient Blackswan. p. 119. ISBN 9788125017936. 45. ^ wang, stephanie qian. "Androgen Excess and PCOS Society". www.ae-society.org. Retrieved 10 November 2016. ## External links[edit] Classification D * ICD-10: E25, E28.1 * ICD-9-CM: 255.2 * MeSH: D017588 External resources * MedlinePlus: 001165 * eMedicine: article/273153 * 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	Hyperandrogenism	c0206081	7,451	wikipedia	https://en.wikipedia.org/wiki/Hyperandrogenism	2021-01-18T18:56:17	{"mesh": ["D017588"], "umls": ["C0206081"], "icd-10": ["E28.1"], "wikidata": ["Q10529545"]}
## Clinical Features Efe Pygmies from the Ituri forest of northeast Zaire have the shortest mean adult stature of any population on earth, with a mean adult male height of 4 feet, 8 inches, and a mean adult female height of 4 feet, 5 inches (Diamond, 1991). Biochemical Features Rimoin et al. (1969) found that African Pygmies failed to respond to exogenous human growth hormone (GH; 139250) in the presence of normal serum levels of growth hormone and somatomedin, or insulin-like growth factor-1 (IGF1; 147440), suggesting a defect in end-organ responsiveness to one or both hormones. Merimee et al. (1981) demonstrated isolated deficiency of IGF1 in Pygmies of the Central African Republic, and proposed a genetically determined basis of growth deficiency in this population. However, protein deficiency may also have been responsible for the low IGF1 levels (Underwood et al., 1982). In African Pygmies in Zaire, Merimee et al. (1987) found that prepubertal Pygmy children and controls did not differ in linear growth or in serum concentrations of IGF1 and IGF2 (147470). However, they found that adolescent Pygmy boys and girls had one-third the mean serum concentration of IGF1 of control adolescents who were similar in age and Tanner stage of development. IGF2 and testosterone levels were normal in all groups. Merimee et al. (1987) postulated that short stature in Pygmies was due to the absence of accelerated growth during puberty and that IGF1 was a principal factor responsible for normal pubertal growth. In cultures of B lymphocytes derived from Pygmies, Merimee et al. (1989) found a significant decrease in IGF1 secretion when stimulated by GH compared to normal control cells (4.24 ng/ml compared to 12.3 ng/ml in controls), although the cultures had similar cell density. In a longitudinal growth study comparing Efe Pygmy children and children of non-Pygmy rural African farmers of known age from birth to age 5 years, Bailey (1991) found that suppression of Pygmy growth occurs from birth, not solely at puberty. Bailey (1991) emphasized that previous studies of Pygmy growth were of individuals of estimated, not known, age. In 5 of 7 Pygmies, Geffner et al. (1995) found a decrease in IGF1 levels compared to controls. In vitro studies on T cells isolated from the Pygmies showed no colony growth in response to IGF1 or to growth hormone compared to controls. There was no difference in growth response of the cells to insulin. By in vitro analysis of 6 cell lines from Pygmies, Hattori et al. (1996) determined that the Pygmy-derived cells showed markedly decreased cell surface expression of IGF1 receptors (IGF1R; 147370) compared to controls, although the affinity of IGF1 binding to the receptor was similar in the 2 cell lines. There was a substantially decreased level of IGF1 receptor mRNA (2 to 13% of control) in the Pygmy cells, with a normal mRNA half-life. Moreover, the IGF1 receptors in the Pygmy cells were not autophosphorylated and did not transmit an intracellular signal in response to physiologic levels of IGF1, indicating a functional defect. Hattori et al. (1996) concluded that the short stature of African Pygmies is related to IGF1 receptor insensitivity, and suggested that human stature in general may be genetically regulated via control of expression of the IGF1R gene. Molecular Genetics Bowcock and Sartorelli (1990) found no difference in the distribution of IGF1 RFLPs in Pygmies versus non-Pygmy black Africans. There was also no correlation of IGF1 genotype with height in the Pygmies. Suspecting an abnormality in the transcriptional regulation of the IGF1 gene in Pygmies, Bowcock and Sartorelli (1990) performed direct sequencing of a DNA region 330-bp upstream of the IGF1 initiation site; no mutations were identified in that region. Hattori et al. (1996) detected no pathogenic mutations by sequence analysis of IGF1R cDNA from transformed T lymphocyte lines derived from Pygmies. In 2 non-Pygmy patients with short stature and IGF1 resistance (see 270450) due to decreased number or function of cell surface IGF1 receptors, Abuzzahab et al. (2003) identified mutations in the IGF1R gene (147370.0001-147370.0003). Abuzzahab et al. (2003) noted that the finding of a reduction in the number of IGF1 receptors in Pygmies was based entirely on in vitro studies of transformed lymphocytes. Animal Model The mouse mutation called pygmy (pg), a recessive that maps to mouse chromosome 10, has only similarity of name to the human condition. In pg mice, Xiang et al. (1990) identified a mutation in the pg gene (HMGA2; 600698). INHERITANCE \- Autosomal recessive \- Multifactorial GROWTH Height \- Short stature from birth \- Average adult male height 142 cm (4'8") \- Average adult female height 135 (4'5") ENDOCRINE FEATURES \- No growth response to exogenous growth hormone (GH, 139250 ) LABORATORY ABNORMALITIES \- Decreased serum insulin-like growth factor-1 (IGF1, 147440 ) \- Decreased secretion of IGF1 in response to GH administration \- Decreased number of IGF1 receptors (IGF1R, 147370 ) on cell surface \- Abnormal IGFR1 function MISCELLANEOUS \- The most studied group is Efe Pygmies from Ituri forest in northeast Zaire ▲ 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	PYGMY	c1849524	7,452	omim	https://www.omim.org/entry/265850	2019-09-22T16:22:58	{"omim": ["265850"], "synonyms": ["Alternative titles", "PYGMY, AFRICAN"]}
Klumpke's paralysis Other namesKlumpke's palsy, Dejerine–Klumpke palsy Brachial plexus. Klumpke paralysis primarily affects C8 and T1. SpecialtyNeurology Klumpke's paralysis is a variety of partial palsy of the lower roots of the brachial plexus.[1][2] The brachial plexus is a network of spinal nerves that originates in the back of the neck, extends through the axilla (armpit), and gives rise to nerves to the upper limb.[3][4][5][6] The paralytic condition is named after Augusta Déjerine-Klumpke.[7][8][9] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Symptoms include intrinsic minus hand deformity,[10] paralysis of intrinsic hand muscles, and C8/T1 Dermatome distribution numbness. Involvement of T1 may result in Horner's syndrome, with ptosis, and miosis. Weakness or lack of ability to use specific muscles of the shoulder or arm.[1][11][12] It can be contrasted to Erb-Duchenne's palsy, which affects C5 and C6. ## Cause[edit] Klumpke's paralysis is a form of paralysis involving the muscles of the forearm and hand, resulting from a brachial plexus injury in which the eighth cervical (C8) and first thoracic (T1) nerves are injured either before or after they have joined to form the lower trunk. The subsequent paralysis affects, principally, the intrinsic muscles of the hand (notably the interossei, thenar and hypothenar muscles)[13] and the flexors of the wrist and fingers (notably flexor carpi ulnaris and ulnar half of the flexor digitorum profundus).[1][6][13][14] Forearm pronators and wrist flexors may be involved, as may dilators of the iris and elevators of the eyelid (both of which may be seen in the case of associated Horner's syndrome). The classic presentation of Klumpke's palsy is the “claw hand” where the forearm is supinated, the wrist extended and the fingers flexed. If Horner syndrome is present, there is miosis (constriction of the pupils) in the affected eye.[citation needed] The injury can result from difficulties in childbirth. The most common aetiological mechanism is caused by a traumatic vaginal delivery. The risk is greater when the mother is small or when the infant is of large weight. Risk of injury to the lower brachial plexus results from traction on an abducted arm, as with an infant being pulled from the birth canal by an extended arm above the head or with someone catching themselves by a branch as they fall from a tree. Lower brachial plexus injuries should be distinguished from upper brachial plexus injuries, which can also result from birth trauma but give a different syndrome of weakness known as Erb's palsy. Other trauma, such as motorcycle accidents, that have similar spinal cord injuries to C8 and T1, also show the same symptoms of Klumpke's paralysis.[citation needed] ## Diagnosis[edit] Electromyography and nerve conduction velocity testing can help to diagnose the location and severity of the lesion. Otherwise, the diagnosis is one made clinically after a thorough neurologic exam.[citation needed] ## Treatment[edit] Treatment effectiveness varies depending on the initial severity of the injury. Physiotherapy is used to increase strength of muscle and improve muscle functions. Electrical modalities such as electric nerve stimulation can also be used.[citation needed] Occupational therapy to provide exercises and coping mechanisms to improve the patient's ability to perform activities of daily living. Goals of therapy are to improve tactile sensation, proprioception, and range of motion.[citation needed] Acute treatment of a severe injury will involve repositioning and splinting or casting of the extremity[citation needed]. ## Epidemiology[edit] Klumpke Palsy is listed as a 'rare disease' by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH). This means that Klumpke palsy, or a subtype of Klumpke palsy, affects fewer than 200,000 people in the US population.[citation needed] ## See also[edit] * Dystocia * Erb's palsy ## References[edit] 1. ^ a b c Warwick, R.; Williams, P.L, eds. (1973). Gray's Anatomy (35th ed.). London: Longman. p.1046 2. ^ Shoja MM, Tubbs RS (August 2007). "Augusta Déjerine-Klumpke: the first female neuroanatomist". Clin Anat. 20 (6): 585–7. doi:10.1002/ca.20474. PMID 17330887. 3. ^ Warwick, R., & Williams, P.L. (1973). pp.1037-1047 4. ^ Tortora, G.J. & Anagnostakos, N.P. (1990). Principles of Anatomy and Physiology (6th ed.). New York: Harper & Row. ISBN 978-0-06-046694-7. pp.370-374 5. ^ Abrahams, P (2002). The Atlas of the Human Body: A Complete Guide to How the Body Works. Leicester, U.K.: Silverdale Books. ISBN 978-1-85605-699-1. pp.76-77 6. ^ a b Shenaq S.M., & Spiegel A.J. Hand, Brachial Plexus Surgery. eMedicine.com. URL: http://www.emedicine.com/plastic/topic450.htm. Accessed on: April 13, 2007. 7. ^ Ulgen BO, Brumblay H, Yang LJ, Doyle SM, Chung KC (August 2008). "Augusta Déjerine-Klumpke, M.D. (1859-1927): a historical perspective on Klumpke's palsy". Neurosurgery. 63 (2): 359–66, discussion 366–7. doi:10.1227/01.NEU.0000320420.25035.A7. PMID 18797367. 8. ^ synd/335 at Who Named It? 9. ^ A. Dejerine-Klumpke: Contribution à l’étude des paralysies radiculaires du plexus brachial. Paralysies radiculaires totales. Paralysies radiculaires inférieures. De la participation des filets sympathiques oculo-pupillaires dans ces paralysies. Revue de médecine 1885, 5: 591-616, 739-90. 10. ^ (Pendleton 942)Pendleton, Heidi McHugh. Pedretti's Occupational Therapy: Practice Skills for Physical Dysfunction, 6th Edition. C.V. Mosby, 052006. 11. ^ Huang YG, Chen L, Gu YD, Yu GR (May 2008). "Histopathological basis of Horner's syndrome in obstetric brachial plexus palsy differs from that in adult brachial plexus injury". Muscle Nerve. 37 (5): 632–7. doi:10.1002/mus.20960. PMID 18236458. 12. ^ Glanze, W.D.; Anderson, K.N.; Anderson, L.E, eds. (1990). Mosby's Medical, Nursing & Allied Health Dictionary (3rd ed.). St. Louis, Missouri: The C.V. Mosby Co. ISBN 978-0-8016-3227-3. pp.576, 667 13. ^ a b Page 512: Lower Radicular Syndrome (Klumpke Paralysis) in: Pedley, Timothy A.; Rowland, Lewis P.; Merritt, Hiram Houston (2010). Merritt's neurology. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-9186-1. 14. ^ Klumpke palsy. Stedman's Dictionary. URL: http://www.emedicine.com/asp/dictionary.asp?exact=Y&keyword=Klumpke+palsy Archived 2007-09-30 at the Wayback Machine. Accessed on: April 13, 2007. ## External links[edit] Classification D * ICD-10: P14.1 * ICD-9-CM: 767.6 * DiseasesDB: 7200 * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Klumpke paralysis	c0270898	7,453	wikipedia	https://en.wikipedia.org/wiki/Klumpke_paralysis	2021-01-18T19:06:45	{"gard": ["3123"], "mesh": ["D020516"], "umls": ["C0270898"], "icd-9": ["767.6"], "icd-10": ["P14.1"], "wikidata": ["Q2336817"]}
Cataract-hypertrichosis-intellectual disability syndrome is characterized by congenital cataract, generalized hypertrichosis and intellectual deficit. It has been described in two Egyptian sibs born to consanguineous parents. It is transmitted as an autosomal recessive trait. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Cataract-hypertrichosis-intellectual disability syndrome	c0796282	7,454	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1375	2021-01-23T19:01:03	{"mesh": ["C537959"], "omim": ["211770"], "umls": ["C0796282"], "icd-10": ["Q87.8"], "synonyms": ["CAHMR syndrome"]}
## Clinical Features Mondino and Brown (1976) described a family of Irish descent in which 5 persons in 4 generations showed markedly deficient lacrimation from infancy and punctate corneal epithelial erosions. Male-to-male transmission was observed. Hypoplasia of the lacrimal glands was suggested by pharmacologic tests and histopathology of the lacrimal gland. There were no associated ocular or adnexal abnormalities. Krueger (1954) described brother and sister with ptosis, distichiasis, conjunctivitis, keratitis, and alacrimia congenita. The father and another brother were said to have defective lacrimation. A nuclear defect was postulated for this disorder, which may be distinct from that reported by Mondino and Brown (1976). Hegab et al. (1991) described a Kuwaiti Arab father and son with severe hypolacrimation. Both showed little tear meniscus and incomplete tear film with blotchy staining of the cornea and punctate staining of the interpalpebral bulbar conjunctiva by fluorescein and Rose Bengal. Impression cytology of the temporal bulbar conjunctiva of the son revealed total absence of goblet cells with moderate enlargement of the epithelial cells. Alacrima occurs in anhidrotic ectodermal dysplasia (305100) and dysautonomia (223900) and in association with ocular and adnexal abnormalities. Inheritance The transmission pattern of alacrimia congenita in the family reported by Mondino and Brown (1976) suggested autosomal dominant inheritance. See 601549 for an autosomal recessive form of the disorder. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Hypoplastic lacrimal gland \- Atretic lacrimal puncta \- Alacrima - hypolacrimation \- Punctate corneal epithelial erosions \- Photophobia ▲ 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	ALACRIMA, CONGENITAL, AUTOSOMAL DOMINANT	c1863199	7,455	omim	https://www.omim.org/entry/103420	2019-09-22T15:41:19	{"mesh": ["C566307"], "omim": ["103420"], "orphanet": ["91416"], "synonyms": ["Alternative titles", "ALACRIMIA CONGENITA, AUTOSOMAL DOMINANT"]}
For other uses, see Red eye (disambiguation). This article may be too technical for most readers to understand. Please help improve it to make it understandable to non-experts, without removing the technical details. (April 2012) (Learn how and when to remove this template message) Red eye Subconjunctival hemorrhage causing red coloration as result of ruptured blood vessel in the eye. SpecialtyOphthalmology A red eye is an eye that appears red due to illness or injury. It is usually injection and prominence of the superficial blood vessels of the conjunctiva, which may be caused by disorders of these or adjacent structures. Conjunctivitis and subconjunctival hemorrhage are two of the less serious but more common causes. Management includes assessing whether emergency action (including referral) is needed, or whether treatment can be accomplished without additional resources. Slit lamp examination is invaluable in diagnosis but initial assessment can be performed using a careful history, testing vision (visual acuity), and carrying out a penlight examination. ## Contents * 1 Diagnosis * 1.1 Visual acuity * 1.2 Ciliary flush * 1.3 Corneal abnormalities * 1.4 Pupillary abnormalities * 1.5 Abnormal intraocular pressure * 1.6 Severe pain * 1.7 Differential diagnosis * 2 See also * 3 References * 4 External links ## Diagnosis[edit] hyphaema – showing blood filling the anterior chamber, causing a horizontal fluid level. Particular signs and symptoms may indicate that the cause is serious and requires immediate attention.[1] Six such signs are: * reduced visual acuity * ciliary flush (circumcorneal injection) * corneal abnormalities including edema or opacities ("corneal haze") * corneal staining * abnormal pupil size * abnormal intraocular pressure The most useful is a smaller pupil in the red eye than none red eye and sensitivity to bright lights.[2] ### Visual acuity[edit] A reduction in visual acuity in a 'red eye' is indicative of serious ocular disease,[3] such as keratitis, iridocyclitis, and glaucoma, and never occurs in simple conjunctivitis without accompanying corneal involvement. ### Ciliary flush[edit] Ciliary flush is usually present in eyes with corneal inflammation, iridocyclitis or acute glaucoma, though not simple conjunctivitis. A ciliary flush is a ring of red or violet spreading out from around the cornea of the eye. ### Corneal abnormalities[edit] The cornea is required to be transparent to transmit light to the retina. Because of injury, infection or inflammation, an area of opacity may develop which can be seen with a penlight or slit lamp. In rare instances, this opacity is congenital.[4] In some, there is a family history of corneal growth disorders which may be progressive with age. Much more commonly, misuse of contact lenses may be a precipitating factor. Whichever, it is always potentially serious and sometimes necessitates urgent treatment and corneal opacities are the fourth leading cause of blindness. Opacities may be keratic, that is, due to the deposition of inflammatory cells, hazy, usually from corneal edema, or they may be localized in the case of corneal ulcer or keratitis. Corneal epithelial disruptions may be detected with fluorescein staining of the eye, and careful observation with cobalt-blue light. Corneal epithelial disruptions would stain green, which represents some injury of the corneal epithelium. These types of disruptions may be due to corneal inflammations or physical trauma to the cornea, such as a foreign body. ### Pupillary abnormalities[edit] In an eye with iridocyclitis, (inflammation of both the iris and ciliary body), the involved pupil will be smaller than the uninvolved, due to reflex muscle spasm of the sphincter muscle of the iris. Generally, conjunctivitis does not affect the pupils. With acute angle-closure glaucoma, the pupil is generally fixed in mid-position, oval, and responds sluggishly to light, if at all. Shallow anterior chamber depth may indicate a predisposition to one form of glaucoma (narrow angle) but requires slit-lamp examination or other special techniques to determine it. In the presence of a "red eye", a shallow anterior chamber may indicate acute glaucoma, which requires immediate attention. ### Abnormal intraocular pressure[edit] Intraocular pressure should be measured as part of the routine eye examination. It is usually only elevated by iridocyclitis or acute-closure glaucoma, but not by relatively benign conditions. In iritis and traumatic perforating ocular injuries, the intraocular pressure is usually low. ### Severe pain[edit] Those with conjunctivitis may report mild irritation or scratchiness, but never extreme pain, which is an indicator of more serious disease such as keratitis, corneal ulceration, iridocyclitis, or acute glaucoma. ### Differential diagnosis[edit] Of the many causes, conjunctivitis is the most common.[1] Others include: Usually nonurgent * blepharitis[5] – a usually chronic inflammation of the eyelids with scaling, sometimes resolving spontaneously * subconjunctival hemorrhage[1] – a sometimes dramatic, but usually harmless, bleeding underneath the conjunctiva most often from spontaneous rupture of the small, fragile blood vessels, commonly from a cough or sneeze * inflamed pterygium[6] – a benign, triangular, horizontal growth of the conjunctiva, arising from the inner side, at the level of contact of the upper and lower eyelids, associated with exposure to sunlight, low humidity and dust. It may be more common in occupations such as farming and welding. * inflamed pinguecula[7] – a yellow-white deposit close to the junction between the cornea and sclera, on the conjunctiva. It is most prevalent in tropical climates with much UV exposure. Although harmless, it can occasionally become inflamed. * dry eye syndrome – caused by either decreased tear production or increased tear film evaporation which may lead to irritation and redness [8] acute glaucoma, angle closure type * airborne contaminants or irritants * tiredness * drug use including cannabis[9] * episcleritis[10] – most often a mild, inflammatory disorder of the 'white' of the eye unassociated with eye complications in contrast to scleritis, and responding to topical medications such as anti-inflammatory drops. Usually urgent * acute angle closure glaucoma[11] – implies injury to the optic nerve with the potential for irreversible vision loss which may be permanent unless treated quickly, as a result of increased pressure within the eyeball. Not all forms of glaucoma are acute, and not all are associated with increased 'intra-ocular' pressure. * injury * keratitis[11] – a potentially serious inflammation or injury to the cornea (window), often associated with significant pain, light intolerance, and deterioration in vision. Numerous causes include virus infection. Injury from contact lenses can lead to keratitis. eye with iritis showing ciliary flush * iritis[1] – together with the ciliary body and choroid, the iris makes up the uvea, part of the middle, pigmented, structures of the eye. Inflammation of this layer (uveitis) requires urgent control and is estimated to be responsible for 10% of blindness in the United States. * scleritis[12] – a serious inflammatory condition, often painful, that can result in permanent vision loss, and without an identifiable cause in half of those presenting with it. About 30–40% have an underlying systemic autoimmune condition. * tick-borne illnesses like Rocky Mountain spotted fever[13] – the eye is not primarily involved, but the presence of conjunctivitis, along with fever and rash, may help with the diagnosis in appropriate circumstances. ## See also[edit] * List of eye diseases and disorders * Ocular straylight ## References[edit] 1. ^ a b c d Cronau, H; Kankanala, RR; Mauger, T (Jan 15, 2010). "Diagnosis and management of red eye in primary care". American Family Physician. 81 (2): 137–44. PMID 20082509. 2. ^ Narayana, S; McGee, S (November 2015). "Bedside Diagnosis of the 'Red Eye': A Systematic Review". The American Journal of Medicine. 128 (11): 1220–1224.e1. doi:10.1016/j.amjmed.2015.06.026. PMID 26169885. 3. ^ Leibowitz HM (2000). "The red eye". N Engl J Med. 343 (5): 345–51. doi:10.1056/nejm200008033430507. PMID 10922425. 4. ^ Rezende RA, Uchoa UB, Uchoa R, Rapuano CJ, Laibson PR, Cohen EJ (2004). "Congenital corneal opacities in a cornea referral practice". Cornea. 23 (6): 565–70. doi:10.1097/01.ico.0000126317.90271.d8. PMID 15256994. 5. ^ Jackson WB (April 2008). "Blepharitis: current strategies for diagnosis and management". Can J Ophthalmol. 43 (2): 170–79. doi:10.3129/i08-016. PMID 18347619. 6. ^ Bradley JC, Yang W, Bradley RH, Reid TW, Schwab IR (July 2010). "The science of pterygia". Br J Ophthalmol. 94 (7): 815–20. doi:10.1136/bjo.2008.151852. PMID 19515643. 7. ^ Sutphin, John, ed. 2007–2008 Basic and Clinical Science Course Section 8: External Disease and Cornea. American Academy Ophthalmology. p. 365. ISBN 1-56055-814-8. 8. ^ "Keratoconjunctivitis, Sicca". eMedicine. WebMD, Inc. January 27, 2010. Retrieved September 3, 2010. 9. ^ American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington DC: American Psychiatric Association; 2000. 10. ^ Jabs DA, Mudun A, Dunn JP, Marsh MJ (October 2000). "Episcleritis and scleritis: clinical features and treatment results". Am J Ophthalmol. 130 (4): 469–76. doi:10.1016/S0002-9394(00)00710-8. PMID 11024419. 11. ^ a b Dargin JM, Lowenstein RA (February 2008). "The painful eye". Emerg Med Clin North Am. 26 (1): 199–216. doi:10.1016/j.emc.2007.10.001. PMID 18249263. 12. ^ Sims, J (December 2012). "Scleritis: presentations, disease associations and management". Postgrad Med J. 88 (1046): 713–18. doi:10.1136/postgradmedj-2011-130282. PMID 22977282. 13. ^ https://www.cdc.gov/mmwr/pdf/rr/rr5504.pdf ## External links[edit] Wikimedia Commons has media related to Red eye (medicine). Classification D * ICD-10: H57.9 * ICD-9-CM: 379.93 * DiseasesDB: 18665 * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Red eye (medicine)	c0235267	7,456	wikipedia	https://en.wikipedia.org/wiki/Red_eye_(medicine)	2021-01-18T18:37:31	{"umls": ["C0235267"], "icd-9": ["379.93"], "icd-10": ["H57.9"], "wikidata": ["Q2610154"]}
A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability characterized by mild global developmental delay, intellectual disability or learning difficulties, behavioral problems (like autistic, hyperactive, or aggressive behavior), variable dysmorphic craniofacial features, and abnormalities of the fingers (brachydactyly, tapering fingers, prominent interphalangeal joints). Additional manifestations are highly variable and include recurrent infections and skeletal anomalies, among others. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome	c4310740	7,457	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=476126	2021-01-23T17:26:32	{"omim": ["617061"]}
Spinocerebellar ataxia 13 (SCA13) is a rare sub-type of spinocerebellar ataxias (SCA), a group of neurological diseases that causes degeneration of the brain and spinal cord. The age when symptoms begin and the type and severity of symptoms of SCA13 can be different from person to person even in the same family. In almost every case, the disease progresses very slowly and does not affect a person's life span. Symptoms most commonly begin in early childhood or later in midlife, but can range from infancy to 60. The childhood forms is often least progressive, but may also include mild to moderate learning problems, taking longer to learn to crawl, walk, or run (delayed development of motor skills), and seizures. The main symptoms of SCA13 include difficulties coordinating movements (ataxia), especially walking; abnormal eye movements (nystagmus); mild to moderate intellectual disability; and involuntary muscle jerks or twitches (myoclonic jerks). Other symptoms may include speech difficulty (dysarthria), difficulty eating (dysphagia), slowness of movements (bradykinesia), mild bladder problems, stiff and brisk deep tendon reflexes, and loss of the sense of vibration. SCA13 is caused by changes or mutations in the KCNC3 gene and it is inherited in an autosomal dominant manner. Since the symptoms of SCA13 can be similar to other types of SCA, genetic testing is used to confirm the diagnosis. In addition, unlike most of the other SCA's, a brain MRI will find loss of brain cells (neurons) in the part of the brain that helps control movement (cerebellum), but no noticeable loss of brain cells in the brain stem or the part of the brain important to higher levels of thinking (cerebral cortex). Treatment may include anti-seizure medications, special assistance in school, speech therapy and communication devices, and/or, later in the disease, aids to help with walking such as a canes and walkers. Normal activity and exercise are recommended. Maintaining a healthy weight may help keep a person walking without assistance longer. The use of alcohol may increase the severity of the uncoordinated movements (ataxia). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Spinocerebellar ataxia 13	c1854488	7,458	gard	https://rarediseases.info.nih.gov/diseases/9611/spinocerebellar-ataxia-13	2021-01-18T17:57:37	{"mesh": ["C537195"], "omim": ["605259"], "umls": ["C1854488"], "orphanet": ["98768"], "synonyms": ["SCA13", "Spinocerebellar ataxia type 13", "Cerebellar ataxia, autosomal dominant with mental retardation", "Autosomal dominant cerebellar ataxia with mental retardation"]}
A rare mycosis characterized by granulomatous inflammation primarily of the lung after inhalation of spores of Histoplasma capsulatum. The severity of clinical disease depends on the immune status of the individual and the size of the inoculum. In immunocompetent persons, the infection usually takes a self-limiting and asymptomatic or relatively mild, flu-like course. In immunocompromised patients, it can become progressive and disseminated, involving multiple organs and presenting with fever, pneumonia, hepatosplenomegaly, skin infiltrates, and endocarditis, among others. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Histoplasmosis	c0019655	7,459	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=390	2021-01-23T19:03:27	{"mesh": ["D006660"], "umls": ["C0019655", "C0153261"], "icd-10": ["B39.0", "B39.1", "B39.2", "B39.3", "B39.4", "B39.5", "B39.9"], "synonyms": ["Darling disease"]}
Chronic graft versus host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted donor cells attack the transplant recipient's body. Symptoms may include skin rash, mouth sores, dry eyes, liver inflammation, development of scar tissue in the skin and joints, and damage to the lungs. The exact cause of chronic GVHD is unknown. It likely results from a complex immune-mediated interaction between the donor and recipient cells. Chronic GVHD is treated with prednisone or other similar anti-inflammatory or immunosuppressive medications. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Chronic graft versus host disease	c0867389	7,460	gard	https://rarediseases.info.nih.gov/diseases/10964/chronic-graft-versus-host-disease	2021-01-18T18:01:18	{"synonyms": ["Chronic GVHD"]}
A number sign (#) is used with this entry because of evidence that intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (IDDFBA) is caused by heterozygous mutation in the FBXO11 gene (607871) on chromosome 2p16. Clinical Features Gregor et al. (2018) reported 18 unrelated patients, ranging in age from 1 to 29 years, with a syndromic intellectual developmental disorder associated with de novo heterozygous mutations in the FBXO11 gene. The patients were identified through collaborative efforts of research groups with exome sequencing data from patients with developmental delay. The severity and additional manifestations varied among the patients. All patients had delayed psychomotor development; intellectual disability ranged from mild to moderate in most patients, with only 4 patients being classified as having severe to profound deficits. Similarly, speech was usually delayed, and a few patients were nonverbal. Patients were able to attend either special or mainstream schools with additional support. Most patients had mildly delayed walking by 2 years, although a few did not achieve independent ambulation until age 5 or 6 years. Only 5 patients had seizures, and the severity ranged from epileptic encephalopathy to a single seizure. Additional common features included short stature, strabismus, hypermetropia, hypotonia, sleeping difficulties, and distal mild skeletal anomalies, such as small hands and feet, tapering fingers, clinodactyly, sandal gap, and flat feet. Most patients had a variety of behavioral abnormalities, such as poor social interaction, autistic features, stereotypic movements, hyperactivity, short attention span, and aggressive outbursts. Dysmorphic features were common, but there was not a distinctive gestalt. Some of these features included small head circumference, downslanting palpebral fissures, strabismus, deep-set eyes, hypertelorism, low-set ears, long philtrum, long eyelashes, narrow mouth, everted lower lip, and long face. Fritzen et al. (2018) reported 2 unrelated boys with IDDFBA. One patient was a 14-year-old boy with global developmental delay apparent during his first years of life. He started walking at the age of 20 months and spoke his first sentences at age 4. He had hyperactivity, impatience, difficulties in focusing his attention, and a hyperkinetic disorder. Dysmorphic features included small head circumference, upslanting palpebral fissures, small and posteriorly rotated ears, and small hands with short fingers and toes. The other patient was a 3-year-old boy with intrauterine growth retardation, hypotonia, delayed psychomotor development, strabismus, short stature, and restless behavior. He also had plagiocephaly, a high forehead, a high frontal hairline, deep-set eyes, a broad tip of the nose with small alae, long philtrum, tented upper lip vermilion, downturned corners of the mouth, and full lips. He had hypospadias and his toenails were small and deep-set. Jansen et al. (2019) reported 24 individuals with borderline to severely impaired intellectual development, 16 of whom also had behavioral problems, including autism spectrum disorder, attention-deficit/hyperactivity disorder, anxiety, and aggression. More than half of the patients had hypotonia and a few had epilepsy. Brain imaging was performed in 17 patients and enlarged ventricles were seen in 6 of them. Three patients had additional brain anomalies, including hypoplasia of the anterior pituitary, bilateral hippocampal malformations and borderline large cerebellum, Chiari 2 malformation, and syringomyelia. Obesity was observed in 7 individuals. The most consistent facial features were a high broad forehead, long palpebral fissures, and a thin upper lip with broad space between the paramedian peaks. Minor hand abnormalities (e.g., brachydactyly or tapering fingers) were seen in half of the patients, and 8 patients had hyperlaxity of the joints. Gastrointestinal problems such as vomiting and feeding difficulties were reported in 11 patients and vision problems were reported in 9 patients. Molecular Genetics In 18 unrelated patients with IDDFBA, Gregor et al. (2018) reported de novo heterozygous mutations in the FBXO11 gene (see, e.g., 607871.0001-607871.0005). The patients were identified through collaborative efforts of research groups with exome sequencing data from patients with developmental delay. There were 10 nonsense, splice site, or frameshift mutations (likely gene-disrupting, LGD) and 8 missense mutations at highly conserved residues distributed throughout the gene. Two additional patients carried larger deletions, including 1 patient with deletion of additional genes. None of the variants were present in the ExAC or gnomAD databases. Functional studies of the variants and studies of patient cells were not performed, but the presence of LGDs and molecular modeling of the missense mutations predicted that all would result in a loss of function and haploinsufficiency. One of the patients (patient 18) was originally reported by Martinez et al. (2017) as part of a large study of 92 patients with intellectual disability who underwent next-generation sequencing of a gene panel. Fritzen et al. (2018) reported 2 unrelated patients with IDDFBA associated with de novo heterozygous mutations in the FBXO11 gene (607871.0005 and 607871.0006). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Functional studies of the variants and studies of patient cells were not performed, but both were predicted to result in a loss of function. Jansen et al. (2019) identified 24 individuals with impaired intellectual development with behavior problems and dysmorphic features who had heterozygosity for de novo variant in or partial deletion of the FBXO11 gene. Among the 24 individuals, 22 variants were identified by next-generation sequencing, including 2 in-frame deletions, 11 missense variants, 1 canonical splice site variant, and 8 nonsense or frameshift variants leading to premature termination or degraded transcript. The remaining 2 variants were identified using chromosome microarray and consisted of partial deletions of FBXO11: a 21-kb intragenic deletion of exons 2-13 and a 170-kb deletion disrupting the 3-prime end of FBXO11 by deleting exons 12-24. Population Genetics Based on the number of patients identified with FBXO11 variants among a total cohort of over 14,000 patients studied, Jansen et al. (2019) estimated the frequency of a de novo disease-causing variant in FBXO11 in an unbiased cohort of individuals with intellectual disability and autism spectrum disorder to be in the range of 1:500-1:1000. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature (in some patients) HEAD & NECK Head \- Small head circumference \- Plagiocephaly \- High forehead Face \- Dysmorphic facial features, variable \- Long face \- Long philtrum Ears \- Low-set ears \- Small ears \- Posteriorly rotated ears Eyes \- Downslanting palpebral fissures \- Hypertelorism \- Deep-set eyes \- Strabismus \- Hypermetropia \- Long eyelashes Mouth \- Small mouth \- Everted lower lip \- Downturned corners of the mouth SKELETAL Hands \- Small hands \- Tapering fingers \- Clinodactyly Feet \- Small feet \- Sandal gap \- Flat feet MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Delayed walking (2 to 5 years) \- Speech delay \- Intellectual disability, variable, mild to severe \- Seizures (in some patients) Behavioral Psychiatric Manifestations \- Poor social interaction \- Autistic features \- Stereotypic movements \- Hyperactivity \- Short attention span \- Aggressive outbursts \- Hyperkinetic disorder MISCELLANEOUS \- Onset in infancy or first years of life \- Variable severity \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the F-box only protein 11 gene (FBXO11, 607871.0001 ) ▲ 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	INTELLECTUAL DEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND BEHAVIORAL ABNORMALITIES	None	7,461	omim	https://www.omim.org/entry/618089	2019-09-22T15:43:45	{"omim": ["618089"]}
