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Prion pruritus is the intense itching during the prodromal period of the Creutzfeldt–Jakob disease.[1]:402 ## See also[edit] * Pruritus ## References[edit] 1. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 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	Prion pruritus	None	5,300	wikipedia	https://en.wikipedia.org/wiki/Prion_pruritus	2021-01-18T18:57:42	{"wikidata": ["Q7245359"]}
A rare subtype of CMT1 characterized by a variable clinical presentation. Onset within the first two years of life with a delay in walking is not uncommon; however, onset may occur later. CMT1E is caused by point mutations in the PMP22 (17p12) gene. The disease severity depends on the particular PMP22 mutation, with some cases being very mild and even resembling hereditary neuropathy with liability to pressure palsies, while others having an earlier onset with a more severe phenotype (reminiscent of Dejerine-Sottas syndrome) than that seen in CMT1A, caused by gene duplication. These severe cases may also report deafness and much slower motor nerve conduction velocities compared to CMT1A patients. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Charcot-Marie-Tooth disease type 1E	c1861669	5,301	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90658	2021-01-23T18:12:42	{"gard": ["9190"], "mesh": ["C538078", "C537986"], "omim": ["118300"], "umls": ["C1861669", "C2931686", "C3495591"], "icd-10": ["G60.0"], "synonyms": ["CMT1E", "Charcot-Marie-Tooth disease-deafness syndrome", "Charcot-Marie-Tooth disease-hearing loss syndrome"]}
A number sign (#) is used with this entry because Bjornstad syndrome (BJS) is caused by homozygous or compound heterozygous mutation in the BCS1L gene (603647) on chromosome 2q35. Description Bjornstad syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and pili torti. The hearing loss is congenital and of variable severity. Pili torti (twisted hairs), a condition in which the hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair very brittle, is usually recognized early in childhood (Selvaag, 2000). Clinical Features Bjornstad (1965) first commented on this association. Among 8 cases of pili torti, 5 had nerve deafness. Reed (1966) observed 4 additional cases, and Robinson and Johnston (1967) reported a case. Deafness was evident in the first year of life. The syndrome occurred in sibs among the cases of Bjornstad (1965) and Reed (1966). Crandall et al. (1973) described 3 male sibs with neurosensory deafness, alopecia due to pili torti, and secondary hypogonadism. This may be the same disorder. Indeed, the cases of Crandall et al. (1973) had been observed (and referred to) by Reed (1966). Van Buggenhout et al. (1998) described severe mental retardation in association with Bjornstad syndrome. This was apparently a unique observation. Siddiqi et al. (2013) reported a large consanguineous Pakistani family in which 5 individuals had Bjornstad syndrome. The patients had scalp hair at birth that began to fall out around age 2 to 3 months. Eyelashes also fell out. The hair fibers were twisted around their axes and were devoid of any pigment. All patients had light eye color and anhidrosis, although teeth, nails, palms, and soles were normal. Affected males had short stature. Audiometric measurements showed variable degrees of progressive sensorineural hearing loss. Inheritance The transmission pattern of Bjornstad syndrome in the family reported by Siddiqi et al. (2013) was consistent with autosomal recessive inheritance. Mapping Lubianca Neto et al. (1998) evaluated a large kindred with Bjornstad syndrome in which 8 members inherited pili torti and prelingual sensorineural hearing loss as autosomal recessive traits. They reported that the disease gene maps to chromosome 2q34-q36. A genomewide search using polymorphic loci demonstrated linkage between the disease gene segregating in this kindred and D2S434 (maximum 2-point lod score = 4.98 at theta = 0.0). Haplotype analysis of recombination events located the disease gene in a 3-cM region between D2S1371 and D2S163. Hinson et al. (2007) performed refined genetic mapping of the Bjornstad syndrome locus on 2q and narrowed the assignment to a 2-Mb region between D2S2210 and D2S2244. Molecular Genetics By DNA sequencing of 44 genes within the critical region for Bjornstad syndrome on chromosome 2q, Hinson et al. (2007) identified mutations in the BCS1L gene (e.g., 603647.0008) in affected members of families segregating for the disorder. One of the families had previously been reported by Lubianca Neto et al. (1998). In 5 affected individuals of a consanguineous Pakistani family with Bjornstad syndrome, Siddiqi et al. (2013) identified a homozygous missense mutation in the BCS1L gene (Y301N; 603647.0013). Functional studies of the variant were not performed. Pathogenesis Mutations in the BCS1L gene had previously been found to cause mitochondrial complex III deficiency (124000), manifested by neonatal renal tubulopathy, encephalopathy, and liver failure, and GRACILE syndrome (603358), a severe disorder of intrauterine growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death. To understand how BCS1L mutations cause widely different clinical phenotypes, Hinson et al. (2007) reviewed the locations of defects on the BCS1L protein structure and compared the function of mutant BCS1L in yeast and in human lymphocytes. They found that all BCS1L mutations altered assembly of the mitochondrial respirasome, reduced activity of the electron transport chain, and increased the production of reactive oxygen species. The production of reactive oxygen species correlated with the clinical severity of different BCS1L mutations. The data indicated that in addition to mitochondrial heteroplasmy and variable energy requirements of tissues, tissue-specific sensitivities to reactive oxygen species contribute to the variability of the manifestations of mitochondrial defects. Hinson et al. (2007) noted that mutations that cause the Bjornstad syndrome illustrate the exquisite sensitivity of ear and hair tissues to mitochondrial function, particularly to the production of reactive oxygen species. Models of the effects of aminoglycoside antibiotics and excessive noise on hearing support a critical role for increased levels of reactive oxygen species in ototoxicity. Mitochondrial disease is often manifested by a variety of hair abnormalities (Bodemer et al., 1999). INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, sensorineural progressive Eyes \- Light-colored eyes GENITOURINARY \- Hypogonadism (in some patients) SKIN, NAILS, & HAIR Skin \- Anhidrosis Hair \- Pili torti \- Loss of hair \- Sparse, short hair growth \- Brittle hair \- Hair lacks pigment NEUROLOGIC Central Nervous System \- Mental retardation (in some patients) MISCELLANEOUS \- Hearing loss typically begins between 3 and 4 years of age \- Hair loss begins in first years of life \- Variable severity MOLECULAR BASIS \- Caused by mutation in the BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone gene (BCS1L, 603647.0008 ) ▲ 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	BJORNSTAD SYNDROME	c0266006	5,302	omim	https://www.omim.org/entry/262000	2019-09-22T16:23:32	{"doid": ["0050677"], "mesh": ["C537633"], "omim": ["262000"], "orphanet": ["123"], "synonyms": ["Alternative titles", "PILI TORTI AND NERVE DEAFNESS", "PTD"]}
Dermatitis herpetiformis (DH) and celiac disease (CD; 212750) are gluten-sensitive diseases. In classic CD the small intestine is predominantly affected, whereas in DH the skin is also affected, showing typical rash and IgA deposits. Reunala (1996) reported on the familial incidence of DH in a prospective study started in 1969 in Finland. A total of 1,018 patients with DH were diagnosed and questioned for positive family histories. Of the 999 unrelated DH patients, 105 (10.5%) had 1 or several affected first-degree relatives. Disease in the relatives was either DH (4.4%) or CD (6.1%). Analysis of the 105 families showed that 13.6% of parents, 18.7% of sibs, and 14% of children were affected, a segregation pattern that fitted well to a mendelian dominant mode of inheritance. Gender may also be important because the first-degree relatives affected with DH were more often females and those affected with CD twice as often females as males. DH and CD have a common immunogenetic background; both disorders are associated with HLA alleles DQA10501 (see 146880) and B10201 (see 142857). Karell et al. (2002) evaluated the role of the HLA-DQ locus in 25 families in which both classic CD and DH occurred in sibs. By using a family-based approach, they assumed that within each family, variation in environmental factors was substantially lower than in the standard case-control setting, and that the problems related to population stratification could be avoided. Results from Finnish family material comprising 25 discordant and 85 concordant sib pairs, and from case-control material comprising 71 unrelated Hungarian DH and 68 classic CD patients, together indicated that the HLA-DQ locus did not differ between the 2 major outcomes of gluten-sensitive enteropathy. The authors concluded that non-HLA-DR;DQ factors are crucial for the different clinical manifestations of gluten sensitivity. Using ELISA, Sardy et al. (2002) found that sera from both CD and DH reacted with tissue transglutaminase (TGM2; 190196) and epidermal transglutaminase (TGM3; 600238), but the DH antibodies had a markedly higher avidity for TGM3. Immunofluorescence and confocal microscopy demonstrated that IgA precipitates in the papillary dermis of DH patients contained TGM3, but not keratinocyte transglutaminase (TGM1; 190195) or TGM2. Sardy et al. (2002) concluded that TGM3 is the dominant autoantigen in DH, explaining why skin symptoms rather than intestinal symptoms appear in a proportion of patients with gluten-sensitive disease. Animal Model Marietta et al. (2004) developed a mouse model for DH by backcrossing DQ8+ mice lacking endogenous MHC II (Ab0 DQ8+ mice) with NOD mice. Fifteen of 90 NOD DQ8+ mice that were sensitized to gluten developed blistering pathology similar to that seen in DH. Neutrophil infiltration of the dermis, deposition of IgA at the dermal-epidermal junction, and a complete reversal of the blistering phenomenon with the administration of a gluten-free diet with or without dapsone were observed. None of the blistering mice had IgA or IgG endomysial antibodies or IgA antibodies to guinea pig tissue transglutaminase in their sera, and none of 3 blistering mice examined had small bowel pathology. Inheritance \- Autosomal dominant Misc \- Affected first-degree relatives more often females Lab \- Associated with HLA DQA10501 (146880) and B10201 (142857) Skin \- Dermatitis herpetiformis ▲ 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	DERMATITIS HERPETIFORMIS, FAMILIAL	c0011608	5,303	omim	https://www.omim.org/entry/601230	2019-09-22T16:15:11	{"mesh": ["D003874"], "omim": ["601230"], "orphanet": ["1656"], "synonyms": ["Alternative titles", "DH"]}
## Description Anterior polar cataracts are small opacities on the anterior surface of the lens. They usually do not interfere with vision (Moross et al., 1984). The preferred title/symbol of this entry was formerly 'Cataract, Anterior Polar, 2; CTAA2.' Mapping By genetic linkage analysis with microsatellite markers in a 4-generation pedigree, Berry et al. (1996) identified a locus for an autosomal dominant anterior polar cataract on 17p. A maximum lod score of 4.01 at theta = 0.05 was obtained for marker D17S849 and a maximum lod score of 4.17 at theta = 0.05 for D17S796. Multipoint analysis gave a maximum lod score of 5.2. History Hejtmancik (1998) presented a table of 9 loci, including this one, that had been implicated in nonsyndromal cataract and mapped to specific chromosomal sites. Eyes \- Anterior polar cataract 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	CATARACT 24	c1855179	5,304	omim	https://www.omim.org/entry/601202	2019-09-22T16:15:14	{"doid": ["0110257"], "mesh": ["C538282"], "omim": ["601202"], "icd-10": ["Q12.0"], "orphanet": ["98992", "91492", "98988"], "synonyms": ["CATARACT 24, ANTERIOR POLAR", "Alternative titles", "CATARACT, ANTERIOR POLAR, 2"]}
A number sign (#) is used with this entry because epidermolytic palmoplantar keratoderma is caused by heterozygous mutation in the keratin-9 gene (KRT9; 607606) on chromosome 17q12. A mild form of epidermolytic palmoplantar keratoderma is caused by mutation in the keratin-1 gene (KRT1; 139350) on chromosome 12q. Description Palmoplantar keratoderma (PPK) is a common hereditary cutaneous disorder characterized by marked hyperkeratosis on the surface of palms and soles (Hennies et al., 1995). PPK has been classified into diffuse, focal, and punctate forms according to the pattern of hyperkeratosis on the palms and soles (Lucker et al., 1994). Diffuse PPK develops at birth or shortly thereafter and involves the entire palm and sole with a sharp cutoff at an erythematous border; there are no lesions outside the volar skin, and, in particular, no follicular or oral lesions. In contrast, focal PPK is a late-onset form in which focal hyperkeratotic lesions develop in response to mechanical trauma; an important distinguishing feature is the presence of lesions at other body sites, e.g., oral and follicular hyperkeratosis (Stevens et al., 1996). Palmoplantar keratodermas can be further subdivided histologically into epidermolytic and nonepidermolytic PPK (Risk et al., 1994). ### Genetic Heterogeneity of Palmoplantar Keratoderma Nonepidermolytic palmoplantar keratoderma (NEPPK; 600962) is caused by mutation in the KRT1 gene. A focal form of NEPPK (FNEPPK1; 613000) is caused by mutation in the KRT16 gene (148067). Another focal form, FNEPPK2 (616400), is caused by mutation in the TRPV3 gene (607066); mutation in TRPV3 can also cause Olmsted syndrome (OLMS; 614594), a severe mutilating form of PPK. The diffuse Bothnian form of NEPPK (PPKB; 600231) is caused by mutation in the AQP5 gene (600442). The Nagashima type of nonepidermolytic diffuse PPK (PPKN; 615598) is caused by mutation in the SERPINB7 gene (603357). A generalized form of epidermolytic hyperkeratosis (EHK; 113800), also designated bullous congenital ichthyosiform erythroderma (BCIE), is caused by mutation in the keratin genes KRT1 and KRT10 (148080). For a discussion of punctate PPK, see 148600; for a discussion of striate PPK, see 148700. Nomenclature Vorner (1901) provided an early description of epidermolytic hyperkeratosis limited to the palms and soles, whereas Thost (1880) and Unna (1883) reported what appeared to be a nonepidermolytic form of palmoplantar keratoderma; the designations 'Vorner' and 'Unna-Thost' thus became eponymous for the epidermolytic and nonepidermolytic forms of the disorder, respectively. However, Kuster and Becker (1992) and Kuster et al. (2002) reinvestigated the Thost kindred and found features of epidermolytic hyperkeratosis in several descendants; Lind et al. (1994) stated that the designation 'Unna-Thost' is misleading and should be avoided. Clinical Features Localized epidermolytic hyperkeratosis was first described by Vorner (1901). Blasik et al. (1981), Fritsch et al. (1978), and Camisa and Williams (1985) reported affected families. In an affected father and daughter, Moriwaki et al. (1988) noted a decrease in 67-kD keratin (KRT1; 139350) in the involved epidermis and the appearance of 48-kD keratin. Southern blot analysis using 67-kD keratin cDNA showed no abnormality in the gene for 67-kD keratin. Kanitakis et al. (1987) reported a Greek family with EPPK in which 21 individuals over 6 generations were affected, all of whom developed diffuse PPK before 2 months of age and had no other cutaneous or systemic disease. Kanitakis et al. (1987) reviewed 27 published families or cases of EPPK, which in all instances appeared to be inherited as an autosomal dominant trait. The disease was present at birth or developed during the first weeks of life as a palmoplantar erythema which subsequently became covered with a thick horny layer. The clinical features were almost invariable from one patient to another, with disease involving the entire volar surface and sometimes extending to the lateral aspects of the fingers and toes. The hyperkeratosis was diffuse, thick, and uniform, but in some cases demonstrated deep fissures or pits, and a thin, erythematous rim was sometimes present. In rare cases, small hyperkeratotic plaques were present over the dorsa of the hands. Some patients had hyperhidrosis; palmoplantar blistering was exceptional. Mucous membrane, adnexal, or tooth abnormalities were not present. Keratosis palmaris et plantaris as described by Thost (1880) and Unna (1883) and later delineated by Greither (1952) is characterized by diffuse hyperkeratosis of the palms and soles which usually becomes evident between the ages of 3 and 12 months. Low serum vitamin A has been found in some cases. Goette (1974) described successful use of topical vitamin A. A PPK family reported by Anderson and Klintworth (1961) had clinodactyly also, possibly as an independent trait (see 148520). Gamborg Nielsen (1985) did a follow-up study on hereditary palmoplantar keratoderma originally surveyed in the northernmost county of Sweden (Norrbotten) by Bergstrom (1967). Two clinical types were found: a common form with the usual autosomal dominant inheritance and a severe form thought to have autosomal recessive inheritance (see 244850). Mal de Meleda (248300) is a recessive form of keratosis palmoplantaris in which the phenotype includes hyperhidrosis and perioral erythema. Alsaleh and Teebi (1990) described 2 affected sons of phenotypically normal, consanguineous Arab parents. They presented with patchy eczematous skin lesions followed by palmoplantar keratoderma and raised serum levels of IgE. Nogita et al. (1991) described the disorder in a 32-year-old Japanese man who had knuckle-pad-like lesions over the dorsal aspect of the proximal interphalangeal joints since the age of 3 or 4 months and whose father had had the same skin disease. Reis et al. (1994) studied multiple unrelated German pedigrees with marked hyperkeratosis restricted to the palms and soles, including the family originally described by Thost (1880) and the family studied by Reis et al. (1992). Histopathologic analysis in at least 1 patient from each family revealed typical signs of epidermolytic hyperkeratosis, consisting of a thickened granular layer with large irregularly shaped keratohyalin granules located in the granular layer of the epidermis and perinuclear vacuolization of the keratinocytes. The thickness of the scales varied among patients between and within families. Torchard et al. (1994) studied a large 4-generation French kindred with EPPK, originally reported by Blanchet-Bardon et al. (1987). The EPPK lesions in this family appeared on the entire surface of the palms and soles, demarcated from normal skin by a distinct band of erythema, and display the typical histopathologic features of epidermolytic hyperkeratosis resulting from abnormal tonofilament aggregations. Several affected members of this family also developed breast or ovarian cancer. Hatsell et al. (2001) studied 3 Scottish kindreds segregating autosomal dominant PPK in which affected members displayed palmoplantar hyperkeratosis that varied in severity and had been present since childhood. In the most severely affected cases, there was confluent plantar keratoderma on weight-bearing surfaces, sparing the instep, and normal skin bordering the keratoderma displayed a violaceous erythema. In milder cases, there was patchy plantar keratoderma in weight-bearing areas, resembling focal keratoderma. There was no generalized transgradient keratoderma, but several individuals had developed marked local callosities on dorsal toes or fingers at sites of rubbing. The remaining skin looked entirely normal except for mild hyperkeratosis of the knees in 1 man, and nails, hair, and teeth were normal. Although epidermolysis was not identified by light microscopy in biopsies from 3 patients, electron microscopy revealed that a minority of keratinocytes in the spinous and granular layers appeared to be undergoing cytolysis, with tonofilaments forming tight clumps or aggregates at the cell surface, often adjacent to desmosomes. These changes did not appear to affect clusters of adjacent cells and were thus less disruptive than those typically seen in epidermolytic hyperkeratosis (113800) where blistering is associated with extensive cell lysis. Kuster et al. (2002) performed a follow-up study of the now 8-generation pedigree with EPPK, originally described by Vorner (1901), involving 32 affected individuals (17 males and 15 females). Examination of an affected 42-year-old man and his affected 15-year-old daughter and 9-year-old son showed the typical diffuse yellow-grayish keratoses over the entire surface of the palms and soles, sharply bordered by red margins; all had clubbing of the nails and knuckle pad-like keratoses on the finger joints with variable expression. The father and son showed slightly increased palmoplantar hidrosis, but this was not observed in the daughter. Mycotic infection of the plantar scales was also found in the father and son. Histopathologic examination confirmed epidermolytic hyperkeratosis. ### Unilateral Palmoplantar Verrucous Nevus Terrinoni et al. (2000) described a patient with a localized thickening of the skin in parts of the right palm and the right sole, following the Blaschko lines. Light microscopy showed hyperkeratosis, vacuolar degeneration of keratinocytes in the upper spinosum and granular layer, pyknotic nuclei, and a thickened granular layer containing an increased number of keratohyaline granules. Histologic findings were consistent with the diagnosis of disease similar to localized palmoplantar epidermolytic hyperkeratosis, or focal EPPK, and ultrastructural analysis suggested a keratin defect. The authors proposed that this clinical entity be referred to as 'unilateral palmoplantar verrucous nevus,' rather than localized or focal epidermolytic palmoplantar keratoderma, as the lesions are present only on one side of the body and follow the lines of Blaschko. ### Epidermolytic Palmoplantar Keratoderma Associated With Knuckle Pads Lu et al. (2003) studied a family from Shandong, China, with autosomal dominant EPPK associated with knuckle pads. Both the hyperkeratosis and knuckle pads were friction-related. Lu et al. (2003) stated that aggravation of the hyperkeratosis by friction had not previously been reported. The right hand of each right-handed affected member showed more severe hyperkeratosis than the less frequently used left hand. The knuckle pads on the right hand were likewise more prominent than those on the left hand. Furthermore, the knuckle pad on the more frequently used proximal interphalangeal joint of the index finger was more severely affected than that on the less frequently used interphalangeal joint of the thumb. One patient showed EPPK symptoms approximately 5 months after birth, whereas another showed EPPK symptoms at a little more than 1 year after birth. Chiu et al. (2007) reported a large 5-generation Taiwanese family with EPPK in which 13 affected members had severe epidermolytic hyperkeratosis, surrounded by a characteristic erythematous border on the palmoplantar surface. In addition, 6 adults among the 13 affected individuals had prominent knuckle pads on the dorsal aspect of the fingers and to a lesser extent the toes. For each right-handed patient, both the hyperkeratosis and knuckle pads were more severe on the right hand than on the left. The age of onset of palmoplantar hyperkeratosis was in the early months of life. Skin biopsies showed the characteristic features of epidermolytic hyperkeratosis. Codispoti et al. (2009) studied a 4-generation southern Italian family in which 11 of 24 members had EPPK. In all patients, the lesions initially appeared around 2 months of age, presenting a diffuse PPK with a well-demarcated erythematous border; none had any involvement of hair, teeth, or nails. One patient showed hyperkeratotic pad-like plaques on the metacarpophalangeal and proximal interphalangeal joints, which were more severe on the more frequently used right hand. Histologic analysis of a knuckle-pad biopsy showed hyperkeratosis and epidermolysis, with vacuolar degeneration of keratinocytes in the upper spinous and granular layers, pyknotic nuclei, and a thickened granular layer containing an increased number of keratohyalin granules. Inheritance Klaus et al. (1970) demonstrated dominant inheritance and male-to-male transmission. Alsaleh and Teebi (1990) suggested the existence of an autosomal recessive form, but because of the high background frequency of consanguinity in Kuwait where the patients were observed, and because of the possibility of gonadal mosaicism, the evidence for recessive inheritance was not strong in the small family studied by them. Population Genetics Covello et al. (1998) found the point prevalence of EPPK in Northern Ireland to be 4.4 per 100,000. Mapping In a large family with epidermolytic palmoplantar keratoderma, Reis et al. (1992) mapped the disease locus to 17q11-q23 by linkage analysis using microsatellite DNA polymorphisms; maximum lod score = 6.66 with D17S579 at theta = 0.00. Thus, the disease mutation maps to the same region as the type I (acidic) keratin gene cluster (e.g., 148080). One acidic keratin, keratin-9 (KRT9; 607606), is expressed only in the terminally differentiated epidermis of palms and soles; thus, the KRT9 gene was considered a candidate for the site of the mutation in epidermolytic palmoplantar keratoderma. In a large 4-generation French kindred with EPPK, originally reported by Blanchet-Bardon et al. (1987), in which 8 of 10 affected females over 40 years of age also developed breast or ovarian cancer, Torchard et al. (1994) obtained a maximum 2-point lod score for EPPK of 6.62 between markers THRA1 and D17S8000 on chromosome 17q21. Linkage between EPPK and breast/ovarian cancer yielded a maximum lod score of 0.92 at theta = 0.08. ### Heterogeneity Hatsell et al. (2001) screened 6 affected individuals from a 6-generation Scottish family segregating a mild form of EPPK in an autosomal dominant fashion and identified a common haplotype for microsatellite markers spanning the type II keratin cluster on chromosome 12q13; no linkage was seen for markers mapping to 17q12-q21. Molecular Genetics In 5 unrelated German pedigrees with epidermolytic PPK, including the family originally described by Thost (1880) and the family previously studied by Reis et al. (1992) with linkage to chromosome 17q11-q23, Reis et al. (1994) identified heterozygosity for a missense mutation in the KRT9 gene (R162W; 607606.0001). Two other missense mutations were also detected in 1 EPPK kindred each, N160K (607606.0004) and R162Q (607606.0005), respectively. All 3 mutations involved highly conserved residues in coil 1A of KRT9. In 4 affected members of a large 4-generation French kindred with EPPK originally reported by Blanchet-Bardon et al. (1987), in which 8 of 10 affected females over 40 years of age also developed breast or ovarian cancer, Torchard et al. (1994) identified a missense mutation in the KRT9 gene (N160Y; 607606.0003). The mutation was not found in unaffected family members or in 20 unrelated controls. Noting that the KRT9 gene is not expressed in the mammary gland, Torchard et al. (1994) stated that the most likely explanation for the association of EPPK with hereditary breast/ovarian cancer syndrome is that the 2 conditions resulted from distinct genetic events on chromosome 17q in linked genes. Covello et al. (1998) studied 4 Northern Irish EPPK kindreds and identified heterozygosity for missense mutations in exon 1 of KRT9 in all of the families: R162Q and M156T (607606.0010) in 1 family each, and M156V (607606.0006) in 2 families. In a patient with unilateral palmoplantar verrucous nevus, Terrinoni et al. (2000) reported somatic mosaicism for a 12-bp deletion in the KRT16 gene in a biopsy from lesional epidermis. In 3 Scottish families with a mild form of EPPK, Hatsell et al. (2001) identified a splice site mutation in the KRT1 gene (139350.0014). Kuster et al. (2002) analyzed the KRT9 gene in members of the EPPK pedigree originally described by Vorner (1901) and identified heterozygosity for a missense mutation in affected individuals (607606.0013). In a family from Shandong, China, with autosomal dominant epidermolytic palmoplantar keratoderma associated with knuckle pads, Lu et al. (2003) identified a heterozygous missense mutation in the KRT9 gene (L160F; 607606.0012). In affected members a 5-generation Taiwanese family with EPPK associated with knuckle pads, Chiu et al. (2007) identified heterozygosity for the common R163W mutation in the KRT9 gene (607606.0001), previously designated R162W. In a 4-generation southern Italian family in which 11 of 24 members had EPPK, 1 of whom also had knuckle pads, Codispoti et al. (2009) identified heterozygosity for the R163W mutation. Quantitative RT-PCR analysis of a knuckle-pad skin biopsy revealed an almost 90-fold increase in KRT9 expression compared to control. Genotype/Phenotype Correlations Both epidermolytic and nonepidermolytic forms of palmoplantar keratoderma have been observed with various mutations in the KRT1 gene (139350). Kimonis et al. (1994) suggested that the specific region of the keratin protein affected by mutation might be a major determining factor in the different clinical and histologic consequences. Mutations of the KRT1 and KRT9 genes that are associated with the epidermolytic form of PPK affect the central regions of the protein that are important for filament assembly and stability, and for that reason lead to cellular degeneration or disruption. On the other hand, the mutation of the KRT1 gene (139350.0004) that Kimonis et al. (1994) found in association with nonepidermolytic PPK (600962) was located in the amino-terminal variable end region, which may be involved in supramolecular interactions of keratin filaments rather than stability. INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Localized epidermolytic hyperkeratosis \- Thick, waxy skin of palms and soles with well-defined erythematous border \- Keratosis palmaris \- Keratosis plantaris \- Hyperkeratosis on dorsal surface of fingers and toes (knuckle pads, in some patients) \- Palmoplantar epidermolytic hyperkeratosis along Blaschko lines (rare) Skin Histology \- Thickened granular layer of epidermis \- Large irregularly shaped keratohyalin granules \- Perinuclear vacuolization of keratinocytes Electron Microscopy \- Cytolysis of keratinocytes in spinous and granular layers \- Aggregated tonofilaments at cell surface MOLECULAR BASIS \- Caused by mutation in the keratin 1 gene (KRT1, 139350.0014 ) \- Caused by mutation in the keratin 9 gene (KRT9, 607606.0001 ) ▲ 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	PALMOPLANTAR KERATODERMA, EPIDERMOLYTIC	c0343110	5,305	omim	https://www.omim.org/entry/144200	2019-09-22T16:39:57	{"doid": ["0080223"], "omim": ["144200"], "orphanet": ["2199"], "synonyms": ["Alternative titles", "PPKE", "KERATODERMA, EPIDERMOLYTIC PALMOPLANTAR", "PALMOPLANTAR KERATODERMA, VORNER TYPE", "HYPERKERATOSIS, LOCALIZED EPIDERMOLYTIC", "KERATOSIS PALMARIS ET PLANTARIS FAMILIARIS", "TYLOSIS", "KERATOSIS OF GREITHER"]}
Tumid lupus erythematosus Other names"Lupus erythematosus tumidus"[1] Tumid lupus erythematosus is a rare, but distinctive entity in which patients present with edematous erythematous plaques, usually on the trunk.[2] Lupus erythematosus tumidus (LET) was reported by Henri Gougerot and Burnier R. in 1930. It is a photosensitive skin disorder, a different subtype of cutaneous lupus erythematosus (CLE) from discoid lupus erythematosus (DLE) or subacute CLE (SCLE).[3] LET is usually found on sun-exposed areas of the body. Skin lesions are edematous, urticarialike annular papules and plaques. Topical corticosteroids are not effective as treatment for LET, but many will respond to chloroquine. LET resolves with normal skin, no residual scarring, no hyperpigmentation or hypopigmentation. Cigarette smokers who have LET may not respond very well to chloroquine.[4][5] It has been suggested that it is equivalent to Jessner lymphocytic infiltrate of the skin.[6] ## See also[edit] * Lupus erythematosus * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. Page 159. ISBN 0-7216-2921-0. 3. ^ Gougerot H, Burnier R. Lupus érythémateux "tumidus". Bull Soc Fr Dermatol Syphiligr. 1930;37:1291-1292. 4. ^ Kuhn A, Richter-Hintz D, Oslislo C, Ruzicka T, Megahed M, Lehmann P. Lupus erythematosus tumidus, a neglected subset of cutaneous lupus erythematosus. Report of 40 cases. Arch Dermatol. 2000;136(8):1033-1041. 5. ^ Callen JP. Management of skin disease in patients with lupus erythematosus. Best Pract Res Clin Rheumatol. 2002;16(2):245-264. 6. ^ "Jessner Lymphocytic Infiltration of the Skin: eMedicine Dermatology". Retrieved 2010-05-22. 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	Tumid lupus erythematosus	c0406636	5,306	wikipedia	https://en.wikipedia.org/wiki/Tumid_lupus_erythematosus	2021-01-18T19:10:43	{"gard": ["13003"], "umls": ["C0406636"], "orphanet": ["90283"], "wikidata": ["Q3267714"]}
Aggressive digital papillary adenocarcinoma Other namesDigital papillary adenocarcinoma[1] and Papillary adenoma[2] SpecialtyDermatology/oncology Aggressive digital papillary adenocarcinoma is a cutaneous condition characterized by an aggressive malignancy involving the digit between the nailbed and the distal interphalangeal joint spaces.[1]:670 ## See also[edit] * Mucinous carcinoma * List of cutaneous conditions ## References[edit] 1. ^ a b James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. * v * t * e Skin cancer of the epidermis Tumor Carcinoma BCC * Forms * Aberrant * Cicatricial * Cystic * Fibroepithelioma of Pinkus * Infltrative * Micronodular * Nodular * Pigmented * Polypoid * Pore-like * Rodent ulcer * Superficial * Nevoid basal cell carcinoma syndrome SCC * Forms * Adenoid * Basaloid * Clear cell * Signet-ring-cell * Spindle-cell * Marjolin's ulcer * Bowen's disease * Bowenoid papulosis * Erythroplasia of Queyrat * Actinic keratosis Adenocarcinoma * Aggressive digital papillary adenocarcinoma * Extramammary Paget's disease Ungrouped * Merkel cell carcinoma * Microcystic adnexal carcinoma * Mucinous carcinoma * Primary cutaneous adenoid cystic carcinoma * Verrucous carcinoma * Malignant mixed tumor Benign tumors Acanthoma * Forms * Large cell * Fissuring * Clear cell * Epidermolytic * Melanoacanthoma * Pilar sheath acanthoma * Seboacanthoma * Seborrheic keratosis * Warty dyskeratoma Keratoacanthoma * Generalized eruptive * Keratoacanthoma centrifugum marginatum * Multiple * Solitary Wart * Verruca vulgaris * Verruca plana * Plantar wart * Periungual wart Other Epidermal nevus * Syndromes * Epidermal nevus syndrome * Schimmelpenning syndrome * Nevus comedonicus syndrome * Nevus comedonicus * Inflammatory linear verrucous epidermal nevus * Linear verrucous epidermal nevus * Pigmented hairy epidermal nevus syndrome * Systematized epidermal nevus * Phakomatosis pigmentokeratotica Other nevus * Nevus unius lateris * Patch blue nevus * Unilateral palmoplantar verrucous nevus * Zosteriform speckled lentiginous nevus Ungrouped * Cutaneous horn This Epidermal nevi, neoplasms, cysts 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	Aggressive digital papillary adenocarcinoma	None	5,307	wikipedia	https://en.wikipedia.org/wiki/Aggressive_digital_papillary_adenocarcinoma	2021-01-18T18:39:14	{"umls": ["CL053818"], "wikidata": ["Q4692274"]}
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. (May 2014) (Learn how and when to remove this template message) Gastrointestinal intraepithelial neoplasia (GIN or GIIN), also known as "digestive epithelial dysplasia" is abnormal growth (cellular dysplasia) of digestive epithelial cells in the digestive mucosa. Gastrointestinal intraepithelial neoplasia is the potentially premalignant transformation. Since 2000, they are classified according to the Vienna classification.[1] ## References[edit] 1. ^ Kabbinavar, F. F.; Hambleton, J; Mass, R. D.; Hurwitz, H. I.; Bergsland, E; Sarkar, S (2005). "Combined analysis of efficacy: The addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer". Journal of Clinical Oncology. 23 (16): 3706–12. doi:10.1200/JCO.2005.00.232. PMID 15867200. This oncology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Gastrointestinal intraepithelial neoplasia	c0920207	5,308	wikipedia	https://en.wikipedia.org/wiki/Gastrointestinal_intraepithelial_neoplasia	2021-01-18T18:55:58	{"umls": ["C0920207"], "wikidata": ["Q18343530"]}
Swimmer's itch Cercarial dermatitis on lower legs, four days after spending a day in the shallows of a lake SpecialtyInfectious disease Swimmer's itch or cercarial dermatitis, is a short-term allergic immune reaction occurring in the skin of humans that have been infected by water-borne schistosomes. Symptoms, which include itchy, raised papules, commonly occur within 1–2 days of infection and do not generally last more than 2–3 weeks. However, people repeatedly exposed to cercariae develop heavier symptoms with faster onset.[1] Cercarial dermatitis is common in freshwater, brackish and marine habitats worldwide.[2] Incidence may be on the rise, although this may also be attributed to better monitoring. Nevertheless, the condition has been regarded as emerging infectious disease.[3] There are no permanent effects to people from this condition.[4] Orally administered hydroxyzine, an antihistamine, is sometimes prescribed to treat swimmer's itch and similar dermal allergic reactions. In addition, bathing in oatmeal, baking soda, or Epsom salts can also provide relief of symptoms.[5] ## Contents * 1 Cause * 2 Risk factors * 3 Control * 4 See also * 5 References * 6 External links ## Cause[edit] Swimmer's itch probably has been around as long as humans. The condition was known to exist as early as the 1800s, but it was not until 1928 that a biologist found that the dermatitis was caused by the larval stage of a group of flatworm parasites in the family Schistosomatidae.[6] The genera most commonly associated with swimmer's itch in humans are Trichobilharzia[1] and Gigantobilharzia. It can also be caused by schistosome parasites of non-avian vertebrates, such as Schistosomatium douthitti, which infects snails and rodents. Other taxa reported to cause the reaction include Bilharziella polonica and Schistosoma bovis. In marine habitats, especially along the coasts, swimmer's itch can occur as well.[7] These parasites use both freshwater snails and vertebrates as hosts in their parasitic life cycles as follows: 1. Once a schistosome egg is immersed in water, a short-lived, non-feeding, free-living stage known as the miracidium emerges. The miracidium uses cilia to follow chemical and physical cues thought to increase its chances of finding the first intermediate host in its life cycle, a freshwater snail. 2. After infecting a snail, it develops into a mother sporocyst, which in turn undergoes asexual reproduction, yielding large numbers of daughter sporocysts, which asexually produce another short-lived, free-living stage, the cercaria. 3. Cercariae use a tail-like appendage (often forked in genera causing swimmer's itch) to swim to the surface of the water; and use various physical and chemical cues in order to locate the next and final (definitive) host in the life cycle, a bird. These larvae can accidentally come into contact with the skin of a swimmer. The cercaria penetrates the skin and dies in the skin immediately. The cercariae cannot infect humans, but they cause an inflammatory immune reaction. This reaction causes initially mildly itchy spots on the skin. Within hours, these spots become raised papules which are intensely itchy. Each papule corresponds to the penetration site of a single parasite. Life-cycle of swimmers itch 4. After locating a bird, the parasite penetrates through the skin (usually the feet), dropping the forked tail in the process. Inside the circulatory system, the immature worms (schistosomula) develop into mature male and female worms, mate and migrate through the host's circulatory system (or nervous system in case of T. regenti) to the final location (veins feeding the gastrointestinal tract) within the host body. There they lay eggs in the small veins in the intestinal mucosa from which they make their way into the lumen of the gut, and are dumped into the water when the bird defecates. One European species, Trichobilharzia regenti, instead infects the bird host's nasal tissues and larvae hatch from the eggs directly in the tissue during drinking/feeding of the infected birds.[8] ## Risk factors[edit] Image of infectious cercariae Humans usually become infected after swimming in lakes or other bodies of slow-moving fresh water. Some laboratory evidence indicates snails shed cercariae most intensely in the morning and on sunny days, and exposure to water in these conditions may therefore increase risk. Duration of swimming is positively correlated with increased risk of infection in Europe[9] and North America,[10] and shallow inshore waters may harbour higher densities of cercariae than open waters offshore. Onshore winds are thought to cause cercariae to accumulate along shorelines.[11] Studies of infested lakes and outbreaks in Europe and North America have found cases where infection risk appears to be evenly distributed around the margins of water bodies[9] as well as instances where risk increases in endemic swimmer's itch "hotspots".[11] Children may become infected more frequently and more intensely than adults but this probably reflects their tendency to swim for longer periods inshore, where cercariae also concentrate.[12] Stimuli for cercarial penetration into host skin include unsaturated fatty acids, such as linoleic and linolenic acids. These substances occur naturally in human skin and are found in sun lotions and creams based on plant oils. ## Control[edit] Mechanical removal of snails in Lake Annecy, France Various strategies targeting the mollusc and avian hosts of schistosomes, have been used by lakeside residents in recreational areas of North America to deal with outbreaks of swimmer's itch. In Michigan, for decades, authorities used copper sulfate as a molluscicide to reduce snail host populations and thereby the incidence of swimmer's itch.[citation needed] The results with this agent have been inconclusive, possibly because: * Snails become tolerant * Local water chemistry reduces the molluscicide's efficacy * Local currents diffuse it * Adjacent snail populations repopulate a treated area[13] More importantly, perhaps, copper sulfate is toxic to more than just molluscs, and the effects of its use on aquatic ecosystems are not well understood.[citation needed] Another method targeting the snail host, mechanical disturbance of snail habitat, has been also tried in some areas of North America[11] and Lake Annecy in France, with promising results. Some work in Michigan suggests that administering praziquantel to hatchling waterfowl can reduce local swimmer's itch rates in humans.[14] Work on schistosomiasis showed that water-resistant topical applications of the common insect repellent DEET prevented schistosomes from penetrating the skin of mice.[15] Public education of risk factors,[16] a good alternative to the aforementioned interventionist strategies, can also reduce human exposure to cercariae.[17] ## See also[edit] * Schistosomiasis * Sea louse ## References[edit] 1. ^ a b Macháček, Tomáš; Turjanicová, Libuše; Bulantová, Jana; Hrdý, Jiří; Horák, Petr; Mikeš, Libor (2018-10-09). "Cercarial dermatitis: a systematic follow-up study of human cases with implications for diagnostics". Parasitology Research. 117 (12): 3881–3895. doi:10.1007/s00436-018-6095-0. ISSN 0932-0113. PMID 30302587. S2CID 52945883. 2. ^ "Avian Schistosome Biodiversity". www.schistosomes.net. Retrieved 2016-03-07. 3. ^ Horák, Petr; Mikeš, Libor; Lichtenbergová, Lucie; Skála, Vladimír; Soldánová, Miroslava; Brant, Sara Vanessa (January 2015). "Avian schistosomes and outbreaks of cercarial dermatitis". Clinical Microbiology Reviews. 28 (1): 165–190. doi:10.1128/CMR.00043-14. ISSN 1098-6618. PMC 4284296. PMID 25567226. 4. ^ "With warm weather, Swimmers Itch makes annual appearance". dnr.wi.gov. Retrieved 2016-03-07. 5. ^ In CDC. "Swimmers Itch FAQS." retrieved May 12, 2014 6. ^ "Swimmer's Itch in Michigan" (PDF). State of Michigan. 2014. Retrieved 5 March 2015. 7. ^ Brant S, Cohen A, James D, Hui L, Hom A, Loker E (2010). "Cercarial Dermatitis Transmitted by Exotic Marine Snail". Emerging Infectious Diseases. 16 (9): 1357–65. doi:10.3201/eid1609.091664. PMC 3294964. PMID 20735918. 8. ^ Horák P., Kolářová L., Dvořák J. (1998). "Trichobilharzia regenti n. sp. (Schistosomatidae, Bilharziellinae), a new nasal schistosome from Europe" (PDF). Parasite. 5 (4): 349–357. doi:10.1051/parasite/1998054349. PMID 9879557.CS1 maint: multiple names: authors list (link) 9. ^ a b Chamot E, Toscani L, Rougemont A (1998). "Public health importance and risk factors for cercarial dermatitis associated with swimming in Lake Leman at Geneva, Switzerland". Epidemiol. Infect. 120 (3): 305–14. doi:10.1017/S0950268898008826. PMC 2809408. PMID 9692609. 10. ^ Lindblade KA (1998). "The epidemiology of cercarial dermatitis and its association with limnological characteristics of a northern Michigan lake". J. Parasitol. 84 (1): 19–23. doi:10.2307/3284521. JSTOR 3284521. PMID 9488332. 11. ^ a b c Leighton BJ, Zervos S, Webster JM (2000). "Ecological factors in schistosome transmission, and an environmentally benign method for controlling snails in a recreational lake with a record of schistosome dermatitis". Parasitol. Int. 49 (1): 9–17. doi:10.1016/S1383-5769(99)00034-3. PMID 10729712. 12. ^ Verbrugge LM, Rainey JJ, Reimink RL, Blankespoor HD (2004). "Prospective study of swimmer's itch incidence and severity". J. Parasitol. 90 (4): 697–704. doi:10.1645/GE-237R. PMID 15357056. S2CID 43205388. 13. ^ Blankespoor, H. D., Reimink, R. L. (1991). "The control of swimmer's itch in Michigan: Past, present, and future". Michigan Academician. 24 (1): 7–23.CS1 maint: multiple names: authors list (link) 14. ^ Blankespoor, C. L., Reimink, R. L., Blankespoort, H. D. (2001). "Efficacy of praziquantel in treating natural schistosome infections in common mergansers". Journal of Parasitology. 87 (2): 424–6. doi:10.1645/0022-3395(2001)087[0424:EOPITN]2.0.CO;2. PMID 11318576.CS1 maint: multiple names: authors list (link) 15. ^ Salafsky, B., Ramaswamy, K., He, Y. X., Li, J., Shibuya, T. (November 1999). "Development and evaluation of LIPODEET, a new long-acting formulation of N, N-diethyl-m-toluamide (DEET) for the prevention of schistosomiasis". Am. J. Trop. Med. Hyg. 61 (5): 743–50. doi:10.4269/ajtmh.1999.61.743. PMID 10586906.CS1 maint: multiple names: authors list (link) 16. ^ Prevention, CDC-Centers for Disease Control and (2019-04-24). "CDC - Cercarial Dermatitis - Publications". www.cdc.gov. Retrieved 2020-08-09. 17. ^ "Swimmer's Itch Reported at Lakes". Bureau of Land Management. ## External links[edit] Classification D * ICD-10: B65.3 * ICD-9-CM: 120.3 * DiseasesDB: 32723 Wikimedia Commons has media related to Schistosome cercarial dermatitis. * v * t * e Parasitic disease caused by helminthiases Flatworm/ platyhelminth infection Fluke/trematode (Trematode infection) Blood fluke * Schistosoma mansoni / S. japonicum / S. mekongi / S. haematobium / S. intercalatum * Schistosomiasis * Trichobilharzia regenti * Swimmer's itch Liver fluke * Clonorchis sinensis * Clonorchiasis * Dicrocoelium dendriticum / D. hospes * Dicrocoeliasis * Fasciola hepatica / F. gigantica * Fasciolosis * Opisthorchis viverrini / O. felineus * Opisthorchiasis Lung fluke * Paragonimus westermani / P. kellicotti * Paragonimiasis Intestinal fluke * Fasciolopsis buski * Fasciolopsiasis * Metagonimus yokogawai * Metagonimiasis * Heterophyes heterophyes * Heterophyiasis Cestoda (Tapeworm infection) Cyclophyllidea * Echinococcus granulosus / E. multilocularis * Echinococcosis * Taenia saginata / T. asiatica / T. solium (pork) * Taeniasis / Cysticercosis * Hymenolepis nana / H. diminuta * Hymenolepiasis Pseudophyllidea * Diphyllobothrium latum * Diphyllobothriasis * Spirometra erinaceieuropaei * Sparganosis * Diphyllobothrium mansonoides * Sparganosis Roundworm/ Nematode infection Secernentea Spiruria Camallanida * Dracunculus medinensis * Dracunculiasis Spirurida Filarioidea (Filariasis) * Onchocerca volvulus * Onchocerciasis * Loa loa * Loa loa filariasis * Mansonella * Mansonelliasis * Dirofilaria repens * D. immitis * Dirofilariasis * Wuchereria bancrofti / Brugia malayi / \|B. timori * Lymphatic filariasis Thelazioidea * Gnathostoma spinigerum / G. hispidum * Gnathostomiasis * Thelazia * Thelaziasis Spiruroidea * Gongylonema Strongylida (hookworm) * Hookworm infection * Ancylostoma duodenale / A. braziliense * Ancylostomiasis / Cutaneous larva migrans * Necator americanus * Necatoriasis * Angiostrongylus cantonensis * Angiostrongyliasis * Metastrongylus * Metastrongylosis Ascaridida * Ascaris lumbricoides * Ascariasis * Anisakis * Anisakiasis * Toxocara canis / T. cati * Visceral larva migrans / Toxocariasis * Baylisascaris * Dioctophyme renale * Dioctophymosis * Parascaris equorum Rhabditida * Strongyloides stercoralis * Strongyloidiasis * Trichostrongylus spp. * Trichostrongyliasis * Halicephalobus gingivalis Oxyurida * Enterobius vermicularis * Enterobiasis Adenophorea * Trichinella spiralis * Trichinosis * Trichuris trichiura (Trichuriasis / Whipworm) * Capillaria philippinensis * Intestinal capillariasis * C. hepatica [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Swimmer's itch	c0546996	5,309	wikipedia	https://en.wikipedia.org/wiki/Swimmer%27s_itch	2021-01-18T18:52:58	{"gard": ["9747"], "umls": ["C0546996"], "wikidata": ["Q191672"]}
Nodular regenerative hyperplasia Other namesNodular regenerative hyperplasia of the liver Human liver(normal) ComplicationsPortal hypertension Nodular regenerative hyperplasia is a form of liver hyperplasia associated with portal hypertension. Nodular regenerative hyperplasia (NRH) is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules. NRH may lead to the development of non-cirrhotic portal hypertension. There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series. NRH may develop via autoimmune, hematological, infectious, neoplastic, or drug-related causes. It is associated with rheumatoid arthritis, Felty syndrome, myeloproliferative disorders, liver, kidney and bone marrow transplantation, cytotoxic drugs like azathioprine, mercaptopurine, thioguanine, antiretroviral drugs for HIV like didanosine and vitamin A. There is also association between NRH and platinum-based drugs, such as chemotherapy with oxaliplatin. The disease is usually asymptomatic, slowly or non-progressive unless complications of portal hypertension develop. Accurate diagnosis is made by histopathology, which demonstrates diffuse micronodular transformation without fibrous septa. Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver. While the initial treatment is to address the underlying disease, ultimately the therapy is directed to the management of portal hypertension. The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension. In this review we detail the epidemiology, pathogenesis, diagnosis, management, and prognosis of NRH.[1] Feathery degeneration is seen in PBC It can be a complication of azathioprine therapy.[2][3] ## References[edit] 1. ^ Hartleb, Marek; Gutkowski, Krzysztof; Milkiewicz, Piotr (2011-03-21). "Nodular regenerative hyperplasia: Evolving concepts on underdiagnosed cause of portal hypertension". World Journal of Gastroenterology. 17 (11): 1400–1409. doi:10.3748/wjg.v17.i11.1400. ISSN 1007-9327. PMC 3070012. PMID 21472097. 2. ^ Daniel F, Cadranel JF, Seksik P, et al. (May 2005). "Azathioprine induced nodular regenerative hyperplasia in IBD patients". Gastroenterol. Clin. Biol. 29 (5): 600–3. doi:10.1016/S0399-8320(05)82136-0. PMID 15980758. 3. ^ Vernier-Massouille G, Cosnes J, Lemann M, et al. (October 2007). "Nodular regenerative hyperplasia in patients with inflammatory bowel disease treated with azathioprine". Gut. 56 (10): 1404–9. doi:10.1136/gut.2006.114363. PMC 2000290. PMID 17504943. ## External links[edit] Classification D * ICD-10: K76.8 External resources * Orphanet: 48372 * 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 This article about a disease, disorder, or medical condition is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Nodular regenerative hyperplasia	c4048264	5,310	wikipedia	https://en.wikipedia.org/wiki/Nodular_regenerative_hyperplasia	2021-01-18T19:04:25	{"gard": ["10929"], "orphanet": ["48372"], "synonyms": ["Non-cirrhotic nodulation"], "wikidata": ["Q3144188"]}
Marshall syndrome is an inherited condition characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Those with Marshall syndrome can also have short stature. Some researchers have argued that Marshall syndrome represents a variant form of Stickler syndrome; but this remains controversial. Marshall syndrome is caused by mutations in the COL11A1 gene and is inherited in an autosomal dominant fashion. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Marshall syndrome	c0265235	5,311	gard	https://rarediseases.info.nih.gov/diseases/6984/marshall-syndrome	2021-01-18T17:59:14	{"mesh": ["C536025"], "omim": ["154780"], "umls": ["C0265235"], "orphanet": ["560"], "synonyms": ["Deafness, myopia, cataract, saddle nose-Marshall type"]}
Occipital pachygyria and polymicrogyria is a rare, genetic, cerebral malformation characterized by the presence of cortical smoothening with loss of secondary and tertiary gyri, associated with an excessive number of small, irregular gyri with increased cortical thickness, located in the occipital lobes. Patients usually present with seizures (including myoclonic-astatic, absence, atypical absence, vision loss, myoclonic-atonic, generalized tonic-clonic) and variable (absent to moderate) developmental and/or intellectual delay. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Occipital pachygyria and polymicrogyria	c3279875	5,312	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=280640	2021-01-23T18:27:45	{"omim": ["614115"], "icd-10": ["Q04.3"], "synonyms": ["Occipital MCD", "Occipital malformations of cortical development"]}
Waardenburg syndrome (WS) is a group of genetic conditions characterized by varying degrees of hearing loss and differences in the coloring (pigmentation) of the eyes, hair, and skin. Signs and symptoms can vary both within and between families. Common features include congenital sensorineural deafness; pale blue eyes, different colored eyes, or two colors within one eye; a white forelock (hair just above the forehead); or early graying of scalp hair before age 30. Various other features may also be present. WS is classified into 4 subtypes (types 1, 2, 3 and 4) based on whether certain features are present and the genetic cause. Mutations in at least 6 different genes are known to cause WS, and it may be inherited in an autosomal dominant (most commonly) or autosomal recessive manner. Treatment depends on the specific symptoms present. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Waardenburg syndrome	c3266898	5,313	gard	https://rarediseases.info.nih.gov/diseases/5525/waardenburg-syndrome	2021-01-18T17:57:10	{"mesh": ["D014849"], "omim": ["193500"], "orphanet": ["3440"], "synonyms": ["Van der Hoeve Halbertsma Waardenburg Gualdi Syndrome", "Mende Syndrome"]}
## Summary ### Clinical characteristics. SUCLG1-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria is characterized in the majority of affected newborns by hypotonia, muscle atrophy, feeding difficulties, and lactic acidosis. Affected infants commonly manifest developmental delay / cognitive impairment, growth retardation / failure to thrive, hepatopathy, sensorineural hearing impairment, dystonia, and hypertonia. Notable findings in some affected individuals include hypertrophic cardiomyopathy, epilepsy, myoclonus, microcephaly, sleep disturbance, rhabdomyolysis, contractures, hypothermia, and/or hypoglycemia. Life span is shortened, with median survival of 20 months. ### Diagnosis/testing. The diagnosis of SUCLG1-related mtDNA depletion syndrome is established in a proband by the identification of biallelic pathogenic variants in SUCLG1 on molecular genetic testing. ### Management. Treatment of manifestations: Management is supportive and is best provided by a multidisciplinary team. Treatment may include physical therapy to help maintain muscle function and prevent joint contractures, nutritional support by a dietitian, use of a nasogastric tube or gastrostomy tube feedings, chest physiotherapy, and aggressive antibiotic treatment of chest infections. When present, seizures are treated using standard antiepileptic drugs. Surveillance: The suggested evaluations (with frequency varying according to the needs of the child) can include developmental and neurologic assessment, nutritional and growth assessment, echocardiogram, liver function tests, hearing evaluation, and ophthalmologic examination. ### Genetic counseling. SUCLG1-related mtDNA depletion syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the SUCLG1 pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings SUCLG1-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria (MMA) typically manifests at birth or during early infancy and should be suspected in individuals with a combination of the following supportive clinical, brain MRI, laboratory, and muscle biopsy findings. Clinical features Present in >50%: * Developmental delay and cognitive impairment * Hypotonia * Muscle atrophy * Feeding difficulties Present in 20%-50%: * Growth retardation / failure to thrive * Hepatopathy * Sensorineural hearing impairment * Dystonia * Hypertonia Present in <20%: * Hypertrophic cardiomyopathy * Recurrent respiratory infections, respiratory distress, and apnea * Recurrent vomiting and gastroesophageal reflux disease * Ptosis and strabismus * Epilepsy, myoclonus, and microcephaly * Hyperhidrosis * Sleep disturbance * Rhabdomyolysis * Contractures * Hypothermia Brain MRI findings [Carrozzo et al 2016] * Basal ganglia hyperintensities (80%) * Cerebral atrophy (30%) * Leukoencephalopathy (20%) Supportive laboratory findings * Urine organic acid analysis * Elevation of urinary methylmalonic acid (MMA) in all affected children. Urinary MMA ranges from 10 to 500 mmol/mol creatinine (normal <3 mmol/mol creatinine). Note: In classic methylmalonic aciduria urinary MMA is ~1,000-10,000 mmol/mol creatinine, and in defects of cobalamin metabolism urinary MMA is ~100s mmol/mol creatinine (see Differential Diagnosis). * Several other metabolites that may be elevated in urine include methylcitrate, 3-methylglutaconic acid, 3-hydroxyisovaleric acid, and Krebs cycle intermediates (e.g., succinate, fumarate, 2-ketoglutarate). * Plasma MMA level is elevated in all affected children and ranges from 1 to10 mmol/L (normal <0.3 mmol/L). Note: In classic methylmalonic aciduria plasma MMA is ~100-1,000 mmol/L, and in defects of cobalamin metabolism plasma MMA is ~10s mmol/L (see Differential Diagnosis). * Acylcarnitine profile can show elevated C3; thus, this condition can potentially be detected by newborn screening. * Plasma and CSF lactate levels are elevated in most affected individuals. * Hypoglycemia can occasionally occur [Carrozzo et al 2016]. Muscle biopsy, typically performed during the evaluation of individuals with mitochondrial diseases, can show variable abnormalities or can occasionally be normal. The following findings can suggest the diagnosis: * Increased fiber size variability, atrophic fibers, intracellular lipid accumulation, ragged-red fibers (RRF), and COX-deficient fibers * Structurally altered mitochondria with abnormal cristae on electron microscopy * Abnormal electron transport chain activity. The most common abnormalities are combined complex I and IV deficiencies, combined complex I, III, and IV deficiencies, and isolated complex IV deficiency. * Reduced mtDNA content; typically 15%-50% of tissue- and age-matched controls [Ostergaard et al 2007, Valayannopoulos et al 2010, Randolph et al 2011, Landsverk et al 2014] ### Establishing the Diagnosis The diagnosis of SUCLG1-related mtDNA depletion syndrome is established in a proband by the identification of biallelic pathogenic variants in SUCLG1 on molecular genetic testing (see Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (multigene panel) and genomic testing (comprehensive genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of SUCLG1-related mtDNA depletion syndrome is broad, children with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from other inherited mitochondrial disorders are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 The phenotypes of SUCLG1-related mtDNA depletion syndrome and SUCLA2-related mtDNA depletion syndrome are difficult to distinguish and both are associated with elevated MMA. Therefore, when the phenotypic and laboratory findings suggest the diagnosis of SUCLG1-related mtDNA depletion syndrome, molecular genetic testing approaches can include SUCLG1 and SUCLA2 testing or use of a multigene panel: * SUCLG1 and SUCLA2 testing. Sequence analysis of SUCLG1 and SUCLA2 is performed first. If only one pathogenic variant is found, gene-targeted deletion/duplication analysis of that gene could be considered; however, to date no exon or whole-gene deletions of either gene have been reported. * A multigene panel that includes SUCLG1, SUCLA2, and other genes related to mtDNA depletion syndromes (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. Of note, given the rarity of SUCLG1-related mtDNA depletion syndrome, some panels for mtDNA depletion syndromes may not include this gene. (3) 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. #### Option 2 When the phenotype is indistinguishable from many other inherited mitochondrial disorders, molecular genetic testing approaches can include genomic testing (comprehensive genome sequencing) and/or gene-targeted testing (multigene panel): * Comprehensive genome 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. * A multigene panel for inherited mitochondrial disorders may also be considered. ### Table 1. Molecular Genetic Testing Used in SUCLG1-Related mtDNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria View in own window Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method SUCLG1Sequence analysis 321/21 4 Gene-targeted deletion/duplication analysis 5None reported to date 4 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Carrozzo et al [2016] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. ## Clinical Characteristics ### Clinical Description To date 29 individuals with SUCLG1-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria (MMA) have been reported [Ostergaard et al 2007, Ostergaard et al 2010, Rivera et al 2010, Rouzier et al 2010, Valayannopoulos et al 2010, Van Hove et al 2010, Randolph et al 2011, Sakamoto et al 2011, Honzik et al 2012, Navarro-Sastre et al 2012, Landsverk et al 2014, Carrozzo et al 2016, Chu et al 2016, Donti et al 2016, Liu et al 2016, Pupavac et al 2016]. The clinical description here is based on the findings reported in these 29 individuals. The common clinical manifestations are summarized in Table 2 [Carrozzo et al 2016]. ### Table 2. Clinical Manifestations of SUCLG1-Related mtDNA Depletion Syndrome View in own window FrequencyManifestations >50% * Developmental delay & cognitive impairment * Hypotonia * Muscle atrophy * Feeding difficulties * Lactic acidosis 20%-50% * Growth retardation / failure to thrive * Hepatopathy * Sensorineural hearing impairment * Dystonia * Hypertonia <20% * Hypertrophic cardiomyopathy * Recurrent respiratory infections * Respiratory distress * Apnea * Recurrent vomiting * Gastroesophageal reflux disease * Ptosis * Strabismus * Epilepsy * Myoclonus * Microcephaly * Choreoathetosis * Hyperhidrosis * Sleep disturbance * Rhabdomyolysis * Contractures * Hypothermia * Hypoglycemia Age of onset and phenotypic spectrum. Although SUCLG1-related mtDNA depletion syndrome can present from the prenatal period to age one year, the majority of affected infants present at birth [Carrozzo et al 2016]. The majority have an uncomplicated pregnancy and normal birth weight; however, five neonates had intrauterine growth restriction (IUGR) or were small for gestational age (SGA) [Ostergaard et al 2007, Randolph et al 2011, Carrozzo et al 2016]. Rare prenatal manifestations may include oligohydramnios and abnormal fetal heart rate [Carrozzo et al 2016]. The majority of affected infants present with early-onset encephalomyopathy and neurocognitive problems as well as hepatopathy, feeding and growth problems, and cardiorespiratory complications. Death from severe metabolic acidosis during the neonatal period (fatal infantile lactic acidosis) has been reported in five infants [Ostergaard et al 2007, Rivera et al 2010]. Neurocognitive. The majority of affected children demonstrate developmental delay, cognitive impairment, hypotonia, and muscle atrophy. Other, less frequent, neurologic manifestations include: sensorineural hearing impairment, dystonia, hypertonia, epilepsy, myoclonus, microcephaly, choreoathetosis, ptosis, and strabismus. Hepatopathy. Approximately 40% of affected individuals have liver involvement manifesting as hepatomegaly, steatosis, and elevated liver enzymes. One affected infant developed intermittent episodes of liver failure [Van Hove et al 2010]. Feeding and growth. Failure to thrive, growth retardation, and feeding difficulties, often necessitating tube feeding, occur commonly. Recurrent vomiting and gastroesophageal reflux disease (GERD) occasionally occur. The feeding difficulties, recurrent vomiting, and GERD can cause or contribute to growth failure. Cardiac. Hypertrophic cardiomyopathy was reported in 15% of affected children. Ventricular hypertrophy is typically mild and appears in the neonatal period or infancy [Carrozzo et al 2016]. Respiratory. Recurrent respiratory infections are reported in some. Respiratory distress due to muscle weakness, apnea, and abnormal breathing has been reported. Congenital malformations. One affected infant had multiple congenital anomalies including cleft lip and palate, aortic coarctation, patent ductus arteriosus, patent foramen ovale, shortening of the left femur and both humeri, dilation of the left renal collecting system, and accessory left kidney [Landsverk et al 2014]. Other congenital anomalies reported in single infants each are interrupted aortic arch, polydactyly, and hypospadias [Ostergaard et al 2007, Rivera et al 2010]. Metabolic derangements. In addition to elevated MMA, the majority of affected children develop lactic acidosis that can be severe and life threatening. Hypoglycemia was occasionally reported. Others. Other, less frequent, manifestations include hyperhidrosis, hypothermia, sleeping disturbance, rhabdomyolysis, and joint contractures. Prognosis. Life span is shortened, with median survival of 20 months. Two thirds (14/21) of affected children died during childhood – five in the neonatal period and nine during infancy and early childhood [Carrozzo et al 2016]. ### Genotype-Phenotype Correlations Pathogenic SUCLG1 missense variants can result in some residual enzyme activity, and hence a milder phenotype. Survival in children with biallelic pathogenic missense variants was longer (median age: 18 months) than in children with biallelic loss-of-function variants (splice site, frameshift, and nonsense variants) (median age: birth) [Carrozzo et al 2016]. ### Nomenclature Succinyl-CoA ligase deficiency can result from either biallelic pathogenic variants in SUCLG1 (SUCLG1-related mtDNA depletion syndrome) or biallelic pathogenic variants in SUCLA2 (SUCLA2-related mtDNA depletion syndrome). ### Prevalence SUCLG1-related mtDNA depletion syndrome is rare; the exact prevalence is unknown. To date 29 individuals with SUCLG1-related mtDNA depletion have been reported in families of different ethnic origins [Ostergaard et al 2007, Ostergaard et al 2010, Rivera et al 2010, Rouzier et al 2010, Valayannopoulos et al 2010, Van Hove et al 2010, Randolph et al 2011, Sakamoto et al 2011, Honzik et al 2012, Navarro-Sastre et al 2012, Landsverk et al 2014, Carrozzo et al 2016, Chu et al 2016, Donti et al 2016, Liu et al 2016, Pupavac et al 2016]. ## Differential Diagnosis SUCLG1-related mtDNA depletion syndrome needs to be differentiated from other mtDNA depletion syndromes, a genetically and clinically heterogeneous group of autosomal recessive disorders that are characterized by a severe reduction in mtDNA content leading to impaired energy production in affected tissues and organs. Table 3 includes the currently known mtDNA depletion syndromes. Mitochondrial DNA depletion syndromes occur as a result of defects in mtDNA maintenance caused by pathogenic variants in nuclear genes that function in either mitochondrial nucleotide synthesis (e.g., TK2, SUCLA2, SUCLG1, RRM2B, DGUOK, and TYMP) or mtDNA replication (e.g., POLG and TWNK [C10orf2]). The function of FBXL4 is not yet known. Mitochondrial DNA depletion syndromes are phenotypically classified into hepatocerebral, encephalomyopathic, neurogastrointestinal, and myopathic forms [El-Hattab & Scaglia 2013]. ### Table 3. Mitochondrial DNA Depletion Syndromes View in own window Phenotype 1GeneMitochondrial DNA Depletion Syndrome #, TypeReference 2 Hepato-cerebralDGUOK3, hepatocerebral type POLG4A, Alpers typePOLG-Related Disorders MPV176, hepatocerebral typeMPV17-Related Hepatocerebral mtDNA Depletion Syndrome TWNK (C10orf2)7, hepatocerebral typeOMIM 271245 TFAM15, hepatocerebral typeOMIM 617156 Encephalo- myopathicSUCLA25, encephalomyopathic type w/methylmalonic aciduriaSUCLA2-Related mtDNA Depletion Syndrome, Encephalomyopathic Form w/Methylmalonic Aciduria FBXL413, encephalomyopathic typeFBXL4-Related Encephalomyopathic mtDNA Depletion Syndrome SUCLG19, encephalomyopathic type w/methylmalonic aciduriaSUCLG1-Related mtDNA Depletion Syndrome, Encephalomyopathic Form w/Methylmalonic Aciduria RRM2B8A, encephalomyopathic type w/renal tubulopathyRRM2B-Related Mitochondrial Disease OPA114, encephalocardiomyopathic typeOMIM 616896 ABATEncephalomyopathic typeOMIM 613163 Neurogastro- intestinalTYMP1, MNGIE typeMitochondrial Neurogastrointestinal Encephalopathy Disease POLG4B, MNGIE typePOLG-Related Disorders RRM2B8B, MNGIE typeRRM2B-Related Mitochondrial Disease MyopathicTK22, myopathic typeTK2-Related mtDNA Depletion Syndrome, Myopathic Form AGK10, cardiomyopathic type (Sengers syndrome)OMIM 212350 MGME111, myopathic typeOMIM 615084 SLC25A412B, cardiomyopathic typeOMIM 615418 1\. Within each phenotypic category, mtDNA depletion syndromes are ordered by relative prevalence. 