Glycogen storage disease type VII (GSDVII) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in muscle cells. A lack of glycogen breakdown interferes with the function of muscle cells. There are four types of GSDVII. They are differentiated by their signs and symptoms and the age at which symptoms first appear. The classical form of GSDVII is the most common form. Its features usually appear in childhood. This form is characterized by muscle pain and cramps, often following moderate exercise; strenuous exercise can lead to nausea and vomiting. During exercise, muscle tissue can be abnormally broken down, releasing a protein called myoglobin. This protein is processed by the kidneys and released in the urine (myoglobinuria). If untreated, myoglobinuria can damage the kidneys and lead to kidney failure. Some people with the classical form of GSDVII develop high levels of a waste product called uric acid in the blood (hyperuricemia) because the damaged kidneys are unable to remove uric acid effectively. Affected individuals may also have elevated levels of a molecule called bilirubin in the blood that can cause yellowing of the skin and whites of the eyes (jaundice). Individuals with classical GSDVII often have elevated levels of an enzyme called creatine kinase in their blood. This finding is a common indicator of muscle disease. Infants with the severe infantile form of GSDVII have low muscle tone (hypotonia) at birth, which leads to muscle weakness (myopathy) that worsens over time. Affected infants have a weakened and enlarged heart (cardiomyopathy) and difficulty breathing normally. Individuals with this form of GSDVII usually do not survive past their first year of life. In the late-onset form of GSDVII, myopathy is typically the only feature. The muscle weakness appears in adulthood, although some individuals have difficulty with sustained exercise starting in childhood. The weakness generally affects the muscles closest to the center of the body (proximal muscles). The hemolytic form of GSDVII is characterized by hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, causing a shortage of red blood cells (anemia). People with the hemolytic form of GSDVII do not experience any signs or symptoms of muscle pain or weakness related to the disorder. ## Frequency GSDVII is thought to be a rare condition; more than 100 cases have been described in the scientific literature. ## Causes Mutations in the PFKM gene cause GSDVII. This gene provides instructions for making one piece (the PFKM subunit) of an enzyme called phosphofructokinase, which plays a role in the breakdown of glycogen. The phosphofructokinase enzyme is made up of four subunits and is found in a variety of tissues. Different combinations of subunits are found in different tissues. In muscles used for movement (skeletal muscles), the phosphofructokinase enzyme is composed solely of PFKM subunits. In skeletal muscle, the cells' main source of energy is stored as glycogen. Glycogen can be broken down rapidly into the simple sugar glucose when energy is needed, for instance to maintain normal blood sugar levels between meals or for energy during exercise. Phosphofructokinase is involved in the sequence of events that breaks down glycogen to provide energy to muscle cells. PFKM gene mutations result in the production of PFKM subunits that have little or no function. As a result, no functional phosphofructokinase is formed in skeletal muscles, and glycogen cannot be completely broken down. Partially broken down glycogen then builds up in muscle cells. Muscles that do not have access to glycogen as an energy source become weakened and cramped following moderate strain, such as exercise, and in some cases, begin to break down. In other tissues, other subunits that make up the phosphofructokinase enzyme likely compensate for the lack of PFKM subunits, and the enzyme is able to retain some function. This compensation may help explain why other tissues are not affected by PFKM gene mutations. It is unclear why some individuals with GSDVII are affected with more severe forms of the disorder than others. ### Learn more about the gene associated with Glycogen storage disease type VII * PFKM ## 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	Glycogen storage disease type VII	c0017926	7,462	medlineplus	https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-vii/	2021-01-27T08:25:19	{"gard": ["5686"], "mesh": ["D006014"], "omim": ["232800"], "synonyms": []}
Khosravi et al. (1998) described 3 sibs (2 males, 1 female) with multiple congenital anomalies, poor growth, seizures, and progressive central nervous system degeneration leading to death in infancy. Radiographic changes were similar and included moderate shortness of long bones, platyspondyly, and hypoplastic pelvis. Autopsies showed diffuse encephalomyelopathy and enlargement of the lateral and third ventricles. Lysosomal enzyme activities were normal. Collagen type II analysis on 2 of the sibs indicated normal collagen. Although the radiographic and chondroosseous morphologic findings in these sibs bore certain similarities to Dyggve-Melchior-Clausen syndrome (223800), their clinical course did not fit that condition. Thus, Khosravi et al. (1998) suggested that they represent a new syndrome of bone dysplasia and CNS degeneration inherited as an autosomal recessive. Two of the sibs died at age 5 months; 1 died at the age of almost 4 months after being on respiratory assistance for 7 weeks. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Failure to thrive HEAD & NECK Face \- Flat face \- Long philtrum \- Micrognathia Ears \- Stenotic external auditory canal Eyes \- Prominent eyes Nose \- Depressed nasal bridge \- Short, upturned nose Neck \- Short neck CARDIOVASCULAR Heart \- Ventricular hypertrophy \- Patent foramen ovale RESPIRATORY \- Apnea CHEST External Features \- Small chest Ribs Sternum Clavicles & Scapulae \- Elongated clavicles ABDOMEN Gastrointestinal \- Meckel diverticulum GENITOURINARY External Genitalia (Male) \- Inguinal hernia Internal Genitalia (Male) \- Cryptorchidism SKELETAL Spine \- Wafer-thin platyspondyly Pelvis \- Wide sacrosciatic notch \- Hypoplastic pelvis \- Trident configuration of acetabular roof Limbs \- Radial hypoplasia \- Ulnar hypoplasia \- Rhizomelic limb shortening \- Irregular proximal humeral metaphyses \- Gracile long bones Hands \- Transverse palmar creases \- Prominent palmar flexion creases \- Brachydactyly \- Ulnar deviation of the hands SKIN, NAILS, & HAIR Skin \- Transverse palmar creases \- Prominent palmar flexion creases \- Cutis marmorata Hair \- Fragile scalp hair \- Sparse hair NEUROLOGIC Central Nervous System \- Progressive CNS degeneration \- Seizure \- Progressive ventriculomegaly \- Small cerebellum \- Brain atrophy \- Encephalomyelopathy \- Thin corpus callosum \- Diffuse, severe neuronal loss \- Gliosis \- Generalized myelin loss PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios MISCELLANEOUS \- Death in early infancy ▲ 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	SKELETAL DYSPLASIA AND PROGRESSIVE CENTRAL NERVOUS SYSTEM DEGENERATION, LETHAL	c1865117	7,463	omim	https://www.omim.org/entry/602613	2019-09-22T16:13:34	{"mesh": ["C566514"], "omim": ["602613"]}
Septo-optic dysplasia Other namesde Morsier syndrome[1][2] The optic nerve is underdeveloped in this condition SpecialtyOphthalmology Septo-optic dysplasia (SOD), known also as de Morsier syndrome, is a rare congenital malformation syndrome that features a combination of the underdevelopment of the optic nerve, pituitary gland dysfunction, and absence of the septum pellucidum (a midline part of the brain). Two or more of these features need to be present for a clinical diagnosis — only 30% of patients have all three.[3] French doctor Georges de Morsier first recognized the relation of a rudimentary or absent septum pellucidum with hypoplasia of the optic nerves and chiasm in 1956.[4] ## Contents * 1 Signs and symptoms * 1.1 Optic nerve underdevelopment * 1.2 Pituitary hormone abnormalities * 1.3 Mid-line brain abnormalities * 2 Causes * 2.1 Genetic * 2.2 Environmental * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 History * 7 References * 8 External links ## Signs and symptoms[edit] The symptoms of SOD can be divided into those related to optic nerve underdevelopment, pituitary hormone abnormalities, or mid-line brain abnormalities. Symptoms may vary greatly in their severity.[5] ### Optic nerve underdevelopment[edit] About one quarter of people with SOD have significant visual impairment in one or both eyes, as a result of optic nerve underdevelopment. There may also be nystagmus (involuntary eye movements, often side-to-side) or other eye abnormalities.[5] ### Pituitary hormone abnormalities[edit] Underdevelopment of the pituitary gland in SOD leads to hypopituitarism, most commonly in the form of growth hormone deficiency.[5] ### Mid-line brain abnormalities[edit] In SOD mid-line brain structures, such as the corpus callosum and the septum pellucidum may fail to develop normally, leading to neurological problems such as seizures or development delay.[6] ## Causes[edit] SOD results from an abnormality in the development of the embryonic forebrain at 4-6 weeks of pregnancy.[5] There is no known single cause of SOD, but it is thought that both genetic and environmental factors may be involved.[6] ### Genetic[edit] Rare familial recurrence has been reported, suggesting at least one genetic form (HESX1).[7] In addition to HESX1, mutations in OTX2, SOX2 and PAX6 have been implicated in SOD.[6] Genetic abnormalities are identified in fewer than one per cent of patients.[5] ### Environmental[edit] There have been suggestions that the use of drugs or alcohol during pregnancy may increase the risk of SOD.[5] ## Diagnosis[edit] A diagnosis of SOD is made when at least two of the following triad are present: optic nerve underdevelopment; pituitary hormone abnormalities; or mid-line brain abnormalities. Diagnosis is usually made at birth or during childhood, and a clinical diagnosis can be confirmed by MRI scans.[5] ## Treatment[edit] There is no cure for SOD. Pituitary insufficiency can be treated with hormones.[5] ## Epidemiology[edit] A European survey put the prevalence of SOD at somewhere in the region of 1.9 to 2.5 per 100,000 live births, with the United Kingdom having a particularly high rate and with increased risk for younger mothers.[8] ## History[edit] In 1941 Dr David Reeves at the Children's Hospital Los Angeles described an association between underdevelopment of the optic nerve with an absent septum pellucidum. Fifteen years later French doctor Georges de Morsier reported his theory that the two abnormalities were connected and coined the term septo-optic dysplasia. In 1970 American doctor William Hoyt made the connection between the three features of SOD and named the syndrome after de Morsier.[9] ## References[edit] 1. ^ synd/2548 at Who Named It? 2. ^ G. de Morsier. Études sur les dysraphies, crânioencéphaliques. III. Agénésie du septum palludicum avec malformation du tractus optique. La dysplasie septo-optique. Schweizer Archiv für Neurologie und Psychiatrie, Zurich, 1956, 77: 267-292. 3. ^ Gleason, CA; Devascar, S (5 October 2011). "Congenital malformations of the Central Nervous System". Avery's Diseases of the Newborn (9 ed.). Saunders. p. 857. ISBN 978-1437701340. 4. ^ Daroff, Robert B.; Jankovic, Joseph; Mazziotta, John C.; Pomeroy, Scott L. (2015-10-25). Bradley's neurology in clinical practice (Seventh ed.). London. ISBN 9780323339162. OCLC 932031625. 5. ^ a b c d e f g h Webb, E; Dattani, M (2010). "Septo-optic dysplasia". European Journal of Human Genetics. 18 (4): 393–397. doi:10.1038/ejhg.2009.125. PMC 2987262. PMID 19623216. 6. ^ a b c "OMIM". Genetics Home Reference - Septo-Optic Dysplasia. Retrieved 16 July 2015. 7. ^ Dattani MT, Martinez-Barbera JP, Thomas PQ, et al. (1998). "Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse". Nat. Genet. 19 (2): 125–33. doi:10.1038/477. PMID 9620767. S2CID 28880292. 8. ^ Garne, E; et al. (September 2018). "Epidemiology of septo-optic dysplasia with focus on prevalence and maternal age – A EUROCAT study". European Journal of Medical Genetics. 61 (9): 483–488. doi:10.1016/j.ejmg.2018.05.010. PMID 29753093. 9. ^ Borchert, Mark (2012). "Reappraisal of the Optic Nerve Hypoplasia Syndrome" (PDF). Journal of Neuro-Opthalmology. 32 (1): 58–67. doi:10.1097/WNO.0b013e31824442b8. PMID 22330852. S2CID 12131899. ## External links[edit] Classification D * ICD-10: Q04.4 * ICD-9-CM: 742.2 * OMIM: 182230 * MeSH: D025962 * DiseasesDB: 32732 * 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 * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Septo-optic dysplasia	c0338503	7,464	wikipedia	https://en.wikipedia.org/wiki/Septo-optic_dysplasia	2021-01-18T18:28:38	{"gard": ["7627"], "mesh": ["D025962"], "umls": ["C0338503"], "icd-9": ["742.2"], "orphanet": ["3157"], "wikidata": ["Q2756703"]}
Donohue syndrome insulin receptor SpecialtyEndocrinology, rheumatology, medical genetics Donohue syndrome (also known as leprechaunism) is an extremely rare and severe genetic disorder. Leprechaunism derives its name from the hallmark elvish features (small stature, bulging eyes, thick lips, and upturned nostrils) exhibited by the affected individuals. The disease is caused by a mutation in the INSR gene, which contains the genetic information for the formation of insulin receptors.[1] As a result, affected individuals have either a decreased number of insulin receptors, or insulin receptor with greatly impaired functionality. The lack and impairment of insulin receptor functionality leads to an inability to regulate blood glucose levels through severe insulin resistance. This will ultimately lead to affected development of tissues and organs throughout the body. In addition to the physical abnormalities, leprechaunism is also characterized by endocrine system abnormalities that can lead to conditions such as hyperglycemia (high blood glucose levels), hypoglycemia (low blood glucose levels), hyperinsulemia (high blood insulin levels), and the enlargement of certain sex organs such as the penis in males, and the clitoris in females. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 Prognosis * 7 Epidemiology * 8 Eponym * 9 Future research * 10 See also * 11 References * 12 External links ## Signs and symptoms[edit] Facial features indicative of Donohue syndrome include protuberant and low-set ears, flaring nostrils, unusually large mouth, thick lips, and widely spaced eyes. Physical features include stunted growth (including during gestation), lack of subcutaneous adipose tissue, muscle atrophy, hirsutism (excessive body hair growth), and dysplasia (nail malformation).[2] Additionally, a condition known as acanthosis nigricans is present in affected individuals. In acanthosis nigricans, patches of skin darken and thicken to gain a velvet-like appearance. Gender specific features also include enlarged clitoris and breasts, as well as ovarian cysts in affected females, and enlarged penis in affected males.[2] In the Journal of Pediatric Medicine, Donohue and Uchida described affected sisters whose growth appeared to have ended in the seventh month of gestation, both born alive but dying before four months of age.[3] Very early death (or spontaneous abortion) is the norm, although sufferers sometimes live longer than a decade.[3] Endocrine related abnormalities as a result of insulin receptor malfunction include insulin resistance, hypoglycemia and hyperglycemia (depending on whether or not the individual has eaten) and hyperinsulemia. A much milder form of the disease, in which there is some insulin resistance but normal growth and subcutaneous fat distribution, is also known.[4] It is caused by a less severe mutation of the same gene. ## Cause[edit] Donohue syndrome has an autosomal recessive pattern of inheritance. Donohue syndrome is an autosomal recessive genetic disorder. The mutations responsible for the disorder are found on the short arm chromosome 19 (19p13.2) within the coding sequence of the INSR gene (insulin receptor) causing the production of inactive receptor molecules.[5] There are several mutations that can be responsible for the disease, as any mutation that severely impairs the functionality of the insulin receptor will have similar effects. The INSR gene spans over one hundred and twenty thousand base pairs, which contain twenty-two exons coding for a protein that consists of 1382 amino acids.[6] Some of the introns may or may not be spliced out depending on the kind of cell.[7] Known mutations to the gene which can cause Donohue syndrome include a nonsense mutation that resulted in early termination of the protein, an addition or deletion mutation that resulted in a frame shift,[8] a single missense mutation[9] and in the milder form mentioned above, a single codon change that altered isoleucine to methionine in the receptor protein.[9] Some mutations to the gene instead result in insulin resistant diabetes without Donohue syndrome.[9] Because mutations in the gene are extremely rare, most cases result from consanguineous matings, for example, between cousins.[9] However, the exact mutation need not be the same. Disease can be caused by inheritance of two different mutant alleles, one from each parent, in which case the patient is a compound heterozygote.[10] A heterozygous individual (i.e. one who is a carrier for the disease, having only one normal allele for the insulin receptor) will not be affected. Two heterozygous parents have, in theory, a one in four chance of having a child with the disease, and two thirds of their unaffected children will be carriers. However, because spontaneous abortion (miscarriage) often results when the fetus has the disease, in actuality the proportion of children born alive with Donohue syndrome will be lower than 25%.[9] It is possible to do a genetic test to identify carriers, but because it is so rare, this is not usually done unless there is reason to suspect that the individual being tested is a carrier, for instance having an affected sibling or cousin. As expected for a genetic disease that can be caused by many different mutations, it is not limited to a specific ethnic group, and has been seen in people of various races.[citation needed] ## Pathophysiology[edit] The cause of the disease is the lack of a fully functional insulin receptor, which has a profound effect during fetal development and thereafter. In one case, it was found (by culturing pancreatic cells) that the receptor produced by the mutant allele is only about 15% as effective as the normal receptor.[3] The beta cells in the pancreas, which make and store insulin and release it on an as-needed basis, are often found to be very large or numerous.[3] The role of insulin in the body is to facilitate the entrance of glucose into the cell. Once insulin binds to the insulin receptors on the cell surface, the insulin receptors will send a signal that will ultimately bring the glucose transporter protein GLUT4 to attach to the cell membrane. Additionally, once insulin is bound to the insulin receptors, it will also initiate several signaling cascades that will promote cell growth and differentiation, protein synthesis, glucose synthesis, and the inhibition of gluconeogenesis through several metabolic pathways. A malfunctioning insulin receptor would thus not be able to properly initiate the signaling cascades for the aforementioned cellular processes. Many of the problems associated with Donohue syndrome may be due to the insulin receptor binding the insulin-like growth factor, regulating the growth of the embryo, in addition to its well-known role in the regulation of blood sugar.[11] ## Diagnosis[edit] There are a few ways to diagnose Donohue syndrome. Due to the nature of the disorder, Donohue syndrome can be diagnosed either genetically, symptomatically, or both. Because Donohue syndrome is a genetic disorder, genetic testing can be performed to diagnose the disease. These genetic tests include diagnostic testing, carrier testing, predictive and pre-symptomatic testing, as well as forensic testing. Prenatally, amniocentesis can be performed to determine if the child will have Donohue syndrome.[12] Additionally, the disorder can be diagnosed through laboratory testing to measure blood insulin levels and defective insulin receptors. ## Treatment[edit] While there currently is no cure for Donohue syndrome, treatments for those with the disease are tailored specifically to the symptoms present in each individual. It is often that a team of medical professionals will come together to treat a patient with this condition in their specific realm of practice such as pediatrics, endocrinology, and dermatology.[2] Treatment will often address specific dysfunctions in the patient, such as skin defects, hormonal imbalances, and normal progression of child growth.[citation needed] ## Prognosis[edit] The prognosis is quite dire, with early death usual.[13] In fact, most patients die in their first year except in milder forms of the disease, but few are known to have lived longer.[14] The variation is unsurprising given the diversity of mutations causing the disease. ## Epidemiology[edit] Donohue syndrome is an extremely rare disorder that occurs in one of every million births worldwide. Several dozen cases have been reported in the medical community, and in the reported cases of the disorder, it has been found that the females are twice as likely to have the disorder as men.[citation needed] ## Eponym[edit] Donohue syndrome was first identified in 1948 by Canadian pathologist William L. Donohue (1906–1985).[15] The name leprechaunism has been largely abandoned because of the perception of the name by some parents of patients as insulting.[16] ## Future research[edit] The National Institute of Diabetes and Digestive Kidney Diseases sponsored a phase 2 clinical study in 2001 that would look at the effectiveness of leptin to treat severe insulin resistance. In the study, two children with severe insulin resistance of ages 11 and 13 with known a known defect in the insulin receptor. The goal for the study was to see if leptin could overcome insulin receptor defects by initiating molecules in the insulin-signal cascade.[17] While no outcomes have yet been reported to date, the direction in which this clinical trial is heading is promising. ## See also[edit] * Patterson pseudoleprechaunism syndrome * Rabson–Mendenhall syndrome * Williams syndrome ## References[edit] 1. ^ Reference, Genetics Home. "Donohue syndrome". Genetics Home Reference. Retrieved 2019-11-19. 2. ^ a b c "Leprechaunism". NORD (National Organization for Rare Disorders). Retrieved 2019-11-19. 3. ^ a b c d Online Mendelian Inheritance in Man (OMIM): Insulin Receptor - 147670 4. ^ al-Gazali LI, Khalil M, Devadas K (1993). "A syndrome of insulin resistance resembling leprechaunism in five sibs of consanguineous parents". J. Med. Genet. 30 (6): 470–5. doi:10.1136/jmg.30.6.470. PMC 1016418. PMID 8326490. 5. ^ Longo N, Wang Y, Smith SA, Langley SD, DiMeglio LA, Giannella-Neto D (2002). "Genotype-phenotype correlation in inherited severe insulin resistance". Hum. Mol. Genet. 11 (12): 1465–75. doi:10.1093/hmg/11.12.1465. PMID 12023989. 6. ^ NCBI Sequence Viewer v2.0 7. ^ Benecke H, Flier JS, Moller DE (1992). "Alternatively spliced variants of the insulin receptor protein. Expression in normal and diabetic human tissues". J. Clin. Invest. 89 (6): 2066–70. doi:10.1172/JCI115819. PMC 295926. PMID 1602013. 8. ^ Psiachou H, Mitton S, Alaghband-Zadeh J, Hone J, Taylor SI, Sinclair L (1993). "Leprechaunism and homozygous nonsense mutation in the insulin receptor gene". Lancet. 342 (8876): 924. doi:10.1016/0140-6736(93)91970-W. PMID 8105179. S2CID 8869552. 9. ^ a b c d e Online Mendelian Inheritance in Man (OMIM): Insulin Receptor - 147670 10. ^ Elsas LJ, Endo F, Strumlauf E, Elders J, Priest JH (1985). "Leprechaunism: an inherited defect in a high-affinity insulin receptor". Am. J. Hum. Genet. 37 (1): 73–88. PMC 1684537. PMID 3883764. 11. ^ Personal communication with J. Bell, Ph.D. 12. ^ Reference, Genetics Home. "Donohue syndrome". Genetics Home Reference. Retrieved 2019-11-19. 13. ^ Longo N, Wang Y, Smith SA, Langley SD, DiMeglio LA, Giannella-Neto D (2002). "Genotype-phenotype correlation in inherited severe insulin resistance". Hum. Mol. Genet. 11 (12): 1465–75. doi:10.1093/hmg/11.12.1465. PMID 12023989. 14. ^ Online Mendelian Inheritance in Man (OMIM): Insulin Receptor - 147670 15. ^ Donohue WL; Edwards, HE (1948). "Dysendocrinism". The Journal of Pediatrics. 32 (6): 739–48. doi:10.1016/S0022-3476(48)80231-3. PMID 18866943. 16. ^ Online Mendelian Inheritance in Man (OMIM): Insulin Receptor - 147670 17. ^ "Search of: "Leprechaunism" - List Results - ClinicalTrials.gov". www.clinicaltrials.gov. Retrieved 2019-11-24. ## External links[edit] Classification D * ICD-10: E34.8 * OMIM: 246200 * MeSH: D056731 * DiseasesDB: 30801 External resources * Orphanet: 508 * v * t * e Congenital abnormality syndromes Craniofacial * Acrocephalosyndactylia * Apert syndrome * Carpenter syndrome * Pfeiffer syndrome * Saethre–Chotzen syndrome * Sakati–Nyhan–Tisdale syndrome * Bonnet–Dechaume–Blanc syndrome * Other * Baller–Gerold syndrome * Cyclopia * Goldenhar syndrome * Möbius syndrome Short stature * 1q21.1 deletion syndrome * Aarskog–Scott syndrome * Cockayne syndrome * Cornelia de Lange syndrome * Dubowitz syndrome * Noonan syndrome * Robinow syndrome * Silver–Russell syndrome * Seckel syndrome * Smith–Lemli–Opitz syndrome * Snyder–Robinson syndrome * Turner syndrome Limbs * Adducted thumb syndrome * Holt–Oram syndrome * Klippel–Trénaunay–Weber syndrome * Nail–patella syndrome * Rubinstein–Taybi syndrome * Gastrulation/mesoderm: * Caudal regression syndrome * Ectromelia * Sirenomelia * VACTERL association Overgrowth syndromes * Beckwith–Wiedemann syndrome * Proteus syndrome * Perlman syndrome * Sotos syndrome * Weaver syndrome * Klippel–Trénaunay–Weber syndrome * Benign symmetric lipomatosis * Bannayan–Riley–Ruvalcaba syndrome * Neurofibromatosis type I Laurence–Moon–Bardet–Biedl * Bardet–Biedl syndrome * Laurence–Moon syndrome Combined/other, known locus * 2 (Feingold syndrome) * 3 (Zimmermann–Laband syndrome) * 4/13 (Fraser syndrome) * 8 (Branchio-oto-renal syndrome, CHARGE syndrome) * 12 (Keutel syndrome, Timothy syndrome) * 15 (Marfan syndrome) * 19 (Donohue syndrome) * Multiple * Fryns syndrome * v * t * e Cell surface receptor deficiencies G protein-coupled receptor (including hormone) Class A * TSHR (Congenital hypothyroidism 1) * LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia, Male-limited precocious puberty) * FSHR (Follicle-stimulating hormone insensitivity, XX gonadal dysgenesis) * GnRHR (Gonadotropin-releasing hormone insensitivity) * EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2) * AVPR2 (Nephrogenic diabetes insipidus 1) * PTGER2 (Aspirin-induced asthma) Class B * PTH1R (Jansen's metaphyseal chondrodysplasia) Class C * CASR (Familial hypocalciuric hypercalcemia) Class F * FZD4 (Familial exudative vitreoretinopathy 1) Enzyme-linked receptor (including growth factor) RTK * ROR2 (Robinow syndrome) * FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome) * FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome) * FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome) * INSR (Donohue syndrome * Rabson–Mendenhall syndrome) * NTRK1 (Congenital insensitivity to pain with anhidrosis) * KIT (KIT Piebaldism, Gastrointestinal stromal tumor) STPK * AMHR2 (Persistent Müllerian duct syndrome II) * TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia) * TGFBR1/TGFBR2 (Loeys–Dietz syndrome) GC * GUCY2D (Leber's congenital amaurosis 1) JAK-STAT * Type I cytokine receptor: GH (Laron syndrome) * CSF2RA (Surfactant metabolism dysfunction 4) * MPL (Congenital amegakaryocytic thrombocytopenia) TNF receptor * TNFRSF1A (TNF receptor associated periodic syndrome) * TNFRSF13B (Selective immunoglobulin A deficiency 2) * TNFRSF5 (Hyper-IgM syndrome type 3) * TNFRSF13C (CVID4) * TNFRSF13B (CVID2) * TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A) Lipid receptor * LRP: LRP2 (Donnai–Barrow syndrome) * LRP4 (Cenani–Lenz syndactylism) * LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1) * LDLR (LDLR Familial hypercholesterolemia) Other/ungrouped * Immunoglobulin superfamily: AGM3, 6 * Integrin: LAD1 * Glanzmann's thrombasthenia * Junctional epidermolysis bullosa with pyloric atresia EDAR (EDAR hypohidrotic ectodermal dysplasia) * PTCH1 (Nevoid basal-cell carcinoma syndrome) * BMPR1A (BMPR1A juvenile polyposis syndrome) * IL2RG (X-linked severe combined immunodeficiency) See also cell surface receptors [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Donohue syndrome	c0271695	7,465	wikipedia	https://en.wikipedia.org/wiki/Donohue_syndrome	2021-01-18T18:28:00	{"gard": ["6885"], "mesh": ["D056731"], "umls": ["C0271695", "C0265344"], "orphanet": ["508"], "wikidata": ["Q2467739"]}