2\. See hyperlinked GeneReview or OMIM phenotype entry for more information. Among mtDNA depletion syndromes, methylmalonic acid (MMA) is elevated only in SUCLG1\- and SUCLA2-related mtDNA depletion syndromes. The phenotypes of SUCLG1-related mtDNA depletion syndrome and SUCLA2-related mtDNA depletion syndrome may be difficult to be differentiate (see Table 4). SUCLA2-related mtDNA depletion syndrome is characterized by onset of the following features in infancy or childhood: psychomotor retardation, hypotonia, dystonia, muscular atrophy, sensorineural hearing impairment, postnatal growth retardation, and feeding difficulties. Other, less frequent, features include distinctive facial features, contractures, kyphoscoliosis, gastroesophageal reflux, ptosis, choreoathetosis, ophthalmoplegia, and epilepsy. Of note, hepatopathy and cardiomyopathy, which have been reported in SUCLG1-related mtDNA depletion syndrome, have not been described in SUCLA2-related mtDNA depletion syndrome [Carrozzo et al 2016]. ### Table 4. Comparison of the Phenotypes of SUCLG1-Related mtDNA Depletion Syndrome and SUCLA2-Related mtDNA Deletion Syndromes View in own window Mitochondrial DNA Depletion Syndrome Clinical FindingSUCLG1-RelatedSUCLA2-Related Age at onsetMajority present at birthInfancy or childhood Median survival20 months20 years Developmental delay>50%>75% Hypotonia>50%>75% Muscular atrophy>50%25%-50% Feeding problemsEqually common Failure to thriveEqually common Liver involvement40%Not reported Hearing impairment20%-50%>75% Dystonia25%-50%>75% Hypertonia25%-50%<20% Hypertrophic cardiomyopathy14%Not reported On brain MRI:Basal ganglia hyperintensities80%70% Cerebral atrophy30%70% Leukoencephalopathy20%15% Carrozzo et al [2016] ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with SUCLG1-related mtDNA depletion syndrome the following evaluations are recommended: * Comprehensive neurologic examination and developmental/cognitive assessment. The following diagnostic modalities can be considered to assess the degree of neurologic involvement: * Brain MRI (if not performed during the diagnostic evaluation) to establish the degree of central nervous system involvement * EEG if seizures are suspected * Echocardiogram to assess for cardiomyopathy * Liver function tests including transaminases, albumin, total and direct bilirubin, and coagulation profile * Audiologic evaluation * Ophthalmologic examination for evidence of ptosis and/or strabismus * Nutritional evaluation and swallowing assessment for feeding difficulties and growth failure * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Management is best provided by a multidisciplinary team including specialists in neurology, audiology, child development, gastroenterology, cardiology, nutrition, and clinical genetics. Treatments include the following: * Physical therapy to help maintain muscle function and prevent joint contractures * Standard treatment with antiepileptic drugs for seizures * Nutritional support by a dietitian and the use of a nasogastric tube or gastrostomy tube feedings to address feeding difficulties and failure to thrive * Chest physiotherapy, aggressive antibiotic treatment of chest infections, and artificial ventilation (including assisted nasal ventilation or intubation and the use of a tracheostomy and ventilator) for respiratory insufficiency * Hypertrophic cardiomyopathy and hepatopathy, when present, require standard management by cardiologists and hepatologists, respectively. ### Surveillance No clinical guidelines for surveillance are available. The following evaluations are suggested, with frequency varying according to the needs of the child: * Developmental and neurologic assessment * Nutritional and growth assessment * Echocardiogram * Liver function tests * Hearing evaluation * Ophthalmologic examination ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation A group of mtDNA depletion syndromes is caused by defects in genes encoding proteins involved in maintenance of the mitochondrial deoxyribonucleotide pool. Because in vitro experimental studies have demonstrated improved mtDNA content following deoxyribonucleotide supplementation, this could potentially be a treatment for some mtDNA depletion syndromes [Cámara et al 2014]. 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	SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria	None	5,314	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK425223/	2021-01-18T20:57:34	{"synonyms": ["SUCLG1 Deficiency", "SUCLG1-Related Succinyl-CoA Ligase Deficiency"]}
A number sign (#) is used with this entry because preaxial polydactyly II, triphalangeal thumb-polysyndactyly syndrome, and isolated triphalangeal thumb are all caused by heterozygous mutation in an SHH (600725) regulatory element (ZRS) that resides in intron 5 of the LMBR1 gene (605522) on chromosome 7q36. Clinical Features The thumb in this malformation is usually opposable and possesses a normal metacarpal. This form of polydactyly consists of duplication of the distal phalanx, giving a 'duck-bill' appearance. Reported families include the second in the paper by Haas (1939), and those described by Atwood and Pond (1917), Hefner (1940) and Ecke (1962). The proband of a family studied by Temtamy and McKusick (1978) had opposable triphalangeal thumbs, all 3 phalanges being well developed, and duplication of the great toes. The trait had passed through at least 6 generations. Merlob et al. (1985) described a kindred in which persons in 4 and perhaps 5 generations had opposable triphalangeal thumbs associated with duplication of the great toe. They reviewed syndromes with triphalangeal thumbs and reemphasized the significant distinction between the opposable (true triphalangeal) and nonopposable (finger-like) thumb. The latter condition may require surgical pollicization for satisfactory function. Radhakrishna et al. (1993) described a very extensive family from a village in the Rajkot district of Gujarat in India in which many members in 5 generations showed preaxial polydactyly with a well-formed extra digit, triphalangeal thumbs, and duplication of the big toes. They observed that 'the extra digit was functional and flexed like a normal finger.' Ray (1987) reported a large family from another area of India, Andhra Pradesh, with preaxial polydactyly and, in some persons, bilateral duplication of the big toe. Since the thumb was not triphalangeal, this may have been a different entity (174400). Nicolai and Hamel (1988) described a large family in which multiple members exhibited a spectrum of pre- and postaxial anomalies of the limbs inherited as an autosomal dominant. In another study of this family, Tsukurov et al. (1994) found that the hand malformations were typically bilateral but usually asymmetric. Both pre- and postaxial polydactyly and syndactyly were present. In all affected individuals the thumb was triphalangeal and the index finger was normal. Malformations of the feet were present in some affected persons but were usually less severe than those observed in the hands. Variable expression of the disease gene was demonstrated by asymmetries in limb deformities of affected individuals and the differences observed between monozygotic twins. Heutink et al. (1994) studied 2 large Dutch kindreds from 'a relatively isolated population' with an estimated prevalence of triphalangeal thumb of 1 in 1,000. Within the families the expression of thumb anomalies was highly variable and ranged from an opposable thumb with a delta phalanx to an extreme form of preaxial polydactyly with a triphalangeal index finger instead of a thumb, 2 extra hypoplastic rays radial to the 'thumb' (septadactyly), hypoplastic thenar muscles, and, occasionally, syndactyly between the fourth and fifth rays. The description suggested that of preaxial polydactyly II. Temtamy (1994) pointed out that dermatoglyphics can help differentiate preaxial polydactyly of a triphalangeal thumb from preaxial polydactyly of an index finger. A duplicate of the 'a' triradius and line is present in the latter. Zguricas et al. (1994) reported the phenotypic features of the families studied by Heutink et al. (1994). Seidman (1994) indicated that polyphalangy seemed to be the most consistent feature in the families reported by Tsukurov et al. (1994) and Heutink et al. (1994); that the same haplotype was found in affected members of all 3 families, suggesting founder effect; and that a genealogic connection had been established between the 2 Dutch families. Hing et al. (1995) likewise cited evidence that further genealogic investigation of the kindreds described by Heutink et al. (1994), combined with haplotype analysis, demonstrated that they are part of a very large Belgian family and are probably carrying the same mutation. Balci et al. (1999) described a Turkish family with triphalangeal thumb-polysyndactyly syndrome. Characteristic findings in this family were triphalangeal thumb, webbing between third, fourth, and fifth fingers associated with bony synostosis in the distal phalanges of the same fingers, and pre- and postaxial polysyndactyly of the feet. Some affected members of the family showed a more severe phenotype with complete syndactyly of all fingers giving a 'cup-like' appearance to the hands. Kantaputra and Chalidapong (2000) reported a Thai man with triphalangeal thumb-polysyndactyly syndrome whose daughter had tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome (188740). The authors proposed that these conditions are actually the same disorder with wide variability. They suggested this condition be called 'tibial hemimelia-polysyndactyly-triphalangeal thumbs syndrome.' Klopocki et al. (2008) described a large 4-generation family segregating an autosomal dominant phenotype comprising triphalangeal thumbs, preaxial and/or postaxial synpolydactyly, and cutaneous/osseous syndactyly of fingers III-V or IV/V. The phenotype varied among affected individuals, and the latter features occurred either in isolation or in combination. In general, the feet were less severely affected than the hands. There were no other organ anomalies or dysmorphic features. Semerci et al. (2009) reported a large partially consanguineous 3-generation Turkish family in which 22 individuals had triphalangeal thumb-preaxial polydactyly syndrome affecting only the hands. Eleven individuals were evaluated clinically. There was some intrafamilial variability: all had 3 phalanges in the thumb and 6 metacarpals. Three had triphalangism in an extra digit. Other affected members had an extra hypoplastic digit with 2 phalanges. Molecular analysis identified a heterozygous mutation in the ZRS of intron 5 of the LMBR1 gene (605522.0012). One affected individual was homozygous for the mutation, born of consanguineous affected parents, but did not have a more severe phenotype. Mapping In the family originally reported by Nicolai and Hamel (1988), Tsukurov et al. (1994) found linkage of the malformation to a highly polymorphic locus containing a short tandem repeat sequence (STR), D7S550, located at 7q36; maximum lod score = 6.85 at theta = 0.0. This region is homologous to a segment of mouse chromosome 5 where 2 nonallelic mutations, 'hammer-toe' (Hm) and 'hemimelic extra toes' (Hx), have been mapped. In 2 large Dutch kindreds, Heutink et al. (1994) studied the transmission and linkage relationships of triphalangeal thumb. Using microsatellite DNA polymorphisms, they demonstrated that the locus, which they symbolized TPT, maps near the telomere of 7q. The combined maximum lod score for the 2 families was 12.61 at theta = 0.0 with marker D7S559. Hing et al. (1995) used the designation preaxial polydactyly type II for the disorder they studied in a 6-generation North American Caucasian kindred of presumed English descent. They demonstrated linkage to the 7q36 region and identified a submicroscopic chromosomal deletion segregating with the phenotype, which they symbolized PPD2. Comparison of the haplotypes in this kindred with those in the previously described ones yielded evidence of an independent mutational event. The chromosomal deletion was demonstrated by absence of a parental allele or loss of heterozygosity for the D7S594 marker in PPD2 individuals. To facilitate mapping the boundaries of the chromosome 7 deletion, Hing et al. (1995) constructed human/rodent hybrid cell lines to segregate the human chromosome 7 containing the PPD2 allele (an apparent deletion) from the normal chromosome 7 allele. They concluded that the deletion was in-phase with the anomalous phenotype (and the causative mutation) but not causative of the abnormality. Zguricas et al. (1999) reported linkage analysis of 12 families of different ethnic origin with preaxial polydactyly. The 2 Dutch families reported by Heutink et al. (1994) and Zguricas et al. (1994) were supplemented by 7 additional Dutch families, a British family, a Turkish family, and 2 Cuban families, 1 of which (Cuban family A) exhibited tibial aplasia in addition to preaxial polydactyly and triphalangeal thumbs (see 188740). Eleven of the kindreds investigated were found to be linked to chromosome 7q36, and haplotype analysis showed recombination events with markers D7S550 and D7S2423, reducing the critical region to 1.9 cM. Heus et al. (1999) constructed a detailed physical map of the candidate region for this form of preaxial polydactyly. They used a combination of methods to identify and position 11 transcripts within this map. By recombination analysis on families with preaxial polydactyly, they reduced the candidate region to approximately 450 kb. Mapping to the refined candidate region were the homeobox gene HLXB9 (142994), a putative receptor (LMBR1; 605522), and 2 transcripts of unknown function. All 4 transcripts were analyzed and sequenced in patients with preaxial polydactyly, but no pathogenic mutations were identified. In a Turkish family with triphalangeal thumb-polysyndactyly syndrome, Balci et al. (1999) found linkage of the disorder to 7q36. Dobbs et al. (2000) performed linkage analysis in 2 Iowa kindreds with triphalangeal thumb and found a maximum lod score of 6.23 at marker D7S559 on chromosome 7q36. In a Chinese family segregating triphalangeal thumb-polysyndactyly syndrome, Wang et al. (2007) identified a 1.7-cM candidate region between markers D7S2465 and D7S2423. Molecular Genetics Lettice et al. (2003) showed that chromosome 7q36-associated preaxial polydactyly II results from point mutations in an SHH (600725) regulatory element. SHH, normally expressed in the zone of polarizing activity (ZPA) posteriorly in the limb bud, is expressed in an additional ectopic site at the anterior margin in mouse models of PPD. Lettice et al. (2003) identified an enhancer element that drives normal SHH expression in the ZPA. The regulator, designated ZPA regulatory sequence (ZRS), lies within intron 5 of the LMBR1 gene, 1 Mb from the target gene SHH. The ZRS contained point mutations that segregated with polydactyly in 3 unrelated families with PPD2 (605522.0002, 605522.0004, and 605522.0005) and in 1 family with tibial hypoplasia with polydactyly (see 188740 and 605522.0003) as well as in the Hx mouse mutant. Gurnett et al. (2007) studied 4 families with triphalangeal thumb and preaxial polydactyly, 2 of which were previously reported by Dobbs et al. (2000), and identified 2 mutations in 3 families (605522.0007 and 605522.0008, respectively). At least 1 affected member in each of the 3 families with mutations had preaxial polydactyly in addition to triphalangeal thumb; the affected mother and son in the fourth family had only triphalangeal thumb. A genotype/phenotype correlation was suggested by the 5-generation family, which showed reduced penetrance with 4 unaffected carriers who had affected offspring, and a milder phenotype with 18 of 19 affected members manifesting only triphalangeal thumb. In 9 affected members of a large 4-generation family segregating autosomal dominant triphalangeal thumb-polysyndactyly syndrome, Klopocki et al. (2008) identified heterozygosity for a 589-kb duplication encompassing the ZRS in the LMBR1 gene (605522.0009). The duplication was not found in 6 clinically unaffected family members. In 5 Han Chinese families with triphalangeal thumb-polysyndactyly syndrome (TPT-PS), some of which also had features of syndactyly type IV (186200), Sun et al. (2008) identified heterozygous duplications involving the ZRS, ranging from 131 kb to 398 kb (see, e.g., 605522.0006 and 605522.0010). Using quantitative PCR assays, the authors defined a common overlapping segment of 32,757 bp, which contains the ZRS enhancer. The duplications cosegregated with the limb phenotype in all 5 families and were not found in unaffected family members or in 50 unrelated Han Chinese controls. One of the families with TPT-PS had been previously studied by Wang et al. (2007) and found to have a point mutation (see 605522.0006) in intron 5 of the LMBR1 gene. Sun et al. (2008) suggested that the point mutation might represent a rare polymorphism. Furniss et al. (2008) identified a mutation in the ZRS (295T-C; 605522.0011) in the LMBR1 gene in 3 unrelated probands from southern England with bilateral triphalangeal thumb, 1 of whom also had unilateral preaxial polydactyly. The mutation was found in heterozygous state in all affected individuals except for the mother of 1 proband, who was homozygous for the mutation, and it was also detected in 4 unaffected obligate carriers and 1 unaffected individual at 50% prior risk; it was not found in 381 ethnically matched controls. Analysis of the 3 pedigrees demonstrated a common haplotype at 4 flanking microsatellite loci, indicating a likely founder effect for the 295C allele. Furniss et al. (2008) concluded that 295T-C is a dominant mutation with reduced penetrance and is a common cause of triphalangeal thumb in southern England. In the proband of the Turkish family with triphalangeal thumb-polysyndactyly syndrome mapping to chromosome 7q36 that was originally studied by Balci et al. (1999), Wieczorek et al. (2010) used a qPCR technique for CNV detection and identified a duplication involving the LMBR1 gene, including the ZRS region, that was subsequently detected in 8 affected family members but was not present in unaffected family members or in 35 Turkish controls. The 276-kb duplication was designated arr7q36.3(156,061,302x2,156,088,827-156,354,638x3,156,354,579x2). Wieczorek et al. (2010) stated that because of the complex and repetitive nature of this genomic region, they were unable to determine the exact orientation of the duplication. In affected members of 2 unrelated French families with preaxial polydactyly II, Albuisson et al. (2011) identified 2 different heterozygous mutations in the ZRS region of the LMBR1 gene (297G-A; 605522.0013 and 334T-G; 605522.0014, respectively) that occurred in highly conserved nucleotides within predicted binding sites for the transcription factors SOX9 (608160) and PAX3 (606597), respectively. The mutations were fully penetrant in both families. In mouse, both Sox9 and Pax3 are concomitantly expressed with Shh in the embryonic developing limb bud at the time of digit patterning. Albuisson et al. (2011) suggested that SOX9 and PAX3 may regulate SHH from the ZRS. VanderMeer et al. (2014) studied 2 large unrelated 5-generation Mexican kindreds segregating autosomal dominant triphalangeal thumb and and/or preaxial polydactyly. In the first family, 31 affected individuals had isolated triphalangeal thumb, 14 had preaxial polydactyly with triphalangeal thumbs, and the proband had tibial and radioulnar hypoplasia with preaxial polydactyly of the hands and feet as well as short triphalangeal thumbs. In the second family, 6 affected individuals had isolated triphalangeal thumbs, 2 had preaxial polydactyly, 2 had preaxial polydactyly and triphalangeal thumbs, and 2 had mild radioulnar synostosis. In both families, affected individuals were heterozygous for a point mutation in the ZRS region of LMBR1 (c.402C-T; 605522.0021) except for the more severely affected proband in the first family, who was homozygous for the mutation, suggestive of a dosage effect. Limbs \- Preaxial polydactyly \- Duplication of distal thumb phalanx \- Opposable triphalangeal thumbs \- Duplication of great toes 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	POLYDACTYLY, PREAXIAL II	c1868114	5,315	omim	https://www.omim.org/entry/174500	2019-09-22T16:36:07	{"doid": ["1148"], "mesh": ["C536311", "C536563"], "omim": ["174500"], "icd-10": ["Q74.0"], "orphanet": ["2950", "93336"], "synonyms": ["TRIPHALANGEAL THUMB-POLYDACTYLY SYNDROME", "POLYDACTYLY OF TRIPHALANGEAL THUMB", "Alternative titles", "TPT-PS syndrome"]}
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: "Nonossifying fibroma" – news · newspapers · books · scholar · JSTOR (September 2017) Nonossifying fibroma Other namesFibroxanthoma X-ray of nonossifying fibroma of distal tibia. SpecialtyRheumatology A nonossifying fibroma is a common benign bone tumor in children and adolescents.[1] However, it is controversial whether it represents a true neoplasm or rather a developmental disorder of growing bone. Radiographically, the tumor presents as a well marginated radiolucent lesion, with a distinct multilocular appearance. These foci consist of collagen rich connective tissue, fibroblasts, histiocytes and osteoclasts. They originate from the growth plate, and are located in adjacent parts of the metaphysis and diaphysis of long bones, most often of the legs. No treatment is needed in asymptomatic patients and spontaneous remission with replacement by bone tissue is to be expected. Multiple nonossifying fibromas occur in Jaffe-Campanacci syndrome in combination with cafe-au-lait spots, mental retardation, hypogonadism, ocular and cardiovascular abnormalities. The oldest case of nonossifying fibroma has been identified on the mandible of Qafzeh 9, an early anatomically modern human dated to 90–100 000 yrs B.P.[2] ## Contents * 1 Additional images * 2 See also * 3 References * 4 External links ## Additional images[edit] An ossified non-ossifying fibroma on CT ## See also[edit] * Fibroma * Ossifying fibroma ## References[edit] 1. ^ Bowers, Leah M.; Cohen, Donald M.; Bhattacharyya, Indraneel; Pettigrew, James C.; Stavropoulos, Mary F. (25 September 2012). "The Non-ossifying Fibroma: A Case Report and Review of the Literature". Head and Neck Pathology. 7 (2): 203–210. doi:10.1007/s12105-012-0399-7. ISSN 1936-055X. PMC 3642261. PMID 23008139. 2. ^ Coutinho Nogueira D, Dutour O, Coqueugniot H, Tillier A.-m., (2019) Qafzeh 9 mandible (ca 90–100 kyrs BP, Israel) revisited : μ-CT and 3D reveal new pathological conditions, International Journal of Paleopathology, Vol 26, pp.104-110, https://doi.org/10.1016/j.ijpp.2019.06.002 ## External links[edit] * Media related to Nonossifying fibroma at Wikimedia Commons * Wheeless' Textbook of Orthopaedics: Nonossifying Fibroma Classification D * ICD-10: M89.8 * ICD-9-CM: 733.99 External resources * eMedicine: article/389590 * v * t * e Bone and joint disease Bone Inflammation endocrine: * Osteitis fibrosa cystica * Brown tumor infection: * Osteomyelitis * Sequestrum * Involucrum * Sesamoiditis * Brodie abscess * Periostitis * Vertebral osteomyelitis Metabolic * Bone density * Osteoporosis * Juvenile * Osteopenia * Osteomalacia * Paget's disease of bone * Hypophosphatasia Bone resorption * Osteolysis * Hajdu–Cheney syndrome * Ainhum * Gorham's disease Other * Ischaemia * Avascular necrosis * Osteonecrosis of the jaw * Complex regional pain syndrome * Hypertrophic pulmonary osteoarthropathy * Nonossifying fibroma * Pseudarthrosis * Stress fracture * Fibrous dysplasia * Monostotic * Polyostotic * Skeletal fluorosis * bone cyst * Aneurysmal bone cyst * Hyperostosis * Infantile cortical hyperostosis * Osteosclerosis * Melorheostosis * Pycnodysostosis Joint Chondritis * Relapsing polychondritis Other * Tietze's syndrome Combined Osteochondritis * Osteochondritis dissecans Child leg: * hip * Legg–Calvé–Perthes syndrome * tibia * Osgood–Schlatter disease * Blount's disease * foot * Köhler disease * Sever's disease spine * * Scheuermann's_disease arm: * wrist * Kienböck's disease * elbow * Panner disease This article about a disease of musculoskeletal and connective tissue is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Nonossifying fibroma	c0334067	5,316	wikipedia	https://en.wikipedia.org/wiki/Nonossifying_fibroma	2021-01-18T18:48:29	{"icd-9": ["733.99"], "icd-10": ["M89.8"], "wikidata": ["Q1985123"]}
Linear and whorled nevoid hypermelanosis Other namesLinear nevoid hyperpigmentation SpecialtyMedical genetics Linear and whorled nevoid hypermelanosis (also known as "Linear nevoid hyperpigmentation," "Progressive cribriform and zosteriform hyperpigmentation," "Reticulate and zosteriform hyperpigmentation," "Reticulate hyperpigmentation of Iijima and Naito and Uyeno," "Zebra-like hyperpigmentation in whorls and streaks," and "Zebra-line hyperpigmentation"[1]) is a disorder of pigmentation that develops within a few weeks of birth and progresses for one to two years before stabilizing.[2]:549 There is linear and whorled hyperpigmentation following the lines of Blaschko without preceding bullae or verrucous lesions.[2]:549 It is important to exclude other pigmentary disorders following the Blaschko lines before making a diagnosis of linear and whorled nevoid hypermelanosis. The differential diagnoses include incontinentia pigmenti, linear epidermal nevus, hypomelanosis of Ito and Goltz syndrome. Recently, a case of linear and whorled nevoid hypermelanosis was reported in a Malaysian Chinese girl.[3] ## See also[edit] * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ Bolognia, Jean L.; et al. (2007). Dermatology. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ a b James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. 3. ^ Yap FBB. Linear and whorled nevoid hypermelanosis in a Malaysian Chinese girl. Egyptian Dermatology Online Journal 2008; 4(2). ## External links[edit] Classification D * ICD-10: L81.4 * OMIM: 614323 External resources * Orphanet: 79150 * v * t * e Pigmentation disorders/Dyschromia Hypo-/ leucism Loss of melanocytes Vitiligo * Quadrichrome vitiligo * Vitiligo ponctué Syndromic * Alezzandrini syndrome * Vogt–Koyanagi–Harada syndrome Melanocyte development * Piebaldism * Waardenburg syndrome * Tietz syndrome Loss of melanin/ amelanism Albinism * Oculocutaneous albinism * Ocular albinism Melanosome transfer * Hermansky–Pudlak syndrome * Chédiak–Higashi syndrome * Griscelli syndrome * Elejalde syndrome * Griscelli syndrome type 2 * Griscelli syndrome type 3 Other * Cross syndrome * ABCD syndrome * Albinism–deafness syndrome * Idiopathic guttate hypomelanosis * Phylloid hypomelanosis * Progressive macular hypomelanosis Leukoderma w/o hypomelanosis * Vasospastic macule * Woronoff's ring * Nevus anemicus Ungrouped * Nevus depigmentosus * Postinflammatory hypopigmentation * Pityriasis alba * Vagabond's leukomelanoderma * Yemenite deaf-blind hypopigmentation syndrome * Wende–Bauckus syndrome Hyper- Melanin/ Melanosis/ Melanism Reticulated * Dermatopathia pigmentosa reticularis * Pigmentatio reticularis faciei et colli * Reticulate acropigmentation of Kitamura * Reticular pigmented anomaly of the flexures * Naegeli–Franceschetti–Jadassohn syndrome * Dyskeratosis congenita * X-linked reticulate pigmentary disorder * Galli–Galli disease * Revesz syndrome Diffuse/ circumscribed * Lentigo/Lentiginosis: Lentigo simplex * Liver spot * Centrofacial lentiginosis * Generalized lentiginosis * Inherited patterned lentiginosis in black persons * Ink spot lentigo * Lentigo maligna * Mucosal lentigines * Partial unilateral lentiginosis * PUVA lentigines * Melasma * Erythema dyschromicum perstans * Lichen planus pigmentosus * Café au lait spot * Poikiloderma (Poikiloderma of Civatte * Poikiloderma vasculare atrophicans) * Riehl melanosis Linear * Incontinentia pigmenti * Scratch dermatitis * Shiitake mushroom dermatitis Other/ ungrouped * Acanthosis nigricans * Freckle * Familial progressive hyperpigmentation * Pallister–Killian syndrome * Periorbital hyperpigmentation * Photoleukomelanodermatitis of Kobori * Postinflammatory hyperpigmentation * Transient neonatal pustular melanosis Other pigments Iron * Hemochromatosis * Iron metallic discoloration * Pigmented purpuric dermatosis * Schamberg disease * Majocchi's disease * Gougerot–Blum syndrome * Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis * Lichen aureus * Angioma serpiginosum * Hemosiderin hyperpigmentation Other metals * Argyria * Chrysiasis * Arsenic poisoning * Lead poisoning * Titanium metallic discoloration Other * Carotenosis * Tar melanosis Dyschromia * Dyschromatosis symmetrica hereditaria * Dyschromatosis universalis hereditaria See also * Skin color * Skin whitening * Tanning * Sunless * Tattoo * removal * Depigmentation This Genodermatoses article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Linear and whorled nevoid hypermelanosis	c1304501	5,317	wikipedia	https://en.wikipedia.org/wiki/Linear_and_whorled_nevoid_hypermelanosis	2021-01-18T18:56:09	{"gard": ["11004"], "umls": ["C1304501"], "icd-10": ["L81.4"], "orphanet": ["79150"], "wikidata": ["Q13643669"]}
Polydactyly of a biphalangeal thumb or PPD1 is the most common form of preaxial polydactyly of fingers (see this term), a limb malformation syndrome, that is characterized by the duplication of one or more skeletal components of a biphalangeal thumb. Hands are preferentially affected (in bilateral), and the right hand is more commonly involved than the left. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Polydactyly of a biphalangeal thumb	c1395852	5,318	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93339	2021-01-23T17:04:49	{"gard": ["4417"], "mesh": ["C536332"], "omim": ["174400"], "umls": ["C1395852"], "icd-10": ["Q69.1"], "synonyms": ["PPD1", "Preaxial polydactyly type 1"]}
A number sign (#) is used with this entry because congenital generalized lipodystrophy type 4 (CGL4) is caused by homozygous or compound heterozygous mutation in the PTRF gene (603198) on chromosome 17q21. Description Congenital generalized lipodystrophy type 4 combines the phenotype of classic Berardinelli-Seip lipodystrophy (608594) with muscular dystrophy and cardiac conduction anomalies (Hayashi et al., 2009). For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594). Clinical Features Rajab et al. (2002) described 10 patients from Oman who had congenital generalized lipodystrophy as well as striking abnormalities in both skeletal and nonskeletal muscle, including reduced exercise tolerance and percussion myoedema. Ghanem (1993) had described percussion myoedema in Berardinelli-Seip lipodystrophy. None of the children reported by Rajab et al. (2002) had insulin resistance or early endocrine abnormalities. All 10 had had hypertrophic pyloric stenosis operated on in the first 6 weeks of life. The veins were very prominent (phlebomegaly) in the skin and cutis marmorata was present. Cardiac abnormalities with cardiac hypertrophy and arrhythmias were features later in childhood, including a history of sudden death in some of the sibs. Rajab et al. (2002) suggested that this group may represent a new clinical syndrome with lipodystrophy at a novel locus. In a follow-up report of these patients, Rajab et al. (2010) emphasized that 1 had multiple cardiac conduction defects, including ventricular and supraventricular tachycardia, bradycardia, and features of long QT syndrome. In addition to skeletal muscle involvement manifest as exercise intolerance and percussion-induced rapid contractions, there was also evidence of smooth muscle involvement, including hypertrophic pyloric stenosis and esophageal dysmotility. There was also spinal rigidity, hyperlordosis, osteopenia, delayed bone age, and recurrent bacterial infections. Rajab et al. (2010) reported a 12-year-old girl from the U.K. who had a similar phenotype. Her parents were related as first cousins. She had neonatal hypotonia, increased serum creatine kinase, lack of subcutaneous fat, and pronounced muscle bulk. She later developed proximal muscle weakness, muscle stiffness, and exercise-induced myalgia, as well as rippling muscles. Other features included massive smooth muscle hypertrophy, frequent infections, atlantoaxial instability, osteoporosis, hepatomegaly with elevated transaminases, insulin resistance, and elevated triglycerides. She died at age 13 years from sudden cardiac death due to ventricular fibrillation. Skeletal muscle biopsy showed absent PTRF immunostaining; adipose cells showed lack of caveolin-1 (CAV1; 601253) expression; and fibroblasts showed a severe reduction of caveolae. Simha et al. (2008) reported 2 sibs, born of nonconsanguineous Mexican parents, with CGL and no mutations in known lipodystrophy genes. Clinical features included generalized loss of subcutaneous fat from birth, acanthosis nigricans, acromegaloid habitus, umbilical prominence, hepatosplenomegaly, and hypoleptinemia. One sib had insulin resistance. Features unusual for congenital lipodystrophy included preservation of bone marrow fat, generalized muscle weakness associated with increased serum creatine kinase, and atlantoaxial dislocation requiring surgical intervention. Simha et al. (2008) concluded that the disorder represented a novel subtype of CGL. Rajab et al. (2010) suggested that the family reported by Simha et al. (2008) may have had this form of CGL. Shastry et al. (2010) reported follow-up of the sibs reported by Simha et al. (2008), who were 14 and 8 years old, respectively. The sister had developed worsening hypertension and ventricular tachycardia resembling catecholaminergic polymorphic ventricular tachycardia (CPVT). She also had increased hepatic fat. The brother had learning disabilities and a complex tachycardia resembling polymorphic ventricular tachycardia. Neither had evidence of QT prolongation, and both had percussion-induced muscle mounding. The carrier parents had slightly high serum triglycerides, although neither had lipodystrophy. Hayashi et al. (2009) reported 5 unrelated Japanese patients with CGL4 and muscular dystrophy. All had generalized loss of subcutaneous adipose tissue in several areas, including the face, from infancy or early childhood. Two patients had distal muscle weakness, 1 had generalized muscle weakness, and all 3 had muscle hypertrophy and percussion-induced muscle mounding. One patient had myalgia and muscle stiffness. One patient had cardiac arrhythmia, and another had atrial fibrillation, but 3 had no cardiac abnormalities. Skeletal anomalies included lordosis in 1, contractures in 2, and scoliosis in 2. None had intellectual deficit or acanthosis nigricans. Variable features included hepatosplenomegaly, fatty liver, acromegaloid features, and advanced bone age. Laboratory studies showed moderate fasting hyperinsulinemia in 2 patients and increased triglycerides in 2. All had moderately increased serum creatine kinase. Skeletal muscle biopsy showed chronic dystrophic changes with marked variation in muscle fiber size, internalized nuclei, a few necrotic and regenerating fibers, and increased interstitial fibrosis. Caveolin-3 (CAV3; 601253) immunoreactivity was greatly reduced in the sarcolemma, but cytoplasmic staining was remarkably increased, a pattern similar to that seen in the patients with muscular dystrophy caused by CAV3 mutations (see, e.g., RMD2, 606072). Shastry et al. (2010) reported a Mexican brother and sister with CGL4, who were 11 years and 16 months old, respectively, at the time of the report. Both had pyloric stenosis in infancy and then developed loss of subcutaneous fat from the face and extremities. Other features included umbilical prominence with protuberant abdomen, hepatomegaly, painless muscle mounding, and systolic murmur, but no arrhythmias or prolonged QT interval. Laboratory studies showed hypertriglyceridemia and increased serum creatine kinase. The brother had postprandial hyperinsulinemia, restricted joint movement, muscle weakness, and atlantoaxial instability. The sister showed mild developmental delay. The carrier parents showed some metabolic abnormalities, including increased serum triglycerides and insulin intolerance, although neither had lipodystrophy. Molecular Genetics In 4 unrelated Japanese patients with congenital generalized lipodystrophy type 4 and muscular dystrophy, Hayashi et al. (2009) identified a homozygous truncating mutation in exon 2 of the PTRF gene (696insC; 603198.0001). A fifth Japanese patient was compound heterozygous for the 696insC mutation and another truncating mutation (525delG; 603198.0002). In 10 patients from Oman with lipodystrophy, muscular dystrophy, and cardiac conduction defects reported by Rajab et al. (2002), Rajab et al. (2010) identified a homozygous truncating mutation in the PTRF gene (160delG; 603198.0003), resulting in complete loss of protein function. A girl from the U.K. with a similar phenotype was homozygous for another truncating mutation (362dupT; 603198.0004). Rajab et al. (2010) noted that the symptoms of the patients combine the features in individuals with CAV1 mutations, such as those in CGL3 (612526), and features in individuals with CAV3 mutations, such as those in rippling muscle disease (RMD2; 606072), since the PTRF gene product in essential for caveolae biogenesis. PTRF is expressed in many tissues, but highest mRNA levels are found in adipocytes, smooth muscle, skeletal muscle, heart, and osteoblasts, consistent with the tissues affected in patients with CGL4. The nervous system is spared. In 3 patients, including 2 sibs, with CGL4, Shastry et al. (2010) identified 2 different homozygous truncating mutations in the PTRF gene (603198.0005-603198.0006). In addition, the affected sibs reported by Simha et al. (2008) were found to be compound heterozygous for 2 truncating PTRF mutations (603198.0007 and 603198.0008). Animal Model Liu et al. (2008) found that Ptrf-knockout mice were viable and of normal weight, but had a metabolic phenotype of significantly reduced adipose tissue mass, higher circulating triglyceride levels, glucose intolerance, and hyperinsulinemia, consistent with a lipodystrophy. Cells from various tissues of Ptrf-knockout mice, including lung epithelium, intestinal smooth muscle, skeletal muscle, and endothelial cells showed no detectable caveolae cells. These cells also had markedly decreased expression of all 3 caveolin isoforms, although some tissues showed increased mRNA, a possible compensatory response. The findings indicated that cavin, which is encoded by the PTRF gene, is required for the formation and/or stabilization of morphologically defined caveolae. Liu et al. (2008) suggested that the absence of cavin impairs the ability of adipocyte to store triglycerides, which in turn leads an increase in circulating lipids, glucose intolerance, and insulin resistance. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive CARDIOVASCULAR Heart \- Long QT syndrome \- Atrial fibrillation \- Arrhythmia \- Tachycardia \- Bradycardia ABDOMEN External Features \- Protruding abdomen \- Prominent umbilicus Liver \- Hepatomegaly \- Fatty liver Spleen \- Splenomegaly Gastrointestinal \- Poor feeding \- Dysphagia \- Constipation \- Ileus \- Esophageal dilatation \- Esophageal dysmotility \- Hypertrophic pyloric stenosis \- Smooth muscle hypertrophy in the gastrointestinal tract SKELETAL \- Joint contractures \- Osteopenia \- Osteoporosis Spine \- Spinal rigidity \- Hyperlordosis \- Scoliosis \- Atlanto-axial instability SKIN, NAILS, & HAIR Hair \- Acanthosis nigricans \- Hirsutism (less common) MUSCLE, SOFT TISSUES \- Muscle weakness, proximal \- Muscle weakness, generalized \- Exercise intolerance \- Percussion-induced muscle mounding (muscle rippling) \- Muscle hypertrophy \- Prominent muscular appearance \- Myalgia \- Muscle stiffness \- Muscle biopsy shows dystrophic changes \- Decreased sarcolemmal immunostaining for PTRF \- Secondary loss of sarcolemmal caveolin-3 \- Decreased caveolae in muscle tissue \- Loss of subcutaneous fat, generalized ENDOCRINE FEATURES \- Hyperinsulinemia \- Insulin resistance \- Acromegaloid features \- Decreased growth hormone secretion (1 patient) IMMUNOLOGY \- Transient IgA deficiency (1 patient) \- Recurrent infections \- Defective humoral immunity LABORATORY ABNORMALITIES \- Increased serum creatine kinase \- Increased serum triglycerides \- Abnormal liver enzymes MISCELLANEOUS \- Onset in infancy or early childhood \- Sudden death due to cardiac arrhythmia may occur MOLECULAR BASIS \- Caused by mutation in the RNA polymerase I and transcript release factor gene (PTRF, 603198.0001 ) ▲ 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	LIPODYSTROPHY, CONGENITAL GENERALIZED, TYPE 4	c0221032	5,319	omim	https://www.omim.org/entry/613327	2019-09-22T15:59:03	{"doid": ["0111138"], "mesh": ["D052497"], "omim": ["613327"], "orphanet": ["528", "228429"], "synonyms": ["Alternative titles", "BERARDINELLI-SEIP CONGENITAL LIPODYSTROPHY, TYPE 4, WITH MUSCULAR DYSTROPHY", "LIPODYSTROPHY, BERARDINELLI-SEIP CONGENITAL, TYPE 4, WITH MUSCULAR DYSTROPHY"]}
A very rare syndrome characterized by extreme microcephaly and early death, within the first year. ## Epidemiology It has been described only in the Old Order Amish of Lancaster County Pennsylvania. In this population, birth prevalence is about 1/500. ## Clinical description Microcephaly is a microcephalia vera (MV), evident at birth or through 22-week fetal ultrasound. Affected children have high urinary levels of alpha-ketoglutaric acid. ## Etiology All affected infants are homozygous for the same mutation of the SLC25A19 gene on chromosome 17 (17q25.3). ## Genetic counseling The condition follows an autosomal recessive pattern of inheritance. ## Prognosis Prognosis is very poor: the average life span of affected infants is between five and six months. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Amish lethal microcephaly	c1846648	5,320	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99742	2021-01-23T17:43:15	{"gard": ["8606"], "mesh": ["C538247"], "omim": ["607196"], "umls": ["C1846648"], "icd-10": ["Q02"]}
Pseudallescheriasis is a fungal infection caused by Pseudallescheria species, such as Pseudallescheria boydii.[1] ## See also[edit] * Scedosporiosis ## References[edit] 1. ^ Pseudallescheria / Scedosporium: emerging therapy-refractory opportunists in humans This infectious disease article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Pseudallescheriasis	None	5,321	wikipedia	https://en.wikipedia.org/wiki/Pseudallescheriasis	2021-01-18T18:47:12	{"wikidata": ["Q25100293"]}
A number sign (#) is used with this entry because of evidence that susceptibility to obesity is conferred by homozygous variation in the ADCY3 gene (600291) on chromosome 2p23. For a phenotypic description and a discussion of genetic heterogeneity of body mass index (BMI), see 606641. Description Patients with biallelic mutations in the ADCY3 gene show hyperphagia within the first 2 years of life and develop severe obesity. Other features include hyposmia or anosmia, and some patients exhibit mild to moderate intellectual disability (Saeed et al., 2018). Clinical Features Saeed et al. (2018) reported 4 children with severe early-onset obesity from 3 consanguineous Pakistani families, as well as an obese boy from a European American family. Hyperphagia in the probands was first reported between 6 months and 2 years of age. Other features included anosmia in 3 patients and hyposmia in 2, and 2 probands exhibited mild to moderate intellectual disability. In addition, the oldest patient, a 15-year-old Pakistani girl, had undergone menarche at age 14 years but had no subsequent menstrual cycles; she also exhibited hyperlipidemia and insulin resistance. No dysmorphic features were observed in the patients. Family members were all normal weight, except for the parents of 1 of the Pakistani patients (family 2), who were upper-middle class and accustomed to fat- and carbohydrate-enriched food. Molecular Genetics Stergiakouli et al. (2014) performed genomewide association studies involving BMI and height-adjusted BMI ('BMI[x]') in a British and a Dutch cohort of children (ALSPAC and Generation R, respectively). A missense SNP in the ADCY3 gene (rs11676272) showed evidence of genomewide significance in the ASPAC cohort (p = 4 x 10(-9)), but only when height was adjusted for, and this association was replicated in the Generation R cohort (p = 0.0001). Analysis of ADCY3 expression in lymphoblastoid cell lines showed a strong association between the rare (adiposity-increasing) G allele at rs11676272 and reduced levels of ADCY3 expression (p = 1 x 10(-53)). The authors concluded that rs11676272 represents a functional polymorphism in ADCY3 that is associated with fat mass in childhood, and noted that the effect size is comparable to common variation at the FTO locus (610966), but only when height is correctly taken into account. Saeed et al. (2018) characterized the rs11676272 (S107P) variant in BHK cells, and observed that the mutant showed catalytic activity comparable to that of wildtype ADCY3. Grarup et al. (2018) identified a splice site variant in the ADCY3 gene (600291.0001) with a minor allele frequency of 2.3% in a Greenlandic study population of 4,038 individuals. The 7 homozygous carriers had BMIs, body fat percentages, and waist circumferences that were all significantly greater than those of the remaining study population, and an association with type 2 diabetes (T2D) was found that remained significant after adjustment for BMI. Homozygous carriers showed severely decreased RNA expression, whereas heterozygotes had an intermediate expression level. In addition, analysis of exome-sequencing data from 18,176 samples from the Accelerating Medicines Partnership Type 2 Diabetes Knowledge Portal (AMP-T2D) database identified heterozygosity for 7 predicted loss-of-function variants in ADCY3 in 8 individuals, and there was enrichment of carriers of ADCY3 variants among T2D cases compared to nondiabetic controls (odds ratio, 8.6; p = 0.044). In 138 probands with severe early-onset obesity from consanguineous Pakistani families, Saeed et al. (2018) performed whole-exome sequencing, and in 4 severely obese children from 3 families, they identified homozygous mutations in the ADCY3 gene (see, e.g., 600291.0002 and 600291.0003). Independent whole-exome sequencing in an obese boy from a nonconsanguineous European American family revealed compound heterozygosity for mutations in ADCY3 (600291.0004 and 600291.0005). All mutations occurred at highly conserved sites, and all segregated with disease in the respective families. INHERITANCE \- Autosomal recessive GROWTH Weight \- Obesity, early-onset HEAD & NECK Nose \- Hyposmia \- Anosmia ABDOMEN Gastrointestinal \- Hyperphagia, early-onset NEUROLOGIC Central Nervous System \- Intellectual disability, mild to moderate (in some patients) Behavioral Psychiatric Manifestations \- Hyperphagia, early-onset ENDOCRINE FEATURES \- Elevated insulin levels \- Insulin resistance \- Elevated leptin levels \- Elevated cortisol levels LABORATORY ABNORMALITIES \- Hyperlipidemia MISCELLANEOUS \- Onset of hyperphagia reported between 6 months and 2 years of age \- The oldest reported patient underwent menarche at age 14 years but had no subsequent menstrual cycles MOLECULAR BASIS \- Caused by mutation in the adenylate cyclase 3 gene (ADCY3, 600291.0001 ) ▲ 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	BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 19	c4693522	5,322	omim	https://www.omim.org/entry/617885	2019-09-22T15:44:29	{"omim": ["617885"], "synonyms": ["Alternative titles", "OBESITY, SUSCEPTIBILITY TO"]}
A number sign (#) is used with this entry because of evidence that cranioectodermal dysplasia-2 (CED2) is caused by compound heterozygous mutation in the WDR35 gene (613602) on chromosome 2p24. Description Cranioectodermal dysplasia (CED), also known as Sensenbrenner syndrome, is a rare autosomal recessive heterogeneous ciliopathy that is primarily characterized by skeletal abnormalities, including craniosynostosis, narrow rib cage, short limbs, and brachydactyly, and ectodermal defects. Nephronophthisis leading to progressive renal failure, hepatic fibrosis, heart defects, and retinitis pigmentosa have also been described (summary by Arts et al., 2011). For a discussion of genetic heterogeneity of cranioectodermal dysplasia, see CED1 (218330). Clinical Features Gilissen et al. (2010) reported 2 unrelated Dutch boys with a similar phenotype that was reminiscent of Sensenbrenner syndrome. Both had short stature (less than 2.5 SD below the average), dolichocephaly, craniosynostosis, narrow thorax with pectus excavatum, short limbs, and brachydactyly. Facial features included narrow palpebral fissures, telecanthus with hypertelorism, low-set simple ears, everted lower lip, and short neck. Teeth abnormalities included widely spaced, hypoplastic, and fused teeth. Both had joint laxity, inguinal hernia, and webbed fingers. There was no evidence of renal or hepatic disease, and both had normal intelligence. Bacino et al. (2012) studied a Mexican family in which 4 sibs exhibited features that were characteristic of Sensenbrenner syndrome but also overlapped those of short-rib polydactyly syndromes (see SRTD7, 614091). Findings included cystic hygroma, dolichocephaly (associated with sagittal synostosis in 1 sib), prominent or tall forehead, low-set simple ears, high-arched or cleft palate, short stature, narrow thorax with short ribs, brachydactyly, polydactyly, hepatomegaly, renal and cardiac anomalies, and developmental delay. One sib was alive at 4 years of age, 2 of the sibs died at 9 months and 13 months of age, and an affected fetus was terminated at 21 weeks' gestation. Lin et al. (2013) studied an 8-month-old boy with multisutural craniosynostoses resulting in a small 'cloverleaf' cranium, bitemporal narrowing, tall forehead, and posteriorly displaced anterior fontanel. Head CT showed closure of the metopic, left coronal, and sagittal sutures, and partial closure of the left lambdoid suture. Facial dysmorphic features included markedly upslanting and large palpebral fissures, epicanthal folds, flat nasal bridge, upturned nares, and long smooth philtrum. Scalp hair, eyebrows, and eyelashes were sparse. Neck skin was redundant, limbs were short, and fingers were short and broad. Smith et al. (2016) described a 15-year-old boy from a consanguineous Pakistani family who exhibited a relatively mild skeletal ciliopathy, presenting at age 10 years for evaluation of short stature, renal cysts, and dental anomalies. He had multiple missing permanent teeth, chronic renal failure, and hypertension; other features included narrow chest, short ribs, brachydactyly, and abnormal echogenicity of the liver. Walczak-Sztulpa et al. (2017) reported 2 Polish sisters with Sensenbrenner syndrome. The proband was 9 years old, and her older sister had died at age 4 months of respiratory, hepatic, and renal insufficiency. Dysmorphic features included short stature with rhizomelic shortening of limbs, short fingers, preaxial polydactyly of the left hand, narrow chest, craniosynostosis with dolichocephaly, high anterior hairline, epicanthal folds and telecanthus, depressed nasal bridge, and low-set ears. Ectodermal abnormalities included joint and skin laxity, slow-growing fine sparse hair, and small, abnormally shaped, and widely spaced teeth. The proband presented with chronic tubulointerstitial renal disease, with abnormal echogenicity on renal ultrasound, reduced glomerular filtration, proteinuria, and prehypertension; the authors designated the renal disease as nephronophthisis. Molecular Genetics By exome sequencing in 2 unrelated Dutch boys with cranioectodermal dysplasia, Gilissen et al. (2010) identified compound heterozygous mutations in the WDR35 gene (613602.0001-613602.0004). Gilissen et al. (2010) postulated that the WDR35 mutations resulted in ciliary dysfunction due to disrupted intraflagellar transport. Using exome capture in a 4-year-old Mexican boy with CED, Bacino et al. (2012) identified homozygosity for a missense mutation in the WDR35 gene (L520P; 613602.0008). The unaffected parents and 2 unaffected sibs were heterozygous for the mutation, which was not found in public variant databases. DNA was unavailable from 3 more affected sibs in the family, including 2 who died at 9 months and 13 months, and an affected fetus terminated at 21 weeks' gestation. In an 8-month-old boy with CED and multisutural craniosynostoses, who was negative for mutation in the IFT122 gene (606045), Lin et al. (2013) performed whole-exome sequencing and identified compound heterozygosity for missense mutations in the WDR35 gene, H1031Y (613602.0009) and Y1068C (613602.0010). In a 15-year-old Pakistani boy with skeletal ciliopathy, Smith et al. (2016) performed autozygosity mapping and candidate gene sequencing, and identified homozygosity for a missense mutation in the WDR35 gene (W1153C; 613602.0012). His fourth-cousin parents were each heterozygous for the mutation, which was not found in public variant databases. The authors stated that the mutation was the most distal yet reported, noting that it corresponded to a relatively mild phenotype in this patient. In a 9-year-old Polish girl with Sensenbrenner syndrome, Walczak-Sztulpa et al. (2017) sequenced the candidate genes IFT122 and WDR35 and identified compound heterozygosity for mutations in the WDR35 gene: L641X (613602.0015) and D841V(613602.0016). The authors noted that this family exhibited intrafamilial variability, in that the proband's affected older sister had more severe expression of the phenotype and had died in infancy. Pathogenesis Arts et al. (2011) observed similar ciliary defects in fibroblasts from 1 of the CED2 patients with mutations in WDR35 reported by Gilissen et al. (2010) and from a patient with CED3 (614099) and mutation in the IFT43 gene (614068.0001): both showed accumulation of IFTB-complex proteins in the distal part of the ciliary axoneme and in the ciliary tip, whereas in the cilia of control fibroblasts, those proteins were less abundant and primarily located at the basal body and transition zone. Arts et al. (2011) concluded that CED results from defects in retrograde intraflagellar transport. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Dolichocephaly \- Plagiocephaly Face \- Frontal bossing \- Tall forehead \- Bitemporal narrowing \- Midface hypoplasia \- Full cheeks \- Long smooth philtrum \- Broad philtrum \- Micrognathia \- Retrognathia Ears \- Low-set ears \- Simple ears Eyes \- Telecanthus \- Narrow palpebral fissures \- Hypertelorism \- Sparse eyebrows \- Sparse eyelashes \- Narrow palpebral fissures \- Upslanting palpebral fissures \- Epicanthal folds \- Telecanthus \- Hypertelorism Nose \- Broad nasal bridge \- Depressed nasal bridge Mouth \- Everted lower lip \- High-arched palate \- Cleft palate (in some patients) Teeth \- Small teeth \- Widely spaced teeth \- Dental fusion \- Missing multiple permanent teeth Neck \- Short neck \- Cystic hygroma CARDIOVASCULAR Heart \- Patent foramen ovale \- Patent ductus arteriosus \- Atrial septal defect \- Small aortic isthmus \- Left ventricular hypertrophy \- Right atrioventricular dilation Vascular \- Hypertension CHEST External Features \- Narrow chest Ribs Sternum Clavicles & Scapulae \- Pectus excavatum Short ribs \- Horizontal ribs ABDOMEN External Features \- Inguinal hernia, bilateral Liver \- Hepatomegaly \- Acute cholangitis \- Cholestasis \- Extensive bile duct proliferation \- Hypoplasia of intrahepatic bile ducts \- Portal fibrosis \- Biliary cirrhosis \- Abnormal echogenicity \- Abnormal liver function tests \- Hyperbilirubinemia, conjugated Spleen \- Accessory spleens \- Splenomegaly GENITOURINARY Kidneys \- Renal tubular acidosis, type 1 distal \- Renal failure \- Increased cortical echogenicity \- Renal cysts SKELETAL \- Joint laxity Skull \- Craniosynostosis \- Sagittal synostosis \- Metopic synostosis \- Coronal synostosis, unilateral \- Lambdoid synostosis, unilateral \- Cloverleaf skull Limbs \- Rhizomelic limb shortening \- Mesomelic limb shortening Hands \- Brachydactyly \- Polydactyly \- Clinodactyly \- Syndactyly Feet \- Brachydactyly \- Polydactyly, postaxial \- Syndactyly SKIN, NAILS, & HAIR Hair \- Sparse eyebrows \- Sparse eyelashes \- Sparse hair \- Skin laxity MUSCLE, SOFT TISSUES \- Inguinal hernia NEUROLOGIC Central Nervous System \- Developmental delay (in some patients) PRENATAL MANIFESTATIONS Amniotic Fluid \- Hydrops fetalis \- Polyhydramnios MOLECULAR BASIS \- Caused by mutation in the WD repeat-containing protein 35 gene (WDR35, 613602.0001 ) ▲ 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	CRANIOECTODERMAL DYSPLASIA 2	c0432235	5,323	omim	https://www.omim.org/entry/613610	2019-09-22T15:58:07	{"doid": ["0050577"], "mesh": ["C562966"], "omim": ["613610"], "orphanet": ["1515"], "genereviews": ["NBK154653"]}
A number sign (#) is used with this entry because of evidence that Webb-Dattani syndrome (WEDAS) is caused by homozygous mutation in the ARNT2 gene (606036) on chromosome 15q25. One such family has been reported. Description Webb-Dattani syndrome is an autosomal recessive disorder characterized by frontotemporal hypoplasia, globally delayed development, and pituitary and hypothalamic insufficiency due to hypoplastic development of these brain regions. Patients present soon after birth with multiple pituitary hormonal deficiencies and subsequently develop microcephaly, seizures, and spasticity. Other features include postretinal blindness and renal abnormalities (summary by Webb et al., 2013). Clinical Features Webb et al. (2013) reported 6 children from a highly consanguineous Saudi Arabian kindred with a congenital brain malformation syndrome and other abnormalities. Features that became apparent in the first month of life included hypernatremia due to diabetes insipidus, central hypothyroidism due to thyroid-stimulating hormone deficiency, growth failure due to growth hormone deficiency, and adrenocorticotropic deficiency. None of the patients had hypoglycemia. Brain MRI showed an abnormal hypothalamo-pituitary axis with absent posterior pituitary bright spot, thin pituitary stalk, and hypoplastic anterior pituitary gland. The frontal and temporal lobes were hypoplastic, with a thin corpus callosum and global delay in brain myelination, particularly in the motor and occipital cortices. All children developed secondary microcephaly, severe global developmental delay, and seizures within the first year of life. Patients had total body spastic cerebral palsy, with abnormal hip posture and hip dislocation in 4. In addition, all patients showed no clinical response to light, with minimal pupil responses. Funduscopic and retinal examinations were normal, but 2 children showed evidence of postretinal pathway dysfunction. Other features included severe gastroesophageal reflux, hydronephrosis, vesicoureteral reflux, and a neurogenic bladder. Renal glomerular function was normal. All affected individuals had dysmorphic features, including prominent forehead, deep-set eyes, well-grooved philtrum, and retrognathia. Three patients died before 5 years of age. There was a history of multiple miscarriages in 1 branch of the family, suggestive of a degree of prenatal lethality. Inheritance The transmission pattern of Webb-Dattani syndrome in the family reported by Webb et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 6 children, born of consanguineous Saudi Arabian parents, with Webb-Dattani syndrome, Webb et al. (2013) identified a homozygous truncating mutation in the ARNT2 gene (606036.0001). The mutation was found by a combination of homozygosity mapping and whole-exome sequencing. Analysis of patient cells indicated that the mutation resulted in nonsense-mediated mRNA and complete loss of ARNT2 function. INHERITANCE \- Autosomal recessive GROWTH Height \- Poor linear growth HEAD & NECK Head \- Microcephaly, postnatal (up to -6.4 SD) Face \- Prominent forehead \- Well-grooved philtrum \- Retrognathia Eyes \- Deep-set eyes \- Blindness, postretinal ABDOMEN Gastrointestinal \- Gastroesophageal reflux GENITOURINARY External Genitalia (Male) \- Cryptorchidism Kidneys \- Hydronephrosis \- Vesicoureteral reflux Bladder \- Neurogenic bladder SKELETAL Pelvis \- Hip dislocation NEUROLOGIC Central Nervous System \- Global developmental delay, severe \- Seizures \- Spasticity \- Abnormal hypothalamo-pituitary axis \- Absent posterior pituitary bright spot \- Thin pituitary stalk \- Hypoplastic anterior pituitary gland \- Thin corpus callosum \- Frontotemporal hypoplasia \- Delayed myelination ENDOCRINE FEATURES \- Pituitary insufficiency \- Hypothalamic insufficiency \- Growth hormone deficiency \- Adrenocorticotropin deficiency \- Cortisol insufficiency \- Thyroid stimulating hormone deficiency \- Hypernatremia \- Diabetes insipidus \- Hypothyroidism, central LABORATORY ABNORMALITIES \- Hypernatremia MISCELLANEOUS \- Onset soon after birth \- One consanguineous Saudi Arabian family has been reported (last curated August 2014) MOLECULAR BASIS \- Caused by mutation in the aryl hydrocarbon receptor nuclear translocator-2 gene (ARNT2, 606036.0001 ) ▲ 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	WEBB-DATTANI SYNDROME	c4014708	5,324	omim	https://www.omim.org/entry/615926	2019-09-22T15:50:32	{"omim": ["615926"], "orphanet": ["370006"], "synonyms": ["Alternative titles", "HYPOTHALAMO-PITUITARY-FRONTOTEMPORAL HYPOPLASIA WITH VISUAL AND RENAL ANOMALIES"]}