Pseudoxanthoma elasticum Other namesGrönblad–Strandberg syndrome;[1] Groenblad-Strandberg syndrome Pseudoxanthoma elasticum of the posterior lateral neck. Note the yellowish slightly raised bumps characteristic of this condition. SpecialtyMedical genetics Pseudoxanthoma elasticum (PXE) is a genetic disease that causes mineralization of elastic fibers in some tissues. The most common problems arise in the skin and eyes, and later in blood vessels in the form of premature atherosclerosis.[2][3][4] PXE is caused by autosomal recessive mutations in the ABCC6 gene on the short arm of chromosome 16 (16p13.1).[3][5][6] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Pathophysiology * 4 Diagnosis * 4.1 Differential diagnosis * 5 Treatment * 6 Epidemiology * 7 History * 8 Images * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] Usually, pseudoxanthoma elasticum affects the skin first, often in childhood or early adolescence.[7] Small, yellowish papular lesions form and cutaneous laxity mainly affect the neck, axillae (armpits), groin, and flexural creases (the inside parts of the elbows and knees).[3][8] Skin may become lax and redundant. Many individuals have "oblique mental creases" (horizontal grooves of the chin)[9] PXE first affects the retina through a dimpling of the Bruch membrane (a thin membrane separating the blood vessel-rich layer from the pigmented layer of the retina), that is only visible during ophthalmologic examinations.[10] This is called peau d'orange (a French term meaning "skin of the orange"). Eventually the mineralization of the elastic fibers in the Bruch membrane create cracks called angioid streaks that radiate out from the optic nerve. Angioid streaks themselves do not cause distortion of vision, even if they cross into the foveal area. This symptom is present in almost all PXE patients and is usually noticed a few years after the onset of cutaneous lesions. These cracks may allow small blood vessels that were originally held back by Bruch's membrane to penetrate the retina. These blood vessels sometimes leak, and these retinal hemorrhages may lead to the loss of central vision. Vision loss is a major issue in many PXE patients.[11][3][4] PXE may affect the gastrointestinal and cardiovascular systems. Gastrointestinal bleeding is a rare symptom and usually involved bleeding from the stomach. In the circulatory system, intermittent claudication, a condition in which cramping pain in the leg is induced by exercise, is a prominent feature.[12] At later stages, coronary artery disease may develop, leading to angina and myocardial infarction (heart attack).[13] Cerebral ischemia in PXE is caused by small vessel occlusive disease. Other rare neurological complications may include intracranial aneurysms, subarachnoid and intracerebral hemorrhages.[14] ## Genetics[edit] Pseudoxanthoma elasticum has an autosomal recessive pattern of inheritance. 80% of clinical cases of pseudoxanthoma elasticum have detectable mutations in the ABCC6 gene.[15][16][17][18] Mutations in almost all parts of the gene have been described, of all types (missense, nonsense, splice alteration, insertion, small deletion or large deletion). Although there have been reports of autosomal dominant inheritance, the inheritance is typically autosomal recessive (both parents need to be carriers, and there is a 25% chance that a child will inherit both abnormal copies of the gene and therefore develop the condition).[3] Strong genetic linkage was found with mutations in the ABCC6 gene, which codes for the ABCC6 protein, which is a membrane transporter from the large ATP-binding cassette transporter family. The protein is expressed in most organs, but mainly in the liver and kidney. ABCC6 mediates ATP release in the liver. This is the main source of circulating pyrophosphate (PPi), and individuals affected by PXE have strongly reduced plasma PPi levels, explaining their mineralization disorder.[19] One study suggested that mutations causing total absence of an ABCC6 protein caused a more severe disease,[20] but this could not be confirmed in a subsequent case series.[21] Given the variations in age of onset and severity it is likely that other unknown risk factors (genetic, environmental, and lifestyle) may be involved.[3] Premature atherosclerosis is also associated with mutations in the ABCC6 gene, even in those without PXE.[22] A syndrome almost indistinguishable from hereditary PXE has been described in patients with hemoglobinopathies (sickle-cell disease and thalassemia) through a poorly understood mechanism.[3] In addition, there appears to be another PXE-like syndrome with a similar phenotype but as a result of problems with another gene, gamma-glutamyl carboxylase.[23] Mutations in ABCC6 can also cause generalized arterial calcification of infancy.[24] In some cases of PXE, mutations in ABCC6 cannot be found, and other genes such as ENPP1 may be implicated[25] ## Pathophysiology[edit] In PXE, there is mineralization (accumulation of calcium and other minerals) and fragmentation of the elastin-containing fibers in connective tissue, but primarily in the midlaminar layer of the dermis, Bruch's membrane and the midsized arteries.[26] Recent studies have confirmed that PXE is a metabolic disease, and that its features arise because metabolites of vitamin K cannot reach peripheral tissues.[27] Low levels of PPi cause mineralization in peripheral tissues.[19] ## Diagnosis[edit] Histopathology of pseudoxanthoma elasticum: Fragmentation and calcification of middermal elastic fibers on Alizarin Red staining.[28] The diagnostic criteria for PXE are the typical skin biopsy appearance and the presence of angioid streaks in the retina. Criteria were established by consensus of clinicians and researchers at the 2010 biennial research meeting of the PXE Research Consortium.[29] and confirmed at the 2014 meeting[30] These consensus criteria state that definitive PXE is characterized by two pathogenic mutations in the ABCC6 or ocular findings – angioid streaks > 1 DD or peau d’orange in an individual <20 years of age together with skin findings: * Characteristic pseudoxanthomatous papules and plaques on the neck or flexural creases. * Diagnostic histopathological changes in lesional skin: Calcified elastic fibers in the mid and lower dermis, confirmed by positive calcium stain ### Differential diagnosis[edit] The differential diagnosis PXE-like papillary dermal elastolysis: Small flesh-colored papules in the neck region.[28] Histopathology of PXE-like papillary dermal elastolysis: Loss of elastic fibers in the papillary dermis and abnormal pattern in the reticular dermis (arrow)[28] Pseudoxanthoma elasticum versus histopathological differential diagnoses on light microscopy (LM) and electron microscopy (EM)[28] Pseudoxanthoma elasticum LM: Mid-dermal calcification and fragmentation of elastic fibers EM: Mineralization in elastic fiber core PXE-like disease with coagulation deficiency LM: Middermal calcification and fragmentation of elastic fibers EM: Mineralization in elastic fiber periphery Hemoglobinopathies LM: Middermal calcification and fragmentation of elastic fibers EM: Mineralization in elastic fiber core PXE-like papillary dermal elastolysis LM: Selective elastic tissue elimination in the papillary dermis and presence of melanophages White fibrous papulosis of the neck LM: Dermal fibrosis in papillary and mid-reticular dermis Late-onset focal dermal elastosis EM: Decrease of elastic fibers; fragmentation of remaining fibers LM: Accumulation of elastic fibers in mid- and reticular dermis without fragmentation or calcification Perforating calcific elastosis LM: Middermal calcification and degeneration of elastic fibers with transepidermal elimination Buschke-Ollendorff syndrome LM: Increased amount of hypertrophic elastic fibers in dermis EM: Altered translucent elastic fibers Elastosis perforans serpiginosa LM: Transepidermal or perifollicular perforating canals Papular elastorrhexis LM: Thickening of collagen bundles next to loss and fragmentation of elastic fibers Upper dermal elastolysis LM: Complete loss of elastic fibers in the upper dermis Middermal elastolysis LM: Complete absence of elastic fibers in the middermis Linear focal elastosis LM: Massive basophilic fibers; clumping of elastic fibers in papillary dermis Elastoderma LM: Increased, intertwining thin elastic fibers in papillary and upper reticular dermis Calcinosis cutis LM: Deposits of calcium in the dermis ## Treatment[edit] There is no confirmed treatment that directly interferes with the disease process.[5][6] Cosmetic surgery to remove excessive skin has been used to improve aesthetic appearance in PXE patients[5] but because of the non-life-threatening nature of these symptoms, should be used with caution.[6] One of the most critical symptom of PXE is choroidal neovascularization which can lead to deterioration of central vision. Photodynamic therapy has been used as a treatment, but this has been replaced with endothelial growth factor (VEGF) inhibitors (such as bevacizumab, ranibizumab, and aflibercept)[6] with efficacy similar to their use in treatment of age-related macular degeneration.[4] To limit cardiovascular symptoms, reduction of cardiovascular risk factors through lifestyle changes is recommended.[6] Generally clinicians recommend avoidance of non-steroidal anti-inflammatory drugs (NSAIDS) that increase bleeding risk, such as aspirin, and ibuprofen to prevent eye and gastrointestinal bleeding.[6] Formerly, dietary restriction of calcium was tried with no benefit, and in fact accelerated mineralization in mice.[31] There are a number of potential treatments that are currently being tested or have just undergone testing including magnesium,[32] etidronate,[33] PPi,[34] and tissue-nonspecific alkaline phosphatase inhibitors.[35] Given that ABCC6 heterozygous mutations result in few symptoms of PXE, this disease is a candidate for gene therapy. Some initial proof-of-principle experiments have been done in mice that have relieved some of symptoms of PXE, but as with all gene therapy treatments, there are many hurdles that must be over come including insuring that the treatment will be long-lasting and reducing the risk of insertional mutagenesis and severe immune reactions.[6] ## Epidemiology[edit] The reported prevalence of pseudoxanthoma elasticum is about 1:25,000. Females are twice as likely to be affected as males. The disease occurs in all ethnicities, but Afrikaners are more likely to have PXE as a result of a founder effect (i.e., higher prevalence in the small group of people from whom Afrikaners descend).[36] ## History[edit] The first description of PXE that distinguished it from other xanthoma conditions was by Dr Ferdinand-Jean Darrier in 1896.[37] The eponym "Grönblad-Strandberg syndrome" is used in older literature, after two physicians who made further discoveries in the disease manifestations.[38] PXE has the distinction of being the only disease for which a layperson is the discover of the mutated gene. The ABCC6 gene mutation was discovered simultaneously by four research teams, all of which published at the same time. The principal investigators were (in order of the date of publication): Jouni Uitto,[15] Arthur Bergen,[16] Charles Boyd,[17] and Klaus Lindpainter.[18] The gene was patented by Charles D. Boyd, Katalin Csiszar, Olivier LeSaux, Zsolt Urban, Sharon Terry, and assigned to PXE International by these co-inventors. Between the filing and 2013, when the Supreme Court of the United States declared that genes may not be patented.[39] PXE International freely licensed the gene to any lab for clinical testing and research. PXE International continues to hold and maintain other patents (diagnosis and treatment patents).[40][41] PXE International, a support organization, was founded in 1995, by Patrick and Sharon Terry,[42][43][44][45] following the diagnosis of their two children. It has a registry of 4,600 affected individuals. ## Images[edit] * Pseudoxanthoma elasticum of the posterior lateral neck. * Pseudoxanthoma elasticum of the left axillary fold. ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ Li Q, van de Wetering K, Uitto J (February 2019). "Pseudoxanthoma Elasticum as a Paradigm of Heritable Ectopic Mineralization Disorders: Pathomechanisms and Treatment Development". review. The American Journal of Pathology. 189 (2): 216–225. doi:10.1016/j.ajpath.2018.09.014. PMC 6412714. PMID 30414410. 3. ^ a b c d e f g Chassaing N, Martin L, Calvas P, Le Bert M, Hovnanian A (December 2005). "Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations". review. Journal of Medical Genetics. 42 (12): 881–92. doi:10.1136/jmg.2004.030171. PMC 1735972. PMID 15894595. 4. ^ a b c Finger RP, Charbel Issa P, Ladewig MS, Götting C, Szliska C, Scholl HP, Holz FG (2009). "Pseudoxanthoma elasticum: genetics, clinical manifestations and therapeutic approaches". review. Survey of Ophthalmology. 54 (2): 272–85. doi:10.1016/j.survophthal.2008.12.006. PMID 19298904. 5. ^ a b c Marconi B, Bobyr I, Campanati A, Molinelli E, Consales V, Brisigotti V, et al. (August 2015). "Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment". review. Intractable & Rare Diseases Research. 4 (3): 113–22. doi:10.5582/irdr.2015.01014. PMC 4561240. PMID 26361562. 6. ^ a b c d e f g Germain DP (May 2017). "Pseudoxanthoma elasticum". review. Orphanet Journal of Rare Diseases. 12 (1): 85. doi:10.1186/s13023-017-0639-8. PMC 5424392. PMID 28486967. 7. ^ Naouri M, Boisseau C, Bonicel P, Daudon P, Bonneau D, Chassaing N, Martin L (September 2009). "Manifestations of pseudoxanthoma elasticum in childhood". The British Journal of Dermatology. 161 (3): 635–9. doi:10.1111/j.1365-2133.2009.09298.x. PMID 19519828. 8. ^ Neldner KH, Struk B (2003). Pseudoxanthoma Elasticum. Connective Tissue and Its Heritable Disorders. John Wiley & Sons, Ltd. pp. 561–583. doi:10.1002/0471221929.ch11. ISBN 9780471221920. 9. ^ Lebwohl M, Lebwohl E, Bercovitch L (April 2003). "Prominent mental (chin) crease: a new sign of pseudoxanthoma elasticum". primary. Journal of the American Academy of Dermatology. 48 (4): 620–2. doi:10.1067/mjd.2003.195. PMID 12664032. 10. ^ Gliem M, Müller PL, Birtel J, Hendig D, Holz FG, Charbel Issa P (June 2016). "Frequency, Phenotypic Characteristics and Progression of Atrophy Associated With a Diseased Bruch's Membrane in Pseudoxanthoma Elasticum". primary. Investigative Ophthalmology & Visual Science. 57 (7): 3323–30. doi:10.1167/iovs.16-19388. PMID 27367499. 11. ^ Risseeuw S, Ossewaarde-van Norel J, Klaver CC, Colijn JM, Imhof SM, van Leeuwen R (August 2019). "Visual Acuity in Pseudoxanthoma Elasticum". primary. Retina. 39 (8): 1580–1587. doi:10.1097/IAE.0000000000002173. PMID 29652691. 12. ^ Lefthériotis G, Abraham P, Le Corre Y, Le Saux O, Henrion D, Ducluzeau PH, et al. (November 2011). "Relationship between ankle brachial index and arterial remodeling in pseudoxanthoma elasticum". primary. Journal of Vascular Surgery. 54 (5): 1390–4. doi:10.1016/j.jvs.2011.04.041. PMC 5529101. PMID 21723076. 13. ^ Kranenburg G, de Jong PA, Mali WP, Attrach M, Visseren FL, Spiering W (January 2017). "Prevalence and severity of arterial calcifications in pseudoxanthoma elasticum (PXE) compared to hospital controls. Novel insights into the vascular phenotype of PXE". primary. Atherosclerosis. 256: 7–14. doi:10.1016/j.atherosclerosis.2016.11.012. PMID 27940376. 14. ^ Kauw F, Kranenburg G, Kappelle LJ, Hendrikse J, Koek HL, Visseren FL, et al. (February 2017). "Cerebral disease in a nationwide Dutch pseudoxanthoma elasticum cohort with a systematic review of the literature". review. Journal of the Neurological Sciences. 373: 167–172. doi:10.1016/j.jns.2016.12.053. PMID 28131180. 15. ^ a b Ringpfeil F, Lebwohl MG, Christiano AM, Uitto J (May 2000). "Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter". primary. Proceedings of the National Academy of Sciences of the United States of America. 97 (11): 6001–6. Bibcode:2000PNAS...97.6001R. doi:10.1073/pnas.100041297. PMC 18548. PMID 10811882. 16. ^ a b Bergen AA, Plomp AS, Schuurman EJ, Terry S, Breuning M, Dauwerse H, et al. (June 2000). "Mutations in ABCC6 cause pseudoxanthoma elasticum". primary. Nature Genetics. 25 (2): 228–31. doi:10.1038/76109. PMID 10835643. 17. ^ a b Le Saux O, Urban Z, Tschuch C, Csiszar K, Bacchelli B, Quaglino D, et al. (June 2000). "Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum". primary. Nature Genetics. 25 (2): 223–7. doi:10.1038/76102. PMID 10835642. 18. ^ a b Struk B, Cai L, Zäch S, Ji W, Chung J, Lumsden A, et al. (2000). "Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause pseudoxanthoma elasticum". primary. Journal of Molecular Medicine. 78 (5): 282–6. doi:10.1007/s001090000114. PMID 10954200. 19. ^ a b Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Váradi A, et al. (September 2014). "ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report". primary. Arteriosclerosis, Thrombosis, and Vascular Biology. 34 (9): 1985–9. doi:10.1161/ATVBAHA.114.304017. PMC 6743317. PMID 24969777. 20. ^ Schulz V, Hendig D, Szliska C, Götting C, Kleesiek K (June 2005). "Novel mutations in the ABCC6 gene of German patients with pseudoxanthoma elasticum". primary. Human Biology. 77 (3): 367–84. doi:10.1353/hub.2005.0054. PMID 16392638. 21. ^ Pfendner EG, Vanakker OM, Terry SF, Vourthis S, McAndrew PE, McClain MR, et al. (October 2007). "Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum". primary. Journal of Medical Genetics. 44 (10): 621–8. doi:10.1136/jmg.2007.051094. PMC 2597973. PMID 17617515. 22. ^ Trip MD, Smulders YM, Wegman JJ, Hu X, Boer JM, ten Brink JB, et al. (August 2002). "Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease". primary. Circulation. 106 (7): 773–5. doi:10.1161/01.CIR.0000028420.27813.C0. PMID 12176944. 23. ^ Vanakker OM, Martin L, Gheduzzi D, Leroy BP, Loeys BL, Guerci VI, et al. (March 2007). "Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity". primary. The Journal of Investigative Dermatology. 127 (3): 581–7. doi:10.1038/sj.jid.5700610. PMID 17110937. 24. ^ Li Q, Brodsky JL, Conlin LK, Pawel B, Glatz AC, Gafni RI, et al. (March 2014). "Mutations in the ABCC6 gene as a cause of generalized arterial calcification of infancy: genotypic overlap with pseudoxanthoma elasticum". primary. The Journal of Investigative Dermatology. 134 (3): 658–665. doi:10.1038/jid.2013.370. PMC 3945730. PMID 24008425. 25. ^ Jin L, Jiang Q, Wu Z, Shao C, Zhou Y, Yang L, et al. (May 2015). "Genetic heterogeneity of pseudoxanthoma elasticum: the Chinese signature profile of ABCC6 and ENPP1 mutations". primary. The Journal of Investigative Dermatology. 135 (5): 1294–1302. doi:10.1038/jid.2015.10. PMC 4402129. PMID 25615550. 26. ^ Gheduzzi D, Sammarco R, Quaglino D, Bercovitch L, Terry S, Taylor W, Ronchetti IP (2003). "Extracutaneous ultrastructural alterations in pseudoxanthoma elasticum". primary. Ultrastructural Pathology. 27 (6): 375–84. doi:10.1080/716100800. PMID 14660276. 27. ^ Li Q, Jiang Q, Pfendner E, Váradi A, Uitto J (January 2009). "Pseudoxanthoma elasticum: clinical phenotypes, molecular genetics and putative pathomechanisms". review. Experimental Dermatology. 18 (1): 1–11. doi:10.1111/j.1600-0625.2008.00795.x. PMC 3349969. PMID 19054062. 28. ^ a b c d Hosen, Mohammad J.; Lamoen, Anouck; De Paepe, Anne; Vanakker, Olivier M. (2012). "Histopathology of Pseudoxanthoma Elasticum and Related Disorders: Histological Hallmarks and Diagnostic Clues". Scientifica. 2012: 1–15. doi:10.6064/2012/598262. ISSN 2090-908X. PMC 3820553. PMID 24278718. -Creative Commons Attribution 3.0 Unported license 29. ^ Uitto J, Bercovitch L, Terry SF, Terry PF (July 2011). "Pseudoxanthoma elasticum: progress in diagnostics and research towards treatment : Summary of the 2010 PXE International Research Meeting". review. American Journal of Medical Genetics. Part A. 155A (7): 1517–26. doi:10.1002/ajmg.a.34067. PMC 3121926. PMID 21671388. 30. ^ Uitto J, Jiang Q, Váradi A, Bercovitch LG, Terry SF (June 2014). "Visual Acuity in Pseudoxanthoma Elasticum". review. Expert Opinion on Orphan Drugs. 2 (6): 567–577. doi:10.1517/21678707.2014.908702. PMC 4219573. PMID 25383264. 31. ^ Jiang Q, Uitto J (September 2012). "Restricting dietary magnesium accelerates ectopic connective tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6(-/-) )". primary. Experimental Dermatology. 21 (9): 694–9. doi:10.1111/j.1600-0625.2012.01553.x. PMC 3422765. PMID 22897576. 32. ^ Rose S, On SJ, Fuchs W, Chen C, Phelps R, Kornreich D, et al. (July 2019). "Magnesium supplementation in the treatment of pseudoxanthoma elasticum: A randomized trial". primary. Journal of the American Academy of Dermatology. 81 (1): 263–265. doi:10.1016/j.jaad.2019.02.055. PMID 30826287. 33. ^ Kranenburg G, de Jong PA, Bartstra JW, Lagerweij SJ, Lam MG, Ossewaarde-van Norel J, et al. (March 2018). "Etidronate for Prevention of Ectopic Mineralization in Patients With Pseudoxanthoma Elasticum". primary. Journal of the American College of Cardiology. 71 (10): 1117–1126. doi:10.1016/j.jacc.2017.12.062. PMID 29519353. 34. ^ Dedinszki D, Szeri F, Kozák E, Pomozi V, Tőkési N, Mezei TR, et al. (November 2017). "Oral administration of pyrophosphate inhibits connective tissue calcification". primary. EMBO Molecular Medicine. 9 (11): 1463–1470. doi:10.15252/emmm.201707532. PMC 5666306. PMID 28701330. 35. ^ Li Q, Huang J, Pinkerton AB, Millan JL, van Zelst BD, Levine MA, et al. (February 2019). "-/- Mouse Model of PXE but Not in the Enpp1 Mutant Mouse Models of GACI". primary. The Journal of Investigative Dermatology. 139 (2): 360–368. doi:10.1016/j.jid.2018.07.030. PMC 6342656. PMID 30130617. 36. ^ Le Saux O, Beck K, Sachsinger C, Treiber C, Göring HH, Curry K, et al. (October 2002). "Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa". primary. Human Genetics. 111 (4–5): 331–8. doi:10.1007/s00439-002-0808-1. PMID 12384774. 37. ^ Darrier FJ (1896). "Pseudoxanthoma elasticum". Monatschr Prakt Dermatol (in German). 23: 609–17. 38. ^ synd/1059 at Who Named It? 39. ^ Liptak A (2013-06-13). "Justices, 9-0, Bar Patenting Human Genes". The New York Times. ISSN 0362-4331. Retrieved 2019-08-24. 40. ^ Katalin Csiszar, Olivier LeSaux, Zsolt Urban, Sharon Terry, Charles D. Boyd. United States Patent and Trademark Office. "Methods and Composition for Diagnosing and Treating Pseudoxanthoma Elasticum and Related Conditions". assignment.uspto.gov. Retrieved 2019-08-24.CS1 maint: uses authors parameter (link) 41. ^ Charles D. Boyd, Katalin Csiszar, Olivier LeSaux, Zsolt Urban, Sharon Terry. United States Patent and Trademark Office =. "Methods for Diagnosing Pseudoxanthoma Elasticum". assignment.uspto.gov. Retrieved 2019-08-24.CS1 maint: uses authors parameter (link) 42. ^ Terry SF (2003). "Learning genetics". Health Affairs. 22 (5): 166–71. doi:10.1377/hlthaff.22.5.166. PMID 14515892. 43. ^ Terry SF (March 2016). "Life as a numerator: Putting the person in personal genomics". Applied & Translational Genomics. 8: 40–1. doi:10.1016/j.atg.2016.01.007. PMC 4796705. PMID 27047760. 44. ^ Terry S, Science didn't understand my kids' rare disease until I decided to study it, retrieved 2019-08-24 45. ^ "Sharon Terry: When Siblings Get A Rare Diagnosis, Can Their Parents Find the Cure? TED Radio Hour". NPR.org. Retrieved 2019-08-24. ## External links[edit] * PXE international Classification D * ICD-10: Q82.8 (ILDS Q82.81) * ICD-9-CM: 757.39 * OMIM: 264800 * MeSH: D011561 * DiseasesDB: 10876 External resources * eMedicine: derm/359 oph/475 * Patient UK: Pseudoxanthoma elasticum * pxe at NIH/UW GeneTests * Pseudoxanthoma elasticum at NLM Genetics Home Reference * v * t * e Congenital malformations and deformations of integument / skin disease Genodermatosis Congenital ichthyosis/ erythrokeratodermia AD * Ichthyosis vulgaris AR * Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis * Lamellar ichthyosis * Harlequin-type ichthyosis * Netherton syndrome * Zunich–Kaye syndrome * Sjögren–Larsson syndrome XR * X-linked ichthyosis Ungrouped * Ichthyosis bullosa of Siemens * Ichthyosis follicularis * Ichthyosis prematurity syndrome * Ichthyosis–sclerosing cholangitis syndrome * Nonbullous congenital ichthyosiform erythroderma * Ichthyosis linearis circumflexa * Ichthyosis hystrix EB and related * EBS * EBS-K * EBS-WC * EBS-DM * EBS-OG * EBS-MD * EBS-MP * JEB * JEB-H * Mitis * Generalized atrophic * JEB-PA * DEB * DDEB * RDEB * related: Costello syndrome * Kindler syndrome * Laryngoonychocutaneous syndrome * Skin fragility syndrome Ectodermal dysplasia * Naegeli syndrome/Dermatopathia pigmentosa reticularis * Hay–Wells syndrome * Hypohidrotic ectodermal dysplasia * Focal dermal hypoplasia * Ellis–van Creveld syndrome * Rapp–Hodgkin syndrome/Hay–Wells syndrome Elastic/Connective * Ehlers–Danlos syndromes * Cutis laxa (Gerodermia osteodysplastica) * Popliteal pterygium syndrome * Pseudoxanthoma elasticum * Van der Woude syndrome Hyperkeratosis/ keratinopathy PPK * diffuse: Diffuse epidermolytic palmoplantar keratoderma * Diffuse nonepidermolytic palmoplantar keratoderma * Palmoplantar keratoderma of Sybert * Meleda disease * syndromic * connexin * Bart–Pumphrey syndrome * Clouston's hidrotic ectodermal dysplasia * Vohwinkel syndrome * Corneodermatoosseous syndrome * plakoglobin * Naxos syndrome * Scleroatrophic syndrome of Huriez * Olmsted syndrome * Cathepsin C * Papillon–Lefèvre syndrome * Haim–Munk syndrome * Camisa disease * focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis * Focal palmoplantar and gingival keratosis * Howel–Evans syndrome * Pachyonychia congenita * Pachyonychia congenita type I * Pachyonychia congenita type II * Striate palmoplantar keratoderma * Tyrosinemia type II * punctate: Acrokeratoelastoidosis of Costa * Focal acral hyperkeratosis * Keratosis punctata palmaris et plantaris * Keratosis punctata of the palmar creases * Schöpf–Schulz–Passarge syndrome * Porokeratosis plantaris discreta * Spiny keratoderma * ungrouped: Palmoplantar keratoderma and spastic paraplegia * desmoplakin * Carvajal syndrome * connexin * Erythrokeratodermia variabilis * HID/KID Other * Meleda disease * Keratosis pilaris * ATP2A2 * Darier's disease * Dyskeratosis congenita * Lelis syndrome * Dyskeratosis congenita * Keratolytic winter erythema * Keratosis follicularis spinulosa decalvans * Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome * Keratosis pilaris atrophicans faciei * Keratosis pilaris Other * cadherin * EEM syndrome * immune system * Hereditary lymphedema * Mastocytosis/Urticaria pigmentosa * Hailey–Hailey see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder Developmental anomalies Midline * Dermoid cyst * Encephalocele * Nasal glioma * PHACE association * Sinus pericranii Nevus * Capillary hemangioma * Port-wine stain * Nevus flammeus nuchae Other/ungrouped * Aplasia cutis congenita * Amniotic band syndrome * Branchial cyst * Cavernous venous malformation * Accessory nail of the fifth toe * Bronchogenic cyst * Congenital cartilaginous rest of the neck * Congenital hypertrophy of the lateral fold of the hallux * Congenital lip pit * Congenital malformations of the dermatoglyphs * Congenital preauricular fistula * Congenital smooth muscle hamartoma * Cystic lymphatic malformation * Median raphe cyst * Melanotic neuroectodermal tumor of infancy * Mongolian spot * Nasolacrimal duct cyst * Omphalomesenteric duct cyst * Poland anomaly * Rapidly involuting congenital hemangioma * Rosenthal–Kloepfer syndrome * Skin dimple * Superficial lymphatic malformation * Thyroglossal duct cyst * Verrucous vascular malformation * Birthmark * v * t * e Genetic disorder, membrane: ABC-transporter disorders ABCA * ABCA1 (Tangier disease) * ABCA3 (Surfactant metabolism dysfunction 3) * ABCA4 (Stargardt disease 1, Retinitis pigmentosa 19) * ABCA12 (Harlequin-type ichthyosis, Lamellar ichthyosis 2) ABCB * ABCB4 (Progressive familial intrahepatic cholestasis 3) * ABCB7 (ASAT) * ABCB11 (Progressive familial intrahepatic cholestasis 2) ABCC * ABCC2 (Dubin–Johnson syndrome) * ABCC6 (Pseudoxanthoma elasticum) * ABCC7 (Cystic fibrosis) * ABCC8 (HHF1, TNDM2) * ABCC9 (Dilated cardiomyopathy 1O) ABCD * ABCD1 (Adrenoleukodystrophy, Adrenomyeloneuropathy) ABCG * ABCG5 (Sitosterolemia) * ABCG8 (Gallbladder disease 4, Sitosterolemia) see also ABC transporters [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Pseudoxanthoma elasticum	c3279393	7,466	wikipedia	https://en.wikipedia.org/wiki/Pseudoxanthoma_elasticum	2021-01-18T18:29:41	{"gard": ["9643"], "mesh": ["D011561"], "umls": ["C3279393", "C0376359", "C3279392"], "orphanet": ["758"], "wikidata": ["Q1052391"]}
A number sign (#) is used with this entry because of evidence that Perrault syndrome-2 (PRLTS2) is caused by compound heterozygous mutation in the HARS2 gene (600783) on chromosome 5q31. One such family has been reported. Description Perrault syndrome-2 is an autosomal recessive disorder characterized by sensorineural deafness in both males and females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile (summary by Pierce et al., 2011). For a discussion of genetic heterogeneity of Perrault syndrome, see PRLTS1 (233400). Clinical Features Pallister and Opitz (1979) reported 3 sisters with ovarian dysgenesis and moderate to severe sensorineural deafness. The proband was a 13-year-old girl who lacked pubertal development and was found to have moderately severe hearing loss at age 3. She had some mild dysmorphic features, such as epicanthal folds and scrotal tongue. Pelvic examination showed infantile female external and internal genitalia with gonadal streaks. Two older sisters, ages 36 and 27 years, respectively, had a similar phenotype. Both had primary amenorrhea, sexual infantilism, streak gonads, and sensorineural hearing loss, although 1 had hearing loss first noted as an adult. Two older bothers in their thirties had early-onset sensorineural hearing loss but normal pubertal maturation and fertility. All females had normal 46,XX karyotypes. Both parents had normal hearing. Inheritance The transmission pattern of Perrault syndrome-2 in the family reported by Pallister and Opitz (1979) was consistent with autosomal recessive inheritance. Mapping By genomewide linkage analysis of a family with Perrault syndrome originally reported by Pallister and Opitz (1979), Pierce et al. (2011) found linkage to a 4.142-Mb region on chromosome 5q31 between D5S479 and D5S2508 (Z lod score of 3.10). Molecular Genetics In affected members of a family of European descent with Perrault syndrome, originally reported by Pallister and Opitz (1979), Pierce et al. (2011) identified compound heterozygosity for 2 mutations in the HARS2 gene (600783.0001 and 600783.0002). The mutations were found by linkage analysis followed by candidate gene sequencing. Functional studies showed that the mutations resulted in decreased enzyme activity, and knockdown of the HARS2 homolog in C. elegans caused severe gonadal defects and infertility. As the HARS2 gene encodes a histidyl-tRNA synthetase that functions in mitochondria, Pierce et al. (2011) speculated that aberrations of mitochondrial translation may affect mammalian dysgenesis. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, sensorineural GENITOURINARY External Genitalia (Female) \- Immature genitalia Internal Genitalia (Female) \- Ovarian dysgenesis \- Streak gonads ENDOCRINE FEATURES \- Amenorrhea, primary MISCELLANEOUS \- Onset of deafness in early childhood \- Affected females are infertile \- Affected males have normal pubertal development and are fertile \- One family has been reported (last curated November 2012) MOLECULAR BASIS \- Caused by mutation in the histidyl-tRNA synthetase 2 gene (HARS2, 600783.0001 ) ▲ 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	PERRAULT SYNDROME 2	c0685838	7,467	omim	https://www.omim.org/entry/614926	2019-09-22T15:53:46	{"doid": ["0050857"], "mesh": ["C537286"], "omim": ["614926"], "orphanet": ["2855"], "genereviews": ["NBK242617"]}
Familial thoracic aortic aneurysm and dissection (familial TAAD) involves problems with the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. Familial TAAD affects the upper part of the aorta, near the heart. This part of the aorta is called the thoracic aorta because it is located in the chest (thorax). Other vessels that carry blood from the heart to the rest of the body (arteries) can also be affected. In familial TAAD, the aorta can become weakened and stretched (aortic dilatation), which can lead to a bulge in the blood vessel wall (an aneurysm). Aortic dilatation may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection), allowing blood to flow abnormally between the layers. These aortic abnormalities are potentially life-threatening because they can decrease blood flow to other parts of the body such as the brain or other vital organs, or cause the aorta to break open (rupture). The occurrence and timing of these aortic abnormalities vary, even within the same affected family. They can begin in childhood or not occur until late in life. Aortic dilatation is generally the first feature of familial TAAD to develop, although in some affected individuals dissection occurs with little or no aortic dilatation. Aortic aneurysms usually have no symptoms. However, depending on the size, growth rate, and location of these abnormalities, they can cause pain in the jaw, neck, chest, or back; swelling in the arms, neck, or head; difficult or painful swallowing; hoarseness; shortness of breath; wheezing; a chronic cough; or coughing up blood. Aortic dissections usually cause severe, sudden chest or back pain, and may also result in unusually pale skin (pallor), a very faint pulse, numbness or tingling (paresthesias) in one or more limbs, or paralysis. Familial TAAD may not be associated with other signs and symptoms. However, some individuals in affected families show mild features of related conditions called Marfan syndrome or Loeys-Dietz syndrome. These features include tall stature, stretch marks on the skin, an unusually large range of joint movement (joint hypermobility), and either a sunken or protruding chest. Occasionally, people with familial TAAD develop aneurysms in the brain or in the section of the aorta located in the abdomen (abdominal aorta). Some people with familial TAAD have heart abnormalities that are present from birth (congenital). Affected individuals may also have a soft out-pouching in the lower abdomen (inguinal hernia), an abnormal curvature of the spine (scoliosis), or a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin (dermal capillaries). However, these conditions are also common in the general population. Depending on the genetic cause of familial TAAD in particular families, they may have an increased risk of developing blockages in smaller arteries, which can lead to heart attack and stroke. ## Frequency Familial TAAD is believed to account for at least 20 percent of thoracic aortic aneurysms and dissections. In the remainder of cases, the abnormalities are thought to be caused by factors that are not inherited, such as damage to the walls of the aorta from aging, tobacco use, injury, or disease. While aortic aneurysms are common worldwide, it is difficult to determine their exact prevalence because they usually cause no symptoms unless they rupture. Ruptured aortic aneurysms and dissections are estimated to cause almost 30,000 deaths in the United States each year. ## Causes Mutations in any of several genes are associated with familial TAAD. Mutations in the ACTA2 gene have been identified in 14 to 20 percent of people with this disorder, and TGFBR2 gene mutations have been found in 2.5 percent of affected individuals. Mutations in several other genes account for smaller percentages of cases. The ACTA2 gene provides instructions for making a protein called smooth muscle alpha (α)-2 actin, which is found in vascular smooth muscle cells. Layers of these cells are found in the walls of the aorta and other arteries. Within vascular smooth muscle cells, smooth muscle α-2 actin forms the core of structures called sarcomeres, which are necessary for muscles to contract. This ability to contract allows the arteries to maintain their shape instead of stretching out as blood is pumped through them. ACTA2 gene mutations that are associated with familial TAAD change single protein building blocks (amino acids) in the smooth muscle α-2 actin protein. These changes likely affect the way the protein functions in smooth muscle contraction, interfering with the sarcomeres' ability to prevent the arteries from stretching. The aorta, where the force of blood pumped directly from the heart is most intense, is particularly vulnerable to this stretching. Abnormal stretching of the aorta results in the aortic dilatation, aneurysms, and dissections that characterize familial TAAD. TGFBR2 gene mutations are also associated with familial TAAD. The TGFBR2 gene provides instructions for making a protein called transforming growth factor-beta (TGF-β) receptor type 2. This receptor transmits signals from the cell surface into the cell through a process called signal transduction. Through this type of signaling, the environment outside the cell affects activities inside the cell. In particular, the TGF-β receptor type 2 protein helps control the growth and division (proliferation) of cells and the process by which cells mature to carry out specific functions (differentiation). It is also involved in the formation of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells. TGFBR2 gene mutations alter the receptor's structure, which disturbs signal transduction. The disturbed signaling can impair cell growth and development. It is not known how these changes result in the specific aortic abnormalities associated with familial TAAD. Mutations in other genes, some of which have not been identified, are also associated with familial TAAD. ### Learn more about the genes associated with Familial thoracic aortic aneurysm and dissection * ACTA2 * FBN1 * MYH11 * SMAD3 * TGFBR1 * TGFBR2 Additional Information from NCBI Gene: * MYLK * PRKG1 ## Inheritance Pattern Familial TAAD is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell can be sufficient to cause the condition. In most cases, an affected person has one affected parent. However, some people who inherit an altered gene never develop the aortic abnormalities associated with the condition; this situation is known as reduced penetrance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Familial thoracic aortic aneurysm and dissection	c0392775	7,468	medlineplus	https://medlineplus.gov/genetics/condition/familial-thoracic-aortic-aneurysm-and-dissection/	2021-01-27T08:25:41	{"gard": ["2249"], "mesh": ["C536230"], "omim": ["607086", "607087", "132900", "611788", "613780", "615436"], "synonyms": []}
Lhermitte-Duclos disease (LDD) is a very rare, benign (non-cancerous) brain tumor, called a dysplastic gangliocytoma of the cerebellum, that is characterized by abnormal development and enlargement of the cerebellum, and an increased intracranial pressure. LDD manifests most commonly in the third and fourth decades of life. Symptoms may include headache, nausea, cerebellar dysfunction, hydrocephalus, ataxia (problems with movement and coordination), and visual disturbances. Other features may include an enlarged brain (megalencephaly), hydromyelia, extra fingers or toes (polydactyly), partial gigantism, and/or a large tongue (macroglossia). Lhermitte-Duclos disease can occur as an isolated condition; it is also associated with a hereditary cancer syndrome called Cowden disease. Although the exact cause is unknown, mutations in the PTEN gene have been identified in some individuals with LDD. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Lhermitte-Duclos disease	c0391826	7,469	gard	https://rarediseases.info.nih.gov/diseases/6901/lhermitte-duclos-disease	2021-01-18T17:59:25	{"mesh": ["D006223"], "omim": ["158350"], "umls": ["C0391826"], "orphanet": ["65285"], "synonyms": ["Dysplastic gangliocytoma of the cerebellum"]}
For a phenotypic description and a discussion of genetic heterogeneity of bipolar disorder, see 125480. Mapping Ferreira et al. (2008) tested 1.8 million variants in 4,387 cases of bipolar disorder and 6,209 controls from 3 independent samples and identified a region of strong association with SNP rs1006737 in the CACNA1C gene (114205) on chromosome 12p13.3. [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	MAJOR AFFECTIVE DISORDER 9	c2700440	7,470	omim	https://www.omim.org/entry/612372	2019-09-22T16:01:40	{"mesh": ["C567531"], "omim": ["612372"], "synonyms": ["Alternative titles", "BIPOLAR AFFECTIVE DISORDER"]}