Dissociative disorder For the New York City-based publisher, see Fugue State Press. Fugue state Other namesFugue state, psychogenic fugue SpecialtyPsychiatry Dissociative fugue, formerly fugue state or psychogenic fugue, is a dissociative disorder[1] and a rare psychiatric disorder characterized by reversible amnesia for personal identity, including the memories, personality, and other identifying characteristics of individuality. The state can last days, months or longer. Dissociative fugue usually involves unplanned travel or wandering and is sometimes accompanied by the establishment of a new identity. It is a facet of dissociative amnesia, according to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). After recovery from a fugue state, previous memories usually return intact, and further treatment is unnecessary. Additionally, an episode of fugue is not characterized as attributable to a psychiatric disorder if it can be related to the ingestion of psychotropic substances, to physical trauma, to a general medical condition, or to dissociative identity disorder,[clarification needed] delirium, or dementia.[2] Fugues are precipitated by a series of long-term traumatic episodes. It is most commonly associated with childhood victims of sexual abuse who learn over time to dissociate memory of the abuse (dissociative amnesia). ## Contents * 1 Signs and symptoms * 2 Diagnosis * 2.1 Definition * 3 Prognosis * 4 Cases * 5 See also * 6 References * 7 External links ## Signs and symptoms[edit] Symptoms of a dissociative fugue include mild confusion and once the fugue ends, possible depression, grief, shame, and discomfort. People have also experienced a post-fugue anger.[3] Another symptom of the fugue state can consist of loss of one's identity.[4] ## Diagnosis[edit] A doctor may suspect dissociative fugue when people seem confused about their identity or are puzzled about their past or when confrontations challenge their new identity or absence of one. The doctor reviews symptoms and does a physical examination to exclude physical disorders that may contribute to or cause memory loss. Sometimes dissociative fugue cannot be diagnosed until people return to their pre-fugue identity and are distressed to find themselves in unfamiliar circumstances, sometimes with awareness of "lost time". The diagnosis is usually made retroactively when a doctor reviews the history and collects information that documents the circumstances before people left home, the travel itself, and the establishment of an alternative life. Functional amnesia can also be situation-specific, varying from all forms and variations of traumas or generally violent experiences, with the person experiencing severe memory loss for a particular trauma. Committing homicide; experiencing or committing a violent crime such as rape or torture; experiencing combat violence; attempting suicide; and being in automobile accidents and natural disasters have all induced cases of situation-specific amnesia (Arrigo & Pezdek, 1997; Kopelman, 2002a). As Kopelman (2002a) notes, however, care must be exercised in interpreting cases of psychogenic amnesia when there are compelling motives to feign memory deficits for legal or financial reasons. However, although some fraction of psychogenic amnesia cases can be explained in this fashion, it is generally acknowledged that true cases are not uncommon. Both global and situationally-specific amnesia are often distinguished from the organic amnesic syndrome, in that the capacity to store new memories and experiences remains intact. Given the very delicate and oftentimes dramatic nature of memory loss in such cases, there usually is a concerted effort to help the person recover their identity and history. This will allow the subject to be recovered sometimes spontaneously when particular cures are encountered. ### Definition[edit] The cause of the fugue state is related to dissociative amnesia, (Code 300.12 of the DSM-IV codes[5]) which has several other subtypes:[6] selective amnesia, generalised amnesia, continuous amnesia, and systematised amnesia, in addition to the subtype "dissociative fugue".[1] Unlike retrograde amnesia (which is popularly referred to simply as "amnesia", the state where someone forgets events before brain damage), dissociative amnesia is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, DSM-IV Codes 291.1 & 292.83) or a neurological or other general medical condition (e.g., amnestic disorder due to a head trauma, DSM-IV Code 294.0).[7] It is a complex neuropsychological process.[8] As the person experiencing a dissociative fugue may have recently suffered the reappearance of an event or person representing an earlier life trauma, the emergence of an armoring or defensive personality seems to be for some, a logical apprehension of the situation.[citation needed] Therefore, the terminology "fugue state" may carry a slight linguistic distinction from "dissociative fugue", the former implying a greater degree of "motion".[citation needed] For the purposes of this article, then, a "fugue state" occurs while one is "acting out" a "dissociative fugue". The DSM-IV [1] defines "dissociative fugue" as: * sudden, unexpected travel away from home or one's customary place of work, with inability to recall one's past * confusion about personal identity, or the assumption of a new identity * significant distress or impairment The Merck Manual [9] defines "dissociative fugue" as: One or more episodes of amnesia in which the inability to recall some or all of one's past and either the loss of one's identity or the formation of a new identity occur with sudden, unexpected, purposeful travel away from home. In support of this definition, the Merck Manual [9] further defines dissociative amnesia as: An inability to recall important personal information, usually of a traumatic or stressful nature, that is too extensive to be explained by normal forgetfulness. ## Prognosis[edit] The DSM-IV-TR states that the fugue may have a duration from days to months, and recovery is usually rapid. However, some cases may be refractory. An individual usually has only one episode. ## Cases[edit] * Shirley Ardell Mason (1923 — 1998), also known as "Sybil", would disappear and then reappear with no recollection of what happened during the time span. She recalled "being here and then not here" and having no identity of herself; it was claimed by her psychiatrist, Cornelia Wilbur, that she also had dissociative identity disorder. Wilbur's diagnosis of DID was disputed by Wilbur's contemporary Herbert Spiegel. * Jody Roberts, a reporter for the Tacoma News Tribune, disappeared in 1985, only to be found 12 years later in Sitka, Alaska, living under the name of "Jane Dee Williams". While there were some initial suspicions that she had been faking amnesia, some experts have come to believe that she genuinely experienced a protracted fugue state.[10] * David Fitzpatrick, who had dissociative fugue disorder, was profiled in the UK on Five's television series Extraordinary People. He entered a fugue state on December 4, 2005, and is still working on regaining his entire life's memories.[11] * Hannah Upp, a teacher originally from Salem, Oregon,[12] was given a diagnosis of dissociative fugue[13] after she had disappeared from her New York home in August 2008 and was rescued from the New York Harbor 20 days later. News coverage at the time focused on her refusal to speak to detectives right after she was found [12] and that she was seen checking her email at Apple Stores while she was missing.[14][15][16] This coverage has since led to criticism of the often "condemning and discrediting"[13] attitude toward dissociative conditions. On September 3, 2013, she went into another fugue, disappearing from her new job as a teacher's assistant [17] at Crossway Community Montessori in Kensington, Maryland. She was found unharmed September 5, 2013, in Wheaton, Maryland.[18] As of September 14, 2017, she was missing again; she was last seen near Sapphire Beach in her home in St. Thomas right before Hurricane Maria.[19] Three months later her mother and a group of friends were searching for her in the Virgin Islands and surrounding areas.[20] * Jeff Ingram appeared in Denver in 2006 with no memory of his name or where he was from. After his appearance on national television, to appeal for help identifying himself, his fiancée called Denver police identifying him. The episode was diagnosed as dissociative fugue. As of December 2012, Ingram had experienced three incidents of amnesia: in 1994, 2006, and 2007.[21] * Doug Bruce "came to" on a subway train claiming to have no memory of his name or where he was from, nor any identification documents. * Bruneri-Canella case * Benjaman Kyle * Agatha Christie ## See also[edit] * Psychology portal * Depersonalization disorder (DSM-IV Dissociative Disorders 300.6) * Dissociation (psychology) * Dissociative disorders (DSM-IV Dissociative Disorders) * Dissociative identity disorder (formerly multiple personality disorder) (DSM-IV Dissociative Disorders 300.14) * Dromomania, a similar historical diagnosis * Psychogenic amnesia; dissociative amnesia (formerly psychogenic amnesia) (DSM-IV Dissociative Disorders 300.12) * Structured Clinical Interview for DSM-IV * Lost Highway, a film by David Lynch that explores the disorder ## References[edit] 1. ^ a b c Dissociative Fugue (formerly Psychogenic Fugue) (DSM-IV 300.13, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) 2. ^ American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders : DSM-5. Washington, D.C: American Psychiatric Association. ISBN 9780890425541. 3. ^ The Merck Manual 4. ^ "What Is Dissociative Fugue?". WebMD. Retrieved 2019-11-08. 5. ^ "Dissociative Amnesia, DSM-IV Codes 300.12 ( Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition )". Psychiatryonline.com. Archived from the original on 2007-09-28. Retrieved 2011-11-28. 6. ^ Dissociative Amnesia, DSM-IV Code 300.12 ( PsychNet-UK.com ) Archived November 28, 2010, at the Wayback Machine 7. ^ Complete List of DSM-IV Codes ( PsychNet-UK.com ) Archived January 6, 2011, at the Wayback Machine 8. ^ "Background to Dissociation ( The Pottergate Centre for Dissociation & Trauma )". Dissociation.co.uk. Archived from the original on 2012-01-14. Retrieved 2011-11-28. 9. ^ a b Merck Manual 1999 section 15 (Psychiatric Disorders), chapter 188 (Dissociative Disorders) 10. ^ "Experts say that Roberts may indeed have amnesia \| Juneau Empire - Alaska's Capital City Online Newspaper". Juneau Empire. 1997-07-17. Archived from the original on 2011-11-20. Retrieved 2011-11-28. 11. ^ "Shows". Five. 12. ^ a b The Associated Press (2008-09-16). "Update: Missing Oregon teacher rescued from Long Island Sound". OregonLive.com. Retrieved 2013-11-16. 13. ^ a b Aviv, Rachel (2018-03-26). "How a Young Woman Lost Her Identity". The New Yorker. ISSN 0028-792X. Retrieved 2018-03-30. 14. ^ "Hannah Upp Updates Her Status, Remembers Little". Gothamist. Archived from the original on 2015-03-22. 15. ^ "A Life, Interrupted". The New York Times. 2009-03-01. 16. ^ "Missing New York City School Teacher Spotted in Apple Store". Fox News. 2008-09-09. Archived from the original on 2013-12-22. Retrieved 2018-12-05. 17. ^ Mimica, Mila (2013-09-05). "Md. Woman With Rare Form of Amnesia Located". NBC4 Washington. Retrieved 2013-11-16. 18. ^ "Hannah Upp of Kensington found in Wheaton, Md". wusa9.com. 2013-09-05. Archived from the original on 2013-12-13. Retrieved 2013-11-16. 19. ^ "Community asked to help search for missing teacher Hannah Upp". Virgin Island Daily News. September 19, 2017. 20. ^ Staff, SUZANNE CARLSON Daily News. "Hannah Upp's mother asks for help in the search for her missing daughter". The Virgin Islands Daily News. Retrieved 2018-03-30. 21. ^ "For Man With Amnesia, Love Repeats Itself". NPR. 2012-12-13. Retrieved 2013-11-16. ## External links[edit] Classification D * ICD-10: F44.1 * ICD-9-CM: 300.13 * "Dissociative Fugue" from the Merck & Co. website. * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Fugue state	c0860635	5,325	wikipedia	https://en.wikipedia.org/wiki/Fugue_state	2021-01-18T18:38:56	{"icd-9": ["300.13"], "icd-10": ["F44.1"], "wikidata": ["Q951639"]}
Short/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency (also known as 2-methylbutyryl-CoA dehydrogenase deficiency) is a rare disorder in which the body is unable to process proteins properly. Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for the body. People with SBCAD deficiency cannot process a particular amino acid called isoleucine. Most cases of SBCAD deficiency are detected shortly after birth by newborn screening, which identifies abnormal levels of certain compounds in the blood. In individuals with this condition, a compound called 2-methylbutyryl carnitine is elevated in the blood and another called 2-methylbutyrylglycine is elevated in the urine (2-methylbutyrylglycinuria). Most people with SBCAD deficiency have no health problems related to the disorder. A small percentage of affected individuals develop signs and symptoms of the condition, which can begin soon after birth or later in childhood. The initial symptoms often include poor feeding, lack of energy (lethargy), vomiting, and irritability. These symptoms sometimes progress to serious health problems such as difficulty breathing, seizures, and coma. Additional problems can include poor growth, vision impairment, learning disabilities, muscle weakness, and delays in motor skills such as standing and walking. It is unclear why some people with SBCAD deficiency develop health problems and others do not. Doctors suggest that in some cases, signs and symptoms may be triggered by infections, prolonged periods without food (fasting), or an increased amount of protein-rich foods in the diet. ## Frequency SBCAD deficiency is a rare condition; its worldwide prevalence is unknown. This condition is most common among Hmong populations in Southeast Asia and in people of Hmong descent, affecting 1 in 250 to 1 in 500 people in these communities. These individuals do not usually develop health problems related to the condition. ## Causes Mutations in the ACADSB gene cause SBCAD deficiency. This gene provides instructions for making an enzyme called short/branched chain acyl-CoA dehydrogenase (SBCAD), which performs a chemical reaction that helps process the amino acid isoleucine. Mutations in the ACADSB gene reduce or eliminate the activity of this enzyme. With a shortage (deficiency) of SBCAD activity, the body is unable to break down isoleucine properly. Researchers speculate that some features of this disorder, such as lethargy and muscle weakness, occur because isoleucine is not converted to energy. In addition, impairment of SBCAD may allow the buildup of toxic compounds, which can lead to serious health problems. ### Learn more about the gene associated with Short/branched chain acyl-CoA dehydrogenase deficiency * ACADSB ## 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	Short/branched chain acyl-CoA dehydrogenase deficiency	c1864912	5,326	medlineplus	https://medlineplus.gov/genetics/condition/short-branched-chain-acyl-coa-dehydrogenase-deficiency/	2021-01-27T08:25:40	{"gard": ["10322"], "mesh": ["C566487"], "omim": ["610006"], "synonyms": []}
The newly described 5q35 microduplication syndrome is associated with microcephaly, short stature, developmental delay and delayed bone maturation. ## Epidemiology It has been reported in two unrelated patients. ## Clinical description There is no remarkable facial dysmorphism. The clinical picture is opposite to that of patients with Sotos syndrome (macrocephaly, overgrowth and advanced bone age; see this term). ## Etiology This microduplication was identified by microarray-based comparative genomic hybridization (aCGH). The breakpoints of the duplication in both patients map to the proximal and distal low-copy repeats (LCRs), which flank the Sotos critical region. These findings support a non-allelic homologous recombination (NAHR) as the mechanism of duplication, and a dosage effect of the Sotos gene NSD1 (5q35). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	5q35 microduplication syndrome	c4304526	5,327	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228415	2021-01-23T19:08:03	{"icd-10": ["Q92.3"], "synonyms": ["Dup(5)(q35)", "Trisomy 5q35"]}
Diffuse esophageal spasm Other namesDistal esophageal spasm SpecialtyGastroenterology Frequency1 per 100,000 people per year[1] Diffuse esophageal spasm (DES), also known as distal esophageal spasm, is a condition characterized by uncoordinated contractions of the esophagus, which may cause difficulty swallowing (dysphagia) or regurgitation. In some cases, it may cause symptoms such as chest pain, similar to heart disease. In many cases, the cause of DES remains unknown. Certain abnormalities on x-ray imaging are commonly observed in DES, such as a "corkscrew esophagus" or "rosary bead esophagus", although these findings are not unique to this condition. Specialized testing called manometry can be performed to evaluate the motor function of the esophagus, which can help identify abnormal patterns of muscle contraction within the esophagus that are suggestive of DES. The treatment of DES consists primarily of medications, such as acid suppressing agents (like proton-pump inhibitors), calcium channel blockers, hyoscine butylbromide, or nitrates. In only extremely rare cases, surgery may be considered. People with DES have higher incidences of gastroesophageal reflux disease (GERD), neuromuscular diseases, and degenerative neurological disorders. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 4.1 Procedures * 5 Epidemiology * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] DES manifests as intermittent difficulty swallowing solid foods and liquids (dysphagia), and atypical chest pain. The chest pain may appear similar to cardiac chest pain (angina pectoris), so investigating the possible existence of heart disease is often indicated.[2] ## Causes[edit] The causes of diffuse esophageal spasm is unclear.[1] It is thought, however, that many cases are caused by uncontrolled brain signals running to nerve endings. Therefore, suppression medication is often the first-line therapy such as antidepressants and anti-epileptic medication are prescribed. It has also been reported that very cold or hot beverages can trigger an esophageal spasm. Avoidance therapy benefits some people, but it has not been medically proven.[citation needed] Food allergies or intolerances may also be a cause in which spasms may be triggered within hours or days from the offending foods. ## Diagnosis[edit] Corkscrew appearance of the esophagus. Several radiographic findings are suggestive of DES, such as a "corkscrew esophagus" or "rosary bead esophagus" appearance on barium swallow x-ray, although these findings are not unique to DES.[2] ## Treatment[edit] Some may experience instant relief by drinking Coca-Cola. If the spasms are food intolerance induced, then an elimination diet is recommended. Several drugs are used to treat DES, including nitroglycerin, hyoscine butylbromide, calcium channel blockers, hydralazine, and anti-anxiety medications.[2] Acid suppression therapy, such as proton-pump inhibitors, are often the first-line therapy. ### Procedures[edit] Botulinum toxin, which inhibits acetylcholine release from nerve endings, injected above the lower esophageal sphincter may also be used in the treatment of DES. Small studies have suggested benefit from endoscopic balloon dilation in certain patients, but all of the above have a low percentage of success in treating the condition; whilst the treatments work in some sufferers, it does not work for everyone.[3] In extremely rare cases, surgery may be considered.[2] ## Epidemiology[edit] It affects about 1 per 100,000 people per year.[1] ## See also[edit] * Nutcracker esophagus * Esophageal spasm ## References[edit] 1. ^ a b c Goel, S; Nookala, V (January 2019). "Diffuse Esophageal Spasm". StatPearls [Internet]. PMID 31082150. 2. ^ a b c d Harrison's Principles of Internal Medicine. pp. 1905–1906. ISBN 0071802150. 3. ^ Esophageal Spasm~treatment at eMedicine ## External links[edit] Classification D * ICD-10: K22.4 * ICD-9-CM: 530.5 * MeSH: D015155 * DiseasesDB: 32060 External resources * MedlinePlus: 000289 * eMedicine: med/743 Media related to Diffuse esophageal spasm at Wikimedia Commons * Barium swallow images of DES * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Diffuse esophageal spasm	c0014863	5,328	wikipedia	https://en.wikipedia.org/wiki/Diffuse_esophageal_spasm	2021-01-18T18:59:24	{"mesh": ["D015155"], "icd-9": ["530.5"], "wikidata": ["Q1224503"]}
Cogan syndrome SpecialtyRheumatology Cogan syndrome (also Cogan's syndrome) is a rare disorder characterized by recurrent inflammation of the front of the eye (the cornea) and often fever, fatigue, and weight loss, episodes of vertigo (dizziness), tinnitus (ringing in the ears) and hearing loss. It can lead to deafness or blindness if untreated. The classic form of the disease was first described by D. G. Cogan in 1945. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 History * 6 References * 7 Further reading * 8 External links ## Signs and symptoms[edit] Cogan syndrome is a rare, rheumatic disease characterized by inflammation of the ears and eyes. Cogan syndrome can lead to vision difficulty, hearing loss and dizziness. The condition may also be associated with blood-vessel inflammation (called vasculitis) in other areas of the body that can cause major organ damage in 15% of those afflicted or, in a small number of cases, even death. It most commonly occurs in a person's 20s or 30s. The cause is not known. However, one theory is that it is an autoimmune disorder in which the body's immune system mistakenly attacks tissue in the eye and ear.[1] ## Causes[edit] It is currently thought that Cogan syndrome is an autoimmune disease. The inflammation in the eye and ear are due to the patient's own immune system producing antibodies that attack the inner ear and eye tissue. Autoantibodies can be demonstrated in the blood of some patients, and these antibodies have been shown to attack inner ear tissue in laboratory studies. Infection with the bacteria Chlamydia pneumoniae has been demonstrated in some patients prior to the development of Cogan syndrome, leading some researchers to hypothesize that the autoimmune disease may be initiated by the infection. C. pneumoniae is a common cause of mild pneumonia, and the vast majority of patients who are infected with the bacteria do not develop Cogan syndrome.[2] ## Diagnosis[edit] While the white blood cell count, erythrocyte sedimentation rate, and C-reactive protein tests may be abnormal and there may be abnormally high levels of platelets in the blood or too few red blood cells in the blood, none of these findings is a reliable indicator of the disease. A slit-lamp examination is essential. Recent work has suggested that high-resolution MRI and antibodies to inner ear antigens may be helpful. Cogan syndrome can occur in children, and is particularly difficult to recognize in that situation.[3] ## Treatment[edit] For more severe disease, oral corticosteroids may be necessary to reduce the inflammatory response. When large amounts of steroids are required or if the disease is severe and is not responding to steroid therapy, other immunosuppressive medications often are recommended. These immunosuppressive drugs include methotrexate, cyclophosphamide, cyclosporine or azathioprine. In some cases, combinations of these medicines are prescribed. Occasionally, if the disease has damaged blood vessels in the ear, cochlear implantation may be used to restore some sense of hearing.[4] Cinnarizine is mainly used to treat nausea and vomiting associated with motion sickness, vertigo, Ménière's disease, or Cogan syndrome.[5] Studies have shown it to produce significant improvement in hearing loss in some patients.[6] ## History[edit] In 1945, the ophthalmologist David Glendenning Cogan (1908–1993) first described the "nonsyphilitic interstitial keratitis and vestibuloauditory symptoms" that would later bear his name.[7] In 1963, the atypical form of Cogan syndrome, also known as "Logan Syndrome" was first described.[8] ## References[edit] 1. ^ "Cogan's Syndrome". Archived from the original on 2008-10-14. Retrieved 2008-11-06. 2. ^ Timothy C. Hain. "Cogan's Syndrome". Archived from the original on May 17, 2008. Retrieved 2008-11-06. 3. ^ Timothy C. Hain. "Cogan's syndrome". Retrieved 2008-11-06. 4. ^ Chertok, Barbara Liss. "Hearing Is Believing". Hearing Health Foundation. Retrieved 2 December 2020. 5. ^ "Cogan's Syndrome – Treatment". Archived from the original on 2013-01-22. Retrieved 2008-11-06. 6. ^ Timothy C. Hain: Cogan's Syndrome Archived 2008-05-17 at the Wayback Machine at the American Hearing Research Foundation, Chicago, Illinois 2008. 7. ^ Cogan, David G. (1945). "Syndrome of Nonsyphilitic Interstitial Keratitis and Vestibuloauditory Symptoms". Archives of Ophthalmology. 33 (2): 144–9. doi:10.1001/archopht.1945.00890140064007. 8. ^ Bennett FM (April 1963). "Bilateral recurrent episcleritis associated with posterior corneal changes, vestibulo-auditory symptoms and rheumatoid arthritis". American Journal of Ophthalmology. 55: 815–8. doi:10.1016/0002-9394(63)92451-6. PMID 13967466. ## Further reading[edit] * Haynes BF, Kaiser-Kupfer MI, Mason P, Fauci AS (November 1980). "Cogan syndrome: studies in thirteen patients, long-term follow-up, and a review of the literature". Medicine. 59 (6): 426–41. doi:10.1097/00005792-198011000-00003. PMID 6969345. * Gluth MB, Baratz KH, Matteson EL, Driscoll CL (April 2006). "Cogan syndrome: a retrospective review of 60 patients throughout a half century". Mayo Clinic Proceedings. 81 (4): 483–8. doi:10.4065/81.4.483. PMID 16610568. * Norton EW, Cogan DG (May 1959). "Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms; a long-term follow-up". Archives of Ophthalmology. 61 (5): 695–7. doi:10.1001/archopht.1959.00940090697004. PMID 13636563. * Bicknell JM, Holland JV (March 1978). "Neurologic manifestations of Cogan syndrome". Neurology. 28 (3): 278–81. doi:10.1212/wnl.28.3.278. PMID 305011. S2CID 22367876. * Casselman JW, Majoor MH, Albers FW (January 1994). "MR of the inner ear in patients with Cogan syndrome". American Journal of Neuroradiology. 15 (1): 131–8. PMID 8141044. * Allen NB, Cox CC, Cobo M, et al. (March 1990). "Use of immunosuppressive agents in the treatment of severe ocular and vascular manifestations of Cogan's syndrome". The American Journal of Medicine. 88 (3): 296–301. doi:10.1016/0002-9343(90)90157-9. PMID 2309745. * Kundell SP, Ochs HD (July 1980). "Cogan syndrome in childhood". The Journal of Pediatrics. 97 (1): 96–8. doi:10.1016/s0022-3476(80)80142-9. PMID 7381656. ## External links[edit] Classification D * ICD-10: M30.8 * ICD-9-CM: 370.52 * MeSH: D055952 * DiseasesDB: 32705 * SNOMED CT: 26018001 External resources * Orphanet: 1467 * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis * v * t * e Diseases of the outer and middle ear Outer ear * Otitis externa * Otomycosis Middle ear and mastoid * Otitis media * Mastoiditis * Bezold's abscess * Gradenigo's syndrome * Tympanosclerosis * Cholesteatoma * Perforated eardrum Symptoms * Ear pain * Hearing loss Tests * Otoscope * pneumatic * tympanometry [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Cogan syndrome	c0271270	5,329	wikipedia	https://en.wikipedia.org/wiki/Cogan_syndrome	2021-01-18T18:34:52	{"gard": ["1421"], "mesh": ["D055952"], "umls": ["C0271270"], "orphanet": ["1467"], "wikidata": ["Q1106923"]}
SRD5A3-CDG is a rare, non X-linked congenital disorder of glycosylation due to steroid 5 alpha reductase type 3 deficiency characterized by a highly variable phenotype typically presenting with severe visual impairment, variable ocular anomalies (such as optic nerve hypoplasia/atrophy, iris and optic nerve coloboma, congenital cataract, glaucoma), intellectual disability, cerebellar abnormalities, nystagmus, hypotonia, ataxia, and/or ichthyosiform skin lesions. Other reported manifestations include retinitis pigmentosa, kyphosis, congenital heart defects, hypertrichosis and abnormal coagulation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	SRD5A3-CDG	c4317224	5,330	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=324737	2021-01-23T18:37:11	{"gard": ["12397"], "mesh": ["C567328"], "omim": ["612379"], "umls": ["C3150191"], "icd-10": ["E77.8"], "synonyms": ["CDG syndrome type Iq", "CDG-Iq", "CDG1Q", "Congenital disorder of glycosylation type 1q", "Congenital disorder of glycosylation type Iq"]}
A rare systemic autoimmune disease characterized by infiltrates of IgG4-positive plasma cells and lymphocytes in the adventitia of the aorta, resulting in thickening of perivascular tissue or formation of soft tissue masses surrounding the aorta and its major branches (potentially complicated by inflammatory aortic aneurysm), associated with elevated serum IgG4 levels. Preferential location is the infra-renal portion of the abdominal aorta. In addition, medium-sized blood vessels can be involved, and the condition may occur together with IgG4-related disease in other parts of the body. Clinical symptoms are unspecific and include chest or back pain and fever. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	IgG4-related aortitis	None	5,331	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=449400	2021-01-23T18:09:58	{"icd-10": ["I77.6"]}
Pacemaker syndrome Ventricular pacemaker with 1:1 retrograde ventriculoatrial (V-A) conduction to the atria (arrows). SpecialtyCardiology Pacemaker syndrome is a condition that represents the clinical consequences of suboptimal atrioventricular (AV) synchrony or AV dyssynchrony, regardless of the pacing mode, after pacemaker implantation.[1][2] It is an iatrogenic disease—an adverse effect resulting from medical treatment—that is often underdiagnosed.[1][3] In general, the symptoms of the syndrome are a combination of decreased cardiac output, loss of atrial contribution to ventricular filling, loss of total peripheral resistance response, and nonphysiologic pressure waves.[2][4][5] Individuals with a low heart rate prior to pacemaker implantation are more at risk of developing pacemaker syndrome. Normally the first chamber of the heart (atrium) contracts as the second chamber (ventricle) is relaxed, allowing the ventricle to fill before it contracts and pumps blood out of the heart. When the timing between the two chambers goes out of synchronization, less blood is delivered on each beat. Patients who develop pacemaker syndrome may require adjustment of the pacemaker, or fitting of another lead to better coordinate the timing of atrial and ventricular contraction. ## Contents * 1 Signs and symptoms * 1.1 Complications * 2 Causes * 2.1 Risk factors * 3 Pathophysiology * 3.1 Loss of atrial contraction * 3.2 Cannon A waves * 3.3 Increased atrial pressure * 3.4 Increased production of natriuretic peptides * 3.5 VA conduction * 4 Prevention * 5 Treatment * 5.1 Diet * 5.2 Medication * 5.3 Medical care * 5.4 Surgical care * 6 Epidemiology * 7 History * 8 References * 9 External links ## Signs and symptoms[edit] No specific set of criteria has been developed for diagnosis of pacemaker syndrome. Most of the signs and symptoms of pacemaker syndrome are nonspecific, and many are prevalent in the elderly population at baseline. In the lab, pacemaker interrogation plays a crucial role in determining if the pacemaker mode had any contribution to symptoms.[5][6][7] Symptoms commonly documented in patients history, classified according to cause:[2][5][6][8][9] * Neurological \- Dizziness, near syncope, and confusion. * Heart failure \- Dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and edema. * Hypotension \- Seizure, mental status change, diaphoresis, and signs of orthostatic hypotension and shock. * Low cardiac output \- Fatigue, weakness, dyspnea on exertion, lethargy, and lightheadedness. * Hemodynamic \- Pulsation in the neck and abdomen, choking sensation, jaw pain, right upper quadrant (RUQ) pain, chest colds, and headache. * Heart rate related - Palpitations associated with arrhythmias In particular, the examiner should look for the following in the physical examination, as these are frequent findings at the time of admission:[2][5][6][8] * Vital signs may reveal hypotension, tachycardia, tachypnea, or low oxygen saturation. * Pulse amplitude may vary, and blood pressure may fluctuate. * Look for neck vein distension and cannon waves in the neck veins. * Lungs may exhibit crackles. * Cardiac examination may reveal regurgitant murmurs and variability of heart sounds. * Liver may be pulsatile, and the RUQ may be tender to palpation. Ascites may be present in severe cases. * The lower extremities may be edematous. * Neurologic examination may reveal confusion, dizziness, or altered mental status. ### Complications[edit] Studies have shown that patients with Pacemaker syndrome and/or with sick sinus syndrome are at higher risk of developing fatal complications that calls for the patients to be carefully monitored in the ICU. Complications include atrial fibrillation, thrombo-embolic events, and heart failure.[7] ## Causes[edit] ECG of pacemaker syndrome The cause is poorly understood. However several risk factors are associated with pacemaker syndrome.[5][10] ### Risk factors[edit] * In the preimplantation period, two variables are predicted to predispose to the syndrome. First is low sinus rate, and second is a higher programmed lower rate limit. In postimplantation, an increased percentage of ventricular paced beats is the only variable that significantly predicts development of pacemaker syndrome.[10] * Patients with intact VA conduction are at greater risk for developing pacemaker syndrome. Around 90% of patients with preserved AV conduction have intact VA conduction, and about 30-40% of patients with complete AV block have preserved VA conduction. Intact VA conduction may not be apparent at the time of pacemaker implantation or even may develop at any time after implantation.[2][5][10][11] * Patients with noncompliant ventricles and diastolic dysfunction are particularly sensitive to loss of atrial contribution to ventricular filling and have a greater chance of developing the syndrome. This includes patients with cardiomyopathy (hypertensive, hypertrophic, restrictive) and elderly individuals.[5][7][10][12] * Other factors correlated with development of pacemaker syndrome include decreased stroke volume, decreased cardiac output, and decreased left atrial total emptying fraction associated with ventricular pacing.[5][10] ## Pathophysiology[edit] The loss of physiologic timing of atrial and ventricular contractions, or sometimes called AV dyssynchrony, leads to different mechanisms of symptoms production. This altered ventricular contraction will decrease cardiac output, and in turn will lead to systemic hypotensive reflex response with varying symptoms.[1][2][4][5] ### Loss of atrial contraction[edit] Inappropriate pacing in patients with decreased ventricular compliance, which may be caused by diseases such as hypertensive cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and aging, can result in loss of atrial contraction and significantly reduces cardiac output. Because in such cases the atrias are required to provide 50% of cardiac output, which normally provides only 15% - 25% of cardiac output.[8][12] ### Cannon A waves[edit] Main article: Cannon A waves Atrial contraction against a closed tricuspid valve can cause pulsation in the neck and abdomen, headache, cough, and jaw pain.[8][10] ### Increased atrial pressure[edit] Ventricular pacing is associated with elevated right and left atrial pressures, as well as elevated pulmonary venous and pulmonary arterial pressures, which can lead to symptomatic pulmonary and hepatic congestion.[5] ### Increased production of natriuretic peptides[edit] Main article: atrial natriuretic peptide Main article: brain natriuretic peptide Patients with pacemaker syndrome exhibit increased plasma levels of ANP. That's due to increase in left atrial pressure and left ventricular filling pressure, which is due to decreased cardiac output caused by dyssynchrony in atrial and ventricular contraction. ANP and BNP are potent arterial and venous vasodilators that can override carotid and aortic baroreceptor reflexes attempting to compensate for decreased blood pressure. Usually patients with cannon a waves have higher plasma levels of ANP than those without cannon a waves.[1][13][14] ### VA conduction[edit] Main article: VA conduction A major cause of AV dyssynchrony is VA conduction. VA conduction, sometimes referred to as retrograde conduction, leads to delayed, nonphysiologic timing of atrial contraction in relation to ventricular contraction. Nevertheless, many conditions other than VA conduction promote AV dyssynchrony.[1][2][4][8][10] This will further decrease blood pressure, and secondary increase in ANP and BNP.[13][14] ## Prevention[edit] At the time of pacemaker implantation, AV synchrony should be optimized to prevent the occurrence of pacemaker syndrome. Where patients with optimized AV synchrony have shown great results of implantation and very low incidence of pacemaker syndrome than those with suboptimal AV synchronization.[1][4][5] ## Treatment[edit] ### Diet[edit] Diet alone cannot treat pacemaker syndrome, but an appropriate diet to the patient, in addition to the other treatment regimens mentioned, can improve the patient's symptoms. Several cases mentioned below: * For patients with heart failure, low-salt diet is indicated.[15] * For patients with autonomic insufficiency, a high-salt diet may be appropriate.[15] * For patients with dehydration, oral fluid rehydration is needed.[15] ### Medication[edit] No specific drugs are used to treat pacemaker syndrome directly because treatment consists of upgrading or reprogramming the pacemaker.[15] ### Medical care[edit] * For some patients who are ventricularly paced, usually the addition of an atrial lead and optimizing the AV synchrony usually resolves symptoms.[1][4][8][10] * In patients with other pacing modes, other than ventricular pacing, symptoms usually resolve after adjusting and reprogramming of pacemaker parameters, such as tuning the AV delay, changing the postventricular atrial refractory period, the sensing level, and pacing threshold voltage. The optimal values of these parameters for each individual differ. So, achieving the optimal values is by experimenting with successive reprogramming and measurement of relevant parameters, such as blood pressure, cardiac output, and total peripheral resistance, as well as observations of symptomatology.[1][4][8][10] * In rare instances, using hysteresis to help maintain AV synchrony can help alleviate symptoms in ventricularly inhibited paced (VVI) patients providing they have intact sinus node function. Hysteresis reduces the amount of time spent in pacing mode, which can relieve symptoms, particularly when the pacing mode is generating AV dyssynchrony.[4][10] * If symptoms persist after all these treatment modalities, replacing the pacemaker itself is sometimes beneficial and can alleviate symptoms.[1][4][8] * Medical care includes supportive treatment, in case any of the following complications happen, medical team should be ready. Possible complications include heart failure, hypotension, tachycardia, tachypnea, and oxygenation deficit.[1][6][8] ### Surgical care[edit] Sometimes surgical intervention is needed. After consulting an electrophysiologist, possibly an additional pacemaker lead placement is needed, which eventually relieve some of the symptoms.[1][4] ## Epidemiology[edit] The reported incidence of pacemaker syndrome has ranged from 2%[16] to 83%.[11] The wide range of reported incidence is likely attributable to two factors which are the criteria used to define pacemaker syndrome and the therapy used to resolve that diagnosis.[17] ## History[edit] Pacemaker syndrome was first described in 1969 by Mitsui et al. as a collection of symptoms associated with right ventricular pacing.[17][18][19] The name pacemaker syndrome was first coined by Erbel in 1979.[18][20] Since its first discovery, there have been many definitions of pacemaker syndrome, and the understanding of the cause of pacemaker syndrome is still under investigation. In a general sense, pacemaker syndrome can be defined as the symptoms associated with right ventricular pacing relieved with the return of A-V and V-V synchrony.[17] ## References[edit] 1. ^ a b c d e f g h i j k Ellenbogen KA, Gilligan DM, Wood MA, Morillo C, Barold SS (May 1997). "The pacemaker syndrome -- a matter of definition". Am. J. Cardiol. 79 (9): 1226–9. doi:10.1016/S0002-9149(97)00085-4. PMID 9164889. 2. ^ a b c d e f g Chalvidan T, Deharo JC, Djiane P (July 2000). "[Pacemaker syndromes]". Ann Cardiol Angeiol (Paris) (in French). 49 (4): 224–9. PMID 12555483. 3. ^ Baumgartner, William A.; Yuh, David D.; Luca A. Vricella (2007). The Johns Hopkins manual of cardiothoracic surgery. New York: McGraw-Hill Medical Pub. ISBN 978-0-07-141652-8. 4. ^ a b c d e f g h i Frielingsdorf J, Gerber AE, Hess OM (October 1994). "Importance of maintained atrio-ventricular synchrony in patients with pacemakers". Eur. Heart J. 15 (10): 1431–40. doi:10.1093/oxfordjournals.eurheartj.a060408. PMID 7821326. 5. ^ a b c d e f g h i j k Furman S (January 1994). "Pacemaker syndrome". Pacing Clin Electrophysiol. 17 (1): 1–5. doi:10.1111/j.1540-8159.1994.tb01342.x. PMID 7511223. 6. ^ a b c d Nishimura RA, Gersh BJ, Vlietstra RE, Osborn MJ, Ilstrup DM, Holmes DR (November 1982). "Hemodynamic and symptomatic consequences of ventricular pacing". Pacing Clin Electrophysiol. 5 (6): 903–10. doi:10.1111/j.1540-8159.1982.tb00029.x. PMID 6184693. 7. ^ a b c Santini M, Alexidou G, Ansalone G, Cacciatore G, Cini R, Turitto G (March 1990). "Relation of prognosis in sick sinus syndrome to age, conduction defects and modes of permanent cardiac pacing". Am. J. Cardiol. 65 (11): 729–35. doi:10.1016/0002-9149(90)91379-K. PMID 2316455. 8. ^ a b c d e f g h i Petersen HH, Videbaek J (September 1992). "[The pacemaker syndrome]". Ugeskrift for Læger (in Danish). 154 (38): 2547–51. PMID 1413181. 9. ^ Alicandri C, Fouad FM, Tarazi RC, Castle L, Morant V (July 1978). "Three cases of hypotension and syncope with ventricular pacing: possible role of atrial reflexes". Am. J. Cardiol. 42 (1): 137–42. doi:10.1016/0002-9149(78)90998-0. PMID 677029. 10. ^ a b c d e f g h i j Schüller H, Brandt J (April 1991). "The pacemaker syndrome: old and new causes". Clin Cardiol. 14 (4): 336–40. doi:10.1002/clc.4960140410. PMID 2032410. 11. ^ a b Heldman D, Mulvihill D, Nguyen H, et al. (December 1990). "True incidence of pacemaker syndrome". Pacing Clin Electrophysiol. 13 (12 Pt 2): 1742–50. doi:10.1111/j.1540-8159.1990.tb06883.x. PMID 1704534. 12. ^ a b Gross JN, Keltz TN, Cooper JA, Breitbart S, Furman S (December 1992). "Profound "pacemaker syndrome" in hypertrophic cardiomyopathy". Am. J. Cardiol. 70 (18): 1507–11. doi:10.1016/0002-9149(92)90313-N. PMID 1442632. 13. ^ a b Theodorakis GN, Panou F, Markianos M, Fragakis N, Livanis EG, Kremastinos DT (February 1997). "Left atrial function and atrial natriuretic factor/cyclic guanosine monophosphate changes in DDD and VVI pacing modes". Am. J. Cardiol. 79 (3): 366–70. doi:10.1016/S0002-9149(97)89285-5. PMID 9036762. 14. ^ a b Theodorakis GN, Kremastinos DT, Markianos M, Livanis E, Karavolias G, Toutouzas PK (November 1992). "Total sympathetic activity and atrial natriuretic factor levels in VVI and DDD pacing with different atrioventricular delays during daily activity and exercise". Eur. Heart J. 13 (11): 1477–81. doi:10.1093/oxfordjournals.eurheartj.a060089. PMID 1334465. 15. ^ a b c d "Pacemaker Syndrome: Treatment & Medication - eMedicine Cardiology". 2018-04-22. Cite journal requires `\|journal=` (help) 16. ^ Andersen HR, Thuesen L, Bagger JP, Vesterlund T, Thomsen PE (December 1994). "Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome". Lancet. 344 (8936): 1523–8. doi:10.1016/S0140-6736(94)90347-6. PMID 7983951. 17. ^ a b c Farmer DM, Estes NA, Link MS (2004). "New concepts in pacemaker syndrome". Indian Pacing and Electrophysiology Journal. 4 (4): 195–200. PMC 1502063. PMID 16943933. Retrieved 2009-06-19. 18. ^ a b Travill CM, Sutton R (August 1992). "Pacemaker syndrome: an iatrogenic condition". British Heart Journal. 68 (2): 163–6. doi:10.1136/hrt.68.8.163. PMC 1025005. PMID 1389730. Retrieved 2009-06-19. 19. ^ Mitsui T, Hori M, Suma K, et al. The "pacemaking syndrome." In: Jacobs JE, ed. Proceedings of the 8th Annual International Conference on Medical and Biological Engineering. Chicago, IL: Association for the Advancement of Medical Instrumentation;. 1969;29-3. 20. ^ 2 Erbel R. Pacemaker syndrome. AmJ Cardiol 1979;44:771-2. ## External links[edit] Classification D * PreOp Patient Education Permanent Pacemaker Implant Surgery * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Pacemaker syndrome	c0340929	5,332	wikipedia	https://en.wikipedia.org/wiki/Pacemaker_syndrome	2021-01-18T18:59:02	{"umls": ["C0340929"], "icd-9": ["429.4"], "wikidata": ["Q1717013"]}
Neonatal tetanus Other namesMaternal neonatal tetanus (MNT) Neonatal tetanus SpecialtyPediatrics, Infectious disease Neonatal tetanus is a form of generalised tetanus that occurs in newborns. Infants who have not acquired passive immunity from the mother having been immunised are at risk. It usually occurs through infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile instrument. Neonatal tetanus mostly occurs in developing countries, particularly those with the least developed health infrastructure. It is rare in developed countries.[1] ## Contents * 1 Signs and symptoms * 2 Prevention * 2.1 Public health campaigns * 3 Epidemiology * 4 References * 5 Further reading * 6 External links ## Signs and symptoms[edit] In neonatal tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7 days. The fatality rate for infants has been estimated as 70% to 100%; death usually occurs by the age of 2 weeks.[2] On the basis of clinical findings, four different forms of tetanus have been described.[3] The time from exposure to symptoms may be up to several months.[4] The neonate is unable to suck and cry, is rigid, and develops spasms. ## Prevention[edit] A tetanus shot is administered to a child and her mother The spores which cause tetanus are present everywhere, so the only prevention is immunization. Three properly spaced doses of tetanus toxoid vaccine are recommended for women of childbearing age, either before or during pregnancy; this will protect their future babies from neonatal tetanus after delivery.[2] ### Public health campaigns[edit] In 1989, the World Health Congress called for the elimination of neonatal tetanus. UNICEF took the lead, assisted by other United Nations agencies, individual governments, and non-profit organisations. By 2000, the disease was declared as eliminated from 104 of 161 developing countries.[5] "Elimination" is defined as less than 1 case per 1,000 live births in every district of the country.[2] Since tetanus can also strike postpartum mothers, the campaign has been expanded to target both maternal and neonatal tetanus.[2] In many affected countries, there was a lack of awareness of maternal and neonatal tetanus and how to prevent it. Education and immunisation campaigns have been launched in the remaining countries at risk and are targeted particularly at pregnant women.[1] Education focuses on hygienic birth practices and infant cord care as well as the need for immunisation.[6] In Egypt, the number of cases of neonatal tetanus dropped from 4,000 to fewer than 500 annually as the result of an immunisation campaign. In Morocco, neonatal tetanus accounted for 20% of neonatal deaths in 1987 but only 2% in 1992. In 1998 in Uganda, 3,433 tetanus cases were recorded in newborn babies; of these, 2,403 died. After a major public health effort, Uganda in 2011 was certified as having eliminated tetanus.[7] In 2011, Pampers joined with UNICEF to target maternal and neonatal tetanus in Yemen.[8] In 2010, Kiwanis International pledged to raise $110 million to eliminate maternal and neonatal tetanus throughout the world in partnership with UNICEF.[9] On 15 May 2015, the World Health Organization (WHO) declared India free from maternal and neonatal tetanus. India has reduced its infant mortality rate (IMR) from 380 per 1000 live births in 1990, to 40 in 2015, and its maternal mortality rate (MMR) from 540 per 100,000 to 167 in the same years.[10] The national health programme was started in 1983 by the Government of India, when all pregnant women were given two doses of tetanus vaccine. The number of deaths from tetanus dropped from 79,000 in 1990, to less than 500 in 2013 and 2014. ## Epidemiology[edit] Countries that have eliminated maternal neonatal tetanus as of 2018.[11] In 2000, neonatal tetanus was responsible for about 14% (215,000) of all neonatal deaths.[12] In 2008, 59,000 newborns worldwide died as a result of neonatal tetanus.[13][14] In 2005, 57 countries were identified as still at risk, with 27 countries accounting for 90% of cases.[2] As of December 2013 the number of countries at risk was reduced to 25.[15] ## References[edit] 1. ^ a b Roper, Martha H; Vandelaer, Jos H; Gasse, François L (12 September 2007). "Maternal and neonatal tetanus" (PDF). The Lancet. 370 (9603): 1947–1959. doi:10.1016/s0140-6736(07)61261-6. PMID 17854885. Retrieved 1 September 2015. 2. ^ a b c d e "Maternal and Neonatal Tetanus Elimination by 2005" (PDF). UNICEF. Retrieved 17 February 2014. 3. ^ "Tetanus" (PDF). CDC Pink Book. Retrieved 19 January 2014. 4. ^ Brauner, JS; Vieira, SR; Bleck, TP (Jul 2002). "Changes in severe accidental tetanus mortality in the ICU during two decades in Brazil". Intensive Care Medicine. 28 (7): 930–5. doi:10.1007/s00134-002-1332-4. PMID 12122532. S2CID 21772357. 5. ^ "Neonatal tetanus" (PDF). Unicef. Retrieved 19 January 2014. 6. ^ Saleh, JA; Nemecek, J; Jones, C (2015). "Impact of hygienic caring of the umbilical cord in the prevention of neonatal tetanus". WebmedCentral PUBLIC HEALTH. 6 (5). Retrieved 1 September 2015. 7. ^ "Uganda announces elimination of Maternal and Neonatal Tetanus". Unicef Media Centre. Retrieved 19 January 2014. 8. ^ "Pampers and UNICEF aim to eliminate maternal and neonatal tetanus in Yemen". AME info.com. March 29, 2011. Archived from the original on 2 February 2014. Retrieved 19 January 2014. 9. ^ "Maternal and Neonatal Tetanus". UNICEF United States Fund. Retrieved 17 February 2014. 10. ^ "India declared maternal and neonatal tetanus free: Modi". The Hindu. 27 August 2015. Retrieved 1 September 2015. 11. ^ "Year of Maternal Neonatal Tetanus (MNT) elimination". Our World in Data. Retrieved 5 March 2020. 12. ^ "Maternal and Neonatal Tetanus Elimination by 2005" (PDF). UNICEF. November 2000. Retrieved 2007-01-26. 13. ^ "Maternal and Neonatal Tetanus Elimination Initiative" (PDF). Pampers UNICEF 2010 Campaign: 2. 14. ^ Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, Jha P, Campbell H, Walker CF, Cibulskis R, Eisele T, Liu L, Mathers C, Child Health Epidemiology Reference Group of WHO and, UNICEF (Jun 5, 2010). "Global, regional, and national causes of child mortality in 2008: a systematic analysis". Lancet. 375 (9730): 1969–87. doi:10.1016/S0140-6736(10)60549-1. PMID 20466419. S2CID 27812760. 15. ^ "Elimination of Maternal and Neonatal Tetanus". UNICEF. Retrieved 17 February 2014. ## Further reading[edit] * Stanfield, JP; Galazka, A (1984). "Neonatal tetanus in the world today". Bulletin of the World Health Organization. 62 (4): 647–69. PMC 2536335. PMID 6386211. * Blencowe, H; Lawn, J; Vandelaer, J; Roper, M; Cousens, S (Apr 2010). "Tetanus toxoid immunization to reduce mortality from neonatal tetanus". International Journal of Epidemiology. 39 (Suppl 1): i102–9. doi:10.1093/ije/dyq027. PMC 2845866. PMID 20348112. ## External links[edit] Wikimedia Commons has media related to Neonatal tetanus. * Tetanus – Immunization, Vaccines and Biologicals: WHO * Neonatal Tetanus D7341 Insert: UNICEF * Maternal/Neonatal Tetanus (MNT): UNICEF * Maternal and neonatal tetanus-Immunization: UNICEF * Neonatal tetanus RightDiagnosis.com [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Neonatal tetanus	c0343312	5,333	wikipedia	https://en.wikipedia.org/wiki/Neonatal_tetanus	2021-01-18T18:53:27	{"umls": ["C0343312"], "wikidata": ["Q18967592"]}
Congenital hereditary endothelial dystrophy II (CHED II) is a rare subtype of posterior corneal dystrophy (see this term) characterized by a diffuse ground-glass appearance of the corneas and marked corneal thickening from birth with nystagmus, and blurred vision. ## Epidemiology Prevalence of this form of corneal dystrophy is unknown. Most cases have been identified in children of consanguineous parents from Saudi Arabia, India, Pakistan, Myanmar (Burma) and Ireland. ## Clinical description Diffuse ground glass lesions are present from birth and are accompanied by nystagmus. Tearing and photophobia are minimal or absent. The course is relatively stable. Patients also occasionally have sensorineural deafness. The cornea is swollen due to extensive stromal edema. ## Etiology Most cases are caused by homozygous mutations in the SLC4A11 gene. A high degree of mutational heterogeneity has been detected and genetic heterogeneity may exist as no mutations in SLC4A11 or in its promoter region have been detected in some affected families. In CHED II, an increased tendency for the abnormal endothelium to synthesize a homogenous, posterior, non-banded Descemet membrane is observed. ## Genetic counseling Transmission appears to be autosomal recessive. ## Management and treatment Patients with CHED II usually require a penetrating keratoplasty. Procedures for repairing the posterior surface of the cornea, such as a deep lamellar endothelial keratoplasty (DLEK), Descemet stripping endothelial keratoplasty (DSEK), or Descemet stripping automated endothelial keratoplasty (DSAEK) are technically difficult in young children. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Congenital hereditary endothelial dystrophy type II	c1857569	5,334	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=293603	2021-01-23T18:07:34	{"gard": ["6196"], "mesh": ["C536439"], "omim": ["217700"], "umls": ["C1857569"], "icd-10": ["H18.5"], "synonyms": ["Autosomal recessive CHED", "Autosomal recessive congenital hereditary endothelial dystrophy", "CHED2", "CHEDII", "Congenital hereditary endothelial dystrophy type 2", "Infantile hereditary endothelial dystrophy", "Maumenee corneal dystrophy"]}
Acid lipase disease or deficiency is a name used to describe two related disorders of fatty acid metabolism. Acid lipase disease occurs when the enzyme lysosomal acid lipase that is needed to break down certain fats that are normally digested by the body is lacking or missing. This results in the toxic buildup of these fats in the body's cells and tissues. These fatty substances, called lipids, include waxes, oils, and cholesterol. Three rare lipid storage diseases are caused by the deficiency of the enzyme lysosomal acid lipase: * Lysosomal acid lipase deficiency (LAL-D) * Wolman disease (early onset lysosomal acid lipase deficiency) * Cholesteryl ester storage disease (CESD) ## Contents * 1 Epidemiology * 2 Mechanism * 3 Symptoms * 4 Diagnosis * 5 Causes and Prevention * 6 Treatment and Prognosis * 7 Recent Research * 8 References * 9 External links ## Epidemiology[edit] The prevalence of Lysosomal acid lipase deficiency is unknown in the general population. Wolman disease and Cholesteryl ester storage disease are both autosomal recessive diseases. Wolman disease in predominantly found in the Iranian-Jewish community and its prevalence of this disease in offspring among Iranian-Jewish couples is 1 in 4200 births.[1] Cholesteryl ester storage disease is generally found among the German community and couples of German descent. It is estimated that 25 out of 1000000 newborns will develop the disease.[1] ## Mechanism[edit] The lysosomal acid lipase enzyme is found within the compartments of the lysosomes with in the cell.[2] When the lysosomal acid lipase enzyme is functioning properly, fats such as triglycerides and cholesteryl esters are broken down into their simpler lipid components through hydrolysis. After triglycerides are broken down, the fatty acids are used for energy. Cholesteryl esters are broken down into its cholesterol and fatty acid components, this delivers cholesterol to the cell. These lipids are either used by the body or sent to the liver for removal.[2] In acid lipase disease the lysosomal acid lipase enzyme is either lacking or missing. In both CESD and Wolman's disease there is a mutation with in the LIPA gene, which maps to chromosome 10q23.2, has 10 exons and is approximately 45 kb in length,[3] that encodes for the lysosomal acid lipase enzyme.[4] This mutation causes a loss of function in the gene. This results in the toxic buildup of fats in the body's cells and tissues, which causes an array of symptoms. ## Symptoms[edit] In both Wolman disease and Cholesteryl ester storage disease there is a deficiency of lysosomal acid lipase which causes an array of symptoms with in the body. The inability to break down fats in Wolman's disease causes symptoms of:[4] * Abdominal distention * Adrenal calcification * Hepatic failure * Hepatomegaly * Nausea and vomiting * Steatorrhea * Anemia * Ascites * Cachexia * Jaundice * Growth delay. In Cholesteryl ester storage there are alterations in the blood lipoprotein amounts which lead to symptoms such as; hypercholesterolemia, hypertriglyceridemia, and HDL deficiency with abnormal lipid deposition in many organs.[5] The hallmarks of the disease in infants consist of prominent hepatosplenomegaly, diarrhea and vomiting, resulting in malabsorption, growth failure and liver failure. These infants quickly develop liver fibrosis and cirrhosis due to the massive accumulation of cholesteryl esters and triglycerides in the liver.[6] ## Diagnosis[edit] Wolman Disease and Cholesteryl ester storage disease are both diagnosed by observation of previous medical history and symptoms, physical exams, laboratory tests also genetic testing.[4] In laboratory test it is expected that the total serum concentration of cholesterol, low density lipoproteins, and triglycerides will be high and the serum concentration of high density lipoproteins are low for a positive result of acid lipase disease.[7] The genetic tests done are:[7] * Single-gene testing * A multigene panel * (If needed) More comprehensive genomic testing Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek.[8] ## Causes and Prevention[edit] Lysosomal acid lipase enzyme deficiency is caused by a mutation in the LIPA gene which provides instructions for the produce this enzyme. When there are malfunctions in this gene the development of Wolman disease and Cholesteryl ester storage disease take place. Prevention methods of inheriting lysosomal acid lipase deficiency would genetic counseling of the parents who are likely to be carriers of the mutated gene before having offspring. ## Treatment and Prognosis[edit] An FDA approved treatment for Wolman disease is the medication Kanuma or Sebelipase alfa.[4] This drug works as an enzyme replacement therapy which allows the body to begin breaking down triglycerides and cholesteryl esters into their simpler lipid components once again.[9] Some other methods of treating lysosomal acid lipase deficiency and Cholesteryl ester storage disease include; a low-fat diet, the prescription of statins and other lipid-lowering agents, stem cell transplant, and liver transplants.[10] Lifespan for individuals with CESD is expected to be longer than individuals with Wolman disease, and available treatments may prolong life into adulthood. However, approximately 50% of individuals with CESD die in the second decade of life due to complications of liver disease or heart disease.[11] Infants with LAL-D typically present in the first weeks of life and die within 6–12 months due to multi-organ failure.[3] ## Recent Research[edit] There are many studies taking place to further understand how the lysosomal acid lipase disease works at a cellular and molecular level, which can be applied to the development of new treatments for these diseases. One study called "Role of lysosomal acid lipase in the metabolism of plasma low density lipoprotein. Observations in cultured fibroblasts from a patient with cholesteryl ester storage disease." looks at the ability of human fibroblasts to hydrolyzes the cholesteryl esters of exogenous LDL and thus provides the cell with free cholesterol.[6] Other studies look at the fact that acid lipase disease is often under diagnosed. To combat this, scientists are looking at the molecular mechanisms, differential diagnosis, and identification of the hallmarks of acid lipase disease.[3] ## References[edit] * 1. ^ a b "EBSCO Publishing Service Selection Page". web.b.ebscohost.com. Retrieved 2017-11-07.[permanent dead link] 2. ^ a b Reference, Genetics Home. "LIPA gene". Genetics Home Reference. Retrieved 2017-11-07. 3. ^ a b c Reiner, Zeljko (July 2014). "Lysosomal acid lipase deficiency – An under-recognized cause of dyslipidaemia and liver dysfunction". Atherosclerosis. 235 (1): 21–30. doi:10.1016/j.atherosclerosis.2014.04.003. PMID 24792990. 4. ^ a b c d "Wolman disease \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-11-08. 5. ^ "Cholesteryl Ester Storage Disease - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2017-11-08. 6. ^ a b Goldstein, J. L.; Dana, S. E.; Faust, J. R.; Beaudet, A. L.; Brown, M. S. (1975-11-10). "Role of lysosomal acid lipase in the metabolism of plasma low density lipoprotein. Observations in cultured fibroblasts from a patient with cholesteryl ester storage disease". Journal of Biological Chemistry. 250 (21): 8487–8495. ISSN 0021-9258. PMID 172501. 7. ^ a b Hoffman, Erin P.; Barr, Marci L.; Giovanni, Monica A.; Murray, Michael F. (1993). Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E.; Bean, Lora J.H.; Mefford, Heather C.; Stephens, Karen; Amemiya, Anne; Ledbetter, Nikki (eds.). GeneReviews. Seattle (WA): University of Washington, Seattle. PMID 26225414. 8. ^ "How is Genetic Testing Done?". 2017-12-12. 9. ^ "Kanuma® (sebelipase alfa) and lysosomal acid lipase deficiency (LAL-D) \| Alexion, Rare Disease Leader". www.alexion.com. Retrieved 2017-11-08. 10. ^ "American Liver Foundation - Lysosomal Acid Lipase Deficiency (LAL-D)". www.liverfoundation.org. Retrieved 2017-11-08. 11. ^ "lysosomal acid lipase deficiency \| Counsyl". Counsyl. Retrieved 2017-11-08. ## External links[edit] NINDS. Acid Lipase Disease Information Page [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Acid lipase disease	c2936797	5,335	wikipedia	https://en.wikipedia.org/wiki/Acid_lipase_disease	2021-01-18T19:09:55	{"mesh": ["C531854"], "wikidata": ["Q4674074"]}
Adams-Oliver syndrome is a rare condition that is present at birth. The primary features are an abnormality in skin development (called aplasia cutis congenita) and malformations of the limbs. A variety of other features can occur in people with Adams-Oliver syndrome. Most people with Adams-Oliver syndrome have aplasia cutis congenita, a condition characterized by localized areas of missing skin typically occurring on the top of the head (the skull vertex). In some cases, the bone under the skin is also underdeveloped. Individuals with this condition commonly have scarring and an absence of hair growth in the affected area. Abnormalities of the hands and feet are also common in people with Adams-Oliver syndrome. These most often involve the fingers and toes and can include abnormal nails, fingers or toes that are fused together (syndactyly), and abnormally short or missing fingers or toes (brachydactyly or oligodactyly). In some cases, other bones in the hands, feet, or lower limbs are malformed or missing. Some affected infants have a condition called cutis marmorata telangiectatica congenita. This disorder of the blood vessels causes a reddish or purplish net-like pattern on the skin. In addition, people with Adams-Oliver syndrome can develop high blood pressure in the blood vessels between the heart and the lungs (pulmonary hypertension), which can be life-threatening. Other blood vessel problems and heart defects can occur in affected individuals. In some cases, people with Adams-Oliver syndrome have neurological problems, such as developmental delay, learning disabilities, or abnormalities in the structure of the brain. ## Frequency Adams-Oliver syndrome is a rare disorder; its prevalence is unknown. ## Causes Mutations in the ARHGAP31, DLL4, DOCK6, EOGT, NOTCH1, or RBPJ gene can cause Adams-Oliver syndrome. Because some affected individuals do not have mutations in one of these genes, it is likely that other genes that have not been identified are also involved in this condition. Each of the known genes plays an important role during embryonic development, and changes in any one of them can impair this tightly controlled process, leading to the signs and symptoms of Adams-Oliver syndrome. The proteins produced from the ARHGAP31 and DOCK6 genes are both involved in the regulation of proteins called GTPases, which transmit signals that are critical for various aspects of embryonic development. The ARHGAP31 and DOCK6 proteins appear to be especially important for GTPase regulation during development of the limbs, skull, and heart. GTPases are often called molecular switches because they can be turned on and off. The DOCK6 protein turns them on, and the ARHGAP31 protein turns them off. Mutations in the DOCK6 gene lead to production of an abnormally short DOCK6 protein that is likely unable to turn on GTPases, which reduces their activity. Mutations in the ARHGAP31 gene also decrease GTPase activity by leading to production of an abnormally active ARHGAP31 protein, which turns off GTPases when it normally would not. This decline in GTPase activity leads to the skin problems, bone malformations, and other features characteristic of Adams-Oliver syndrome. The proteins produced from the NOTCH1, DLL4, and RBPJ genes are part of a signaling pathway known as the Notch pathway. Notch signaling controls how certain types of cells develop in the growing embryo, including those that form the bones, heart, muscles, nerves, and blood vessels. The Notch1 and DLL4 proteins fit together like a lock and its key to stimulate one part of the Notch pathway, which is important for development of blood vessels. The NOTCH1 and DLL4 gene mutations involved in Adams-Oliver syndrome likely impair Notch1 signaling, which may underlie blood vessel and heart abnormalities in some people with Adams-Oliver syndrome. Researchers suspect that the other features of the condition may be due to abnormal blood vessel development before birth. Signaling through Notch1 and other Notch proteins stimulates the RBP-J protein, produced from the RBPJ gene, to attach (bind) to specific regions of DNA and control the activity of genes that play a role in cellular development in multiple tissues throughout the body. The RBPJ gene mutations involved in Adams-Oliver syndrome alter the region of the RBP-J protein that normally binds DNA. The altered protein is unable to bind to DNA, preventing it from turning on particular genes. These changes in gene activity impair the proper development of the skin, bones, and other tissues, leading to the features of Adams-Oliver syndrome. Little is known about how mutations in the EOGT gene cause Adams-Oliver syndrome. The protein produced from this gene modifies certain proteins by transferring a molecule called N-acetylglucosamine to them. It is thought that the EOGT protein modifies Notch proteins, which stimulate the Notch signaling pathway. However, the impact of the modification on Notch signaling is unclear. At least three mutations in the EOGT gene have been identified in people with Adams-Oliver syndrome, but how the genetic changes contribute to the signs and symptoms of this disorder is still unknown. ### Learn more about the genes associated with Adams-Oliver syndrome * ARHGAP31 * DLL4 * DOCK6 * EOGT * NOTCH1 * RBPJ ## Inheritance Pattern Adams-Oliver syndrome can have different inheritance patterns. When caused by mutations in the ARHGAP31, DLL4, NOTCH1, or RBPJ gene, the condition is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. The altered gene is typically inherited from an affected parent. Some cases associated with NOTCH1 gene mutations result 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. When caused by mutations in the DOCK6 or EOGT gene, Adams-Oliver syndrome is inherited in an autosomal recessive pattern. In conditions with this pattern of inheritance, 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	Adams-Oliver syndrome	c1970140	5,336	medlineplus	https://medlineplus.gov/genetics/condition/adams-oliver-syndrome/	2021-01-27T08:24:47	{"gard": ["5739"], "mesh": ["C566997"], "omim": ["100300", "614219", "614814", "615297", "616028", "616589"], "synonyms": []}