A rare neurologic disease characterized by an unremitting bilateral symmetrical burning sensation of the oral mucosa without clinical evidence of causative lesions. It most frequently occurs in postmenopausal women and typically affects the tongue, less often the palate, lips, or buccal mucosa. It is often associated with dysgeusia and xerostomia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Burning mouth syndrome	c0006430	7,471	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=353253	2021-01-23T18:44:03	{"gard": ["5974"], "mesh": ["D002054"], "umls": ["C0006430", "C2930806"], "icd-10": ["K14.6"], "synonyms": ["BMS", "Oral dysesthesia", "Orodynia", "Stomatodynia", "Stomatopyrosis"]}
A rare joint formation defect characterized by a bony connection between the humerus and the ulna, resulting in fixed flexion of the forearm, usually near 90°. The condition may be associated with upper limb hypoplasia. It may be sporadic or familial and occur uni- or bilaterally. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Humero-ulnar synostosis	c0431799	7,472	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=94056	2021-01-23T17:26:50	{"umls": ["C0431799"], "icd-10": ["Q74.0"], "synonyms": ["Humero-ulnar fusion"]}
A number sign (#) is used with this entry because mitochondrial phosphate carrier deficiency can be caused by mutation in the SLC25A3 gene (600370). Clinical Features Mayr et al. (2007) described 2 sisters, offspring of nonconsanguineous Turkish parents, with mitochondrial phosphate carrier deficiency. The younger sister presented at age 12 hours with cyanosis and muscular hypotonia that necessitated intensive care treatment. Echocardiography revealed hypertrophic cardiomyopathy with low cardiac output. Lactate was constantly elevated in plasma. Cardiac hypertrophy was progressive. Severe muscular hypotonia and failure to thrive persisted. At age 4 months, she died from heart failure. Histologic examination of a muscle biopsy showed lipid myopathy with lipid accumulation in both fiber types, prominent in type I fibers. The elder sister presented at age 10 hours with muscular hypotonia, respiratory distress, metabolic acidosis (pH 6.9), and lactic acidosis that necessitated intensive care treatment. Artificial ventilation was necessary for 3 months. She developed increasing hypertrophic cardiomyopathy. Metabolic workup revealed constantly elevated plasma lactate and an increased lactate:pyruvate ratio of 62. At age 9 months, she died from intractable low-output hypertrophic heart failure. Molecular Genetics In 2 sibs with mitochondrial phosphate carrier deficiency, Mayr et al. (2007) identified homozygosity for a mutation in the alternatively spliced exon 3A of the SLC25A3 gene (600370.0001), which produces the heart/muscle-specific isoform of mitochondrial phosphate carrier protein. In both patients, functional investigation of intact mitochondria showed a deficiency of ATP synthetase in muscle but not in fibroblasts, which correlated with the tissue-specific expression of exon 3A in muscle versus exon 3B in fibroblasts. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	MITOCHONDRIAL PHOSPHATE CARRIER DEFICIENCY	c1835845	7,473	omim	https://www.omim.org/entry/610773	2019-09-22T16:04:05	{"mesh": ["C563665"], "omim": ["610773"], "orphanet": ["91130"], "synonyms": ["Alternative titles", "MPCD"]}
Halogenoderma SpecialtyDermatology Halogenodermas are skin eruptions that result after exposure to halogen-containing drugs or substances. This may last several weeks after drug use is discontinued. This is because of the slow elimination rate of iodides and bromides.[1] Fluoroderma is a particular type of halogenoderma which is caused by fluoride. Fluoride is present in oral hygiene products such as toothpastes and mouth washes, hence this type of acne is seen mostly around the mouth and jawline. Acute fluoroderma has been observed in patients exposed to anaesthetics containing fluoride such as sevoflurane.[2] ## Contents * 1 Cause * 2 Treatment * 3 See also * 4 References * 5 External links ## Cause[edit] This section is empty. You can help by adding to it. (September 2017) ## Treatment[edit] Medications given for halogenoderma may include topical and systemic corticosteroids, diuretics, and cyclosporine.[1] ## See also[edit] * Halogen acne * List of cutaneous conditions ## References[edit] 1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 310. ISBN 978-1-4160-2999-1. 2. ^ Perbet, S.; Salavert, M.; Amarger, S.; Constantin, J.-M.; D'Incan, M.; Bazin, J.-E. (1 July 2011). "Fluoroderma after exposure to sevoflurane". British Journal of Anaesthesia. 107 (1): 106–107. doi:10.1093/bja/aer180. PMID 21685121 – via bja.oxfordjournals.org. ## External links[edit] Classification D * SNOMED CT: 403624005 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	Halogenoderma	c1274946	7,474	wikipedia	https://en.wikipedia.org/wiki/Halogenoderma	2021-01-18T18:41:53	{"umls": ["C1274946"], "wikidata": ["Q5643382"]}
Prader-Willi syndrome (PWS) is a genetic condition that affects many parts of the body. Infants with PWS have severe hypotonia (low muscle tone), feeding difficulties, and slow growth. In later infancy or early childhood, affected children typically begin to eat excessively and become obese. Other signs and symptoms often include short stature, hypogonadism, developmental delays, cognitive impairment, and distinctive behavioral characteristics such as temper tantrums, stubbornness, and obsessive-compulsive tendencies. PWS is caused by missing or non-working genes on chromosome 15. Most cases are not inherited and occur randomly. Rarely, a genetic change responsible for PWS can be inherited. Management of PWS generally depends on the affected person's age and symptoms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration	Prader-Willi syndrome	c0032897	7,475	gard	https://rarediseases.info.nih.gov/diseases/5575/prader-willi-syndrome	2021-01-18T17:58:13	{"mesh": ["D011218"], "omim": ["176270"], "umls": ["C0032897"], "orphanet": ["739"], "synonyms": ["PWS", "Willi-Prader syndrome", "Prader-Labhart-Willi syndrome", "Obesity, muscular hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, and small hands and feet"]}
Behavioral disorder in which an adult fakes an illness in another, most commonly their child Factitious disorder imposed on another Other namesFactitious disorder by proxy, Munchausen syndrome by proxy (MSbP, MbP), fabricated or induced illness by carers (FII), medical child abuse Overview of factitious disorder imposed on another SpecialtyPsychiatry SymptomsVariable[1] CausesUnknown[2] Risk factorsPregnancy related complications, caregiver who was abused as a child or has factitious disorder imposed on self[3] Diagnostic methodRemoving the child from the caregiver results in improvement, video surveillance without the knowledge of the caregiver[4] Differential diagnosisMedical disorder, other forms of child abuse, delusional disorder[5] TreatmentRemoval of the child, therapy[2][4] FrequencyRelatively rare[4] Factitious disorder imposed on another (FDIA), also known as Munchausen syndrome by proxy (MSbP), is a condition in which a caregiver creates the appearance of health problems in another person, typically their child.[6] This may include injuring the child or altering test samples.[6] They then present the person as being sick or injured.[5] The behaviour occurs without a specific benefit to the caregiver.[5] Permanent injury or death of the child may occur as a result of the disorder.[6] The cause of FDIA is unknown.[2] The primary motive may be to gain attention and manipulate physicians.[4] Risk factors for FDIA include pregnancy related complications and a mother who was abused as a child or has factitious disorder imposed on self.[3] Diagnosis is supported when removing the child from the caregiver results in improvement of symptoms or video surveillance without the knowledge of the caregiver finds concerns.[4] Those affected by the disorder have been subjected to a form of physical abuse and medical neglect.[1] Management of FDIA may require putting the child in foster care.[2][4] It is not known how effective therapy is for FDIA; it is assumed it may work for those who admit they have a problem.[4] The prevalence of FDIA is unknown,[5] but it appears to be relatively rare.[4] More than 95% of cases involve a person's mother.[3] The prognosis for the mother is poor.[4] However, there is a burgeoning literature on possible courses of therapy.[3] The condition was first named in 1977 by British paediatrician Roy Meadow.[4] Some aspects of FDIA may represent criminal behavior.[5] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 2.1 Warning signs * 3 Epidemiology * 4 Society and culture * 4.1 Terminology * 4.2 Initial description * 4.3 Controversy * 4.4 Legal status * 4.5 Notable cases * 5 Directed towards animals * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] In factitious disorder imposed on another, a caregiver makes a dependent person appear mentally or physically ill in order to gain attention. To perpetuate the medical relationship, the caregiver systematically misrepresents symptoms, fabricates signs, manipulates laboratory tests, or even purposely harms the dependent (e.g. by poisoning, suffocation, infection, physical injury).[7] Studies have shown a mortality rate of between six and ten percent, making it perhaps the most lethal form of abuse.[8][9] In one study, the average age of the affected individual at the time of diagnosis was 4 years old. Slightly over 50% were aged 24 months or younger, and 75% were under six years old. The average duration from onset of symptoms to diagnosis was 22 months. By the time of diagnosis, six percent of the affected persons were dead, mostly from apnea (a common result of smothering) or starvation, and seven percent had long-term or permanent injury. About half of the affected had siblings; 25% of the known siblings were dead, and 61% of siblings had symptoms similar to the affected or that were otherwise suspicious. The mother was the perpetrator in 76.5% of the cases, the father in 6.7%.[9] Most present about three medical problems in some combination of the 103 different reported symptoms. The most-frequently reported problems are apnea (26.8% of cases), anorexia or feeding problems (24.6% of cases), diarrhea (20%), seizures (17.5%), cyanosis (blue skin) (11.7%), behavior (10.4%), asthma (9.5%), allergy (9.3%), and fevers (8.6%).[9] Other symptoms include failure to thrive, vomiting, bleeding, rash, and infections.[8][10] Many of these symptoms are easy to fake because they are subjective. A parent reporting that their child had a fever in the past 24 hours is making a claim that is impossible to prove or disprove. The number and variety of presented symptoms contribute to the difficulty in reaching a proper diagnosis. Aside from the motive (which is to gain attention or sympathy), another feature that differentiates FDIA from "typical" physical child abuse is the degree of premeditation involved. Whereas most physical abuse entails lashing out at a child in response to some behavior (e.g., crying, bedwetting, spilling food), assaults on the FDIA victim tend to be unprovoked and planned.[11] Also unique to this form of abuse is the role that health care providers play by actively, albeit unintentionally, enabling the abuse. By reacting to the concerns and demands of perpetrators, medical professionals are manipulated into a partnership of child maltreatment.[7] Challenging cases that defy simple medical explanations may prompt health care providers to pursue unusual or rare diagnoses, thus allocating even more time to the child and the abuser. Even without prompting, medical professionals may be easily seduced into prescribing diagnostic tests and therapies that are at best uncomfortable and costly, and at worst potentially injurious to the child.[1] If the health practitioner resists ordering further tests, drugs, procedures, surgeries, or specialists, the FDIA abuser makes the medical system appear negligent for refusing to help a sick child and their selfless parent.[7] Like those with Munchausen syndrome, FDIA perpetrators are known to switch medical providers frequently until they find one that is willing to meet their level of need; this practice is known as "doctor shopping" or "hospital hopping". The perpetrator continues the abuse because maintaining the child in the role of patient satisfies the abuser's needs. The cure for the victim is to separate the child completely from the abuser. When parental visits are allowed, sometimes there is a disastrous outcome for the child. Even when the child is removed, the perpetrator may then abuse another child: a sibling or other child in the family.[7] Factitious disorder imposed on another can have many long-term emotional effects on a child. Depending on their experience of medical interventions, a percentage of children may learn that they are most likely to receive the positive maternal attention they crave when they are playing the sick role in front of health care providers. Several case reports describe Munchausen syndrome patients suspected of themselves having been FDIA victims.[12] Seeking personal gratification through illness can thus become a lifelong and multi-generational disorder in some cases.[7] In stark contrast, other reports suggest survivors of FDIA develop an avoidance of medical treatment with post-traumatic responses to it.[13] This variation possibly reflects broad statistics on survivors of child abuse in general, where around 35% of abusers were a victim of abuse in the past.[14][improper synthesis?] The adult caregiver who has abused the child often seems comfortable and not upset over the child's hospitalization. While the child is hospitalized, medical professionals must monitor the caregiver's visits to prevent an attempt to worsen the child's condition.[15] In addition, in many jurisdictions, medical professionals have a duty to report such abuse to legal authorities.[16] ## Diagnosis[edit] Munchausen syndrome by proxy is a controversial term. In the World Health Organization's International Statistical Classification of Diseases, 10th Revision (ICD-10), the official diagnosis is factitious disorder (301.51 in ICD-9, F68.12 in ICD-10). Within the United States, factitious disorder imposed on another (FDIA or FDIoA) was officially recognized as a disorder in 2013,[5] while in the United Kingdom, it is known as fabricated or induced illness by carers (FII).[17] In DSM-5, the diagnostic manual published by the American Psychiatric Association in 2013, this disorder is listed under 300.19 Factitious disorder. This, in turn, encompasses two types:[5] * Factitious disorder imposed on self – (formerly Munchausen syndrome). * Factitious disorder imposed on another – (formerly Munchausen syndrome by proxy); diagnosis assigned to the perpetrator; the person affected may be assigned an abuse diagnosis (e.g. child abuse). ### Warning signs[edit] Warning signs of the disorder include:[15] * A child who has one or more medical problems that do not respond to treatment or that follow an unusual course that is persistent, puzzling, and unexplained. * Physical or laboratory findings that are highly unusual, discrepant with patient's presentation or history, or physically or clinically impossible. * A parent who appears medically knowledgeable, fascinated with medical details and hospital gossip, appears to enjoy the hospital environment, and expresses interest in the details of other patients' problems. * A highly attentive parent who is reluctant to leave their child's side and who themselves seem to require constant attention. * A parent who appears unusually calm in the face of serious difficulties in their child's medical course while being highly supportive and encouraging of the physician, or one who is angry, devalues staff, and demands further intervention, more procedures, second opinions, and transfers to more sophisticated facilities. * The suspected parent may work in the health-care field themselves or profess an interest in a health-related job. * The signs and symptoms of a child's illness may lessen or simply vanish in the parent's absence (hospitalization and careful monitoring may be necessary to establish this causal relationship). * A family history of similar or unexplained illness or death in a sibling. * A parent with symptoms similar to their child's own medical problems or an illness history that itself is puzzling and unusual. * A suspected emotionally distant relationship between parents; the spouse often fails to visit the patient and has little contact with physicians even when the child is hospitalized with a serious illness. * A parent who reports dramatic, negative events, such as house fires, burglaries, or car accidents, that affect them and their family while their child is undergoing treatment. * A parent who seems to have an insatiable need for adulation or who makes self-serving efforts for public acknowledgment of their abilities. * A child who inexplicably deteriorates whenever discharge is planned. * A child that looks for cueing from a parent in order to feign illness when medical personnel are present. * A child that is overly articulate regarding medical terminology and their own disease process for their age. * A child that presents to the Emergency Department with a history of repeat illness, injury, or hospitalization. ## Epidemiology[edit] FDIA is rare. A study in Italy found that 4 out of more than 700 children admitted to the hospital met the criteria (0.53%). In this study, stringent diagnostic criteria were used, which required at least one test outcome or event that could not possibly have occurred without deliberate intervention by the FDIA person.[18] One study showed that in 93 percent of FDIA cases, the abuser is the mother or another female guardian or caregiver.[11] A psychodynamic model of this kind of maternal abuse exists.[19] FDIA may be more prevalent in the parents of those with a learning difficulty or mental incapacity, and as such the apparent patient could, in fact, be an adult.[citation needed] Fathers and other male caregivers have been the perpetrators in only seven percent of the cases studied.[9] When they are not actively involved in the abuse, the fathers or male guardians of FDIA victims are often described as being distant, emotionally disengaged, and powerless. These men play a passive role in FDIA by being frequently absent from the home and rarely visiting the hospitalized child. Usually, they vehemently deny the possibility of abuse, even in the face of overwhelming evidence or their child's pleas for help.[7][11] Overall, male and female children are equally likely to be the victim of FDIA. In the few cases where the father is the perpetrator, however, the victim is three times more likely to be male.[9] ## Society and culture[edit] ### Terminology[edit] The term "Munchausen syndrome by proxy", in the United States, has never officially been included as a discrete mental disorder by the American Psychiatric Association,[20] which publishes the Diagnostic and Statistical Manual of Mental Disorders (DSM), now in its fifth edition.[5] Although the DSM-III (1980) and DSM-III-R (1987) included Munchausen syndrome, they did not include MSbP. DSM-IV (1994) and DSM-IV-TR (2000) added MSbP as a proposal only, and although it was finally recognized as a disorder in DSM-5 (2013), each of the last three editions of the DSM designated the disorder by a different name. FDIA has been given different names in different places and at different times. What follows is a partial list of alternative names that have been either used or proposed (with approximate dates):[17] * Factitious Disorder Imposed on Another (current) (U.S., 2013) American Psychiatric Association, DSM-5 * Factitious Disorder by Proxy (FDP, FDbP) (proposed) (U.S., 2000) American Psychiatric Association, DSM-IV-TR[21] * Fictitious Disorder by Proxy (FDP, FDbP) (proposed) (U.S., 1994) American Psychiatric Association, DSM-IV * Fabricated or Induced Illness by Carers (FII) (U.K., 2002) The Royal College of Pediatrics and Child Health[22] * Factitious Illness by Proxy (1996) World Health Organization[23] * Pediatric Condition Falsification (PCF) (proposed) (U.S., 2002) American Professional Society on the Abuse of Children proposed this term to diagnose the victim (child); the perpetrator (caregiver) would be diagnosed "factitious disorder by proxy"; MSbP would be retained as the name applied to the 'disorder' that contains these two elements, a diagnosis in the child and a diagnosis in the caretaker.[24] * Induced Illness (Munchausen Syndrome by Proxy) (Ireland, 1999–2002) Department of Health and Children[17] * Meadow's Syndrome (1984–1987) named after Roy Meadow.[25] This label, however, had already been in use since 1957 to describe a completely unrelated and rare form of cardiomyopathy.[26] * Polle Syndrome (1977–1984) coined by Burman and Stevens, from the then-common belief that Baron Münchhausen's second wife gave birth to a daughter named Polle during their marriage.[27][28] The baron declared that the baby was not his, and the child died from "seizures" at the age of 10 months. The name fell out of favor after 1984, when it was discovered that Polle was not the baby's name, but rather was the name of her mother's hometown.[29][30] While it initially included only the infliction of harmful medical care, the term has subsequently been extended to include cases in which the only harm arose from medical neglect, noncompliance, or even educational interference.[1] The term is derived from Munchausen syndrome, a psychiatric factitious disorder wherein those affected feign disease, illness, or psychological trauma to draw attention, sympathy, or reassurance to themselves.[31] Munchausen syndrome by proxy perpetrators, by contrast, are willing to fulfill their need for positive attention by hurting their own child, thereby assuming the sick role onto their child, by proxy. These proxies then gain personal attention and support by taking on this fictitious "hero role" and receive positive attention from others, by appearing to care for and save their so-called sick child.[7] They are named after Baron Munchausen, a literary character based on Hieronymus Karl Friedrich, Freiherr von Münchhausen (1720–1797), a German nobleman and well-known storyteller. In 1785, writer and con artist Rudolf Erich Raspe anonymously published a book in which a fictional version of "Baron Munchausen" tells fantastic and impossible stories about himself, establishing a popular literary archetype of a bombastic exaggerator.[32][33] ### Initial description[edit] "Munchausen syndrome" was first described by R. Asher in 1951[34] as when someone invents or exaggerates medical symptoms, sometimes engaging in self-harm, to gain attention or sympathy. The term "Munchausen syndrome by proxy" was first coined by John Money and June Faith Werlwas in a 1976 paper titled Folie à deux in the parents of psychosocial dwarfs: Two cases[35][36] to describe the abuse-induced and neglect-induced symptoms of the syndrome of abuse dwarfism. That same year, Sneed and Bell wrote an article titled The Dauphin of Munchausen: factitious passage of renal stones in a child.[37] According to other sources, the term was created by the British pediatrician Roy Meadow in 1977.[29][38][39] In 1977, Roy Meadow – then professor of pediatrics at the University of Leeds, England – described the extraordinary behavior of two mothers. According to Meadow, one had poisoned her toddler with excessive quantities of salt. The other had introduced her own blood into her baby's urine sample. This second case occurred during a series of Outpatient visits to the Paediatric Clinic of Dr. Bill Arrowsmith at Doncaster Royal Infirmary. He referred to this behavior as Munchausen syndrome by proxy (MSbP).[40] The medical community was initially skeptical of FDIA's existence, but it gradually gained acceptance as a recognized condition. There are now more than 2,000 case reports of FDIA in the literature. Reports come from developing countries, as well as the U.S., with one case from 2012–2013, in Orlando, Florida, and the most recent in Westchester, New York, in early 2015.[relevant? – discuss] Other reports come from Sri Lanka, Nigeria, and Oman.[41] ### Controversy[edit] See also: List of wrongful convictions in the United States During the 1990s and early 2000s, Roy Meadow was an expert witness in several murder cases involving MSbP/FII. Meadow was knighted for his work for child protection, though later, his reputation, and consequently the credibility of MSbP, became damaged when several convictions of child killing, in which he acted as an expert witness, were overturned. The mothers in those cases were wrongly convicted of murdering two or more of their children, and had already been imprisoned for up to six years.[42][39] One case was that of Sally Clark. Clark was a lawyer wrongly convicted in 1999 of the murder of her two baby sons, largely on the basis of Meadow's evidence. As an expert witness for the prosecution, Meadow asserted that the odds of there being two unexplained infant deaths in one family were one in 73 million. That figure was crucial in sending Clark to jail but was hotly disputed by the Royal Statistical Society, who wrote to the Lord Chancellor to complain.[43] It was subsequently shown that the true odds were much greater once other factors (e.g. genetic or environmental) were taken into consideration, meaning that there was a significantly higher likelihood of two deaths happening as a chance occurrence than Meadow had claimed during the trial. Those odds in fact range from a low of 1:8500 to as high as 1:200.[44] It emerged later that there was clear evidence of a Staphylococcus aureus infection that had spread as far as the child's cerebrospinal fluid.[45] Clark was released in January 2003 after three judges quashed her convictions in the Court of Appeal in London,[45][46] but suffering from catastrophic trauma of the experience, she later died from alcohol poisoning. Meadow was involved as a prosecution witness in three other high-profile cases resulting in mothers being imprisoned and subsequently cleared of wrongdoing: Trupti Patel,[47] Angela Cannings[48] and Donna Anthony.[49] In 2003, Lord Howe, the Opposition spokesman on health, accused Meadow of inventing a "theory without science" and refusing to produce any real evidence to prove that Munchausen syndrome by proxy actually exists. It is important to distinguish between the act of harming a child, which can be easily verified, and motive, which is much harder to verify and which FDIA tries to explain. For example, a caregiver may wish to harm a child out of malice and then attempt to conceal it as illness to avoid detection of abuse, rather than to draw attention and sympathy. The distinction is often crucial in criminal proceedings, in which the prosecutor must prove both the act and the mental element constituting a crime to establish guilt. In most legal jurisdictions, a doctor can give expert witness testimony as to whether a child was being harmed but cannot speculate regarding the motive of the caregiver. FII merely refers to the fact that illness is induced or fabricated and does not specifically limit the motives of such acts to a caregiver's need for attention and/or sympathy. In all, around 250 cases resulting in conviction in which Meadow was an expert witness were reviewed, with few[citation needed] changes, but all where the only evidence was Meadow’s expert testimony were overturned. Meadow was investigated by the British General Medical Council (GMC) over evidence he gave in the Sally Clark trial. In July 2005, the GMC declared Meadow guilty of "serious professional misconduct", and he was struck off the medical register for giving "erroneous" and "misleading" evidence.[50] At appeal, High Court judge Mr. Justice Collins said that the severity of his punishment "approaches the irrational" and set it aside.[51][52] Collins's judgment raises important points concerning the liability of expert witnesses – his view is that referral to the GMC by the losing side is an unacceptable threat and that only the Court should decide whether its witnesses are seriously deficient and refer them to their professional bodies.[53] In addition to the controversy surrounding expert witnesses, an article appeared in the forensic literature that detailed legal cases involving controversy surrounding the murder suspect.[54] The article provides a brief review of the research and criminal cases involving Munchausen syndrome by proxy in which psychopathic mothers and caregivers were the murderers. It also briefly describes the importance of gathering behavioral data, including observations of the parents who commit the criminal acts. The article references the 1997 work of Southall, Plunkett, Banks, Falkov, and Samuels, in which covert video recorders were used to monitor the hospital rooms of suspected FDIA victims. In 30 out of 39 cases, a parent was observed intentionally suffocating their child; in two they were seen attempting to poison a child; in another, the mother deliberately broke her 3-month-old daughter's arm. Upon further investigation, those 39 patients, ages 1 month to 3 years old, had 41 siblings; 12 of those had died suddenly and unexpectedly.[55] The use of covert video, while apparently extremely effective, raises controversy in some jurisdictions over privacy rights. ### Legal status[edit] In most legal jurisdictions, doctors are allowed to give evidence only in regard to whether the child is being harmed. They are not allowed to give evidence in regard to the motive. Australia and the UK have established the legal precedent that FDIA does not exist as a medico-legal entity. In a June 2004 appeal hearing, the Supreme Court of Queensland, Australia, stated: > As the term factitious disorder (Munchausen's Syndrome) by proxy is merely descriptive of a behavior, not a psychiatrically identifiable illness or condition, it does not relate to an organized or recognized reliable body of knowledge or experience. Dr. Reddan's evidence was inadmissible.[56] The Queensland Supreme Court further ruled that the determination of whether or not a defendant had caused intentional harm to a child was a matter for the jury to decide and not for the determination by expert witnesses: > The diagnosis of Doctors Pincus, Withers, and O'Loughlin that the appellant intentionally caused her children to receive unnecessary treatment through her own acts and the false reporting of symptoms of the factitious disorder (Munchausen Syndrome) by proxy is not a diagnosis of a recognized medical condition, disorder, or syndrome. It is simply placing her within the medical term used in the category of people exhibiting such behavior. In that sense, their opinions were not expert evidence because they related to matters that could be decided on the evidence by ordinary jurors. The essential issue as to whether the appellant reported or fabricated false symptoms or did acts to intentionally cause unnecessary medical procedures to injure her children was a matter for the jury's determination. The evidence of Doctors Pincus, Withers, and O'Loughlin that the appellant was exhibiting the behavior of factitious disorder (Munchausen syndrome by proxy) should have been excluded.[57] Principles of law and implications for legal processes that may be deduced from these findings are that: * Any matters brought before a Court of Law should be determined by the facts, not by suppositions attached to a label describing a behavior, i.e., MSBP/FII/FDBP; * MSBP/FII/FDBP is not a mental disorder (i.e., not defined as such in DSM IV), and the evidence of a psychiatrist should not therefore be admissible; * MSBP/FII/FDBP has been stated to be a behavior describing a form of child abuse and not a medical diagnosis of either a parent or a child. A medical practitioner cannot therefore state that a person "suffers" from MSBP/FII/FDBP, and such evidence should also therefore be inadmissible. The evidence of a medical practitioner should be confined to what they observed and heard and what forensic information was found by recognized medical investigative procedures; * A label used to describe a behavior is not helpful in determining guilt and is prejudicial. By applying an ambiguous label of MSBP/FII to a woman is implying guilt without factual supportive and corroborative evidence; * The assertion that other people may behave in this way, i.e., fabricate and/or induce illness in children to gain attention for themselves (FII/MSBP/FDBY), contained within the label is not factual evidence that this individual has behaved in this way. Again therefore, the application of the label is prejudicial to fairness and a finding based on fact. The Queensland Judgment was adopted into English law in the High Court of Justice by Mr. Justice Ryder. In his final conclusions regarding Factitious Disorder, Ryder states that: > I have considered and respectfully adopt the dicta of the Supreme Court of Queensland in R v. LM [2004] QCA 192 at paragraph 62 and 66. I take full account of the criminal law and foreign jurisdictional contexts of that decision but I am persuaded by the following argument upon its face that it is valid to the English law of evidence as applied to children proceedings. > > The terms "Munchausen syndrome by proxy" and "factitious (and induced) illness (by proxy)" are child protection labels that are merely descriptions of a range of behaviors, not a pediatric, psychiatric or psychological disease that is identifiable. The terms do not relate to an organized or universally recognized body of knowledge or experience that has identified a medical disease (i.e. an illness or condition) and there are no internationally accepted medical criteria for the use of either label. > > In reality, the use of the label is intended to connote that in the individual case there are materials susceptible of analysis by pediatricians and of findings of fact by a court concerning fabrication, exaggeration, minimization or omission in the reporting of symptoms and evidence of harm by act, omission or suggestion (induction). Where such facts exist the context and assessments can provide an insight into the degree of risk that a child may face and the court is likely to be assisted as to that aspect by psychiatric and/or psychological expert evidence. > > All of the above ought to be self evident and has in any event been the established teaching of leading pediatricians, psychiatrists and psychologists for some while. That is not to minimize the nature and extent of professional debate about this issue which remains significant, nor to minimize the extreme nature of the risk that is identified in a small number of cases. > > In these circumstances, evidence as to the existence of MSBP or FII in any individual case is as likely to be evidence of mere propensity which would be inadmissible at the fact finding stage (see Re CB and JB supra). For my part, I would consign the label MSBP to the history books and however useful FII may apparently be to the child protection practitioner I would caution against its use other than as a factual description of a series of incidents or behaviors that should then be accurately set out (and even then only in the hands of the pediatrician or psychiatrist/psychologist). I cannot emphasis too strongly that my conclusion cannot be used as a reason to re-open the many cases where facts have been found against a carer and the label MSBP or FII has been attached to that carer's behavior. What I seek to caution against is the use of the label as a substitute for factual analysis and risk assessment.[58] In his book Playing Sick (2004), Marc Feldman notes that such findings have been in the minority among U.S. and even Australian courts. Pediatricians and other physicians have banded together to oppose limitations on child-abuse professionals whose work includes FII detection.