3-methylglutaconic aciduria (3-MGA) type I is an inborn error of leucine metabolism with a variable clinical phenotype ranging from mildly delayed speech to psychomotor retardation, coma, failure to thrive, metabolic acidosis and dystonia. ## Epidemiology The disorder is very rare with less than 20 cases reported in the literature. ## Clinical description Clinical manifestations usually become apparent in the neonatal period or during infancy but the diagnosis may not be made until childhood. Some of the reported patients also displayed hypoglycaemia, spastic quadriparesis, microcephaly, progressive neurological deficit, seizures, vomiting, atrophy of the basal ganglia, severe hypotonia and hepatomegly. ## Etiology The syndrome is caused by mutations in the AUH gene (chromosome 9) encoding 3-methylglutaconyl-CoA hydratase, an enzyme involved in leucine degradation. ## Diagnostic methods As the clinical picture is variable and nonspecific, diagnosis can be made by assay of 3-methylglutaconyl-CoA hydratase activity in fibroblasts or leukocytes, quantitative analysis of urinary organic acid excretion or, more recently, analysis of bodily fluids by NMR spectroscopy. ## Differential diagnosis Patients with 3-MGA type I can be distinguished from those with other forms of 3-MGA (types II, III and IV; see these terms) by the distinctive pattern of metabolite excretion: 3-methylglutaconic acid levels are highly elevated (higher than those detected in other forms of 3-MGA) whereas methylglutaric acid levels are usually only slightly elevated, and there is a high level of 3-hydroxyisovaleric acid excretion (not present in other forms of 3-MGA). ## Antenatal diagnosis Prenatal diagnosis should be possible through detection of high levels of 3-hydroxyisovaleric acid in the amniotic fluid or through enzyme analysis of cultured amniocytes. ## Genetic counseling The syndrome is inherited as an autosomal recessive trait. ## Management and treatment Treatment is largely symptomatic but dietary management with a modest leucine restriction and supplementation with L-carnitine may be beneficial in some cases. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	3-methylglutaconic aciduria type 1	c0342727	5,337	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=67046	2021-01-23T19:09:25	{"gard": ["10321"], "mesh": ["C562801"], "omim": ["250950"], "umls": ["C0342727", "C0342728"], "icd-10": ["E71.1"], "synonyms": ["3-methylglutaconyl-CoA hydratase deficiency", "3MG-CoA hydratase deficiency", "MGA1"]}
Abnormal condition that negatively affects an organism For other uses, see Disease (disambiguation). "Maladies" redirects here. For the 2012 film, see Maladies (film). "Ailment" redirects here. It is not to be confused with Aliment. Scanning electron micrograph of Mycobacterium tuberculosis, a bacterium that causes tuberculosis A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not due to any immediate external injury.[1][2] Diseases are often known to be medical conditions that are associated with specific symptoms and signs.[1][failed verification] A disease may be caused by external factors such as pathogens or by internal dysfunctions. For example, internal dysfunctions of the immune system can produce a variety of different diseases, including various forms of immunodeficiency, hypersensitivity, allergies and autoimmune disorders. In humans, disease is often used more broadly to refer to any condition that causes pain, dysfunction, distress, social problems, or death to the person afflicted, or similar problems for those in contact with the person. In this broader sense, it sometimes includes injuries, disabilities, disorders, syndromes, infections, isolated symptoms, deviant behaviors, and atypical variations of structure and function, while in other contexts and for other purposes these may be considered distinguishable categories. Diseases can affect people not only physically, but also mentally, as contracting and living with a disease can alter the affected person's perspective on life. Death due to disease is called death by natural causes. There are four main types of disease: infectious diseases, deficiency diseases, hereditary diseases (including both genetic diseases and non-genetic hereditary diseases), and physiological diseases. Diseases can also be classified in other ways, such as communicable versus non-communicable diseases. The deadliest diseases in humans are coronary artery disease (blood flow obstruction), followed by cerebrovascular disease and lower respiratory infections.[3] In developed countries, the diseases that cause the most sickness overall are neuropsychiatric conditions, such as depression and anxiety. The study of disease is called pathology, which includes the study of etiology, or cause. ## Contents * 1 Terminology * 1.1 Concepts * 1.2 Types by body system * 1.3 Stages * 1.4 Extent * 2 Classification * 3 Causes * 3.1 Types of causes * 4 Prevention * 5 Treatments * 6 Epidemiology * 6.1 Burdens of disease * 7 Society and culture * 7.1 Language of disease * 8 See also * 9 References * 10 External links ## Terminology[edit] ### Concepts[edit] In many cases, terms such as disease, disorder, morbidity, sickness and illness are used interchangeably; however, there are situations when specific terms are considered preferable.[4] Disease The term disease broadly refers to any condition that impairs the normal functioning of the body. For this reason, diseases are associated with the dysfunction of the body's normal homeostatic processes.[5] Commonly, the term is used to refer specifically to infectious diseases, which are clinically evident diseases that result from the presence of pathogenic microbial agents, including viruses, bacteria, fungi, protozoa, multicellular organisms, and aberrant proteins known as prions. An infection or colonization that does not and will not produce clinically evident impairment of normal functioning, such as the presence of the normal bacteria and yeasts in the gut, or of a passenger virus, is not considered a disease. By contrast, an infection that is asymptomatic during its incubation period, but expected to produce symptoms later, is usually considered a disease. Non-infectious diseases are all other diseases, including most forms of cancer, heart disease, and genetic disease. Acquired disease An acquired disease is one that began at some point during one's lifetime, as opposed to disease that was already present at birth, which is congenital disease. Acquired sounds like it could mean "caught via contagion", but it simply means acquired sometime after birth. It also sounds like it could imply secondary disease, but acquired disease can be primary disease. Acute disease An acute disease is one of a short-term nature (acute); the term sometimes also connotes a fulminant nature Chronic condition or chronic disease A chronic disease is one that persists over time, often characterized as at least six months but may also include illnesses that are expected to last for the entirety of one's natural life. Congenital disorder or congenital disease A congenital disorder is one that is present at birth. It is often a genetic disease or disorder and can be inherited. It can also be the result of a vertically transmitted infection from the mother, such as HIV/AIDS. Genetic disease A genetic disorder or disease is caused by one or more genetic mutations. It is often inherited, but some mutations are random and de novo. Hereditary or inherited disease A hereditary disease is a type of genetic disease caused by genetic mutations that are hereditary (and can run in families) Iatrogenic disease An iatrogenic disease or condition is one that is caused by medical intervention, whether as a side effect of a treatment or as an inadvertent outcome. Idiopathic disease An idiopathic disease has an unknown cause or source. As medical science has advanced, many diseases with entirely unknown causes have had some aspects of their sources explained and therefore shed their idiopathic status. For example, when germs were discovered, it became known that they were a cause of infection, but particular germs and diseases had not been linked. In another example, it is known that autoimmunity is the cause of some forms of diabetes mellitus type 1, even though the particular molecular pathways by which it works are not yet understood. It is also common to know certain factors are associated with certain diseases; however, association and causality are two very different phenomena, as a third cause might be producing the disease, as well as an associated phenomenon. Incurable disease A disease that cannot be cured. Incurable diseases are not necessarily terminal diseases, and sometimes a disease's symptoms can be treated sufficiently for the disease to have little or no impact on quality of life. Primary disease A primary disease is a disease that is due to a root cause of illness, as opposed to secondary disease, which is a sequela, or complication that is caused by the primary disease. For example, a common cold is a primary disease, where rhinitis is a possible secondary disease, or sequela. A doctor must determine what primary disease, a cold or bacterial infection, is causing a patient's secondary rhinitis when deciding whether or not to prescribe antibiotics. Secondary disease A secondary disease is a disease that is a sequela or complication of a prior, causal disease, which is referred to as the primary disease or simply the underlying cause (root cause). For example, a bacterial infection can be primary, wherein a healthy person is exposed to a bacteria and becomes infected, or it can be secondary to a primary cause, that predisposes the body to infection. For example, a primary viral infection that weakens the immune system could lead to a secondary bacterial infection. Similarly, a primary burn that creates an open wound could provide an entry point for bacteria, and lead to a secondary bacterial infection. Terminal disease A terminal disease is one that is expected to have the inevitable result of death. Previously, AIDS was a terminal disease; it is now incurable, but can be managed indefinitely using medications. Illness The terms illness and sickness are both generally used as synonyms for disease; however, the term illness is occasionally used to refer specifically to the patient's personal experience of his or her disease.[6][7][8][9] In this model, it is possible for a person to have a disease without being ill (to have an objectively definable, but asymptomatic, medical condition, such as a subclinical infection, or to have a clinically apparent physical impairment but not feel sick or distressed by it), and to be ill without being diseased (such as when a person perceives a normal experience as a medical condition, or medicalizes a non-disease situation in his or her life – for example, a person who feels unwell as a result of embarrassment, and who interprets those feelings as sickness rather than normal emotions). Symptoms of illness are often not directly the result of infection, but a collection of evolved responses – sickness behavior by the body – that helps clear infection and promote recovery. Such aspects of illness can include lethargy, depression, loss of appetite, sleepiness, hyperalgesia, and inability to concentrate.[10][11][12] Disorder A disorder is a functional abnormality or disturbance. Medical disorders can be categorized into mental disorders, physical disorders, genetic disorders, emotional and behavioral disorders, and functional disorders. The term disorder is often considered more value-neutral and less stigmatizing than the terms disease or illness, and therefore is preferred terminology in some circumstances.[13] In mental health, the term mental disorder is used as a way of acknowledging the complex interaction of biological, social, and psychological factors in psychiatric conditions; however, the term disorder is also used in many other areas of medicine, primarily to identify physical disorders that are not caused by infectious organisms, such as metabolic disorders. Medical condition A medical condition is a broad term that includes all diseases, lesions, disorders, or nonpathologic condition that normally receives medical treatment, such as pregnancy or childbirth. While the term medical condition generally includes mental illnesses, in some contexts the term is used specifically to denote any illness, injury, or disease except for mental illnesses. The Diagnostic and Statistical Manual of Mental Disorders (DSM), the widely used psychiatric manual that defines all mental disorders, uses the term general medical condition to refer to all diseases, illnesses, and injuries except for mental disorders.[14] This usage is also commonly seen in the psychiatric literature. Some health insurance policies also define a medical condition as any illness, injury, or disease except for psychiatric illnesses.[15] As it is more value-neutral than terms like disease, the term medical condition is sometimes preferred by people with health issues that they do not consider deleterious. On the other hand, by emphasizing the medical nature of the condition, this term is sometimes rejected, such as by proponents of the autism rights movement. The term medical condition is also a synonym for medical state, in which case it describes an individual patient's current state from a medical standpoint. This usage appears in statements that describe a patient as being in critical condition, for example. Morbidity Morbidity (from Latin morbidus 'sick, unhealthy') is a diseased state, disability, or poor health due to any cause.[16] The term may refer to the existence of any form of disease, or to the degree that the health condition affects the patient. Among severely ill patients, the level of morbidity is often measured by ICU scoring systems. Comorbidity is the simultaneous presence of two or more medical conditions, such as schizophrenia and substance abuse. In epidemiology and actuarial science, the term "morbidity rate" can refer to either the incidence rate, or the prevalence of a disease or medical condition. This measure of sickness is contrasted with the mortality rate of a condition, which is the proportion of people dying during a given time interval. Morbidity rates are used in actuarial professions, such as health insurance, life insurance, and long-term care insurance, to determine the correct premiums to charge to customers. Morbidity rates help insurers predict the likelihood that an insured will contract or develop any number of specified diseases. Pathosis or pathology Pathosis (plural pathoses) is synonymous with disease. The word pathology also has this sense, in which it is commonly used by physicians in the medical literature, although some editors prefer to reserve pathology to its other senses. Sometimes a slight connotative shade causes preference for pathology or pathosis implying "some [as yet poorly analyzed] pathophysiologic process" rather than disease implying "a specific disease entity as defined by diagnostic criteria being already met". This is hard to quantify denotatively, but it explains why cognitive synonymy is not invariable. Syndrome A syndrome is the association of several medical signs, symptoms, or other characteristics that often occur together, regardless of whether the cause is known. Some syndromes such as Down syndrome are known to have only one cause (an extra chromosome at birth). Others such as Parkinsonian syndrome are known to have multiple possible causes. Acute coronary syndrome, for example, is not a single disease itself but is rather the manifestation of any of several diseases including myocardial infarction secondary to coronary artery disease. In yet other syndromes, however, the cause is unknown. A familiar syndrome name often remains in use even after an underlying cause has been found or when there are a number of different possible primary causes. Examples of the first-mentioned type are that Turner syndrome and DiGeorge syndrome are still often called by the "syndrome" name despite that they can also be viewed as disease entities and not solely as sets of signs and symptoms. Predisease Predisease is a subclinical or prodromal vanguard of a disease. Prediabetes and prehypertension are common examples. The nosology or epistemology of predisease is contentious, though, because there is seldom a bright line differentiating a legitimate concern for subclinical/prodromal/premonitory status (on one hand) and conflict of interest–driven disease mongering or medicalization (on the other hand). Identifying legitimate predisease can result in useful preventive measures, such as motivating the person to get a healthy amount of physical exercise,[17] but labeling a healthy person with an unfounded notion of predisease can result in overtreatment, such as taking drugs that only help people with severe disease or paying for drug prescription instances whose benefit–cost ratio is minuscule (placing it in the waste category of CMS' "waste, fraud, and abuse" classification). Three requirements for the legitimacy of calling a condition a predisease are: * a truly high risk for progression to disease – for example, a pre-cancer will almost certainly turn into cancer over time * actionability for risk reduction – for example, removal of the precancerous tissue prevents it from turning into a potentially deadly cancer * benefit that outweighs the harm of any interventions taken – removing the precancerous tissue prevents cancer, and thus prevents a potential death from cancer.[18] ### Types by body system[edit] Mental Mental illness is a broad, generic label for a category of illnesses that may include affective or emotional instability, behavioral dysregulation, cognitive dysfunction or impairment. Specific illnesses known as mental illnesses include major depression, generalized anxiety disorders, schizophrenia, and attention deficit hyperactivity disorder, to name a few. Mental illness can be of biological (e.g., anatomical, chemical, or genetic) or psychological (e.g., trauma or conflict) origin. It can impair the affected person's ability to work or study and can harm interpersonal relationships. The term insanity is used technically as a legal term. Organic An organic disease is one caused by a physical or physiological change to some tissue or organ of the body. The term sometimes excludes infections. It is commonly used in contrast with mental disorders. It includes emotional and behavioral disorders if they are due to changes to the physical structures or functioning of the body, such as after a stroke or a traumatic brain injury, but not if they are due to psychosocial issues. ### Stages[edit] "Flareup" redirects here. For the Transformers character, see Flareup (Transformers). In an infectious disease, the incubation period is the time between infection and the appearance of symptoms. The latency period is the time between infection and the ability of the disease to spread to another person, which may precede, follow, or be simultaneous with the appearance of symptoms. Some viruses also exhibit a dormant phase, called viral latency, in which the virus hides in the body in an inactive state. For example, varicella zoster virus causes chickenpox in the acute phase; after recovery from chickenpox, the virus may remain dormant in nerve cells for many years, and later cause herpes zoster (shingles). Acute disease An acute disease is a short-lived disease, like the common cold. Chronic disease A chronic disease is one that lasts for a long time, usually at least six months. During that time, it may be constantly present, or it may go into remission and periodically relapse. A chronic disease may be stable (does not get any worse) or it may be progressive (gets worse over time). Some chronic diseases can be permanently cured. Most chronic diseases can be beneficially treated, even if they cannot be permanently cured. Clinical disease One that has clinical consequences; in other words, the stage of the disease that produces the characteristic signs and symptoms of that disease.[19] AIDS is the clinical disease stage of HIV infection. Cure A cure is the end of a medical condition or a treatment that is very likely to end it, while remission refers to the disappearance, possibly temporarily, of symptoms. Complete remission is the best possible outcome for incurable diseases. Flare-up A flare-up can refer to either the recurrence of symptoms or an onset of more severe symptoms.[20] See also: Exacerbation Progressive disease Progressive disease is a disease whose typical natural course is the worsening of the disease until death, serious debility, or organ failure occurs. Slowly progressive diseases are also chronic diseases; many are also degenerative diseases. The opposite of progressive disease is stable disease or static disease: a medical condition that exists, but does not get better or worse. Refractory disease A refractory disease is a disease that resists treatment, especially an individual case that resists treatment more than is normal for the specific disease in question. Subclinical disease Also called silent disease, silent stage, or asymptomatic disease. This is a stage in some diseases before the symptoms are first noted.[21] Terminal phase If a person will die soon from a disease, regardless of whether that disease typically causes death, then the stage between the earlier disease process and active dying is the terminal phase. ### Extent[edit] Localized disease A localized disease is one that affects only one part of the body, such as athlete's foot or an eye infection. Disseminated disease A disseminated disease has spread to other parts; with cancer, this is usually called metastatic disease. Systemic disease A systemic disease is a disease that affects the entire body, such as influenza or high blood pressure. ## Classification[edit] Main article: Nosology Diseases may be classified by cause, pathogenesis (mechanism by which the disease is caused), or by symptom(s). Alternatively, diseases may be classified according to the organ system involved, though this is often complicated since many diseases affect more than one organ. A chief difficulty in nosology is that diseases often cannot be defined and classified clearly, especially when cause or pathogenesis are unknown. Thus diagnostic terms often only reflect a symptom or set of symptoms (syndrome). Classical classification of human disease derives from the observational correlation between pathological analysis and clinical syndromes. Today it is preferred to classify them by their cause if it is known.[22] The most known and used classification of diseases is the World Health Organization's ICD. This is periodically updated. Currently, the last publication is the ICD-11. ## Causes[edit] See also: Cause (medicine) and Transmission (medicine) Only some diseases such as influenza are contagious and commonly believed infectious. The microorganisms that cause these diseases are known as pathogens and include varieties of bacteria, viruses, protozoa, and fungi. Infectious diseases can be transmitted, e.g. by hand-to-mouth contact with infectious material on surfaces, by bites of insects or other carriers of the disease, and from contaminated water or food (often via fecal contamination), etc.[23] Also, there are sexually transmitted diseases. In some cases, microorganisms that are not readily spread from person to person play a role, while other diseases can be prevented or ameliorated with appropriate nutrition or other lifestyle changes. Some diseases, such as most (but not all) forms of cancer, heart disease, and mental disorders, are non-infectious diseases. Many non-infectious diseases have a partly or completely genetic basis (see genetic disorder) and may thus be transmitted from one generation to another. Social determinants of health are the social conditions in which people live that determine their health. Illnesses are generally related to social, economic, political, and environmental circumstances. Social determinants of health have been recognized by several health organizations such as the Public Health Agency of Canada and the World Health Organization to greatly influence collective and personal well-being. The World Health Organization's Social Determinants Council also recognizes Social determinants of health in poverty. When the cause of a disease is poorly understood, societies tend to mythologize the disease or use it as a metaphor or symbol of whatever that culture considers evil. For example, until the bacterial cause of tuberculosis was discovered in 1882, experts variously ascribed the disease to heredity, a sedentary lifestyle, depressed mood, and overindulgence in sex, rich food, or alcohol, all of which were social ills at the time.[24] When a disease is caused by a pathogen (e.g., when the disease malaria is caused by infection by Plasmodium parasites.), the term disease may be misleadingly used even in the scientific literature in place of its causal agent, the pathogen. This language habit can cause confusion in the communication of the cause and effect principle in epidemiology, and as such it should be strongly discouraged.[25] ### Types of causes[edit] Airborne An airborne disease is any disease that is caused by pathogens and transmitted through the air. Foodborne Foodborne illness or food poisoning is any illness resulting from the consumption of food contaminated with pathogenic bacteria, toxins, viruses, prions or parasites. Infectious Infectious diseases, also known as transmissible diseases or communicable diseases, comprise clinically evident illness (i.e., characteristic medical signs or symptoms of disease) resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism. Included in this category are contagious diseases – an infection, such as influenza or the common cold, that commonly spreads from one person to another – and communicable diseases – a disease that can spread from one person to another, but does not necessarily spread through everyday contact. Lifestyle A lifestyle disease is any disease that appears to increase in frequency as countries become more industrialized and people live longer, especially if the risk factors include behavioral choices like a sedentary lifestyle or a diet high in unhealthful foods such as refined carbohydrates, trans fats, or alcoholic beverages. Non-communicable A non-communicable disease is a medical condition or disease that is non-transmissible. Non-communicable diseases cannot be spread directly from one person to another. Heart disease and cancer are examples of non-communicable diseases in humans. ## Prevention[edit] Main article: Preventive medicine Many diseases and disorders can be prevented through a variety of means. These include sanitation, proper nutrition, adequate exercise, vaccinations and other self-care and public health measures. ## Treatments[edit] Main article: Therapy Medical therapies or treatments are efforts to cure or improve a disease or other health problems. In the medical field, therapy is synonymous with the word treatment. Among psychologists, the term may refer specifically to psychotherapy or "talk therapy". Common treatments include medications, surgery, medical devices, and self-care. Treatments may be provided by an organized health care system, or informally, by the patient or family members. Preventive healthcare is a way to avoid an injury, sickness, or disease in the first place. A treatment or cure is applied after a medical problem has already started. A treatment attempts to improve or remove a problem, but treatments may not produce permanent cures, especially in chronic diseases. Cures are a subset of treatments that reverse diseases completely or end medical problems permanently. Many diseases that cannot be completely cured are still treatable. Pain management (also called pain medicine) is that branch of medicine employing an interdisciplinary approach to the relief of pain and improvement in the quality of life of those living with pain.[26] Treatment for medical emergencies must be provided promptly, often through an emergency department or, in less critical situations, through an urgent care facility. ## Epidemiology[edit] Main article: Epidemiology Epidemiology is the study of the factors that cause or encourage diseases. Some diseases are more common in certain geographic areas, among people with certain genetic or socioeconomic characteristics, or at different times of the year. Epidemiology is considered a cornerstone methodology of public health research and is highly regarded in evidence-based medicine for identifying risk factors for diseases. In the study of communicable and non-communicable diseases, the work of epidemiologists ranges from outbreak investigation to study design, data collection, and analysis including the development of statistical models to test hypotheses and the documentation of results for submission to peer-reviewed journals. Epidemiologists also study the interaction of diseases in a population, a condition known as a syndemic. Epidemiologists rely on a number of other scientific disciplines such as biology (to better understand disease processes), biostatistics (the current raw information available), Geographic Information Science (to store data and map disease patterns) and social science disciplines (to better understand proximate and distal risk factors). Epidemiology can help identify causes as well as guide prevention efforts. In studying diseases, epidemiology faces the challenge of defining them. Especially for poorly understood diseases, different groups might use significantly different definitions. Without an agreed-on definition, different researchers may report different numbers of cases and characteristics of the disease.[27] Some morbidity databases are compiled with data supplied by states and territories health authorities, at national levels[28][29] or larger scale (such as European Hospital Morbidity Database (HMDB))[30] which may contain hospital discharge data by detailed diagnosis, age and sex. The European HMDB data was submitted by European countries to the World Health Organization Regional Office for Europe. ### Burdens of disease[edit] Disease burden is the impact of a health problem in an area measured by financial cost, mortality, morbidity, or other indicators. There are several measures used to quantify the burden imposed by diseases on people. The years of potential life lost (YPLL) is a simple estimate of the number of years that a person's life was shortened due to a disease. For example, if a person dies at the age of 65 from a disease, and would probably have lived until age 80 without that disease, then that disease has caused a loss of 15 years of potential life. YPLL measurements do not account for how disabled a person is before dying, so the measurement treats a person who dies suddenly and a person who died at the same age after decades of illness as equivalent. In 2004, the World Health Organization calculated that 932 million years of potential life were lost to premature death.[31] The quality-adjusted life year (QALY) and disability-adjusted life year (DALY) metrics are similar but take into account whether the person was healthy after diagnosis. In addition to the number of years lost due to premature death, these measurements add part of the years lost to being sick. Unlike YPLL, these measurements show the burden imposed on people who are very sick, but who live a normal lifespan. A disease that has high morbidity, but low mortality, has a high DALY and a low YPLL. In 2004, the World Health Organization calculated that 1.5 billion disability-adjusted life years were lost to disease and injury.[31] In the developed world, heart disease and stroke cause the most loss of life, but neuropsychiatric conditions like major depressive disorder cause the most years lost to being sick. Disease category Percent of all YPLLs lost, worldwide[31] Percent of all DALYs lost, worldwide[31] Percent of all YPLLs lost, Europe[31] Percent of all DALYs lost, Europe[31] Percent of all YPLLs lost, US and Canada[31] Percent of all DALYs lost, US and Canada[31] Infectious and parasitic diseases, especially lower respiratory tract infections, diarrhea, AIDS, tuberculosis, and malaria 37% 26% 9% 6% 5% 3% Neuropsychiatric conditions, e.g. depression 2% 13% 3% 19% 5% 28% Injuries, especially motor vehicle accidents 14% 12% 18% 13% 18% 10% Cardiovascular diseases, principally heart attacks and stroke 14% 10% 35% 23% 26% 14% Premature birth and other perinatal deaths 11% 8% 4% 2% 3% 2% Cancer 8% 5% 19% 11% 25% 13% ## Society and culture[edit] Obesity was a status symbol in Renaissance culture: "The Tuscan General Alessandro del Borro", attributed to Andrea Sacchi, 1645.