[59] The April 2007 issue of the journal Pediatrics specifically mentions Meadow as an individual who has been inappropriately maligned. ### Notable cases[edit] Beverley Allitt, a British nurse who murdered four children and injured a further nine in 1991 at Grantham and Kesteven Hospital, Lincolnshire, was diagnosed with Munchausen syndrome by proxy.[60] Wendi Michelle Scott is a Frederick, Maryland, mother who was charged with sickening her four-year-old daughter.[61] The book Sickened, by Julie Gregory, details her life growing up with a mother suffering from Munchausen by proxy, who took her to various doctors, coached her to act sicker than she was and to exaggerate her symptoms, and who demanded increasingly invasive procedures to diagnose Gregory's enforced imaginary illnesses.[62] Lisa Hayden-Johnson of Devon was jailed for three years and three months after subjecting her son to a total of 325 medical actions – including being forced to use a wheelchair and being fed through a tube in his stomach. She claimed her son had a long list of illnesses including diabetes, food allergies, cerebral palsy, and cystic fibrosis, describing him as "the most ill child in Britain" and receiving numerous cash donations and charity gifts, including two cruises.[63] In the mid-1990s, Kathy Bush gained public sympathy for the plight of her daughter, Jennifer, who by the age of 8 had undergone 40 surgeries and spent over 640 days in hospitals[64] for gastrointestinal disorders. The acclaim led to a visit with first lady Hillary Clinton, who championed the Bushs' plight as evidence of need for medical reform. However, in 1996, Kathy Bush was arrested and charged with child abuse and Medicaid fraud, accused of sabotaging Jennifer's medical equipment and drugs to agitate and prolong her illness.[64] Jennifer was moved to foster care where she quickly regained her health. The prosecutors claimed Kathy was driven by Munchausen Syndrome by Proxy, and she was convicted to a five-year sentence in 1999.[65] Kathy was released after serving three years in 2005, always maintaining her innocence, and having gotten back in contact with Jennifer via correspondence.[66] In 2014, 26-year-old Lacey Spears was charged in Westchester County, New York, with second-degree depraved murder and first-degree manslaughter. She fed her son dangerous amounts of salt after she conducted research on the Internet about its effects. Her actions were allegedly motivated by the social media attention she gained on Facebook, Twitter, and blogs. She was convicted of second-degree murder on March 2, 2015,[67] and sentenced to 20 years to life in prison.[68] Dee Dee Blanchard was a Missouri mother who was murdered by her daughter and a boyfriend in 2015 after having claimed for years that her daughter, Gypsy Rose, was sick and disabled; to the point of shaving her head, making her use a wheelchair in public, and subjecting her to unnecessary medication and surgery. Gypsy possessed no outstanding illnesses. Feldman said it is the first case he is aware of in a quarter-century of research where the victim killed the abuser.[69] Their story was shown on HBO's documentary film Mommy Dead and Dearest[70] and is featured in the first season of the Hulu anthology series The Act.[71] Gypsy Rose pleaded guilty to second-degree murder and is serving a ten year sentence, her boyfriend was convicted of first-degree murder and is sentenced to life in prison without parole. Rapper Eminem has spoken about how his mother would frequently take him to hospitals to receive treatment for illnesses that he did not have. His song “Cleanin' Out My Closet” includes a lyric regarding the illness, “...going through public housing systems victim of Münchausen syndrome. My whole life I was made to believe I was sick, when I wasn’t ‘til I grew up and blew up...” His mother's illness resulted in Eminem receiving custody of his younger brother, Nathan.[72] In 2013, Boston Children's Hospital filed a 51A report to take custody of Justina Pelletier, who was 14 at the time. At 21 she was living with her parents. Her parents are suing Boston Children's Hospital, alleging that their civil rights were violated when she was committed to a psychiatric ward and their access to her was limited. At the trial, Pelletier's treating neurologist described how her parents encouraged her to be sick and were endangering her health.[73] ## Directed towards animals[edit] Medical literature describes a subset of FDIA caregivers, where the proxy is a pet rather than another person. These cases are labeled Munchausen syndrome by proxy: pet (MSbP:P). In these cases, pet owners correspond to caregivers in traditional FDIA presentations involving human proxies.[74] No extensive survey has yet been made of the extant literature, and there has been no speculation as to how closely FDIA:P tracks with human FDIA.[citation needed] ## See also[edit] * Psychosomatic illness * Munchausen by Internet * Folie à deux * Hypochondria ## References[edit] 1. ^ a b c d Stirling J; American Academy of Pediatrics Committee on Child Abuse Neglect (May 2007). "Beyond Munchausen syndrome by proxy: identification and treatment of child abuse in a medical setting". Pediatrics. Berlin, Germany: Karger Publishers. 119 (5): 1026–30. doi:10.1542/peds.2007-0563. PMID 17473106. 2. ^ a b c d Jacoby, David B.; Youngson, R. M. (2004). Encyclopedia of Family Health. Marshall Cavendish. p. 1286. ISBN 9780761474869. 3. ^ a b c d Yates, G; Bass, C (October 2017). "The perpetrators of medical child abuse (Munchausen Syndrome by Proxy) - A systematic review of 796 cases". Child Abuse & Neglect. 72: 45–53. doi:10.1016/j.chiabu.2017.07.008. PMID 28750264. 4. ^ a b c d e f g h i j Myers, John E. B. (2005). Myers on Evidence in Child, Domestic, and Elder Abuse Cases. Aspen Publishers Online. pp. 280–282. ISBN 9780735556683. 5. ^ a b c d e f g h American Psychiatric Association (2013), Diagnostic and Statistical Manual of Mental Disorders (5th ed.), Arlington: American Psychiatric Publishing, pp. 324–326, ISBN 978-0890425558 6. ^ a b c "Factitious Disorder Imposed on Self - Psychiatric Disorders". Merck Manuals Professional Edition. Retrieved 28 April 2019. 7. ^ a b c d e f g Criddle, L. (2010). "Monsters in the Closet: Munchausen Syndrome by Proxy" (PDF). CriticalCareNurse. American Association of Critical-Care Nurses. 30 (6): 46–55. doi:10.4037/ccn2010737. PMID 21123232. Archived from the original (PDF) on 2014-02-01. Retrieved 2 February 2012. 8. ^ a b Christie-Smith, D.; Gartner, C. (1 January 2005). "Understanding Munchausen syndrome by proxy". Special Report: Highlights of the 2004 Institute on Psychiatric Services. PsychiatryOnline.org. Retrieved 30 January 2012. 9. ^ a b c d e Sheridan, Mary S. (April 2003). "The deceit continues: an updated literature review of Munchausen Syndrome by proxy". Child Abuse Negl. 27 (4): 431–451. doi:10.1016/S0145-2134(03)00030-9. ISSN 0145-2134. PMID 12686328. Unknown ID:668TR. 10. ^ Sheslow, D.V.; Gavin-Devitt, L.A. (2008). "Munchausen by proxy syndrome". KidsHealth from Nemours. Retrieved 27 August 2010. 11. ^ a b c Schreier, HA (2004). "Munchausen by Proxy". Curr Probl Pediatr Adolesc Health Care. 34 (3): 126–143. doi:10.1016/j.cppeds.2003.09.003. PMID 15039661. 12. ^ Libow, JA. (2002). "Beyond collusion: active illness falsification". Child Abuse Negl. 26 (5): 525–536. doi:10.1016/S0145-2134(02)00328-9. PMID 12079088. 13. ^ Libow, JA. (1995). "Munchausen by proxy victims in adulthood: a first look". Child Abuse Negl. 19 (9): 1131–1142. doi:10.1016/0145-2134(95)00073-H. PMID 8528818. 14. ^ Glasser, M; Kolvin, I; Campbell, D; Glasser, A; Leitch, I; Farrelly, S (2001). "Cycle of child sexual abuse: links between being a victim and becoming a perpetrator". Br J Psychiatry. 179 (6): 482–94, discussion 495–7. doi:10.1192/bjp.179.6.482. PMID 11731348. 15. ^ a b Schreier, Herbert A.; Judith A. Libow (1993). Hurting for Love: Munchausen by Proxy Syndrome. The Guilford Press. ISBN 0-89862-121-6. 16. ^ Elder W, Coletsos IC, Bursztajn HJ. Factitious Disorder/Munchhausen Syndrome. The 5-Minute Clinical Consult. 18th Edition. 2010. Editor: Domino F.J. Wolters Kluwer/Lippincott. Philadelphia.[page needed] 17. ^ a b c Burns, Kenneth (January 2004). "Fabrication or Induction of Illness in a Child: a Critical Review of Labels and Literature Using Electronic Libraries" (PDF). Irish Journal of Applied Social Studies. 5 (1): 74–92. Retrieved 3 February 2012. 18. ^ Ferrara, P; Vitelli, O; Bottaro, G; Gatto, A; Liberatore, P; Binetti, P; Stabile, A (December 2013). "Factitious disorders and Munchausen syndrome: the tip of the iceberg". Journal of Child Health Care : For Professionals Working with Children in the Hospital and Community. 17 (4): 366–74. doi:10.1177/1367493512462262. PMID 23411659. S2CID 21162745. 19. ^ See Anna Motz's The Psychology of Female Violence: Crimes Against the Body (Routledge, 2001 ISBN 978-0-415-12675-5, 2nd ed. forthcoming 2008 ISBN 978-0-415-40387-0). 20. ^ Lasher, Louisa (2011). "MBP Definitions, Maltreatment Behaviors, and Comments". Archived from the original on 2011-08-12. Retrieved 30 January 2012. 21. ^ Diagnostic and statistical manual of mental disorders: DSM-IV-TR. American Psychiatric Association, Task Force on DSM-IV. 2000. ISBN 978-0-89042-025-6. LCCN 00024852. 22. ^ "Fabricated or Induced Illness by Carers (FII)". Professional Reference. patient.info. Retrieved 2 February 2012. 23. ^ de Silva, Prof. D.G. Harendra; Hobbs, Dr Christopher J. (2004). "Managing Child Abuse: A Handbook for Medical Officers" (PDF). World Health Organization. pp. 36–38. Archived from the original (PDF) on 2011-05-22. Retrieved 30 January 2012. 24. ^ Schreier, H. (2002). "Munchausen by Proxy Defined". Pediatrics. 110 (5): 985–8. doi:10.1542/peds.110.5.985. PMID 12415040. 25. ^ "Meadow and Munchausen". The Lancet. 321 (8322): 456. 1983. doi:10.1016/S0140-6736(83)91450-2. S2CID 34872993. 26. ^ Lazoritz, S. (September 1987). "Munchausen by proxy or Meadow's syndrome?". The Lancet. 330 (8559): 631. doi:10.1016/S0140-6736(87)93025-X. PMID 2887921. S2CID 851898. 27. ^ Burman D, Stevens D (27 August 1977). "Munchausen family". The Lancet. London. 310 (8035): 456. doi:10.1016/S0140-6736(77)90639-0. PMID 70666. S2CID 42872268. 28. ^ Verity, CM; Winckworth, C; Burman, D; Stevens, D; White, RJ (18 August 1979). "Polle syndrome: children of Munchausen". British Medical Journal. 2 (6187): 422–423. doi:10.1136/bmj.2.6187.422. PMC 1595620. PMID 486971. 29. ^ a b Meadow R, Lennert T (October 1984). "Munchausen syndrome by proxy or Polle syndrome: which term is correct?". Pediatrics. 74 (4): 554–55. PMID 6384913. 30. ^ Haddy, R. (1993). "The Münchhausen of Munchausen Syndrome: A Historical Perspective" (PDF). Archives of Family Medicine. 2 (2): 141–42. doi:10.1001/archfami.2.2.141. PMID 8275182.[permanent dead link] 31. ^ Factitious Disorder Imposed on Self at eMedicine 32. ^ McCoy, Monica L.; Keen, Stefanie M. (2013). Child Abuse and Neglect: Second Edition. Psychology Press. p. 210. ISBN 978-1136322877. Retrieved July 10, 2015. 33. ^ Olry, R. (June 2002), "Baron Munchhausen and the Syndrome Which Bears His Name: History of an Endearing Personage and of a Strange Mental Disorder" (PDF), Vesalius, VIII (1): 53–57, retrieved July 10, 2015 34. ^ Asher, R. (10 February 1951). "Munchausen's syndrome". The Lancet. 1 (6650): 339–41. doi:10.1016/S0140-6736(51)92313-6. PMID 14805062. 35. ^ Money, John; Werlwas, June (1976). "Folie à deux in the parents of psychosocial dwarfs: Two cases". Bulletin of the American Academy of Psychiatry and the Law. 4 (4): 351–362. PMID 1028417. 36. ^ Money, J. (1986). "Munchausen's Syndrome by Proxy: Update". Journal of Pediatric Psychology. 11 (4): 583–584. doi:10.1093/jpepsy/11.4.583. PMID 3559846. Retrieved 30 January 2012. 37. ^ Sneed, R.C., Bell R.F. (1 July 1976). "The Dauphin of Munchausen: Factitious Passage of Renal Stones in a Child". Pediatrics. 58 (1): 127–130. PMID 934770. Retrieved 30 January 2012.CS1 maint: multiple names: authors list (link) 38. ^ "Definition of Munchausen syndrome by proxy". MedicineNet.com. 39. ^ a b BBC (10 December 2003). "Profile: Sir Roy Meadow". BBC News. Retrieved 1 February 2007. 40. ^ Meadow, Roy (1977). "Munchausen Syndrome by Proxy: the Hinterlands of Child Abuse". The Lancet. 310 (8033): 343–5. doi:10.1016/S0140-6736(77)91497-0. PMID 69945. S2CID 205993879. 41. ^ Brown, Rachel; Feldman, Marc (2001). "Chapter 2". In Adshead, Gwen; Brooke, Deborah (eds.). International Perspectives on Munchausen Syndrome by Proxy. Munchausen's syndrome by proxy: current issues in assessment, treatment and research. London: Imperial College Press. pp. 13–37. ISBN 978-1-86094-134-4. 42. ^ BBC (17 February 2006). "Disappointed and disheartened". BBC News. Retrieved 2 February 2012. 43. ^ Green, Peter (23 January 2002). "Letter from the President to the Lord Chancellor regarding the use of statistical evidence in court cases" (PDF). Royal Statistical Society. Archived from the original (PDF) on 2012-01-05. Retrieved 3 February 2012. 44. ^ BBC (10 December 2003). "The science behind cot deaths". BBC News. Retrieved 2 February 2012. 45. ^ a b Shaikh, Thair (17 March 2007). "Sally Clark, mother wrongly convicted of killing her sons, found dead at home". The Guardian. 46. ^ R v. Clark [2003] EWCA Crim 1020 (11 April 2003) 47. ^ Payne, Stewart (12 June 2003). "Joy for mother cleared of baby deaths". The Telegraph. London. Retrieved 1 February 2007. 48. ^ BBC (10 December 2003). "Mother cleared of killing sons". BBC News. Retrieved 1 February 2007. 49. ^ BBC (11 April 2005). "Anthony latest mother to be freed". BBC News. Retrieved 2 February 2012. 50. ^ BBC (15 July 2005). "Sir Roy Meadow struck off by GMC". BBC News. Retrieved 2 February 2012. 51. ^ Meadow v. General Medical Council [2006] EWHC 146 (Admin) at para. 57 (17 February 2006) 52. ^ BBC (17 February 2006). "Sally Clark doctor wins GMC case". BBC News. Retrieved 2 February 2012. 53. ^ Meadow v. General Medical Council [2006] EWHC 146 (Admin) at para. 21–26 (17 February 2006) 54. ^ Perri, Frank; Lichtenwald, Terrance (2010). "The Last Frontier: Myths & The Female Psychopathic Killer" (PDF). Forensic Examiner. 19 (2): 50–67. 55. ^ Southall, D.P., Plunkett, M.C., Blanks, M.W., Falkov, A.F. & Samuels, M.P. (1997). "Covert video recordings of life-threatening child abuse; lessons for child protection". Pediatrics. 100 (5): 735–760. doi:10.1542/peds.100.5.735. PMID 9346973.CS1 maint: multiple names: authors list (link) 56. ^ R v LM [2004] QCA 192 at para. 67 (4 June 2004) 57. ^ Ibid., at para. 71 58. ^ A County Council v A Mother and A Father and X, Y, Z children [2005] EWHC 31 (Fam) (18 January 2005) 59. ^ Feldman, Marc (2004). Playing sick?: untangling the web of Munchausen syndrome, Munchausen by proxy, malingering & factitious disorder. Philadelphia: Brunner-Routledge. ISBN 0-415-94934-3. 60. ^ "Serial killer nurse Allitt must serve 30 years". The Guardian. 6 December 2007. 61. ^ Leckie, Kate (2007-11-20). "Military wife faces assault charges for making daughter sick". Frederick News Post. Archived from the original on 2011-05-22. Retrieved 2007-11-24. 62. ^ "Growing pains". People.com. Retrieved 1 October 2013. 63. ^ "Devon woman jailed for 'sick son' con". BBC News. 22 January 2010. 64. ^ a b Candiotti, Susan (July 20, 1999). "Florida woman accused of sickening child for 8 years". CNN. 65. ^ Candiotti, Susan (October 7, 1999). "Mother found guilty of child abuse, fraud for making daughter sick". CNN. 66. ^ Renaud, Jean-Paul (July 26, 2005). "Mom, Daughter To Reunite". Sun Sentinel. 67. ^ "ABC News: Mom Convicted..." 68. ^ Associated Press (April 8, 2016). "Mommy blogger gets 20 years to life for salt-poisoning son". NY Post. 69. ^ Keegan, Harrison (July 6, 2016). "Munchausen expert says Gypsy Blanchard case is unprecedented". Springfield News-Leader. Retrieved June 2, 2017. 70. ^ Jung, Helin (May 16, 2017). "Mommy Dead and Dearest Recap & Review - Dee Dee Blanchard HBO True Crime Documentary". Cosmopolitan.com. 71. ^ Truong, Peggy (2019-03-04). "The New Trailer for Joey King's Hulu Series 'The Act' Will Straight Up Give You the Chills". Cosmopolitan. Retrieved 2019-03-14. 72. ^ "Munchausen past and present". Star-Telegram.com. 73. ^ Chen, Angus (2020-02-07). "Neurologist Takes Stand To Defend Care Given To Justina Pelletier At Boston Children's". WBUR-FM. Retrieved 2020-02-09. "In his medical notes at the time, Peters wrote that some of the doctors who’d treated Pelletier suspected “factitious disorder by proxy,” a form of medical abuse involving excessive medical care or symptoms caused by the parent or guardian. “She had multiple diagnoses, a very patchy network of providers. Those are all classic red flags,” Peters said. “And that there were Child Protective Services involved [suggested] there was some form of over-medicalization going on.” Peters said other doctors told him that Pelletier’s parents tended to obsess over potential medical problems. They took her to many different doctors, which increased the likelihood of multiple diagnoses and medications." 74. ^ Tucker HS, Finlay F, Guiton S (2002). "Munchausen syndrome involving pets by proxies". Arch. Dis. Child. 87 (3): 263. doi:10.1136/adc.87.3.263. PMC 1719226. PMID 12193455. ## External links[edit] * v * t * e Abuse Types * Anti-social behaviour * Bullying * Child abuse * neglect * sexual * military * marriage * Cruelty to animals * Disability abuse * Domestic abuse * Elder abuse * Financial * Marriage * Gaslighting * Harassment * Humiliation * Incivility * Institutional abuse * Intimidation * Neglect * Persecution * Professional abuse * Proxy abuse * Psychological abuse * Physical abuse * Police brutality * Religious abuse * Sexual abuse * Stalking * Structural abuse * Verbal abuse * more... Related topics * Abuse of power * Abusive power and control * Child grooming * Complex post-traumatic stress disorder * Dehumanization * Denial * Destabilisation * Exaggeration * Isolation * Just-world hypothesis * Lying * Manipulation * Minimisation * Narcissism * Psychological projection * Psychological trauma * Psychopathy * Rationalization * Traumatic bonding * Victim blaming * Victim playing * Victimisation * v * t * e Baron Munchausen Authors * Rudolf Erich Raspe * Gottfried August Bürger Films * Baron Munchausen's Dream (1911) * Meet the Baron (1933) * Baron Prášil (1940) * Münchhausen (1943) * The Fabulous Baron Munchausen (1961) * The Very Same Munchhausen (1979) * The Secret of the Selenites (1984) * The Adventures of Baron Munchausen (1988) Related * The Extraordinary Adventures of Baron Munchausen (game) * Munchausen syndrome * Munchausen syndrome by proxy * Munchausen by Internet * Münchhausen trilemma * Munchausen number * 14014 Münchhausen * Psychiatry portal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Factitious disorder imposed on another	c0085277	7,476	wikipedia	https://en.wikipedia.org/wiki/Factitious_disorder_imposed_on_another	2021-01-18T18:35:48	{"gard": ["7117"], "mesh": ["D016735"], "umls": ["C0085277"], "wikidata": ["Q1414765"]}
Homocystinuria Other namesCystathionine beta synthase deficiency or CBS deficiency[1] Homocysteine SpecialtyEndocrinology, medical genetics Homocystinuria or HCU[2] is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase.[3] It is an inherited autosomal recessive trait, which means a child needs to inherit a copy of the defective gene from both parents to be affected. Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate.[3] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 4.1 Recommended diet * 5 Prognosis * 6 Society and culture * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] This defect leads to a multi-systemic disorder of the connective tissue, muscles, central nervous system (CNS), and cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normal and early symptoms, if any are present, are vague. Signs and symptoms of homocystinuria that may be seen include the following: * A family history of homocystinuria[4] * Flush across the cheeks * Musculoskeletal * Tall, thin build resembling Marfanoid habitus[1] * Long limbs (dolichostenomelia) * High-arched feet (pes cavus) * Knock knees (genu valgum) * Pectus excavatum and Pectus carinatum * Intellectual disability * Seizures * Psychiatric disease * Eye anomalies: * Ectopia lentis – in contrast to Marfan syndrome which features upward ectopia lentis, downward dislocation is the typical finding of homocystinuria[5] or subluxation of lens * Myopia (nearsightedness) * Glaucoma * Optic atrophy * Retinal detachment[6] * Cataracts * Vascular disease * Homocysteine binds to the endothelium of the blood vessels and activate signaling pathways leading to the release of pro-inflammatory molecules. This may cause the following : * Extensive atheroma formation at a young age which affects many arteries but not the coronary arteries * Intravascular thrombosis ## Cause[edit] It is usually caused by the deficiency of the enzyme cystathionine beta synthase,[3] mutations of other related enzymes such as methionine synthase,[3] or the deficiency of folic acid, vitamin B12 and/or pyridoxine (vitamin B6).[3] ## Diagnosis[edit] The term homocystinuria describes an increased excretion of the thiol amino acid homocysteine in urine (and incidentally, also an increased concentration in plasma). The source of this increase may be one of many metabolic factors, only one of which is CBS deficiency. Others include the re-methylation defects (cobalamin defects, methionine synthase deficiency, MTHFR) and vitamin deficiencies (cobalamin (vitamin B12) deficiency, folate (vitamin B9) deficiency, riboflavin deficiency (vitamin B2), pyridoxal phosphate deficiency (vitamin B6)). In light of this information, a combined approach to laboratory diagnosis is required to reach a differential diagnosis. CBS deficiency may be diagnosed by routine metabolic biochemistry. In the first instance, plasma or urine amino acid analysis will frequently show an elevation of methionine and the presence of homocysteine. Many neonatal screening programs include methionine as a metabolite. The disorder may be distinguished from the re-methylation defects (e.g., MTHFR, methionine synthase deficiency, or the cobalamin defects) in lieu of the elevated methionine concentration.[7] Additionally, organic acid analysis or quantitative determination of methylmalonic acid should help to exclude cobalamin (vitamin B12) defects and vitamin B12 deficiency giving a differential diagnosis.[8] The laboratory analysis of homocysteine itself is complicated because most homocysteine (possibly above 85%) is bound to other thiol amino acids and proteins in the form of disulphides (e.g., cysteine in cystine-homocysteine, homocysteine in homocysteine-homocysteine) via disulfide bonds. Since as an equilibrium process the proportion of free homocystene is variable a true value of total homocysteine (free + bound) is useful for confirming diagnosis and particularly for monitoring of treatment efficacy. To this end it is prudent to perform total homocyst(e)ine analysis in which all disulphide bonds are subject to reduction prior to analysis, traditionally by HPLC after derivatisation with a fluorescent agent, thus giving a true reflection of the quantity of homocysteine in a plasma sample.[9] ## Treatment[edit] No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B6 (also known as pyridoxine).[10] Slightly less than 50% respond to this treatment and need to take supplemental vitamin B6 for the rest of their lives. Those who do not respond require a Low-sulfur diet (especially monitoring methionine), and most will need treatment with trimethylglycine. A normal dose of folic acid supplement and occasionally adding cysteine to the diet can be helpful, as glutathione is synthesized from cysteine (so adding cysteine can be important to reduce oxidative stress). Betaine (N,N,N-trimethylglycine) is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine, i.e., increasing flux through the re-methylation pathway independent of folate derivatives (which is mainly active in the liver and in the kidneys). The re-formed methionine is then gradually removed by incorporation into body protein. The methionine that is not converted into protein is converted to S-adenosyl-methionine which goes on to form homocysteine again. Betaine is, therefore, only effective if the quantity of methionine to be removed is small. Hence treatment includes both betaine and a diet low in methionine. In classical homocystinuria (CBS, or cystathione beta synthase deficiency), the plasma methionine level usually increases above the normal range of 30 micromoles/L and the concentrations should be monitored as potentially toxic levels (more than 400 micromoles/L) may be reached. ### Recommended diet[edit] Low-protein food is recommended for this disorder, which requires food products low in particular types of amino acids (e.g., methionine).[citation needed][11] ## Prognosis[edit] The life expectancy of patients with homocystinuria is reduced only if untreated. It is known that before the age of 30, almost one quarter of patients die as a result of thrombotic complications (e.g., heart attack).[citation needed] ## Society and culture[edit] One theory suggests that Akhenaten, a pharaoh of the eighteenth dynasty of Egypt, may have suffered from homocystinuria.[12] ## See also[edit] * Cystinuria * Hyperhomocysteinemia ## References[edit] 1. ^ a b Online Mendelian Inheritance in Man (OMIM): 236200 2. ^ https://www.nhs.uk/conditions/homocystinuria/ 3. ^ a b c d e Tao, Le (2020-01-02). First aid for the USMLE step 1 2020 : a student-to-student guide. Bhushan, Vikas,, Sochat, Matthew,, Kallianos, Kimberly,, Chavda, Yash,, Zureick, Andrew H. (Andrew Harrison), 1991-, Kalani, Mehboob. New York. ISBN 9781259837630. OCLC 948547794. 4. ^ Maillot F, Kraus JP, Lee PJ (2008). "Environmental influences on familial discordance of phenotype in people with homocystinuria: a case report". J Med Case Rep. 2 (1): 113. doi:10.1186/1752-1947-2-113. PMC 2377250. PMID 18423051. 5. ^ Peter Nicholas Robinson; Maurice Godfrey (2004). Marfan syndrome: a primer for clinicians and scientists. Springer. pp. 5–. ISBN 978-0-306-48238-0. Retrieved 12 April 2010. 6. ^ Goldman, Lee (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 1362. ISBN 978-1437727883. 7. ^ (eds.), N. Blau ... (2003). Physician's guide to the laboratory diagnosis of metabolic diseases; with 270 tables (2. ed.). Berlin [u.a.]: Springer. ISBN 978-3540425427.CS1 maint: extra text: authors list (link) 8. ^ Refsum, Helga; A. David Smith; Per M. Ueland; Ebba Nexo; Robert Clarke; Joseph McPartlin; Carole Johnston; Frode Engbaek; Jørn Schneede; Catherine McPartlin; John M. Scott (2004). "Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion". Clinical Chemistry. 50 (1): 3–32. doi:10.1373/clinchem.2003.021634. PMID 14709635. 9. ^ Carducci, Claudia; M. Birarelli; M. Nola; I. Antonozzi (1999). "Automated high-performance liquid chromatographic method for the determination of homocysteine in plasma samples". Journal of Chromatography A. 846 (1–2): 93–100. doi:10.1016/S0021-9673(98)01091-7. PMID 10420601. 10. ^ Bakker, R. C.; Brandjes, D. P. (June 1997). "Hyperhomocysteinaemia and associated disease". Pharmacy World & Science : PWS. 19 (3): 126–132. doi:10.1023/A:1008634632501. PMID 9259028. 11. ^ YAP, SUFIN; NAUGHTEN, EILEEN R.; WILCKEN, BRIDGET; WILCKEN, DAVID E.L.; BOERS, GODFRIED H.J. (2000-01-01). "Vascular Complications of Severe Hyperhomocysteinemia in Patients with Homocystinuria Due to Cystathionine β-Synthase Deficiency: Effects of Homocysteine-Lowering Therapy". Seminars in Thrombosis and Hemostasis. 26 (3): 335–340. doi:10.1055/s-2000-8100. ISSN 0094-6176. PMID 11011851. 12. ^ Cavka M, Kelava T (Mar 2010). "Homocystinuria, a possible solution of the Akhenaten's mystery". Coll Antropol. 34: 255–58. PMID 20402329. ## Further reading[edit] * GeneReview/NIH/UW entry on Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency ## External links[edit] Classification D * ICD-10: E72.1 * ICD-10-CM: E72.11 * ICD-9-CM: 270.4 * OMIM: 236200 * MeSH: D006712 * DiseasesDB: 5991 * SNOMED CT: 11282001 External resources * MedlinePlus: 001199 * eMedicine: derm/708 * Patient UK: Homocystinuria * GeneReviews: Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency * 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	Homocystinuria	c0019880	7,477	wikipedia	https://en.wikipedia.org/wiki/Homocystinuria	2021-01-18T19:01:19	{"gard": ["10770"], "mesh": ["D006712"], "umls": ["C0019880"], "icd-9": ["270.4"], "orphanet": ["394"], "wikidata": ["Q994859"]}
A rare staphylococcal toxemia caused by epidermolytic toxins of Staphylococcus aureus and characterized by the appearance of widespread erythematous patches, on which large blisters develop. Upon rupture of these blisters, the skin appears reddish and scalded. The lesions typically begin in the face and rapidly expand to other parts of the body. The disease may be complicated by pneumonia and sepsis. It most commonly affects newborns and infants. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Staphylococcal scalded skin syndrome	c0038165	7,478	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=36236	2021-01-23T18:54:22	{"mesh": ["D013206"], "umls": ["C0038165"], "icd-10": ["L00"], "synonyms": ["Generalized exfoliative disease", "SSSS"]}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article needs attention from an expert in Medicine. Please add a reason or a talk parameter to this template to explain the issue with the article. WikiProject Medicine may be able to help recruit an expert. (September 2018) 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: "Physical disorder" – news · newspapers · books · scholar · JSTOR (December 2008) (Learn how and when to remove this template message) This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Physical disorder" – news · newspapers · books · scholar · JSTOR (September 2018) (Learn how and when to remove this template message) A physical disorder (as a medical term) is often used as a term in contrast to a mental disorder, in an attempt to differentiate medical disorders that have an available mechanical test (such as chemical tests or brain scans), from those disorders which have no laboratory or imaging test, and are diagnosed only by behavioral syndrome (such as those in the Diagnostic and Statistical Manual of Mental Disorders (DSM). Differentiating the physical disorders from mental disorders can be a difficult problem in both medicine and law, most notably because it delves into deep issues, and very old and unresolved arguments in philosophy and religion. Many materialists believe that all mental disorders are physical disorders of some kind, even if tests for them have not yet been developed (and it has been the case that some disorders once widely thought to be purely mental, are known to have physical origins, such as schizophrenia). Some recognized physical disorders produce significant behavioral changes. For example, fever, head trauma, and hyperthyroidism can produce delirium. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Physical disorder	c0683323	7,479	wikipedia	https://en.wikipedia.org/wiki/Physical_disorder	2021-01-18T18:30:12	{"wikidata": ["Q30314000"]}
Intra-operative gross photograph of the spleen attached to the left testis in a 1-year old boy with splenogonadal fusion Splenogonadal fusion is a rare congenital malformation that results from an abnormal connection between the primitive spleen and gonad during gestation. A portion of the splenic tissue then descends with the gonad. Splenogonadal fusion has been classified into two types: continuous, where there remains a connection between the main spleen and gonad; and discontinuous, where ectopic splenic tissue is attached to the gonad, but there is no connection to the orthotopic spleen. Patients with continuous splenogonadal fusion frequently have additional congenital abnormalities, most commonly cryptorchidism.[1] The anomaly was first described in 1883 by Bostroem.[2] Since then more than 150 cases of splenogonadal fusion have been documented.[3] The condition is considered benign.[4] A few cases of testicular neoplasm have been reported in association with splenogonadal fusion.[5][6] The reported cases have occurred in patients with a history of cryptorchidism, which is associated with an elevated risk of neoplasm.[6] Splenogonadal fusion occurs with a male-to-female ratio of 16:1, and is seen nearly exclusively on the left side.[3] The condition remains a diagnostic challenge, but preoperative consideration of the diagnosis may help avoid unnecessary orchiectomy. On scrotal ultrasound, ectopic splenic tissue may appear as an encapsulated homogeneous extratesticular mass, isoechoic with the normal testis. Subtle hypoechoic nodules may be present in the mass.[7] The presence of splenic tissue may be confirmed with a technetium-99m sulfur colloid scan.[8] ## References[edit] 1. ^ Kocher, NJ; Tomaszewski, JJ; Parsons, RB; Cronson, BR; Altman, H; Kutikov, A (Jan 2014). "Splenogonadal fusion: a rare etiology of solid testicular mass". Urology. 83 (1): e1-2. doi:10.1016/j.urology.2013.09.019. PMID 24200197. 2. ^ Khairat, AB; Ismail, AM (Aug 2005). "Splenogonadal fusion: case presentation and literature review". Journal of Pediatric Surgery. 40 (8): 1357–60. doi:10.1016/j.jpedsurg.2005.05.027. PMID 16080949. 3. ^ a b Varma, DR; Sirineni, GR; Rao, MV; Pottala, KM; Mallipudi, BV (Sep 2007). "Sonographic and CT features of splenogonadal fusion". Pediatric radiology. 37 (9): 916–9. doi:10.1007/s00247-007-0526-x. PMID 17581747. 4. ^ Lin, CS; Lazarowicz, JL; Allan, RW; Maclennan, GT (Jul 2010). "Splenogonadal fusion". The Journal of Urology. 184 (1): 332–3. doi:10.1016/j.juro.2010.04.013. PMID 20488470. 5. ^ Imperial, SL; Sidhu, JS (Oct 2002). "Nonseminomatous germ cell tumor arising in splenogonadal fusion". Archives of Pathology & Laboratory Medicine. 126 (10): 1222–5. doi:10.1043/0003-9985(2002)126<1222:NGCTAI>2.0.CO;2. PMID 12296764. 6. ^ a b Lopes RI, de Medeiros MT, Arap MA, Cocuzza M, Srougi M, Hallak J (Jan–Mar 2012). "Splenogonadal fusion and testicular cancer: case report and review of the literature". Einstein (Sao Paulo, Brazil). 10 (1): 92–5. doi:10.1590/s1679-45082012000100019. PMID 23045834. 7. ^ Ferrón, SA; Arce, JD (Dec 2013). "Discontinuous splenogonadal fusion: new sonographic findings". Pediatric radiology. 43 (12): 1652–5. doi:10.1007/s00247-013-2730-1. PMID 23754542. 8. ^ Guarin, U; Dimitrieva, Z; Ashley, SJ (Oct 1975). "Splenogonadal fusion-a rare congenital anomaly demonstrated by 99Tc-sulfur colloid imaging: case report". Journal of Nuclear Medicine. 16 (10): 922–4. PMID 240914. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Splenogonadal fusion	c0266636	7,480	wikipedia	https://en.wikipedia.org/wiki/Splenogonadal_fusion	2021-01-18T18:55:47	{"orphanet": ["457083"], "synonyms": ["SGF"], "wikidata": ["Q7578553"]}
Porcine orthorubulavirus Virus classification (unranked): Virus Realm: Riboviria Kingdom: Orthornavirae Phylum: Negarnaviricota Class: Monjiviricetes Order: Mononegavirales Family: Paramyxoviridae Genus: Orthorubulavirus Species: Porcine orthorubulavirus Member virus[1] * La-Piedad-Michoacan-Mexico virus Blue eye disease is caused by La Piedad Michoacán Mexico virus (LPMV), the only member virus of the species Porcine orthorubulavirus in the Paramyxoviridae family.[2][3] Synonyms for the disease include "Blue Eye Syndrome" and "Porcine Paramyxovirus Blue Eye Disease", and "La Piedad Michoacán Paramyxovirus Infection". Blue eye disease is a viral disease that is commonly identified by encephalitis, pneumonia, and respiratory diseases in piglets. It also causes reproductive failure in adult pigs, and rarely identifies with corneal opacity, an eye disorder characterized by scarring of the cornea. ## Contents * 1 Signs and diagnosis * 2 Cause * 3 Diagnosis * 4 Epidemiology * 5 Treatment and control * 6 References * 7 External links ## Signs and diagnosis[edit] Blue eye disease typically begins in piglets that are between 2–21 days old; 90 percent of the pigs that become infected with the disease die. It usually begins with a sudden onset of fever, arched back, or depression. The disease then progresses with neurological symptoms including weakness, ataxia, muscle tremors, abnormal posture, and rigidity of the hind legs. Some other symptoms associated with this disease are conjunctivitis, blindness, nystagmus, constipation, and diarrhea. Younger pigs can suffer from neurological and respiratory signs which can be quite severe. Mature pigs may suffer blueing of the pupils in their eyes and reproductive difficulties.[4] Adults of both sexes may become infertile and sows may suffer from abortions and stillbirths. * Inappetence * Corneal opacity – conjunctivitis * Nervous signs – fits and convulsions * Dog sitting position * Fever * Increased returns * Increased weaning to mating intervals * Stillbirths * Mummified piglets * High mortality in piglets * Swollen testicles * Loss of libido ## Cause[edit] Blue eye disease is caused by the porcine rubulavirus, which first emerged in 1980 throughout parts of Mexico, including La Piedad, Michoacan, Jalisco, and Guanajuato. The virus is transmitted directly and indirectly by fomites and birds and can be found throughout the body, including neurons and most soft tissues. ## Diagnosis[edit] Blue eye disease outbreaks can happen throughout the year but are most common during spring and summer months of April to July. The mortality rate usually rises and falls and between a two- to nine-week time frame. After the epidemic subsides, no more cases occur unless new susceptible pigs are introduced into the farm. In severe outbreaks of the disease a presumptive diagnosis can be made. Serological testing via virus neutralization and haemagglutination inhibition testing can be performed to diagnose the disease. Virus isolation from tissue samples is also possible. Necropsy findings can help confirm the diagnosis. ## Epidemiology[edit] Blue eye disease in swine has only been reported in Mexico. It can affect not only pigs but also dogs, cats, rats, and rabbits. ## Treatment and control[edit] There is no treatment for the disease. Symptomatic treatment for the inflammatory and respiratory signs can be given, but severe cases may require euthanasia. General biosecurity protocols including adequate quarantine, testing, and disinfection can help prevent the entry or spread of the disease into a herd. ## References[edit] 1. ^ "ICTV 9th Report (2011) Paramyxoviridae" (html). International Committee on Taxonomy of Viruses (ICTV). Retrieved 25 January 2019. 2. ^ Stephan, H.; Gay, G.; Ramirez, T. (2 January 1988). "Encephalomyelitis, reproductive failure and corneal opacity (blue eye) in pigs, associated with a paramyxovirus infection". Veterinary Record. 122 (1): 6–10. doi:10.1136/vr.122.1.6. PMID 3363809. S2CID 21575394. 3. ^ "Taxonomy". International Committee on Taxonomy of Viruses. Retrieved 24 March 2020. 4. ^ Mendoza-Magaña, M. L.; Ramírez-Herrera, M. A.; Dueñas-Jiménez, J. M.; Dueñas-Jiménez, S. H. (7 July 2008). "Pig Paramyxovirus of the Blue Eye Disease Binding to a 116 kDa Glycoprotein Expressed in Pig Neuronal Membranes". Journal of Veterinary Medicine, Series B. 48 (7): 489–499. doi:10.1111/j.1439-0450.2001.00462.x. ## External links[edit] * https://web.archive.org/web/20141215002414/http://www.thepigsite.com/pighealth/article/444/blue-eye-disease-be * Porcine Rubulavirus infection, http://www.cfsph.iastate.edu/Factsheets/pdfs/blue_eye_disease.pdf Taxon identifiers * Wikidata: Q18965262 * Wikispecies: Porcine rubulavirus * EoL: 741121 * IRMNG: 11460571 * NCBI: 53179 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Blue eye disease	None	7,481	wikipedia	https://en.wikipedia.org/wiki/Blue_eye_disease	2021-01-18T18:32:19	{"wikidata": ["Q4929100"]}
A rare genetic syndromic intellectual disability characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth digit, developmental delay, coarse facial features, and other variable clinical manifestations. ## Epidemiology More than 150 cases of genetically confirmed Coffin-Siris syndrome (CSS) have been clinically reported to date. Exact prevalence and incidence are not known but the disorder is probably under-recognized. ## Clinical description Coffin-Siris syndrome is a clinically and genetically heterogeneous disorder. It involves a wide range of major and minor clinical findings. Characteristic major features include mild to severe developmental or cognitive delay (in all patients), fifth finger nail/distal phalanx hypoplasia or aplasia (almost all patients at birth), and coarse facial features (commonly observed over time). Distinctive facial features include thick eyebrows and long eyelashes, broad nasal bridge, wide mouth with thick, everted upper and lower lips, and abnormal ear position or shape. Common minor findings include short stature, failure to thrive, feeding difficulties, microcephaly, ophthalmological manifestations (cataracts, ptosis, strabismus), cardiac anomalies (ventricular septal/atrial septal defects, tetralogy of Fallot, patent ductus arteriosus), hypertrichosis (arms, face, back) and sparse scalp hair. Minor findings include neurologic involvement (Dandy-Walker malformation, gyral simplification, agenesis of the corpus callosum, seizures, and hypotonia), hearing loss, joint laxity, genito-urinary and renal malformations and frequent infections. Developmental delay and scoliosis appear in infancy and childhood. ## Etiology Heterozygous mutation or genomic rearrangement in the following nine genes have been reported to be causative for CSS (highest to lowest proportion of reported cases): ARID1B (6q25.3), SMARCA4 (19p13.3), SMARCC2 (12q13.2), ARID1A (1p36.11), SOX11 (2p25.2), DPF2 (11q13.1), SMARCB1 (22q11.23),SMARCE1 (17q21.2) , and ARID2 (12q12). These genes encode subunits of the BAF complex, which is involved in regulation of gene expression during development. ## Diagnostic methods To date there have been no consistent clinical criteria to assist in the diagnosis. The diagnosis is generally based on the presence of major and at least one minor clinical sign and can be confirmed by molecular genetic testing of the causative genes. Recent studies revealed that fifth finger nail/distal phalanx hypoplasia or aplasia is not a mandatory finding. Microdeletions including ARID1B have been reported. ## Differential diagnosis Differential diagnoses include Nicolaides-Baraitser syndrome, brachymorphism-onychodysplasia-dysphalangism, DOOR syndrome, hyperphosphatasia-intellectual deficiency syndrome, Borjeson-Forssman-Lehmann syndrome, Wiedemann-Steiner syndrome, Rubinstein-Taybi syndrome and Cornelia de Lange syndrome. Fetal hydantoin syndrome may mimick Coffin-Siris syndrome. ## Antenatal diagnosis As most mutations are de novo, prenatal diagnosis may be difficult to apply. ## Genetic counseling Autosomal dominant transmission has been reported regarding ARID1B-related disorder, but most cases are related to de novo mutations. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the mutation to offspring. ## Management and treatment Treatment is essentially supportive and symptomatic. Occupational, physical and speech therapy are recommended. Development and feeding should be monitored closely and patients should undergo regular ophthalmological and audiological testing. ## Prognosis The prognosis is poor in severely affected individuals, with aspiration pneumonia and seizures reported in childhood. Association of tumor development including schwannomatosis has been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Coffin-Siris syndrome	c0265338	7,482	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1465	2021-01-23T17:23:20	{"gard": ["6124"], "mesh": ["C536436"], "omim": ["135900", "614607", "614608", "614609", "615866", "616938", "617808", "618027", "618362", "618779"], "umls": ["C0265338"], "icd-10": ["Q87.1"], "synonyms": ["CSS"]}
Shoulder injury This article relies largely or entirely on a single source. Relevant discussion may be found on the talk page. Please help improve this article by introducing citations to additional sources. Find sources: "Glenolabral articular disruption" – news · newspapers · books · scholar · JSTOR (April 2014) The glenolabral articular disruption (GLAD) lesion is a type of shoulder injury. It is difficult to diagnose clinically, and requires surgical repair to correct the damage to the shoulder.[1] ## References[edit] 1. ^ Sanders TG, Tirman PF, Linares R, Feller JF, Richardson R (January 1999). "The glenolabral articular disruption lesion: MR arthrography with arthroscopic correlation". American Journal of Roentgenology. 172 (1): 171–5. doi:10.2214/ajr.172.1.9888763. PMID 9888763. This article about an injury 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	Glenolabral articular disruption	None	7,483	wikipedia	https://en.wikipedia.org/wiki/Glenolabral_articular_disruption	2021-01-18T18:30:28	{"wikidata": ["Q16004474"]}
Purine nucleoside phosphorylase deficiency Other namesPNP-deficiency Purine nucleoside phosphorylase deficiency has an autosomal recessive pattern of inheritance TreatmentAllegeneic hemotopoietic stem cell transplantation (HSCT) Purine nucleoside phosphorylase deficiency, is a rare autosomal recessive[1] metabolic disorder which results in immunodeficiency. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 3.1 Differential diagnosis * 4 Antenatal screening * 5 Treatment * 6 Epidemiology * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] In addition to the symptoms associated with immunodeficiency, such as depletion of T-cells, decline of lymphocyte activity, and an abrupt proliferation of both benign and opportunistic infections — PNP-deficiency is often characterized by the development of autoimmune disorders. lupus erythematosus, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura have been reported with PNP-deficiency.[2]Neurological symptoms, such as developmental decline, hypotonia, and mental retardation have also been reported. ## Cause[edit] The disorder is caused by a mutation of the purine nucleoside phosphorylase (PNP) gene, located at chromosome 14q13.1.[3][4] This mutation was first identified by Eloise Giblett, a professor at the University of Washington, in 1975.[5] PNP is a key enzyme in the purine catabolic[6] pathway, and is required for purine degradation. Specifically, it catalyzes the conversion of inosine to hypoxanthine and guanosine to guanine (both guanine and hypoxanthine will be made into xanthine which will then become uric acid). A deficiency of it leads to buildup of elevated deoxy-GTP (dGTP) levels resulting in T-cell toxicity and deficiency.[4][7] In contrast to adenosine deaminase deficiency (another deficiency of purine metabolism), there is minimal disruption to B cells.[8] PNP deficiency is inherited in an autosomal recessive manner.[1] This means the defective gene responsible for the disorder is located on an autosome (chromosome 14 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.[citation needed] ## Diagnosis[edit] Diagnosis is based on the clinical examination and on laboratory findings showing leukopenia, severe lymphopenia with low CD3, CD4, and CD8 counts and variable B cell function and immunoglobulin levels. Neutropenia has also been reported. Hallmark diagnostic markers of PNP deficiency include hypouricemia, complete or near complete absence of PNP activity in red blood cell lysate and increased urine or blood levels of inosine, guanosine and their deoxy forms. Diagnosis is confirmed by genetic screening of PNP.[citation needed] ### Differential diagnosis[edit] Differential diagnosis includes aplastic anemias, SCID, severe combined immunodeficiency due to adenosine deaminase deficiency, ataxia-telangiectasia, and viral meningoencephalitis. ## Antenatal screening[edit] Measurement of T cell receptor excision circles during newborn screening for SCID can detect some patients suffering from PNP deficiency, although removal of metabolites by maternal PNP may delay the deleterious effects on PNP-deficient lymphocytes. Few newborn screening programs also measure purine metabolites in dried[citation needed] ## Treatment[edit] Supportive treatment, including intravenous immunoglobulin therapy, prophylaxis for Pneumocystis carinii, and physical, occupational, and speech therapy, reduces the risk of infection and may encourage optimal neurologic development for patients.[citation needed] ## Epidemiology[edit] PNP-deficiency is extremely rare. Only 33 patients with the disorder in the United States have been documented.[2] In the United Kingdom only two children have been diagnosed with this disorder in 1994 and 2008.[9] ## See also[edit] * Nezelof syndrome ## References[edit] 1. ^ a b Sasaki Y, Iseki M, Yamaguchi S, Kurosawa Y, Yamamoto T, Moriwaki Y, Kenri T, Sasaki T, Yamashita R (July 1998). "Direct evidence of autosomal recessive inheritance of Arg24 to termination codon in purine nucleoside phosphorylase gene in a family with a severe combined immunodeficiency patient". Human Genetics. 103 (1): 81–85. doi:10.1007/s004390050787. PMID 9737781. S2CID 8373698. 2. ^ a b Markert ML (1991). "Purine nucleoside phosphorylase deficiency". Immunodefic Rev. 3 (1): 45–81. PMID 1931007. 3. ^ Online Mendelian Inheritance in Man (OMIM): 164050 4. ^ a b Snyder FF, Jenuth JP, Mably ER, Mangat RK (Mar 1997). "Point mutations at the purine nucleoside phosphorylase locus impair thymocyte differentiation in the mouse". Proc. Natl. Acad. Sci. U.S.A. 94 (6): 2522–2527. Bibcode:1997PNAS...94.2522S. doi:10.1073/pnas.94.6.2522. PMC 20121. PMID 9122228. 5. ^ Motulsky A, Gartler S. "Biographical Memoirs: Eloise R. Giblett". National Academy of Sciences. 6. ^ Berg, Jeremy M.; Tymoczko, John L.; Stryer, Lubert (2010-12-24). Biochemistry (7th ed.). p. 753. ISBN 9781429229364. 7. ^ Toro A, Grunebaum E (Oct 2006). "TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice". J. Clin. Invest. 116 (10): 2717–2726. doi:10.1172/JCI25052. PMC 1560347. PMID 16964310. 8. ^ "eMedicine - Purine Nucleoside Phosphorylase Deficiency : Article by Alan P Knutsen". Retrieved July 25, 2010. 9. ^ http://www.channel4.com/news/articles/society/health/boy+first+in+uk+with+rare+condition/3022087 ## External links[edit] Classification D * ICD-10: D81.5 * ICD-9-CM: 277.2 * OMIM: 613179 * MeSH: C562587 * DiseasesDB: 11044 External resources * eMedicine: ped/1957 * Orphanet: 760 * v * t * e Lymphoid and complement disorders causing immunodeficiency Primary Antibody/humoral (B) Hypogammaglobulinemia * X-linked agammaglobulinemia * Transient hypogammaglobulinemia of infancy Dysgammaglobulinemia * IgA deficiency * IgG deficiency * IgM deficiency * Hyper IgM syndrome (1 * 2 * 3 * 4 * 5) * Wiskott–Aldrich syndrome * Hyper-IgE syndrome Other * Common variable immunodeficiency * ICF syndrome T cell deficiency (T) * thymic hypoplasia: hypoparathyroid (Di George's syndrome) * euparathyroid (Nezelof syndrome * Ataxia–telangiectasia) peripheral: Purine nucleoside phosphorylase deficiency * Hyper IgM syndrome (1) Severe combined (B+T) * x-linked: X-SCID autosomal: Adenosine deaminase deficiency * Omenn syndrome * ZAP70 deficiency * Bare lymphocyte syndrome Acquired * HIV/AIDS Leukopenia: Lymphocytopenia * Idiopathic CD4+ lymphocytopenia Complement deficiency * C1-inhibitor (Angioedema/Hereditary angioedema) * Complement 2 deficiency/Complement 4 deficiency * MBL deficiency * Properdin deficiency * Complement 3 deficiency * Terminal complement pathway deficiency * Paroxysmal nocturnal hemoglobinuria * Complement receptor deficiency * v * t * e Inborn error of purine–pyrimidine metabolism Purine metabolism Anabolism * Adenylosuccinate lyase deficiency * Adenosine Monophosphate Deaminase Deficiency type 1 Nucleotide salvage * Lesch–Nyhan syndrome/Hyperuricemia * Adenine phosphoribosyltransferase deficiency Catabolism * Adenosine deaminase deficiency * Purine nucleoside phosphorylase deficiency * Xanthinuria * Gout * Mitochondrial neurogastrointestinal encephalopathy syndrome Pyrimidine metabolism Anabolism * Orotic aciduria * Miller syndrome Catabolism * Dihydropyrimidine dehydrogenase deficiency [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Purine nucleoside phosphorylase deficiency	c0268125	7,484	wikipedia	https://en.wikipedia.org/wiki/Purine_nucleoside_phosphorylase_deficiency	2021-01-18T19:06:50	{"gard": ["4606"], "mesh": ["C562587"], "umls": ["C0268125"], "icd-9": ["277.2"], "orphanet": ["760"], "wikidata": ["Q3043155"]}
North Carolina macular dystrophy (NCMD) is an inherited eye disorder that affects the development of the macula, the small, but important part of the eye located in the center of the retina. The macula allows a person to see fine details and do tasks that require central vision, such as reading and driving. It is also important for seeing colors. The severity of changes in the development of the macula varies, causing some people to have little or no vision loss, while others may have severe vision loss. NCMD is considered non-progressive, which means most researchers believe the vision loss does not change after birth. Others believe it may progress slowly through age twelve.[14914] However, vision loss may increase if complications develop, such as new, abnormal blood vessels growing under the retina (choroidal neovascularization). NCMD is caused by changes (mutations) in a region of chromosome 6 (MCDR1 locus), as well as in a region of chromosome 5 (MCDR3 locus). Although there is no cure for NCMD, treatment may include low vision aids such as glasses with high powered lenses, large print reading material, and computer software that can turn text into speech. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	North Carolina macular dystrophy	c0730294	7,485	gard	https://rarediseases.info.nih.gov/diseases/9179/north-carolina-macular-dystrophy	2021-01-18T17:58:39	{"mesh": ["C537835"], "omim": ["136550"], "umls": ["C0730294"], "orphanet": ["75327"], "synonyms": ["NCMD", "Macular dystrophy retinal 1 North Carolina type", "MCDR1", "Central areolar pigment epithelial dystrophy", "CAPED", "Retinal pigment epithelial dystrophy central", "Foveal dystrophy progressive"]}
Underterminate colitis designates a rare inflammatory bowel disease that clinically resembles Crohn’s disease and ulcerative colitis (see these terms) but that cannot be diagnosed as one of them after examination of an intestinal resection specimen. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Undetermined colitis	None	7,486	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=103920	2021-01-23T17:46:15	{"icd-10": ["K52.3"]}
## Description Restless legs syndrome (RLS) is a neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation (Bonati et al., 2003). For additional information and a discussion of genetic heterogeneity of restless legs syndrome, see RLS1 (102300). Mapping Pichler et al. (2006) reported a genomewide linkage analysis of patients with RLS collected from 1 small village that had conserved a high degree of isolation in the Western Alps of South Tyrol (Italy). The population showed increased background linkage disequilibrium (LD) due to the peculiar demographic history that had led to genetic drift and founder effect. Historical documents allowed the reconstruction of extended pedigrees as far back as the 17th century. Using both nonparametric and parametric analyses, Pichler et al. (2006) initially obtained suggestive evidence for a novel locus on chromosome 2q. Follow-up genotyping yielded significant evidence of linkage (nonparametric lod score 5.5, p less than or equal to 0.0000033) between markers D2S311 and D2S317 (11.7 cM). Genotypic data for 20 markers on chromosome 2q were used to examine the pattern of haplotype transmission in all individuals in the 18 families analyzed, in an attempt to identify haplotype sharing among the 37 idiopathic RLS cases. They found that a common 7-marker haplotype in the chromosome 2q33 region was shared identical by descent by all 15 affected members of 3 families. From genealogic studies, they found that these 3 families descended from a common founder couple 10 generations ago. Two-point linkage analysis of this large genealogy resulted in a maximum lod score of 4.1 at theta = 0.0 at marker D2S2242. The remaining 15 families did not descend from a common ancestor; in those families, no common haplotype was observed, and the maximum lod score was 0.4 in 1 family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	RESTLESS LEGS SYNDROME, SUSCEPTIBILITY TO, 4	c1864874	7,487	omim	https://www.omim.org/entry/610439	2019-09-22T16:04:39	{"omim": ["610439"]}
Pseudotyphus of California is a rare, flea-borne Rickettsial disease caused by a Rickettsia felis infection. Patients can be asymptomatic or can present with unspecific symptoms (such as fever, headache, generalized maculopapular rash, myalgia, arthralgia and, ocasionally, eschar, lymphadenopathy, nausea, vomiting, loss of appetite and abdominal pain). Rarely, serious manifestations may occur and include neurological dysfunction (photophobia, hearing loss, and signs of meningitis) and pulmonary compromise. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Pseudotyphus of California	c4706680	7,488	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83316	2021-01-23T16:54:22	{"icd-10": ["A79.8"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-1A (DFNB1A) is caused by homozygous or compound heterozygous mutation in the GJB2 gene (121011), which encodes the gap junction protein connexin-26 (CX26), on chromosome 13q12. Autosomal dominant deafness-3A (DFNA3A; 601544) is an allelic disorder. See also DFNB1B (612645), which is caused by mutation in the GJB6 gene (604418) on chromosome 13q12. Clinical Features Scott et al. (1995) studied a highly inbred Bedouin family with autosomal recessive deafness. The family belonged to a tribe founded approximately 200 years ago by an Arab-Bedouin male who immigrated from Egypt to the southern region of what was then Palestine. He married a local woman and had 7 children, 5 of whom survived to adulthood. Consanguineous marriage had been the rule in the tribe since its third generation. The tribe was then in its seventh generation and consisted of some 3,000 people, all of whom resided in a single geographic area in Israel that is separated from other Bedouin communities. Birth rates within the tribe were high, and polygamy was common. Within the past generation there had been 80 individuals with congenital deafness; all of the affected individuals were descendants of 2 of the 5 adult sons of the founder. The deafness was profound prelingual neurosensory hearing loss with drastically elevated audiometric thresholds at all frequencies. All deaf individuals had an otherwise normal phenotype with the absence of external ear abnormalities, retinopathy, or renal defects, and all were of normal intelligence. Cheng et al. (2005) noted that 4% of 777 unrelated children with hearing loss had medical records that listed an environmental cause for the deafness, and that 11% of those with an unknown etiology were found to have GJB2/GJB6 mutations. Otoacoustic emissions testing to detect functional outer hair cells identified 76 children (10%) with positive emissions, consistent with auditory neuropathy. Five of the patients with auditory neuropathy were homozygous or compound heterozygous for mutations in the GJB2 gene. Cheng et al. (2005) suggested that lack of functional gap junctions due to GJB2 mutations does not necessarily destroy all outer hair cell function. In a survey by Dodson et al. (2011), 127 (54%) of 235 respondents with DFNB1 due to mutations in the GJB2 and/or GJB6 genes reported vestibular dysfunction, compared to 25 (41%) of 61 deaf controls without DFNB1 deafness (p less than 0.03). Most of the DFNB1 patients with vertigo had to lie down for it to subside, and 48% reported that vertigo interfered with activities of daily living. Vertigo was reported by significantly more cases with truncating than nontruncating mutations and was also associated with a family history of dizziness. Dodson et al. (2011) concluded that vestibular dysfunction is more common in DFNB1 deafness than previously recognized. Schimmenti et al. (2008) enrolled 95 infants with hearing loss from whom both exons of Cx26 were sequenced and the Cx30 deletion was assayed in a study comparing infants with and without connexin-related hearing loss. Among the 82 infants who underwent newborn screening, 12 infants had passed; 3 had connexin-related hearing loss. There were no differences in newborn hearing screening pass rate, neonatal complication, or hearing loss severity between infants with and without connexin-related hearing loss. Schimmenti et al. (2008) pointed out that not all infants with connexin-related hearing loss will fail newborn hearing screening. Family history correlates significantly with connexin-related hearing loss. Inheritance Direct genetic evidence for the existence of at least 2 nonallelic, recessive, phenotypically indistinguishable forms of congenital deafness was provided by the rather frequent pedigrees of the type reported by Stevenson and Cheeseman (1956). In only 5 of 32 hereditary deaf by hereditary deaf matings were all children deaf. From this, the authors concluded that there are probably 6 separate loci for recessive congenital deafness, assuming that the mutant genes at each have a similar frequency. See comments of Slatis (1957). Chung et al. (1959) also supported the notion of multiple recessive forms of congenital deafness. Fraser (1964) estimated that half of severe childhood deafness was due to simple mendelian inheritance and that 87% of this group is autosomal recessive. By ingenious mathematical analysis, Morton (1960) concluded that recessive inheritance is responsible for 68% of congenital deafness, that homozygosity at any one of 35 loci can result in this phenotype and that 16% of the normal population are carriers of a gene for congenital deafness. See also Morton (1991). Muhlmann (1930) reported an instance in which 2 individuals with congenital deafness, clearly with autosomal recessive disease because in each case parents were consanguineous and a sib was also affected, married and produced only children with normal hearing. Mengel et al. (1969) presented an instructive pedigree in which 2 congenitally deaf parents had all normal-hearing offspring. One parent came from a Mennonite group with numerous cases of congenital deafness in a recessive pattern. The other parent came from an Amish group which also contained several persons with apparently recessively inherited congenital deafness. Majumder et al. (1989) studied the genetics of prelingual deafness in 133 nuclear families from 25 large pedigrees in India. Segregation analysis revealed a model for prelingual deafness suggestive of unlinked diallelic autosomal loci. Individuals were affected if and only if they were recessive homozygous at both loci. In Israel, Brownstein et al. (1991) studied families in which both parents had congenital deafness. Among 111 such couples in which the deafness was possibly recessive and there was at least 1 child, there were 12 with only deaf children and 5 with both deaf and hearing children. The number of loci for recessive deafness in the whole group was estimated to be 8 or 9. Matings within the same Jewish group (Sephardi, Eastern, or Ashkenazi) gave an estimate of 6.7 loci, whereas interethnic matings gave an estimate of 22 loci. A conclusion of the study for genetic counseling was that deaf spouses from different ethnic groups have a smaller risk for deaf children than those from the same ethnic group. Mapping Guilford et al. (1994) performed linkage analyses using highly polymorphic microsatellite markers in 2 consanguineous families from Tunisia with profound prelingual deafness. A maximum 2-point lod score of 9.88 at theta = 0.01 was found with a marker on chromosome 13q (D13S175). Linkage was also observed with the pericentromeric 13q12 loci D13S115 and D13S143. (Guilford et al. (1994) referred to this disorder as nonsyndromic recessive deafness and used the gene symbol NSRD1.) Chaib et al. (1994) studied a family of French origin with an autosomal dominant form of neurosensory deafness. The deafness was moderate to severe, had a prelingual onset, and affected predominantly the high frequencies. By linkage analysis, they mapped the disorder to chromosome 13q (multipoint maximum lod score of 4.66 at D13S175). The findings suggested that different mutations in the candidate gene could cause either dominant or recessive neurosensory deafness. This situation, with dominant and recessive forms of the same disorder depending on the nature of the specific mutations, has been observed in epidermolysis bullosa dystrophica due to mutations in the COL7A1 gene (120120), in retinitis pigmentosa due to mutations in the rhodopsin gene (RHO; 180380), and in myotonia congenita due to mutations in the CLCN1 gene (118425), to list only 3 examples. From linkage studies in 18 New Zealand and 1 Australian nonconsanguineous kindreds with nonsyndromic presumed congenital sensorineural deafness and a pedigree structure consistent with autosomal recessive inheritance, Maw et al. (1995) found linkage to markers D13S175, D13S143, and D13S115 on chromosome 13. The finding suggested that the DFNB1 locus may make an important contribution to autosomal recessive neurosensory deafness in a Caucasian population. While there was no statistically significant evidence for heterogeneity at any of the 3 marker loci tested, 9 of the 19 families showed cosegregation of marker haplotypes with deafness. In these 9 families, phenotypic variation was observed both within sibships (in 4 families), which indicated that variable expressivity characterized some genotypes at the DFNB1 locus, and between generations (in 2 families), which suggested allelic heterogeneity. Scott et al. (1995) showed that nonsyndromic autosomal recessive deafness in a highly inbred Bedouin family was linked to chromosome 13q12. In 1 of 27 families of Pakistani origin with nonsyndromic recessive deafness, Brown et al. (1996) found linkage to the DFNB1 locus on chromosome 13. Haplotype analysis of markers in the pericentromeric region of 13q suggested a recombination event that mapped DFNB1 proximal to the marker D13S175 and in the vicinity of D13S143. In an erratum, the authors noted that further analysis placed D13S143 distal to D13S175 rather than proximal, and therefore the locus DFNB1 was likely to be located proximal to D13S143, as suggested by Scott et al. (1995). Gasparini et al. (1997) performed a genetic linkage study with 4 microsatellite markers linked to DFNB1 in a total of 48 independent Mediterranean families, of which 30 and 18 were of Italian and Spanish descent, respectively. They concluded that DFNB1 played a role in 79% of Mediterranean families with nonsyndromic neurosensory autosomal recessive deafness. Molecular Genetics Kelsell et al. (1997) identified a homozygous mutation in the GJB2 gene (121011.0002) in affected members of 3 families with autosomal recessive nonsyndromic sensorineural deafness linked to 13q11-q12 (Brown et al., 1996). By immunohistochemical staining, Kelsell et al. (1997) demonstrated that CX26 has a high level of expression in human cochlear cells. Denoyelle et al. (1999) studied 140 children from 104 families with various degrees of sensorineural hearing loss. CX26 mutations were present in 43 (49%) of 88 families with prelingual deafness compared with none of the 16 families with postlingual forms of deafness. CX26-associated deafness varied from mild to profound, and was associated with sloping or flat audiometric curves and a radiologically normal inner ear. Hearing loss was not progressive in 11 of 16 cases tested, and variations in the severity of deafness between sibs were common. Denoyelle et al. (1999) suggested that an important element for genetic counseling is that the severity of hearing loss in DFNB1 is extremely variable and cannot be predicted, even within families. Dahl et al. (2006) identified a homozygous mutation in the GJB2 gene (V37I; 121011.0023) in 4 (8.3%) of 48 Australian children with slight or mild sensorineural hearing loss. All 4 children were of Asian background, and SNP analysis suggested a common founder effect. All 4 children showed bilateral high-frequency sensorineural hearing loss, and 3 also had low-frequency hearing loss. Two additional children who were heterozygous for V37I had mild high-frequency loss maximal at 6kHz, and mild low-frequency loss, respectively. In all, 55 children with slight or mild hearing loss were identified in a screening of 6,240 Australian school children. Tang et al. (2006) analyzed the GJB2 gene in 610 hearing-impaired individuals and 294 controls and identified causative mutations in 10.3% of cases, with equivocal results in 1.8% of cases due to the detection of unclassified, novel, or controversial coding sequence variations or of only a single recessive mutation in GJB2. Thirteen sequence variations were identified in controls, and complex genotypes were observed among Asian controls, 47% of whom carried 2 to 4 sequence variations in the coding region of the GJB2 gene. Iossa et al. (2010) reported an Italian family in which an unaffected mother and 1 of her deaf sons were both heterozygous for an allele carrying 2 GJB2 mutations in cis: the dominant R75Q (121011.0026) and the recessive 35delG (121011.0005), whereas her other deaf son did not carry either of these mutations. The results suggested that the recessive mutation 'canceled out' the effect of the dominant mutation by causing a truncated protein before reaching residue 75. Iossa et al. (2010) suggested that deafness in the 2 sons was due to another genetic cause and highlighted the importance of the report for genetic counseling. ### Deafness, Digenic, GJB2/GJB6 Del Castillo et al. (2002) noted that in many patients (10-42%) with autosomal recessive nonsyndromic deafness who were found to have a mutation in the GJB2 gene, the second mutation remained unidentified. They demonstrated that 22 of 33 unrelated such patients, 9 of whom had evidence of linkage to 13q12, were compound heterozygous for a mutation in the GJB2 gene (35delG; 121011.0005) and a deletion in the GJB6 gene (604418.0004). Two subjects were homozygous for the GJB6 mutation. In the Spanish population, the GJB6 deletion was the second most frequent mutation causing prelingual deafness. The authors concluded that mutations in the GJB2 and GJB6 gene can result in a monogenic or digenic pattern of inheritance of prelingual deafness. Del Castillo et al. (2002) reported the deletion as 342 kb, but Del Castillo et al. (2005) stated that more recent sequencing data indicated that the deletion is 309 kb. Pallares-Ruiz et al. (2002) found a deletion in the GJB6 gene in trans in 4 of 6 deafness patients heterozygous for a GJB2 mutation, suggesting a digenic mode of inheritance. In 4 unrelated Spanish patients with autosomal recessive nonsyndromic hearing impairment who were heterozygous for 1 GJB2 mutant allele and did not carry the GJB6 309-kb deletion, del Castillo et al. (2005) identified a GJB6 232-kb deletion, which they referred to as del(GJB6-D13S1854) (see 604418.0006). The deletion was subsequently found in DFNB1 patients in the United Kingdom, Brazil, and northern Italy; haplotype analysis revealed a common founder shared among chromosomes studied from Spain, the United Kingdom, and Italy. In 255 French patients with a phenotype compatible with DFNB1, Feldmann et al. (2004) found that 32% had biallelic GJB2 mutations, and 6% were compound heterozygous for a GJB2 mutation and the GJB6 342-kb deletion. Profoundly deaf children were more likely to have the biallelic GJB2 or heterozygous GJB2/GJB6 mutations. In a study of 777 unrelated children with hearing loss, Cheng et al. (2005) identified GJB2 or GJB6 mutations in 12%; among those with an affected sib, 20% had GJB2 or GJB6 mutations. Ten patients were compound heterozygous for mutations in the GJB2 and GJB6 genes. In 324 probands with hearing loss and 280 controls, including 135 probands and 280 controls previously reported by Tang et al. (2006), Tang et al. (2008) screened for DNA sequence variations in GJB2 and for deletions in GJB6. The 232-kb GJB6 deletion was not found, and the 309-kb GJB6 deletion was found only once, in a patient of unknown ethnicity who was also heterozygous for a truncating mutation in GJB2. Tang et al. (2008) suggested that the 232- and 309-kb deletions in the GJB6 gene may not be common in all populations. ### Deafness, Digenic, GJB2/GJB3 Liu et al. (2009) reported digenic inheritance of nonsyndromic deafness caused by mutations in the GJB2 and GJB3 (603324) genes. Three of 108 Chinese probands with autosomal recessive deafness and only 1 mutant GJB2 allele (e.g., 121011.0014) were found to be compound heterozygous with a GJB3 mutation (603324.0011; 603324.0012). The findings were consistent with digenic inheritance; the unaffected parents were heterozygous for 1 of the mutant alleles. ### Reviews Willems (2000) reviewed the genetic causes of nonsyndromic sensorineural hearing loss. Petersen and Willems (2006) provided a detailed review of the molecular genetics of nonsyndromic autosomal recessive deafness. Population Genetics In Tunisia, Ben Arab et al. (1990) estimated the frequency of nonsyndromic autosomal recessive sensorineural deafness to be 7 per 10,000. Chaabani et al. (1995) studied 30 deaf couples in Tunisian and estimated that the number of loci for nonsyndromic autosomal recessive deafness in this population was 8.3. Nance et al. (2000) proposed a hypothesis for the high frequency of DFNB1 in many large populations of the world, on the basis of an analysis of the proportion of noncomplementary marriages among the deaf during the 19th century, which suggested that the frequency of DFNB1 may have doubled in the United States during the past 200 years. These so-called noncomplementary marriages between individuals with the same type of recessive deafness are incapable of producing hearing offspring, and the square root of their frequency among deaf marriages provides an upper limit for the prevalence of the most common form of recessive deafness at that time. To explain the increase, they suggested that the combination of intense assortative mating and relaxed selection increased both the gene and the phenotype frequencies for DFNB1. The proposed model assumed that in previous millennia the genetic fitness of individuals with profound congenital deafness was very low and that genes for deafness were then in a mutational equilibrium. The introduction of sign language in Europe in the 17th to 18th centuries was a key event that dramatically improved the social and economic circumstances of the deaf, along with their genetic fitness. In many countries, schools for the deaf were established, contributing to the onset of intense linguistic homogamy, i.e., mate selection based on the ability to communicate in sign language. In some large populations, connexin-26 deafness has been observed but at a much lower frequency. In Mongolia, for example, where there is only 1 residential school for the deaf, sign language was not introduced until 1995. Moreover, the fitness of the deaf is much lower than that of their hearing sibs, assortative mating is much less frequent than in the United States, and connexin mutations account for only 1.3% of all deafness (Pandya et al., 2001). Nance and Kearsey (2004) showed by computer simulation that assortative mating, in fact, can accelerate dramatically the genetic response to relaxed selection. Along with the effects of gene drift and consanguinity, assortative mating also may have played a key role in the joint evolution and accelerated fixation of genes for speech after they first appeared in Homo sapiens 100,000 to 150,000 years ago. In 156 unrelated congenitally deaf Czech patients, Seeman et al. (2004) tested for the presence of mutations in the coding sequence of the GJB2 gene. At least 1 pathogenic mutation was detected in 48.1% of patients. The 3 most common mutations were W24X (121011.0003), 35delG (121011.0005), and 313del14 (121011.0034); the authors stated that testing for only these 3 mutations would detect over 96% of all disease-causing mutations in GJB2 in this population. Testing for 35delG in 503 controls revealed a carrier frequency of 1:29.6 (3.4%) in the Czech Republic. Alvarez et al. (2005) screened the GJB2 gene in 34 Spanish Romani (gypsy) families with autosomal recessive nonsyndromic hearing loss and found mutations in 50%. The predominant allele was W24X (121011.0003), accounting for 79% of DFNB1 alleles. Haplotype analysis suggested that a founder effect is responsible for the high prevalence of this mutation among Spanish gypsies. 35delG (121011.0005) was the second most common allele (17%). Arnos et al. (2008) collected pedigree data on 311 contemporary marriages among deaf individuals that were comparable to those collected by Fay (1898). Segregation analysis of the resulting data revealed that the estimated proportion of noncomplementary matings that can produce only deaf children increased by a factor of more than 5 in the aforegoing 100 years. Additional analysis within their sample of contemporary pedigrees showed that there was a statistically significant linear increase in the prevalence of pathologic GJB2 mutations when the data on 441 probands were partitioned into three 20-year birth cohorts (1920-1980). Arnos et al. (2008) concluded that their data were consistent with the increase in the frequency of DFNB1 predicted by their previous simulation studies, and provided convincing evidence for the important influence that assortative mating can have on the frequency of common genes for deafness. Schimmenti et al. (2008) enrolled 95 infants with hearing loss from whom both exons of Cx26 were sequenced and the Cx30 deletion was assayed in a study comparing infants with and without connexin-related hearing loss. Overall among these 95 patients, biallelic mutations were identified in 24.7%, but in only 9.1% of infants of Hispanic origin. Schimmenti et al. (2008) concluded that connexin-related hearing loss occurs in one quarter of infants in an ethnically diverse hearing loss population but with a lower prevalence in Hispanic infants. Tekin et al. (2010) screened the GJB2 gene in 534 Mongolian probands with nonsyndromic sensorineural deafness and identified biallelic GJB2 mutations in 23 (4.5%) deaf probands. The most common mutation, IVS1+1G-A (121011.0029), appeared to have diverse origins based on multiple associated haplotypes. Tekin et al. (2010) stated that they found a lower frequency of assortative mating (37.5%) and decreased genetic fitness (62%) of the deaf in Mongolia compared to Western populations, which explained the lower frequency of GJB2 deafness in Mongolia. Barashkov et al. (2011) found homozygosity for the IVS1+1G-A mutation in GJB2 in 70 of 86 patients from the Yakut population isolate in eastern Siberia with nonsyndromic hearing impairment. Six patients were compound heterozygous for this mutation and another pathogenic GJB2 mutation. Audiometric examination was performed on 40 patients who were homozygous for the mutation. Most (85%) had severe to profound hearing impairment, 14% had moderate impairment, and 1% had mild hearing loss. There was some variability in hearing thresholds. The carrier frequency for this mutation in this population was estimated to be 11.7%, the highest among 6 eastern Siberian populations analyzed, and the mutation was estimated to be about 800 years old. The findings were consistent with a founder effect, and Barashkov et al. (2011) postulated a central Asian origin for the mutation. Among 15,799 ethnically diverse individuals screened for DFNB1 carrier status, Lazarin et al. (2013) identified 371 carriers (2.3%), for an estimated carrier frequency of approximately 1 in 43. Five 'carrier couples' were identified. Six individuals were identified as homozygotes or compound heterozygotes. Among 756 individuals of east Asian origin, the carrier frequency was 1 in 22. In 6 Guatemalan probands with DFNB1A, Carranza et al. (2016) identified a homozygous truncating mutation in the GJB1 gene (W44X; 121011.0040). Two additional probands with deafness were compound heterozygous for the W44X mutation and another pathogenic mutation. The patients were from a cohort of 133 Guatemalan families with hearing loss who underwent sequencing of the GJB1 gene. The W44X mutation was the most common GJB1 pathogenic variant identified, accounting for 21 of 266 alleles, and 62% of the mutant GJB1 alleles identified. Haplotype analysis indicated a founder effect in this population, and ancestry analysis of individuals with this pathogenic variant showed a close match with Mayans. The W44X mutation always occurred with a benign c.79G-A variant (V27I) in the GJB1 gene. History In the pre-mendelian era, Meniere (1846, 1856) noted the role of parental consanguinity in deafness. Boudin (1862) noted the association between consanguinity and congenital deafness. Groce (1985) traced the history of congenital deafness on Martha's Vineyard, the Massachusetts island. The first deaf person moved to the island in 1694. Groce (1985) estimated that in the 19th century 1 in 155 persons on the island was born deaf. Because there were deaf members in virtually every family in the western part of the island, everyone learned sign language, and the deaf were fully integrated into every aspect of life. Under these circumstances, deafness was not a disability or a handicap. Mengel et al. (1967) found severe deafness in 16 members of a kindred. By history, all were born with at least some hearing but suffered progressive severe loss in later childhood. Sonographic and speech analysis gave further evidence of some hearing in early childhood. Audiologic tests suggested cochlear location of the defect. Although successive generations were affected in some instances, consanguinity and recessive inheritance were thought to account for the finding. Barr and Wedenberg (1964) described a similar disorder in 4 of 7 sibs. Among the 11 children of consanguineous parents, Cremers (1979) observed 2 boys and a girl with progressive sensorineural deafness, first noticed at ages 4, 7 and 11 years. He found 2 reports of a similar deafness and concluded that it was different from the deafness reported by Mengel et al. (1967). A second family was reported by Cremers et al. (1987). Progressive sensorineural hearing loss started mainly in the higher frequencies. They also found an abrupt decline in the audiogram that slowly decreased with the increase of low frequency hearing loss. Ormerod (1960) recognized the following types of congenital deafness, beginning with the most complete form: (1) Michel type--complete lack of development of internal ear. (2) Mondini-Alexander type--development only of a single curved tube representing the cochlea, and similar immaturity of the vestibular canals. (3) Bing-Siebenmann type--bony labyrinth well formed but membranous part and particularly the sense organ poorly developed. This type is often associated with retinitis pigmentosa. (4) Scheibe cochleosaccular type--In this form, which is the most frequent one, the vestibular part is developed and functioning. Malformation is restricted to the membranous cochlea and saccule. This type occurs in Waardenburg syndrome. (5) Siebenmann type--changes mainly in middle ear and often due to thyroid hormone deficiency. The middle ear is involved in myxomatous change which may be embryonic persistence. (6) Microtia and atresia of the meatus--abnormality limited to the external ear. INHERITANCE \- Autosomal recessive \- Digenic (see MISCELLANEOUS) HEAD & NECK Ears \- Hearing loss, sensorineural, prelingual profound \- Vestibular dysfunction (in some patients) MISCELLANEOUS \- About half of patients report vestibular symptoms \- Digenic form caused by simultaneous heterozygous mutations in GJB2 and either GJB3 or GJB6 MOLECULAR BASIS \- Caused by mutation in the gap junction protein, beta-2 gene (GJB2, 121011.0002 ) \- Caused by simultaneous mutation in both the gap junction protein, beta-2 gene (GJB2, 121011.0005 ) and the gap junction protein, beta-6 gene (GJB6, 604418.0004 ) \- Caused by simultaneous mutation in both the gap junction protein, beta-2 gene (GJB2, 121011.0014 ) and the gap junction protein, beta-3 gene (GJB3, 603324.0011 ) ▲ 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	DEAFNESS, AUTOSOMAL RECESSIVE 1A	c2673761	7,489	omim	https://www.omim.org/entry/220290	2019-09-22T16:28:59	{"doid": ["0110475"], "mesh": ["C567134"], "omim": ["220290"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"], "genereviews": ["NBK1434", "NBK1272"]}
Schizophrenia is a brain disorder classified as a psychosis, which means that it affects a person's thinking, sense of self, and perceptions. The disorder typically becomes evident during late adolescence or early adulthood. Signs and symptoms of schizophrenia include false perceptions called hallucinations. Auditory hallucinations of voices are the most common hallucinations in schizophrenia, but affected individuals can also experience hallucinations of visions, smells, or touch (tactile) sensations. Strongly held false beliefs (delusions) are also characteristic of schizophrenia. For example, affected individuals may be certain that they are a particular historical figure or that they are being plotted against or controlled by others. People with schizophrenia often have decreased ability to function at school, at work, and in social settings. Disordered thinking and concentration, inappropriate emotional responses, erratic speech and behavior, and difficulty with personal hygiene and everyday tasks can also occur. People with schizophrenia may have diminished facial expression and animation (flat affect), and in some cases become unresponsive (catatonic). Substance abuse and suicidal thoughts and actions are common in people with schizophrenia. Certain movement problems such as tremors, facial tics, rigidity, and unusually slow movement (bradykinesia) or an inability to move (akinesia) are common in people with schizophrenia. In most cases these are side effects of medicines prescribed to help control the disorder. However, some affected individuals exhibit movement abnormalities before beginning treatment with medication. Some people with schizophrenia have mild impairment of intellectual function, but schizophrenia is not associated with the same types of physical changes in the brain that occur in people with dementias such as Alzheimer disease. Psychotic disorders such as schizophrenia are different from mood disorders, including depression and bipolar disorder, which primarily affect emotions. However, these disorders often occur together. Individuals who exhibit strong features of both schizophrenia and mood disorders are often given the diagnosis of schizoaffective disorder. ## Frequency Schizophrenia is a common disorder that occurs all over the world. It affects almost 1 percent of the population, with slightly more males than females developing the disorder. ## Causes Variations in many genes likely contribute to the risk of developing schizophrenia. In most cases, multiple genetic changes, each with a small effect, combine to increase the risk of developing the disorder. The ways that these genetic changes are related to schizophrenia are not well understood, and the genetics of this disease is an active area of research. The genetic changes can also interact with environmental factors that are associated with increased schizophrenia risk, such as exposure to infections before birth or severe stress during childhood. Deletions or duplications of genetic material in any of several chromosomes, which can affect multiple genes, are also thought to increase schizophrenia risk. In particular, a small deletion (microdeletion) in a region of chromosome 22 called 22q11 may be involved in a small percentage of cases of schizophrenia. Some individuals with this deletion have other features in addition to schizophrenia, such as heart abnormalities, immune system problems, and an opening in the roof of the mouth (cleft palate), and are diagnosed with a condition called 22q11.2 deletion syndrome. ### Learn more about the genes and chromosome associated with Schizophrenia * AKT1 * COMT * YWHAE * chromosome 22 Additional Information from NCBI Gene: * ABCA13 * C4A * DGCR2 * DGCR8 * DRD2 * MIR137 * NOS1AP * NRXN1 * OLIG2 * RTN4R * SYN2 * TOP3B * ZDHHC8 ## Inheritance Pattern The inheritance pattern for schizophrenia is usually unknown. The risk of developing schizophrenia is somewhat higher for family members of affected individuals as compared to the general public; however, most people with a close relative who has schizophrenia will not develop the disorder themselves. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Schizophrenia	c0036341	7,490	medlineplus	https://medlineplus.gov/genetics/condition/schizophrenia/	2021-01-27T08:25:12	{"mesh": ["D012559"], "omim": ["181500"], "synonyms": []}
A number sign (#) is used with this entry because alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus (CMV) infection, and autoimmunity is caused by mutations in the RAG1 gene (179615). Mutations in the RAG1 gene also cause T cell-negative, B cell-negative, natural killer (NK) cell-positive severe combined immunodeficiency (SCID; 601457) and Omenn syndrome (603554). Clinical Features De Villartay et al. (2005) reported 4 unrelated infants born to first cousins of Algerian, Moroccan, Lebanese, and Turkish origin who presented with persistent CMV infection before 1 year of age. In 3 patients, CMV infection was associated with autoantibodies to red cells, causing anemia. Autoantibodies to neutrophils were present in 1 of these patients, and antinuclear autoantibodies were present in 2 of these patients. The numbers of lymphocytes and lymphocyte subsets (i.e., T, B, and NK cells) were normal in 3 patients and low in 1 patient, but the ratio of TCR-alpha (see 186880)/beta (see 186930) to TCR-gamma (see 186970)/delta (see 186810) T cells was nearly inverse the normal ratio in all 4 patients. Molecular Genetics De Villartay et al. (2005) identified homozygous mutations in the RAG1 gene (e.g., 179615.0017) in all 4 patients they reported with alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe CMV infection, and autoimmunity. They concluded that hypomorphic RAG1 mutations result in residual RAG1 activity and are compatible with the presence of both B and T lymphocytes. De Villartay et al. (2005) suggested that the immunologic phenotypes associated with RAG1 mutations are dependent on both genetic background and the microbial environment. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	ALPHA/BETA T-CELL LYMPHOPENIA WITH GAMMA/DELTA T-CELL EXPANSION, SEVERE CYTOMEGALOVIRUS INFECTION, AND AUTOIMMUNITY	c1835931	7,491	omim	https://www.omim.org/entry/609889	2019-09-22T16:05:30	{"mesh": ["C563691"], "omim": ["609889"], "orphanet": ["231154"]}
Chester porphyria is a unique type of porphyria with the signs and symptoms of acute intermittent porphyria (AIP) and the biochemical defects of both AIP and variegate porphyria (VP). Chester porphyria does not conform to any of the recognized types of acute porphyria. The symptoms associated with Chester porphyria are similar to those observed in other acute porphyrias. Treatment is symptomatic. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Chester porphyria	c0268322	7,492	gard	https://rarediseases.info.nih.gov/diseases/10185/chester-porphyria	2021-01-18T18:01:30	{"mesh": ["C536341"], "omim": ["176010"], "umls": ["C0268322"], "synonyms": ["Porphyria, Chester type", "PORC"]}
Straddling or overriding tricuspid valve is a rare, congenital, tricuspid valve malformation characterized by the tricuspid valve that overrides the ventricular septum and communicates with both ventricles, as part of the tension apparatus of the valve crosses the ventricular septal defect and is attached in the left ventricle. The anomaly occurs with other congenital heart defects (transposition of great vessels, left ventricle outflow tract obstruction, double outlet right ventricle, hypoplastic right ventricle), which determine the main clinical manifestation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Straddling or overriding tricuspid valve	None	7,493	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=95461	2021-01-23T16:56:08	{"icd-10": ["Q22.8"]}
## Summary ### Clinical characteristics. All FOXP2-related speech and language disorders, regardless of the underlying genetic alteration, have a core phenotype: childhood apraxia of speech (CAS), a disorder of speech motor programming or planning that affects the production, sequencing, timing, and stress of sounds, syllables, and words. All individuals with CAS – whether caused by an alteration of FOXP2 or of an unknown cause – have difficulties in automatically and accurately sequencing speech sounds into syllables, syllables into words, and words into sentences with the correct prosody. Additional findings in FOXP2-related speech and language disorders can include oral motor dyspraxia (difficulty planning or programming oral movements on command); dysarthria (a neuromuscular-based speech disorder that may affect nasal resonance, voice quality, prosody, and breath support for speech); moderate to severe receptive and expressive language disorder; and reading and spelling impairments. The underlying genetic cause of FOXP2-related speech and language disorders is either disruption of FOXP2 only (referred to in this GeneReview as FOXP2-only-related speech and language disorder) or large copy number variants (i.e., contiguous gene deletions), structural variants (i.e., chromosome translocation or inversion), or maternal uniparental disomy of chromosome 7 (UPD7) involving FOXP2 (here referred to as FOXP2-plus speech and language disorders). The genetic alteration determines if only speech and language problems are present (FOXP2-only-related speech and language disorder) or if more global developmental and behavioral issues are likely to be present as well (FOXP2-plus speech and language disorder). In FOXP2-only-related disorders, nonverbal (performance) IQ is typically more preserved compared to verbal IQ. Fine motor skills may be impaired (e.g., buttoning clothes, tying shoelaces), yet gross motor skills are normal. Autistic features and dysmorphic findings have been reported in a few affected individuals. In FOXP2-plus-related disorders oral motor deficits, global developmental delay, and autism spectrum disorder are common. ### Diagnosis/testing. The diagnosis of a FOXP2-related speech and language disorder is established in a proband by detection of one of the following: * A large non-recurrent contiguous gene deletion that includes FOXP2 (52% of affected individuals) * A sequence variant within FOXP2 (~29%) * Maternal uniparental disomy of chromosome 7 (UPD7) that reduces FOXP2 expression (~11%) * A structural variant (e.g., chromosome translocation, inversion) that disrupts FOXP2 (~8%) ### Management. Treatment of manifestations: Optimally management of the speech and/or language disorder is determined by a speech pathologist based on the individual's findings (typically: presence and severity of CAS, dysarthria, language deficits, and literacy impairments). A clinical psychologist or neuropsychologist may provide strategies to help manage deficits in specific cognitive domains and an occupational therapist and physiotherapist can provide strategies to help with fine and gross motor deficits, respectively. Surveillance: Follow-up evaluations with standardized tests by a speech and language pathologist. Evaluation of relatives at risk: Clarification of the genetic status of pre-symptomatic relatives at risk identifies as early as possible those who would benefit from prompt evaluation for speech and language disorders and initiation of treatment. ### Genetic counseling. Recurrence risk for sibs of proband with a FOXP2-related speech and language disorder depends on the genetic alteration: Non-recurrent contiguous gene deletions (80% are de novo and the remainder are inherited in an autosomal dominant manner) FOXP2 sequence variants (~70% are de novo and the remainder are inherited in an autosomal dominant manner) Maternal UPD7 (no increased risk to sibs) A structural variant (e.g., chromosome translocation, inversion. If one parent has a structural variant, the risk to sibs is increased and depends on the specific structural variant.) Prenatal testing and preimplantation genetic testing are possible if the causative genetic alteration has been identified in an affected family member. ## Diagnosis ### Suggestive Findings A FOXP2-related speech and language disorder should be suspected in a child with childhood apraxia of speech (CAS) [American Speech-Language-Hearing Association 2007] (also known as developmental verbal dyspraxia, verbal dyspraxia, or speech dyspraxia) and additional clinical findings. CAS * Children with CAS have difficulties in automatically and accurately sequencing speech sounds into syllables, syllables into words, and words into sentences. * The diagnosis of CAS is made by assessment by a speech-language pathologist (also known as a speech and language therapist in the UK). CAS is challenging to diagnose in a child younger than age three years: speech development is delayed in these children, and thus key manifestations are typically not seen or able to be elicited until the child has acquired sufficient speech to complete the verbal assessment tasks. Additional clinical findings * Delayed speech development * Poor oral motor function (e.g., excessive drooling, early feeding difficulties) * Oral motor difficulties and/or oral motor dyspraxia * Dysarthria * Receptive and expressive language impairment * Low average IQ, typically with poorer verbal IQ compared to nonverbal IQ (and average nonverbal IQ reported in some) * Mild dysmorphology may rarely be present * Autistic features may rarely be present * Reading and spelling impairment * Fine and gross motor impairment ### Establishing the Diagnosis The diagnosis of a FOXP2-related speech and language disorder is established in a proband by detection of ONE of the following (see Table 1): * A large non-recurrent contiguous gene deletion that includes FOXP2 (52% of affected individuals) * A sequence variant within FOXP2 (~29%) * Maternal uniparental disomy of chromosome 7 (UPD7) that reduces FOXP2 expression (~11%) * A structural variant (e.g., translocation, inversion) that disrupts FOXP2 (~8%). Molecular genetic testing approaches can include a combination of gene-targeted testing (multigene panel or single-gene testing) and genomic testing (chromosomal microarray [CMA] and comprehensive genomic sequencing) depending on the phenotype. Gene-targeted testing requires the clinician to determine which gene(s) are likely involved, whereas genomic testing may not. Because the phenotype of FOXP2-related speech and language disorders is broad, children with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas a more severe phenotype that includes developmental delay (DD)/intellectual disability (ID) may be indistinguishable from many other inherited disorders with DD/ID and is more likely to be diagnosed using genomic testing (see Option 2). Option 1. Gene-targeted testing. When the clinical findings suggest the diagnosis of a FOXP2-related speech and language disorder, molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of FOXP2 is performed first, followed by gene-targeted deletion/duplication analysis. * A multigene panel that includes FOXP2 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. ((2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. Methylation testing for maternal uniparental disomy (UPD) of chromosome 7 should be considered in individuals with verbal dyspraxia and features suggestive of Silver-Russell syndrome, since UPD accounted for about 12% of cases in one study [Feuk et al 2006]. Note: FOXP2 has not been demonstrated to be an imprinted gene. Although FOXP2 is located on chromosome 7, the mechanistic relationship between UPD7 and FOXP2 function has not been established. Option 2. Genomic testing. When the phenotype is indistinguishable from many other inherited disorders with language delay and developmental delay/intellectual disability, molecular genetic testing approaches can include genomic testing (CMA, comprehensive genomic sequencing, and karyotype): * CMA should be the first genetic test as about 52% of FOXP2-related speech and language disorders are caused by large non-recurrent deletions that encompass FOXP2 and flanking DNA. * Further testing to consider: * Comprehensive genomic sequencing (when clinically available) includes exome sequencing and genome sequencing. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. * Karyotype. An apparently balanced translocation or pericentromeric inversion involving 7q31.1, the FOXP2 locus, has been observed in about 8% of FOXP2-plus-related disorders and FOXP2-only-related disorders. Note: A multigene panel for inherited disorders of speech delay and developmental delay/intellectual disability may be considered. ### Table 1. Molecular Genetic Testing Used in FOXP2-Related Speech and Language Disorders View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method FOXP2-plusFOXP2-only FOXP2CMA 3, 434/65 (52%) 5, 6NA Sequence analysis 7NA19/65 (29%) 8 Methylation testing (to detect UPD)7/65 (~11%) 9NA Karyotype (to detect structural variants)5/65 (~8%) 10NA Gene-targeted deletion/duplication analysis 11Unknown 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics and Table 3 for information on reported genetic alterations and phenotypes. 3\. Deletion/duplication analysis (genomic approach) detects deletion of FOXP2 and other contiguous genes using a chromosomal microarray (CMA) that specifically includes this gene/chromosome segment. 4\. ClinGen-19248. Standardized clinical annotation and interpretation for genomic variants from the Clinical Genome Resource (ClinGen) project (formerly the International Standards for Cytogenomic Arrays [ISCA] Consortium). 5\. Feuk et al [2006], Zeesman et al [2006], Lennon et al [2007], Palka et al [2012], Rice et al [2012], Zilina et al [2012], Adegbola et al [2015], Reuter et al [2017] 6\. One affected individual had mosaicism for a large deletion [Palka et al 2012]. 7\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice-site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 8\. Lai et al [2001], MacDermot et al [2005], Roll et al [2010], Laffin et al [2012], Turner et al [2013], Reuter et al [2017] 9\. Feuk et al [2006] 10\. Lai et al [2000], Lai et al [2001], Feuk et al [2006], Shriberg et al [2006], Tomblin et al [2009], Moralli et al [2015] 11\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. ## Clinical Characteristics ### Clinical Description FOXP2-related speech and language disorders – regardless of the underlying genetic alteration – have a core phenotype: childhood apraxia of speech (CAS), a disorder of speech motor programming or planning that affects the production, sequencing, timing, and stress of sounds, syllables, and words. Individuals with CAS (whether caused by an alteration of FOXP2 or of an unknown cause) have difficulties in automatically and accurately sequencing speech sounds into syllables, syllables into words, and words into sentences with the correct prosody. Additional findings in FOXP2-related speech disorders can include oral motor dyspraxia (difficulty planning or programming oral movements on command); dysarthria (a neuromuscular-based speech disorder that may affect nasal resonance, voice quality, prosody, and breath support for speech); moderate to severe receptive and expressive language disorder; reading and spelling impairments; more preserved non-verbal IQ compared to verbal IQ; and fine motor difficulties. "Autistic features" or a diagnosis of autism spectrum disorder (ASD) has been reported in some, but not all cases. Similarly typically mild dysmorphology has been reported in a few cases only. The underlying genetic alteration of FOXP2-related speech and language disorders is one of the following: * Disruption of FOXP2 only – here referred to as FOXP2-only-related speech and language disorders * Large copy number variants (i.e., contiguous gene deletions) or structural variants (i.e., translocation or inversion) involving FOXP2 – here referred to as FOXP2-plus speech and language disorders The genetic alteration determines if only speech and language problems are present (FOXP2-only-related speech and language disorder) or if more global developmental and behavioral issues are likely to be present as well (FOXP2-plus speech and language disorder). In FOXP2-only-related disorders nonverbal (performance) IQ is typically relatively preserved compared to verbal IQ and gross motor skills are normal. In FOXP2-plus-related disorders oral motor deficits, global developmental delay, and autism spectrum disorders are commonly seen. To date, available evidence suggests that heterozygous pathogenic variants in FOXP2 (including whole- or partial-gene deletions) cause the motor speech disorder known as childhood apraxia of speech (CAS) which interferes non-selectively with multiple aspects of language, including phonology, grammar, and literacy. The interactions between these communication disorder subtypes are not well understood. Language and literacy difficulties may be influenced by or even result from CAS, or these phenotypes may actually be features of the same broad communication disorder. Childhood apraxia of speech (CAS), a disorder of speech motor planning/programming, is the core phenotype of FOXP2-related speech and language disorders [Watkins et al 2002, Laffin et al 2012, Turner et al 2013]. CAS affects the production, sequencing, timing, and stress of sounds, syllables, and words [American Speech-Language-Hearing Association 2007]; thus, children with CAS have difficulties in automatically and accurately sequencing speech sounds into syllables, syllables into words, and words into sentences with appropriate prosody. First words are reported to appear between ages 18 months and seven years in children with FOXP2-only-related disorders [Vargha-Khadem et al 1995, MacDermot et al 2005, Laffin et al 2012, Reuter et al 2017] and FOXP2-plus-related disorders [Feuk et al 2006, Zeesman et al 2006, Lennon et al 2007, Zilina et al 2012, Rice et al 2012]. FOXP2-related speech and language disorders are typically diagnosed around age three to four years, but may be considered earlier when the family history is positive. In the first decade of life, speech is highly unintelligible, even to close friends and family. Although speech development and intelligibility improve over time, speech never develops to the same level as age-matched peers; intelligibility may remain reduced even in the third and fourth decades of life [Fee 1995, Shriberg et al 2006]. Note: The Fee [1995] study of members of the KE family was conducted prior to the identification of a causative FOXP2 heterozygous pathogenic variant in affected family members by Lai et al [2001]. In contrast, for typically developing children, speech sound acquisition is mastered by around age eight years [Dodd et al 2003] with intelligibility as high as 97% as early as age three years [Flipsen 2006]. Although CAS comprises certain core features, it is important to note that the severity and features of CAS change across the life span [Royal College of Speech and Language Therapists 2011] and while referred to as "core" features, they are not necessarily present in all individuals with CAS [American Speech-Language-Hearing Association 2007]. Core features, agreed upon by a consensus panel, include the following: * Inconsistent speech errors (e.g., producing the same syllable or word differently across repetitions of the same word such as "ubella," "umbrella," "umbarella" for umbrella) * Lengthened and disrupted co-articulatory transitions (e.g., oral groping behaviors during speech; difficulty sequencing phonemes and syllables; difficulty maintaining syllable integrity; hypernasality [thought to be due to incoordination of velum for denoting oral/nasal contrasts]; slowed and disrupted diadochokinetic sequences [e.g., when asked to repeat "pa-ta-ka"]) * Inappropriate prosody (e.g., lexical stress errors, equal stress across words giving a robotic-sounding presentation) In addition, children with CAS tend to lag behind their peers in acquiring the sounds of their language system; hence, their phonetic inventory may be reduced for the child's age. Children with CAS may use a more restricted range of consonants and vowels than age-matched peers. For example, they will simplify syllable shapes, reducing a consonant-consonant-vowel shape (CCV) (e.g., "sta") or a CCCV shape ("stra") to a consonant-vowel (CV) shape ("sa"). Although CAS is distinct from other speech disorders (e.g., stuttering, phonologic disorder) and language disorders (e.g., specific language impairment), these additional diagnoses can technically co-occur with CAS. Additional common speech- and language-related comorbidities in FOXP2-related speech and language disorders can include the following – irrespective of underlying genetic alteration: * Oral motor dyspraxia, an inability or difficulty in planning or programming of oral movements on command, including single movements in isolation (e.g., commands such as "blow"; "bite"; "stick out your tongue") or sequences of oral movements (e.g., commands such as "bite and blow"; "touch your bottom lip with your tongue and then your top lip"). Oral dyspraxia has been more commonly reported than oral motor deficits per se in FOXP2-only-related disorders [Vargha-Khadem et al 1998, Alcock et al 2000, Lai et al 2000, MacDermot et al 2005, Turner et al 2013], in contrast to FOXP2-plus-related disorders [Zeesman et al 2006, Feuk et al 2006]. * Dysarthria, which is typically classified as spastic [Shriberg et al 2006, Morgan et al 2010, Turner et al 2013]. Typical dysarthric features include hypernasality, impaired laryngeal quality, and difficulties modulating pitch and loudness. * Moderate to severe receptive and expressive language disorder [Vargha-Khadem et al 1995, Zeesman et al 2006, Tomblin et al 2009]. Expressive language is usually poorer than receptive language, with expressive language likely confounded by the presence of CAS. Impaired performance across both semantic and syntactic language domains has been reported in FOXP2-related speech and language disorders [Watkins et al 2002, Vargha-Khadem et al 2005, Turner et al 2013]. Affected semantic domains include naming accuracy and lexical decision making; affected syntactic domains include past tense production for regular and irregular verbs. * Reading and spelling impairments, which are evident once literacy develops [Vargha-Khadem et al 2005]. Difficulties with real word and non-word reading, spelling, and phonologic awareness skills have been noted in some individuals with FOXP2-related speech and language disorders [Watkins et al 2002, Turner et al 2013]. Of note, the literacy skills of affected individuals have rarely been discussed in case reports and – given the link between speech and literacy disorders – deficits are likely to be underrecognized. Other features of FOXP2-only-related disorders * Generally stronger nonverbal (performance) IQ compared to verbal IQ [Vargha-Khadem et al 1995, Watkins et al 2002, Turner et al 2013, Reuter et al 2017] and compared to children with FOXP2-plus-related disorders [Tomblin et al 2009, Rice et al 2012]. Based on data from the largest family reported to date (which also has the most comprehensive IQ phenotyping available), it appears that in addition to lower verbal IQ (presumably affected by CAS and comorbid expressive language deficits), nonverbal (performance) IQ may also be lower than average in some areas (e.g., coding subtest; see Watkins et al [2002). Further, relative strengths in nonverbal IQ have been previously reported in block design and object assembly subtests of IQ measures [Watkins et al 2002], notably tasks relying on visual processing. * Normal fine and gross motor skills are seen in some affected individuals [Lai et al 2001, Watkins et al 2002, MacDermot et al 2005] but others with FOXP2-only disorders [Reuter et al 2017], or FOXP2-plus-related disorders [Rice et al 2012] have fine motor deficits. Fine or gross motor impairments are reported as relatively mild compared to the marked speech production deficits [Lai et al 2000]. Overall however, relatively little attention has been given in the literature to the possible presence of general motor deficits. * Some features of ASD have been observed and formal diagnoses of ASD have been made in a small number of recently reported individuals; however, the data suggest that these behavioral issues are not a core feature [Reuter et al 2017]. * Mild dysmorphology reported in a small number of individuals, included high arch palate, horizontal eyebrows, simply folded ears [Reuter et al 2017] submucous cleft palate was reported in one individual [Liégeois et al 2016] Other features of FOXP2-plus-related disorders * Oral motor deficits commonly reported [Lennon et al 2007, Zilina et al 2012, Laffin et al 2012] * "Global" developmental delay (presumably involving speech, cognitive, gross, and fine motor abilities) [Feuk et al 2006] * Autism spectrum disorder (ASD) [Feuk et al 2006, Zilina et al 2012] or presence of features of ASD such as repetitive behaviors and unusual interests [Zeesman et al 2006]. Of note, many individuals with FOXP2-only-related disorders are explicitly stated not to meet diagnostic criteria for ASD [Feuk et al 2006, Lennon et al 2007, Rice et al 2012], suggesting that these features may relate to disruption of neighboring genes on chromosome 7. * Facial dysmorphology [Zeesman et al 2006, Lennon et al 2007, Zilina et al 2012, Reuter et al 2017]. Oral structures are typically intact in the absence of a cleft lip or palate, but a high arched palate has been reported in one individual [Palka et al 2012]. Neuroimaging Clinical brain MRIs of individuals with a FOXP2-related speech and language disorder reportedly appear normal on visual inspection [Vargha-Khadem et al 1998]. In contrast, sophisticated quantitative MRI data acquisition and analysis techniques suggest that bilateral subcortical volume reductions are strong markers of FOXP2 disruption in childhood based on findings in (1) members of the KE family with the FOXP2 pathogenic variant p.Arg553His compared to unaffected family members [Vargha-Khadem et al 2005] and (2) one individual with the FOXP2 pathogenic variant Gln415ValfsTer5 [Turner et al 2013, Liégeois et al 2016]. Because data are limited further studies are required to understand the generalizability of this finding. Click here (pdf) for detailed information on neuroimaging findings in the KE family, the first (and largest) family for which published imaging data are reported. ### Genotype-Phenotype Correlations The specific genetic alteration responsible for a FOXP2-related speech and language disorder does not predict clinical severity. However, the phenotype of FOXP2-plus-related disorders tends to be more severe overall (given the increased risk for the additional clinical features of global developmental delay and a formal diagnosis of autism spectrum disorder) compared to the phenotype of FOXP2-only-related disorders. See Table 3 for reported genetic alterations and phenotypes. ### Penetrance The penetrance for this severe speech and language disorder is high, close to 100% based on reported cases. ### Nomenclature Prior to the discovery of FOXP2, the locus "speech language disorder-1 (SPCH1)" was assigned to the chromosome region linked to the CAS phenotype [Fisher et al 1998]. ### Prevalence The population prevalence of childhood apraxia of speech (CAS) has not been determined by any epidemiologic study. The most commonly referenced estimate of prevalence is 1-2:1000 population [Shriberg et al 1997]. Of note, no data are available to determine what proportion of CAS is caused by disruption of FOXP2 only or large copy number variants or structural variants involving FOXP2. In a cohort with a severe speech disorder, one of 49 individuals had a confirmed FOXP2-related speech and language disorder, whereas a previously unreported FOXP2 variant of uncertain clinical significance was detected in two additional unrelated individuals [MacDermot et al 2005]. In an independent cohort with a CAS diagnosis, a previously unreported FOXP2 variant of uncertain clinical significance was detected in one of 24 individuals [Laffin et al 2012]. Of note, beyond these studies of CAS, other studies of cohorts with different disorders of speech and language development have not reported individuals with pathogenic FOXP2 coding variants (e.g., see Han et al [2014] for a study of developmental stuttering, Gauthier et al [2003] for a study of autistic disorder, and Newbury et al [2002] for a study of autism and specific language impairment). ## Differential Diagnosis The prelinguistic developmental history of children with childhood apraxia of speech (CAS) (e.g., restricted babbling or feeding difficulties) is very similar to that seen in other neurodevelopmental speech or language conditions (e.g., specific language impairment, phonologic disorder) or even other neurodevelopmental disorders in which language impairment may occur such as autism spectrum disorders (ASDs). Hence, early signs are not usually sufficiently discriminating to enable a differential diagnosis prior to a child gaining some speech production abilities. The primary feature of the FOXP2-related speech and language disorders is CAS, a rare diagnosis. Other developmental speech and language disorders, such as stuttering and phonologic production disorder, are distinguishable on a speech and language assessment. While CAS is rare, it may also be observed in a range of other conditions. The following may be considered in the differential diagnosis. Unknown cause of CAS. Although the clinical manifestations and developmental history of children with CAS of unknown cause is almost indistinguishable from that of children with FOXP2-related CAS, speech prognosis appears poorer for individuals with FOXP2-related CAS. No studies have systematically compared the two populations. Known causes of CAS. Disorders to consider in the differential diagnosis of FOXP2-related speech and language disorders are listed in Table 2. The clinical features of these disorders vary; most can be diagnosed by chromosomal microarray (CMA). ### Table 2. Disorders to Consider in the Differential Diagnosis of FOXP2-Related Speech and Language Disorders View in own window Disease NameGene or Critical RegionMOICASClinical Features of the Differential Diagnosis Disorder Overlapping (in addition to CAS)Distinguishing 16p11.2 microdeletionAUTS14AD 1, 2+ * ID, ASD, DD * Expressive language skills more severely impaired than receptive language * Epilepsy or recurrent seizures * Dysmorphic features (e.g., low-set ears, partial syndactyly) 7q11.23 duplication syndromeWBSCRAD\+ 3 * DD * Appropriate nonverbal pragmatic abilities in socially comfortable situations * Oral apraxia * Phonologic disorder * Expressive language disorder * Hypotonia * Dysmorphic features (brachycephaly, broad forehead, straight eyebrows, broad nasal tip, low insertion of the columella, short philtrum, thin upper lip, minor ear anomalies, facial asymmetry) * Social anxiety * Developmental coordination disorder In some: * Macrocephaly * Visually detectable MRI abnormalities (e.g., vermis hypoplastic, ventriculomegaly, vermis hypoplasia) * Signs of cerebellar dysfunction KANSL1-related intellectual disability syndromeKANSL1AD 1+ * Early oral motor & feeding difficulties * DD * Oral dyspraxia * Expressive language abilities better than receptive language * Literacy problems * ID * Hypotonia * Dysmorphic features (elongated face, bulbous nasal tip) * Seizures * Visual &/or hearing deficits * Heart problems GRIN2A-related disorders 4 OMIMGRIN2AAD± * Oral dyspraxia * Dysarthria * Aphasia * Epilepsy Worster-Drought syndrome 5 OMIMAD– * Cerebral palsy 6 * Oral dyspraxia * Dysarthria * Mild fine & gross movement difficulties * Epilepsy * Moderate learning difficulties * Club feet * Restricted joint movement Floating-Harbor syndrome 7SRCAPAD 1\+ 7 * Dysarthria * Hypernasality * Severe expressive & receptive language & literacy impairment * Short stature * Delayed bone age * Characteristic facies * Aggression in childhood Galactosemia 8GALTAR\+ 9 * Expressive/receptive language impairment * Typical or borderline-low IQ to more severe IQ depending on type of galactosemia 10 * Dysarthria * Movement coordination disorder, primarily affecting balance & manual dexterity * Voice dysfunction * Liver function issues AD = autosomal dominant; AR = autosomal recessive; ASD = autism spectrum disorder; CAS = childhood apraxia of speech; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance 1\. Most pathogenic variants are de novo in the proband. 2\. Fedorenko et al [2016] 3\. Velleman & Mervis [2011] 4\. Landau Kleffner syndrome and epilepsy-aphasia syndromes 5\. Clark et al [2000] 6\. Cerebral palsy may be associated with brain damage or malformation such as bilateral perisylvian polymicrogyria (excessive and small gyri). 7\. White et al [2010] 8\. The prevalence of motor speech disorder in this group is high; in one study ~25% of children had CAS [Shriberg et al 2011]. 9\. Potter et al [2013] 10\. Individuals with the Gln188Arg/Gln188Arg genotype may be at increased risk for cognitive and language impairments. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and management needs for an individual with a FOXP2-related speech and language disorder, the following evaluations conducted by a trained and specialized speech-language pathologist are recommended: * Detailed developmental history including early oral motor and feeding abilities, speech sound development, motor milestones, and cognitive development * Family history of speech disorder * Oral-facial structural examination to determine if any structural abnormalities are present * Assessment of oral motor function including: * Examination of cranial nerve function for evidence of asymmetry, reduced or increased tone, and/or poor coordination of neuromuscular movements * Examination for evidence of oral motor dyspraxia (e.g., can the patient perform oral movements on command in isolation [e.g., "bite" or "blow"] or in sequence [e.g., "kiss and blow"; "kiss, blow, and bite"]) * Speech sound assessment including a test of single words, sounds in isolation, and connected speech to determine the child's phonetic inventory (i.e., has the child acquired age-appropriate speech sounds) and to determine if the child has articulation errors, phonologic errors, apraxic errors, dysarthric errors, or a combination of these errors. The presence of resonance or nasality deficits signals the need to consider whether such structurally based velopharyngeal port incompetence is present by referral to an ear, nose, and throat specialist and possibly videopalatography. * Language assessment to determine the presence of receptive and/or expressive language impairments across the domains of semantics, syntax, and morphology * Literacy assessment or pre-literacy (phonologic awareness) for evidence of reading and spelling difficulties * Social skills assessment for the presence of autistic features Additional evaluations: * Referral to a neuropsychologist or clinical psychologist to determine the extent of any coexisting cognitive and learning impairments and to examine for the presence of behaviors associated with autism spectrum disorder * Referral to a physiotherapist if gross motor movement difficulties are reported and an occupational therapist if fine motor movement difficulties are observed * Consideration of MRI to evaluate for the presence of a neurologic lesion if indicated * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Speech and language deficits. A speech pathologist will utilize treatments targeted to the specific findings in an affected individual; hence, the importance of a thorough initial assessment to establish the extent of disease and management needs for an individual. No single recommended treatment exists. The optimal approach should be determined based on the individual's findings regarding: * CAS [American Speech-Language-Hearing Association 2007, Morgan & Vogel 2008, Royal College of Speech and Language Therapists 2011]; * Dysarthria [Pennington et al 2009]; * Language deficits [Law et al 2003]; * Literacy impairments [Snowling & Hulme 2012]. Cognitive deficits. A clinical psychologist or neuropsychologist may provide strategies to help manage deficits in specific cognitive or social skill domains. Fine and gross motor deficits. An occupational therapist and physiotherapist can provide strategies to help with these issues. ### Surveillance The following are appropriate: * Routine care by a general pediatrician * Follow-up evaluations with standardized tests by a speech and language pathologist ### Evaluation of Relatives at Risk It is appropriate to clarify the genetic status of apparently asymptomatic sibs of an affected individual by molecular genetic testing of the FOXP2 genetic alteration in the family to identify as early as possible those who would benefit from prompt evaluation and initiation of treatment. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation A number of therapies for childhood apraxia of speech (CAS) are under investigation [Morgan & Vogel 2008, Murray et al 2014, Murray et al 2015]. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	FOXP2-Related Speech and Language Disorders	None	7,494	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK368474/	2021-01-18T21:27:20	{"synonyms": []}
Lowe syndrome is a condition that primarily affects the eyes, brain, and kidneys. This disorder occurs almost exclusively in males. Infants with Lowe syndrome are born with thick clouding of the lenses in both eyes (congenital cataracts), often with other eye abnormalities that can impair vision. About half of affected infants develop an eye disease called infantile glaucoma, which is characterized by increased pressure within the eyes. Many individuals with Lowe syndrome have delayed development, and intellectual ability ranges from normal to severely impaired. Behavioral problems and seizures have also been reported in children with this condition. Most affected children have weak muscle tone from birth (neonatal hypotonia), which can contribute to feeding difficulties, problems with breathing, and delayed development of motor skills such as sitting, standing, and walking. Kidney (renal) abnormalities, most commonly a condition known as renal Fanconi syndrome, frequently develop in individuals with Lowe syndrome. The kidneys play an essential role in maintaining the right amounts of minerals, salts, water, and other substances in the body. In individuals with renal Fanconi syndrome, the kidneys are unable to reabsorb important nutrients into the bloodstream. Instead, the nutrients are excreted in the urine. These kidney problems lead to increased urination, dehydration, and abnormally acidic blood (metabolic acidosis). A loss of salts and nutrients may also impair growth and result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. Progressive kidney problems in older children and adults with Lowe syndrome can lead to life-threatening renal failure and end-stage renal disease (ESRD). ## Frequency Lowe syndrome is an uncommon condition. It has an estimated prevalence of 1 in 500,000 people. ## Causes Mutations in the OCRL gene cause Lowe syndrome. The OCRL gene provides instructions for making an enzyme that helps modify fat (lipid) molecules called membrane phospholipids. By controlling the levels of specific membrane phospholipids, the OCRL enzyme helps regulate the transport of certain substances to and from the cell membrane. This enzyme is also involved in the regulation of the actin cytoskeleton, which is a network of fibers that make up the cell's structural framework. The actin cytoskeleton has several critical functions, including determining cell shape and allowing cells to move. Some mutations in the OCRL gene prevent the production of any OCRL enzyme. Other mutations reduce or eliminate the activity of the enzyme or prevent it from interacting with other proteins within the cell. Researchers are working to determine how OCRL mutations cause the characteristic features of Lowe syndrome. Because the OCRL enzyme is present throughout the body, it is unclear why the medical problems associated with this condition are mostly limited to the brain, kidneys, and eyes. It is possible that other enzymes may be able to compensate for the defective OCRL enzyme in unaffected tissues. ### Learn more about the gene associated with Lowe syndrome * OCRL ## Inheritance Pattern This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Most X-linked disorders affect males much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In some cases of Lowe syndrome, an affected male inherits the mutation from a mother who carries one altered copy of the OCRL gene. Other cases result from new mutations in the gene and occur in males with no history of the disorder in their family. Females who carry one mutated copy of the OCRL gene do not have the characteristic features of Lowe syndrome. Most female carriers, however, have changes in the lens of the eye that can be observed with a thorough eye examination. These changes typically do not impair vision. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Lowe syndrome	c0028860	7,495	medlineplus	https://medlineplus.gov/genetics/condition/lowe-syndrome/	2021-01-27T08:25:07	{"gard": ["3295"], "mesh": ["D009800"], "omim": ["309000"], "synonyms": []}
A rare, clinically heterogeneous, multisystemic inflammatory disease characterized by inflammation of the cartilage and proteoglycan rich structures leading to cartilage damage along with joint, ocular and cardiovascular involvement. ## Epidemiology The prevalence and annual incidence of Relapsing polychondritis (RP) are not known. The estimated incidence is 1/285,000. The sex ratio appears to be equal and all ethnic groups seem to be affected (with more cases reported among Caucasians). ## Clinical description Onset is generally sudden and most commonly occurs in the 5th decade of life (age 40 to 55). Cases with early and late onset do occur. RP follows a flaring and remitting course. Clinical manifestations vary from intermittent auricular and nasal chondritis, to occasional organ or life-threatening complications. Unilateral or bilateral external ear inflammation with pain, tenderness, swelling, erythema, and discoloration, limited to the cartilaginous portion of the pinna with characteristic sparing of the lobule, is one of the hallmark features of RP (90-95% of patients). Auricular collapse or inflammation of vestibular structures can lead to conductive or sensorineural hearing loss. Other associated complications include nausea, vomiting, tinnitus, vertigo and ataxia. Nasal chondritis with sudden pain and tenderness is found at some stage of the disease in more than 50% of patients. Nasal cartilage may be severely damaged resulting in saddle nose deformity. Some patients develop potentially serious laryngotracheal involvement with hoarseness, aphonia, stridor and wheezing, dyspnea, or even airway collapse. Joint pain lasting weeks or months is found in most patients (>70%) and is often the presenting feature (30%). Cardiovascular manifestations (25-50%) include large vessel vasculitis, aneurysmal involvement, and aortic or mitral valve disease. Ocular manifestations reported are proptosis, conjunctivitis, ulcerative keratitis, episcleritis/scleritis, uveitis, and periorbital edema. Cutaneous manifestations that may precede chondritis include aphthosis, nodules, purpura, and papules. Neurological manifestations are due to vasculitis of central or peripheral nervous system. Renal involvement is rare. MAGIC syndrome represents a subset of patients with RP who also have mouth and genital ulcers, which are features of Behçet disease. ## Etiology The exact etiopathogenesis of RP is not known but it is thought to be an immune-mediated disease. A complex cytokine network is thought to be involved in the recruitment of infiltrating cells in RP lesions. ## Diagnostic methods There is no single blood or imaging test that can be used to diagnose this condition. The diagnosis is generally based upon the detection of a combination of clinical presentations. According to the most accepted and widely used diagnostic criteria, three of the following six features are required to make a diagnosis of RP: bilateral auricular chondritis, nonerosive seronegative inflammatory polyarthritis, nasal chondritis, ocular inflammation, respiratory tract chondritis, and audiovestibular damage. ## Differential diagnosis Differential diagnoses include granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, Behçet disease, and leprosy. ## Management and treatment Treatment is primarily symptomatic and no standard therapeutic protocol has been established due to the rarity of the disease. In less severe cases, non-steroidal anti-inflammatory drugs, dapsone, and colchicine may be used. In severe cases with organic involvement, systemic corticosteroids (oral prednisolone or rarely intravenous methylprednisolone) are required. Methotrexate, azathioprine, cyclosporine and chlorambucil may constitute an alternative. Use of biological agents like anti TNFs, tocilizumab, anakinra, rituximab and abatacept has been reported with various efficacy in case reports and small case series. A relapsing polychondritis disease activity index (RPDAI) and damage index (RPDAM) has been validated for assessing disease activity and damage respectively. ## Prognosis Prognosis is generally good in the majority of cases, but the disease may occasionally follow a severe, life-threatening course, with respiratory complications (tracheal collapse and infections) as the primary cause of mortality. Cardiovascular involvement may also lead to a fatal outcome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Relapsing polychondritis	c0032453	7,496	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=728	2021-01-23T17:18:13	{"gard": ["7417"], "mesh": ["D011081"], "umls": ["C0032453"], "icd-10": ["M94.1"], "synonyms": ["Polychondropathia"]}
A lysosomal storage disease belonging to the group of sphingolipidoses. ## Epidemiology It is very rare with less than 10 cases reported in the literature so far. ## Clinical description Clinically, it is a severe neurovisceral disease manifesting immediately after birth and following a rapidly progressive fatal course (death between 1 and 4 months in the cases documented so far). The neurological signs and symptoms include hypotonia, massive myoclonic bursts, abnormal ocular movements and dystonia. Grand mal seizures and seizures triggered by tactile stimuli have been described. Patients also develop hepatosplenomegaly. Death usually occurs from respiratory failure following repeated pulmonary infections. ## Etiology The disease is caused by mutations in the PSAP gene (10q21) leading to absence or non-functionality of the prosaposin protein. Prosaposin is the common precursor for proteins required for the in vivo lysosomal degradation of several sphingolipids, and has other important but still poorly understood functions. Under normal conditions, proteolytic processing of prosaposin produces four smaller "sphingolipid activator proteins'' called saposins (or Sap) A, B C and D. An isolated deficiency of each of these factors leads to rare variant genetic forms of Krabbe disease (Sap A), metachromatic leukodystrophy (Sap B), Gaucher disease (Sap C) and, putatively, Farber disease (Sap D; see these terms). In prosaposin deficiency, there is a combined deficiency of all four factors. ## Diagnostic methods The final diagnosis is established by identification of the PSAP mutation(s), but the study of sphingolipids in urine sediment (showing a massive combined excretion of globotriaosylceramide (Gb3), sulfatides and other sphingolipids) is a good orientation test. Low galactosylceramidase in leukocytes has also been reported. Bone marrow/liver biopsies usually show the presence of Gaucher-like macrophages. ## Antenatal diagnosis Prenatal diagnosis is feasible by mutation analysis on uncultured (or cultured) chorionic villi, or amniotic fluid cells. ## Genetic counseling The mode of inheritance is autosomal recessive. ## Management and treatment No specific treatment is available. ## Prognosis Encephalopathy due to prosaposin deficiency is a very severe metabolic disorder with a poor prognosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Encephalopathy due to prosaposin deficiency	c2673635	7,497	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=139406	2021-01-23T18:51:02	{"gard": ["12505"], "mesh": ["C567125"], "omim": ["611721"], "icd-10": ["E75.2"], "synonyms": ["Combined prosaposin deficiency"]}
Maffucci syndrome is a disorder that primarily affects the bones and skin. It is characterized by multiple enchondromas, which are noncancerous (benign) growths of cartilage that develop within the bones. These growths most commonly occur in the limb bones, especially in the bones of the hands and feet; however, they may also occur in the skull, ribs, and bones of the spine (vertebrae). Enchondromas may result in severe bone deformities, shortening of the limbs, and fractures. The signs and symptoms of Maffucci syndrome may be detectable at birth, although they generally do not become apparent until around the age of 5. Enchondromas develop near the ends of bones, where normal growth occurs, and they frequently stop forming after affected individuals stop growing in early adulthood. As a result of the bone deformities associated with Maffucci syndrome, people with this disorder generally have short stature and underdeveloped muscles. Maffucci syndrome is distinguished from a similar disorder that involves enchondromas (Ollier disease) by the presence of red or purplish growths in the skin consisting of tangles of abnormal blood vessels (hemangiomas). In addition to hemangiomas, individuals with Maffucci syndrome occasionally also have lymphangiomas, which are masses made up of the thin tubes that carry lymph fluid (lymphatic vessels). These growths may appear anywhere on the body. Although the enchondromas associated with Maffucci syndrome start out as benign, they may become cancerous (malignant). In particular, affected individuals may develop bone cancers called chondrosarcomas, especially in the skull. People with Maffucci syndrome also have an increased risk of other cancers, such as ovarian or liver cancer. People with Maffucci syndrome usually have a normal lifespan, and intelligence is unaffected. The extent of their physical impairment depends on their individual skeletal deformities, but in most cases they have no major limitations in their activities. ## Frequency Maffucci syndrome is very rare. Since it was first described in 1881, fewer than 200 cases have been reported worldwide. ## Causes In most people with Maffucci syndrome, the disorder is caused by mutations in the IDH1 or IDH2 gene. These genes provide instructions for making enzymes called isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2, respectively. These enzymes convert a compound called isocitrate to another compound called 2-ketoglutarate. This reaction also produces a molecule called NADPH, which is necessary for many cellular processes. IDH1 or IDH2 gene mutations cause the enzyme produced from the respective gene to take on a new, abnormal function. Although these mutations have been found in some cells of enchondromas and hemangiomas in people with Maffucci syndrome, the relationship between the mutations and the signs and symptoms of the disorder is not well understood. Mutations in other genes may also account for some cases of Maffucci syndrome. ### Learn more about the genes associated with Maffucci syndrome * IDH1 * IDH2 ## Inheritance Pattern Maffucci syndrome is not inherited. The mutations that cause this disorder are somatic, which means they occur during a person's lifetime. A somatic mutation occurs in a single cell. As that cell continues to grow and divide, the cells derived from it also have the same mutation. In Maffucci syndrome, the mutation is thought to occur in a cell during early development before birth; cells that arise from that abnormal cell have the mutation, while the body's other cells do not. This situation is called mosaicism. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Maffucci syndrome	c0024454	7,498	medlineplus	https://medlineplus.gov/genetics/condition/maffucci-syndrome/	2021-01-27T08:25:51	{"gard": ["6958"], "mesh": ["D004687"], "omim": ["614569"], "synonyms": []}
Glycogenic acanthosis Endoscopic image of glycogenic acanthosis found incidentally SpecialtyGastroenterology Glycogenic acanthosis are small raised white plaques commonly seen in the esophageal mucosa.[1] It is seen incidentally in 3.5% of gastroscopies.[2] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 References * 4 External links ## Signs and symptoms[edit] On gastroscopy, glycogenic acanthosis is seen as a multitude of small white raised plaques of 2 mm to 10 mm in size, which may be seen throughout the esophagus. They tend to occur on esophageal folds, and may be missed if the esophagus is not well distended with air. It may be seen on esophageal x-rays; it is not seen on standard esophograms, but can be seen with double-contrast studies.[3] Biopsies of the lesions show hypertrophied stratified squamous mucosa with glycogen deposition in the mucosa.[1] Clinically, mild glycogenic acanthosis is a normal finding, and does not progress to esophageal cancer or to stricture.[4] It is not related to leukoplakia, and is not dysplastic or premalignant. It was originally thought to be associated with gastroesophageal reflux disease (GERD), but the association is not entirely clear.[2] One report also shows an association with celiac disease, but again, this has not shown been beyond that. Extensive glycogenic acanthosis has been shown to be associated with Cowden's syndrome.[5] ## Diagnosis[edit] Glycogenic acanthosis is characterized by epithelial hyperplasia, with an increased number of enlarged epithelial cells containing abundant glycogen. There is no associated hyperkeratosis, inflammation, dysplasia, or cellular atypia.[4] ## References[edit] 1. ^ a b Ghahremani GG, Rushovich AM. Glycogenic acanthosis of the esophagus: radiographic and pathologic features. Gastrointest Radiol. 1984;9(2):93-8. PMID 6745598. 2. ^ a b Vadva MD, Triadafilopoulos G. Glycogenic acanthosis of the esophagus and gastroesophageal reflux. J Clin Gastroenterol. 1993 Jul;17(1):79-83. PMID 8409304 3. ^ Glick SN, Teplich SK, Goldstein J, Stead JA, Zitomer N. Glycogenic Acanthosis of the Esophagus. Amer J Radiol 1982139:683-688 4. ^ a b Pathology Outlines website: http://pathologyoutlines.com/esophagus.html#glycogenic Accessed 6 January 2009. 5. ^ Kay PS, Soetikno RM, Mindelzun R, Young HS. Diffuse esophageal glycogenic acanthosis: an endoscopic marker of Cowden's disease. Am J Gastroenterol. 1997 Jun;92(6):1038-40 PMID 9177527 ## External links[edit] * Microscopic images [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [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	Glycogenic acanthosis	c1963768	7,499	wikipedia	https://en.wikipedia.org/wiki/Glycogenic_acanthosis	2021-01-18T18:29:02	{"umls": ["C1963768"], "wikidata": ["Q5572612"]}

Subsets and Splits

No community queries yet

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