[32] It is now generally regarded as a disease. How a society responds to diseases is the subject of medical sociology. A condition may be considered a disease in some cultures or eras but not in others. For example, obesity can represent wealth and abundance, and is a status symbol in famine-prone areas and some places hard-hit by HIV/AIDS.[33] Epilepsy is considered a sign of spiritual gifts among the Hmong people.[34] Sickness confers the social legitimization of certain benefits, such as illness benefits, work avoidance, and being looked after by others. The person who is sick takes on a social role called the sick role. A person who responds to a dreaded disease, such as cancer, in a culturally acceptable fashion may be publicly and privately honored with higher social status.[35] In return for these benefits, the sick person is obligated to seek treatment and work to become well once more. As a comparison, consider pregnancy, which is not interpreted as a disease or sickness, even if the mother and baby may both benefit from medical care. Most religions grant exceptions from religious duties to people who are sick. For example, one whose life would be endangered by fasting on Yom Kippur or during Ramadan is exempted from the requirement, or even forbidden from participating. People who are sick are also exempted from social duties. For example, ill health is the only socially acceptable reason for an American to refuse an invitation to the White House.[36] The identification of a condition as a disease, rather than as simply a variation of human structure or function, can have significant social or economic implications. The controversial recognition of diseases such as repetitive stress injury (RSI) and post-traumatic stress disorder (PTSD) has had a number of positive and negative effects on the financial and other responsibilities of governments, corporations, and institutions towards individuals, as well as on the individuals themselves. The social implication of viewing aging as a disease could be profound, though this classification is not yet widespread. Lepers were people who were historically shunned because they had an infectious disease, and the term "leper" still evokes social stigma. Fear of disease can still be a widespread social phenomenon, though not all diseases evoke extreme social stigma. Social standing and economic status affect health. Diseases of poverty are diseases that are associated with poverty and low social status; diseases of affluence are diseases that are associated with high social and economic status. Which diseases are associated with which states vary according to time, place, and technology. Some diseases, such as diabetes mellitus, may be associated with both poverty (poor food choices) and affluence (long lifespans and sedentary lifestyles), through different mechanisms. The term lifestyle diseases describes diseases associated with longevity and that are more common among older people. For example, cancer is far more common in societies in which most members live until they reach the age of 80 than in societies in which most members die before they reach the age of 50. ### Language of disease[edit] An illness narrative is a way of organizing a medical experience into a coherent story that illustrates the sick individual's personal experience. People use metaphors to make sense of their experiences with disease. The metaphors move disease from an objective thing that exists to an affective experience. The most popular metaphors draw on military concepts: Disease is an enemy that must be feared, fought, battled, and routed. The patient or the healthcare provider is a warrior, rather than a passive victim or bystander. The agents of communicable diseases are invaders; non-communicable diseases constitute internal insurrection or civil war. Because the threat is urgent, perhaps a matter of life and death, unthinkably radical, even oppressive, measures are society's and the patient's moral duty as they courageously mobilize to struggle against destruction. The War on Cancer is an example of this metaphorical use of language.[37] This language is empowering to some patients, but leaves others feeling like they are failures.[38] Another class of metaphors describes the experience of illness as a journey: The person travels to or from a place of disease, and changes himself, discovers new information, or increases his experience along the way. He may travel "on the road to recovery" or make changes to "get on the right track" or choose "pathways".[37][38] Some are explicitly immigration-themed: the patient has been exiled from the home territory of health to the land of the ill, changing identity and relationships in the process.[39] This language is more common among British healthcare professionals than the language of physical aggression.[38] Some metaphors are disease-specific. Slavery is a common metaphor for addictions: The alcoholic is enslaved by drink, and the smoker is captive to nicotine. Some cancer patients treat the loss of their hair from chemotherapy as a metonymy or metaphor for all the losses caused by the disease.[37] Some diseases are used as metaphors for social ills: "Cancer" is a common description for anything that is endemic and destructive in society, such as poverty, injustice, or racism. AIDS was seen as a divine judgment for moral decadence, and only by purging itself from the "pollution" of the "invader" could society become healthy again.[37] More recently, when AIDS seemed less threatening, this type of emotive language was applied to avian flu and type 2 diabetes mellitus.[40] Authors in the 19th century commonly used tuberculosis as a symbol and a metaphor for transcendence. Victims of the disease were portrayed in literature as having risen above daily life to become ephemeral objects of spiritual or artistic achievement. In the 20th century, after its cause was better understood, the same disease became the emblem of poverty, squalor, and other social problems.[39] ## See also[edit] * Medicine portal * Biology portal * Cryptogenic disease, a disease whose cause is currently unknown * Developmental disability, severe, lifelong disabilities attributable to mental or physical impairments * Environmental disease * Host–pathogen interaction * List of incurable diseases * Mitochondrial disease * Plant pathology * Rare disease, a disease that affects very few people * Sociology of health and illness * Syndrome * Philosophy of medicine ## References[edit] 1. ^ a b "Disease" at Dorland's Medical Dictionary 2. ^ White, Tim (19 December 2014). "What is the Difference Between an 'Injury' and 'Disease' for Commonwealth Injury Claims?". Tindall Gask Bentley. Archived from the original on 27 October 2017. Retrieved 6 November 2017. 3. ^ "What is the deadliest disease in the world?". WHO. 16 May 2012. 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Archived from the original on 27 October 2008. Retrieved 20 November 2008. 16. ^ "morbidity". Dorland's Medical Dictionary for Health Consumers. Elsevier. 2007. Retrieved 6 November 2017 – via medical-dictionary.thefreedictionary.com. 17. ^ Lenzer, Jeanne (14 August 2012). "Blood pressure drugs for mild hypertension: Not proven to prevent heart attacks, strokes, or early death". Slate. Archived from the original on 15 August 2012. Retrieved 16 August 2012. 18. ^ Viera, Anthony J. (2011), "Predisease: when does it make sense?" (PDF), Epidemiologic Reviews, 33 (1), pp. 122–34, doi:10.1093/epirev/mxr002, PMID 21624963, S2CID 12090327, "When the goal of preventing adverse health outcomes is kept in mind, this review poses the idea that "predisease" as a category on which to act makes sense only if the following 3 conditions are met. First, the people designated as having predisease must be far more likely to develop the disease than those not so designated. Second, there must be a feasible intervention that, when targeted to people with predisease, effectively reduces the likelihood of developing the disease. Third, the benefits of intervening on predisease must outweigh the harms in the population." 19. ^ "clinical disease". Mosby's Medical Dictionary (9th ed.). Elsevier. 2009. Retrieved 6 November 2017 – via medical-dictionary.thefreedictionary.com. "a stage in the history of a pathological condition that begins with anatomical or physiological changes that are sufficient to produce recognizable signs and symptoms of a disease" 20. ^ Shiel, William C. Jr. (20 June 2019). "Definition of Flare". MedicineNet. Retrieved 21 December 2019. 21. ^ "subclinical". Retrieved 6 November 2017 – via medical-dictionary.thefreedictionary.com. 22. ^ Loscalzo J1, Kohane I, Barabasi AL. Human disease classification in the postgenomic era: a complex systems approach to human pathobiology. Mol Syst Biol. 2007;3:124. Epub 2007 Jul 10. 23. ^ Alexander van Geen, et al. "Impact of population and latrines on fecal contamination of ponds in rural Bangladesh." Science Of The Total Environment 409, no. 17 (August 2011): 3174–82. 24. ^ Olson, James Stuart (2002). Bathsheba's breast: women, cancer & history. Baltimore: The Johns Hopkins University Press. pp. 168–70. ISBN 978-0-8018-6936-5. 25. ^ Marcantonio, Matteo; Pascoe, Emily; Baldacchino, Frederic (January 2017). "Sometimes Scientists Get the Flu. Wrong…!". Trends in Parasitology. 33 (1): 7–9. doi:10.1016/j.pt.2016.10.005. PMID 27856180. 26. ^ Hardy, Paul A.; Hardy, Paul A. J. (1997). Chronic Pain Management: The Essentials. Cambridge University Press. p. 10. ISBN 978-1-900151-85-6. OCLC 36881282. Archived from the original on 3 October 2015. 27. ^ Tuller, David (4 March 2011). "Defining an illness is fodder for debate". The New York Times. Archived from the original on 3 January 2017. 28. ^ "National Hospital Morbidity Database". aihw.gov.au. Australian Institute of Health and Welfare. Archived from the original on 13 August 2013. Retrieved 11 July 2013. 29. ^ "Hospital Morbidity Database (HMDB)". statcan.gc.ca. Statistics Canada. 24 October 2007. Archived from the original on 30 June 2016. Retrieved 21 September 2015. 30. ^ "European Hospital Morbidity Database". who.int. World Health Organization. Archived from the original on 2 September 2013. 31. ^ a b c d e f g h "Disease and injury regional estimates for 2004". who.int. World Health Organization. Archived from the original on 24 December 2010. Standard DALYs (3% discounting, age weights). Also DALY spreadsheet and YLL spreadsheet. 32. ^ Gerten-Jackson, Carol. "The Tuscan General Alessandro del Borro". Archived from the original on 2 May 2009. 33. ^ Haslam DW, James WP (2005). "Obesity". Lancet. 366 (9492): 1197–209. doi:10.1016/S0140-6736(05)67483-1. PMID 16198769. S2CID 208791491. 34. ^ Fadiman, Anne (1997). The spirit catches you and you fall down: a Hmong child, her American doctors, and the collision of two cultures. New York: Farrar, Straus, and Giroux. ISBN 978-0-374-52564-4. 35. ^ Sulik, Gayle (2010). Pink Ribbon Blues: How Breast Cancer Culture Undermines Women's Health. New York: Oxford University Press. ISBN 978-0-19-974045-1. 36. ^ Martin, Judith (2005). Miss Manners' Guide to Excruciatingly Correct Behavior. New York: W.W. Norton & Co. p. 703. ISBN 978-0-393-05874-1. OCLC 57549405. 37. ^ a b c d Gwyn, Richard (1999). "10". In Cameron, Lynne; Low, Graham (eds.). Researching and applying metaphor. Cambridge, England: Cambridge University Press. ISBN 978-0-521-64964-3. OCLC 40881885. 38. ^ a b c Span, Paula (22 April 2014). "Fighting Words Are Rarer Among British Doctors". The New York Times. Archived from the original on 2 July 2014. 39. ^ a b Diedrich, Lisa (2007). Treatments: language, politics, and the culture of illness. Minneapolis: University of Minnesota Press. pp. 8, 29. ISBN 978-0-8166-4697-5. OCLC 601862594. 40. ^ Hanne M, Hawken SJ (December 2007). "Metaphors for illness in contemporary media". Med Humanit. 33 (2): 93–99. doi:10.1136/jmh.2006.000253. PMID 23674429. S2CID 207000141. ## External links[edit] Diseaseat Wikipedia's sister projects * Definitions from Wiktionary * Media from Wikimedia Commons * News from Wikinews * Quotations from Wikiquote * Textbooks from Wikibooks * Resources from Wikiversity * Data from Wikidata * Health Topics, MedlinePlus descriptions of most diseases, with access to current research articles. * OMIM Comprehensive information on genes that cause disease at Online Mendelian Inheritance in Man * CTD The Comparative Toxicogenomics Database is a scientific resource connecting chemicals, genes, and human diseases. * NLM Comprehensive database from the US National Library of Medicine * Health Topics A–Z, fact sheets about many common diseases at Centers for Disease Control * The Merck Manual containing detailed description of most diseases * Report: The global burden of disease from World Health Organization (WHO), 2004 * Free online health-risk assessment by Your Disease Risk at Washington University in St Louis * "Man and Disease", BBC Radio 4 discussion with Anne Hardy, David Bradley & Chris Dye (In Our Time, Dec. 15, 2002) * v * t * e Basic medical terms used to describe disease conditions Signs and symptoms Symptom Syndrome Medical diagnosis Differential diagnosis Prognosis Acute Chronic Cure/Remission Disease Eponymous disease Acronym or abbreviation * v * t * e Pathology Principles of pathology * Disease * Infection * Neoplasia * Cause * Pathogenesis * Hemodynamics * Ischemia * Inflammation * Cell damage * Wound healing Cellular adaptation Atrophy Hypertrophy Hyperplasia Dysplasia Metaplasia Squamous Glandular Cell death Necrosis Coagulative necrosis Liquefactive necrosis Gangrenous necrosis Caseous necrosis Fat necrosis Fibrinoid necrosis Myocytolysis Programmed cell death Apoptosis Pyknosis Karyorrhexis Karyolysis Accumulations pigment Hemosiderin Lipochrome/Lipofuscin Melanin Steatosis Anatomical pathology * Surgical pathology * Cytopathology * Autopsy * Molecular pathology * Forensic pathology * Oral and maxillofacial pathology * Gross examination * Histopathology * Immunohistochemistry * Electron microscopy * Immunofluorescence * Fluorescence in situ hybridization Clinical pathology * Clinical chemistry * Hematopathology * Transfusion medicine * Medical microbiology * Diagnostic immunology * Immunopathology * Enzyme assay * Mass spectrometry * Chromatography * Flow cytometry * Blood bank * Microbiological culture * Serology Authority control * GND: 4032844-2 * HDS: 016312 * LCCN: sh85038411 * NARA: 10640250 * NDL: 00571210 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Disease	c0012634	5,338	wikipedia	https://en.wikipedia.org/wiki/Disease	2021-01-18T18:54:15	{"mesh": ["D004194"], "umls": ["C0012634"], "orphanet": ["377788"], "wikidata": ["Q12136"]}
A number sign (#) is used with this entry because lysinuric protein intolerance (LPI) is caused by homozygous or compound heterozygous mutation in the amino acid transporter gene SLC7A7 (603593) on chromosome 14q11. Description Lysinuric protein intolerance is caused by defective cationic amino acid (CAA) transport at the basolateral membrane of epithelial cells in kidney and intestine. Metabolic derangement is characterized by increased renal excretion of CAA, reduced CAA absorption from intestine, and orotic aciduria (Borsani et al., 1999). See also dibasic amino aciduria I (222690). Clinical Features Perheentupa and Visakorpi (1965) first described 3 Finnish infants with an inborn error of metabolism characterized by protein intolerance and deficient transport of basic amino acids. Blood urea was low and urinary lysine and arginine were increased. Kekomaki et al. (1967) described 10 children, including several pairs of sibs, with vomiting, diarrhea, failure to thrive, hepatomegaly, diffuse cirrhosis, low blood urea, hyperammonemia, and leukopenia. Symptoms were aggravated by high protein intake and relieved by protein restriction. An excess of ornithine, arginine, and lysine, but not of cystine, was excreted in the urine. Intestinal absorption of arginine and lysine was normal. A low concentration of arginine relative to lysine in body fluids was thought responsible for the hyperammonemia and reduced urea synthesis. One of the families was consanguineous. Kekomaki et al. (1968) reported a 23-year-old man with protein intolerance who refused to eat protein-rich food. Institution of cow's milk at age 1 year resulted in prolonged watery diarrhea and retardation of physical development. He grew physically with increased protein intake in his teens, but mental function deteriorated and he had episodic attacks of stupor and asterixis. The liver was enlarged and fatty. His 15-year-old affected sister also had protein intolerance. Oyanagi et al. (1970) described severe mental retardation, physical retardation, mild intestinal malabsorption syndrome, and increased urinary excretion of lysine, ornithine, and arginine in 2 Japanese sisters with second-cousin parents. Cystine excretion was always within normal limits. Malmquist et al. (1971) stated that 13 cases of familial protein intolerance had been observed in Finland. They described a Swedish patient of Finnish origin with intellectual impairment, radiographic evidence of brain atrophy, and marked skeletal fragility. Administration of alanine resulted in elevation of blood ammonia and glucose. Urea cycle function appeared to be normal and the defect was thought to concern the mechanisms by which amino nitrogen is transferred to the urea-synthesizing system. During citrulline infusion, Rajantie et al. (1981) found that LPI patients had increased plasma citrulline levels similar to controls, but excessive excretion compared to controls. Patients had subnormal increases in plasma arginine and ornithine with massive argininuria and moderate ornithinuria. The excretion rates of the third diamino acid lysine and other amino acids remained practically unaltered, thus excluding mutual competition as the cause for the increases. The results suggested that reabsorption in the normal kidney involves partial conversion of citrulline to arginine and ornithine, and that the diamino acid transport defect in LPI is located at the basolateral cell membrane of the renal tubules. This inhibits the efflux of arginine and ornithine, increasing their cellular concentration, which in turn inhibits the metabolic disposal of citrulline, and causes leakage of arginine, ornithine, and citrulline into the tubular lumen. Carpenter et al. (1985) emphasized that childhood osteopenia and osteoporosis were nearly constant complications of lysinuric protein intolerance. Laboratory studies suggested defective transport of ornithine and arginine across the plasma membrane of liver cells and across the basolateral membrane of renotubular cells. The defect in transport of dibasic amino acids results in lack of sufficient ornithine to support activity of hepatic ornithine transcarbamylase (OTC; 300461). Episodic hyperammonemia occurs, similar to that observed in OTC deficiency (311250). Shaw et al. (1989) described a 36-year-old man and his 32-year-old brother who presented in adult life with hyperammonemic coma due to lysinuric protein intolerance. They were of normal intellect and had maintained good health, until presentation in their thirties, by unconscious dietary protein avoidance. Parto et al. (1994) described the clinical courses and autopsy findings of 4 pediatric LPI patients. All had developed acute respiratory insufficiency. In addition to pulmonary hemorrhages, 3 of them had pulmonary alveolar proteinosis and 1 had cholesterol granulomas. Three patients had clinically obvious renal insufficiency, but all 4 showed histologic signs of immune complex-mediated glomerulonephritis. The patients also developed hepatic insufficiency with fatty degeneration or cirrhosis. All patients showed anemia, thrombocytopenia, and a severe bleeding tendency. Bone marrow of 3 patients was hypercellular, but the number of megakaryocytes was decreased in 2 cases. Amyloid was present in the lymph nodes and spleen. Bone specimens showed osteoporosis. Parto et al. (1994) concluded that in addition to being at risk of protein malnutrition in the active growth phase, probably due to higher requirements for total nitrogen and amino acids, pediatric patients with lysinuric protein intolerance are predisposed to develop pulmonary alveolar proteinosis and glomerulonephritis. McManus et al. (1996) reported a 21-year-old woman who had presented at 8 months of age with persistent vomiting and failure to thrive. At that time there was a marked increase in urinary lysine excretion and ornithine and arginine to a lesser extent. The urinary orotic acid concentration was also raised and casein protein loading tests increased the concentrations of all plasma amino acids except lysine, ornithine, and arginine. A protein-restricted diet was recommended and supplements of lysine, arginine, and citrulline were prescribed. During the teenage years, compliance with the diet and amino acid supplements was poor, and she developed osteoporosis. She showed gradual deterioration with episodic disturbances of liver function and hyperammonemia 2 years before her death. Immediately before death she became comatose, had persistently raised serum ammonia concentrations, metabolic acidosis, and a coagulopathy. She died despite intensive therapy, including intravenous arginine for the hyperammonemia. Postmortem examination revealed hepatic micronodular cirrhosis with extensive fatty changes. The lungs showed pulmonary alveolar proteinosis. Immunofluorescence and electron microscopy revealed glomerulonephritis with predominant IgA deposition. McManus et al. (1996) suggested that the glomerulopathy may have been related to the failure of the normal role of the liver in clearance of immune complexes from the circulation. Pulmonary hemorrhage and alveolar proteinosis had also been previously described in Finnish cases. In a 3-year-old boy of Norwegian descent with LPI and immune complex disease consistent with systemic lupus erythematosus (SLE; 152700), Parsons et al. (1996) presented evidence suggesting that the immune complex disease may be the basis of the respiratory problems. In 4 patients with LPI, Duval et al. (1999) found features that fulfilled the diagnostic criteria for familial hemophagocytic lymphohistiocytosis (HPLH1; 267700). Mature histiocytes and neutrophil precursors participated in hemophagocytosis in the bone marrow. Serum levels of ferritin and lactate dehydrogenase were elevated, hypercytokinemia was present, and soluble interleukin-2 receptor levels were increased up to 18.6-fold. Duval et al. (1999) suggested that the diagnosis of LPI should be considered in any patient presenting with hemophagocytic lymphohistiocytosis. Biochemical Features Smith et al. (1988) found that, contrary to their findings in cultured skin fibroblasts, LPI red cells showed normal net uptake and efflux of cationic amino acids. Inheritance The studies of Kekomaki et al. (1967) and Norio et al. (1971), who called the condition 'lysinuric protein intolerance,' confirmed autosomal recessive inheritance. Diagnosis Sperandeo et al. (2008) noted that the diagnosis of LPI is often difficult because of vague clinical presentation. Classic symptoms of protein intolerance may remain unnoticed during the first and second decades of life due to unconscious avoidance of dietary protein. However, patients usually present with gastrointestinal symptoms soon after weaning. ### Prenatal Diagnosis Sperandeo et al. (1999) demonstrated the feasibility of prenatal diagnosis of LPI by linkage analysis. Clinical Management In a 4-year-old girl with LPI, Carpenter et al. (1985) found that oral citrulline therapy resulted in 'substantial increase in protein tolerance..., striking acceleration of linear growth, as well as increase in bone mass...' Whereas impairment of urea production in LPI results from a defect in the uptake of ornithine in liver cells, citrulline, which is metabolized to arginine and ornithine, is absorbed by a mechanism that is unaffected in LPI. Mapping By genomewide linkage analysis of 20 Finnish LPI families, Lauteala et al. (1997) found linkage to chromosome 14q (maximum pairwise lod scores of 5.82 at marker D14S742 and 6.91 at D14S283). Haplotype analysis identified a 10-cM candidate interval between D14S72 and MYH7 (160760), which had previously been mapped to 14q12. There was strong evidence for a founder effect in Finland. By linkage analysis, Lauteala et al. (1998) concluded that LPI in non-Finnish cases is due to mutation in the same gene on 14q. They studied 19 non-Finnish families, of which 13 were Italian, 1 Swedish, 1 Latvian, 2 Moroccan, 1 Saudi Arabian, and 1 Turkish. These families showed no linkage disequilibrium except in an Italian family cluster. Molecular Genetics In 31 Finnish patients with lysinuric protein intolerance, Torrents et al. (1999) identified homozygosity for a founder mutation in the SLC7A7 gene (603593.0001). Borsani et al. (1999) defined the Finnish mutation as a splice acceptor change resulting in a frameshift and premature translation termination. Torrents et al. (1999) identified compound heterozygosity for 2 SLC7A7 mutations (603593.0005; 603593.0006) in a Spanish LPI patient. In affected members of 2 unrelated Italian LPI families, Borsani et al. (1999) identified 2 different homozygous mutations in the SLC7A7 gene (603593.0002 and 603593.0003, respectively). Noguchi et al. (2000) identified SLC7A7 mutations (603593.0008; 603593.0009) in Japanese LPI patients. Mykkanen et al. (2000) performed mutation screening of 20 non-Finnish LPI patients and found 10 novel mutations in the SLC7A7 gene. Sperandeo et al. (2008) identified 9 novel mutations in the SLC7A7 gene, and noted that a total of 43 different mutations had been identified in over 100 patients with LPI. Mutations were spread throughout the gene with no apparent genotype/phenotype correlations. Font-Llitjos et al. (2009) identified 11 mutations in the SLC7A7, including 7 novel mutations, in 11 patients from 9 unrelated families with LPI. Two of the mutations were large deletions involving exons 4 to 11 and exons 6 through 11 (603593.0011), respectively. These deletions were identified using multiplex ligation probe amplification (MLPA) assays and were found to result from the recombination of Alu repeats at introns 3 and 5, respectively, and the same AluY sequence in the 3-prime region of the SLC7A7 gene. Patients with the large deletions had the most severe phenotypes, likely resulting from dramatic loss of transport function. INHERITANCE \- Autosomal recessive GROWTH Height \- Decreased stature Other \- Failure to thrive \- Centripetal obesity \- Thin extremities RESPIRATORY Lung \- Interstitial changes on chest X-ray \- Respiratory insufficiency \- Alveolar proteinosis \- Pulmonary hemorrhage ABDOMEN Liver \- Hepatomegaly Pancreas \- Pancreatitis Spleen \- Splenomegaly Gastrointestinal \- Nausea \- Vomiting \- Diarrhea \- Aversion to protein-rich food \- Impaired intestinal absorption of cationic amino acids GENITOURINARY Kidneys \- Chronic renal disease \- Impaired renal absorption of cationic amino acids SKELETAL \- Osteoporosis \- Delayed bone age \- Frequent fractures SKIN, NAILS, & HAIR Skin \- Loose skin \- Hyperelastic skin Hair \- Thin, sparse hair MUSCLE, SOFT TISSUES \- Hypotonia \- Muscle weakness \- Muscle atrophy NEUROLOGIC Central Nervous System \- Coma may occur after force feeding of high protein diet \- Mental delay or retardation (uncommon) Behavioral Psychiatric Manifestations \- Psychotic episodes have been rarely reported METABOLIC FEATURES \- Postprandial hyperammonemia \- Hyperammonemic coma HEMATOLOGY \- Anemia \- Leukopenia \- Thrombocytopenia \- Bone marrow may show hemophagocytosis LABORATORY ABNORMALITIES \- Urinary excretion of cationic amino acids (lysine, arginine, ornithine) \- Decreased blood levels of cationic amino acids \- Hyperammonemia after protein intake \- Orotic aciduria \- Increased serum lactate hydrogenase \- Increased serum ferritin MISCELLANEOUS \- Highly variable phenotype \- Onset in infancy after weaning from being breast-fed \- Patients look as if they have protein deficiency or malnutrition \- Incidence in Finland is 1 in 76,000 births \- Incidence in Japan is 1 in 57,000 MOLECULAR BASIS \- Caused by mutation in the solute carrier family 7 (cationic amino acid transporter, y+ system), member 7 gene (SLC7A7, 603593.0001 ) ▲ 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	LYSINURIC PROTEIN INTOLERANCE	c0268647	5,339	omim	https://www.omim.org/entry/222700	2019-09-22T16:28:43	{"doid": ["0060439"], "mesh": ["C562687"], "omim": ["222700"], "orphanet": ["470"], "synonyms": ["Alternative titles", "DIBASIC AMINO ACIDURIA II"], "genereviews": ["NBK1361"]}
Medication phobia Other namesPharmacophobia SpecialtyPsychology Medication phobia, also known as pharmacophobia, is a fear of the use of pharmacological treatments.[1] In severe, excessive and irrational cases it may be a type of specific phobia. While lack of awareness by patient or doctor of adverse drug reactions can have serious consequences, having a phobia of medications can also have serious detrimental effects on patient health, for example refusal of necessary pharmacological interventions.[2][3][4] Medication phobia can also lead to problems with medication compliance.[5] Medication phobia can also present in parents who are concerned about giving medications to their children,[6] fearing that the medications will do more harm than good.[7] Medication phobia can be triggered by unpleasant adverse reactions to medications which are sometimes prescribed inappropriately or at excessive doses. Lack of awareness of the patient's predisposition to adverse effects (e.g. anxious patients and the elderly) and failure to attribute the adverse effects to the drug serves to compound the phobia.[8][9] Starting at low doses and slowly increasing the medication dosage can avoid medication phobia secondary to adverse effects from developing.[9] Fears of medication use is also prevalent in people who have experienced unpleasant withdrawal effects from psychotropic drugs.[10] Sometimes patients wrongly associate symptoms of an acute disease or illness with medications used to treat the disease or illness. This form of pharmacophobia can be treated by attempting to convince the patient to take test doses of the drug or another drug in the same drug class to prove to the patient that the symptoms were not due to the drug but due to the illness the drug was taken to treat.[11] ## See also[edit] * List of phobias ## References[edit] 1. ^ Bossini, L.; Martinucci, M.; Paolini, K.; Castrogiovanni, P. (Jan 2005). "Panic-agoraphobic spectrum and light sensitivity in a general population sample in Italy". Can J Psychiatry. 50 (1): 39–45. doi:10.1177/070674370505000108. PMID 15754664.[permanent dead link] 2. ^ Marks, R. (2001). "Pharmaphilia and pharmaphobia". Clin Dermatol. 19 (1): 69–71. doi:10.1016/S0738-081X(00)00215-7. PMID 11369491. 3. ^ "Drugs that call for extra caution. Heed these warnings, but don't let "pharmaphobia" threaten your heart". Heart Advis. 9 (12): 4–5. Dec 2006. PMID 17299872. 4. ^ Naess, K. (Sep 1974). "[Editorial: "Pharmaphobia"]". Tidsskr Nor Laegeforen. 94 (25): 1544–5. PMID 4424846. 5. ^ KLE HON; TF LEUNG (2008). "Killing Many Birds with One Stone" (PDF). HK J Paediatr (New Series). Hong Kong: Hong Kong Journal of Pediatrics. 13: 135–138. 6. ^ Winner, Paul; Rothner, David (23 Jan 2001). Headache In Children And Adolescents. BC Decker. p. 100. ISBN 1-55009-125-5. 7. ^ Diamond, Seymour; Diamond, Amy (2001). Headache and your child: the complete guide to understanding and treating migraines and other headaches in children and adolescents. New York: Simon Schuster. p. 56. ISBN 978-0-684-87309-1. 8. ^ M.d. Kamath, Bob (30 May 2007). Is Your Balloon About to Pop?. Booksurge Llc. p. 173. ISBN 978-1-4196-6556-1. 9. ^ a b HOSPICE AND PALLIATIVE CARE ORGANIZATION, OHIO (2001). PALLIATIVE CARE POCKET CONSULTANT. Kendall Hunt Publishing. p. 25. ISBN 978-0-7872-8701-6. 10. ^ Ashton CH (2002). "Benzodiazepines: how they work & how to withdraw". The Ashton Manual. benzo.org.uk. Retrieved 2009-05-27. 11. ^ Mastrovich, JD; Patterson, R; Davison, R; Harris, KE (2001). "Using test dose challenges to restore essential therapy in patients with idiopathic anaphylaxis and pharmacophobia: report of a patient with idiopathic anaphylaxis and statin phobia". Allergy Asthma Proc. 22 (5): 303–9. PMID 11715221. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Medication phobia	None	5,340	wikipedia	https://en.wikipedia.org/wiki/Medication_phobia	2021-01-18T18:59:06	{"wikidata": ["Q6806658"]}
Candidid SpecialtyDermatology Candidid is a skin condition, an id reaction, similar to dermatophytids.[1]:311 ## See also[edit] * Candidiasis * List of cutaneous conditions ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. ## External links[edit] Classification D * ICD-10: L30.2 (ILDS L30.220) * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji 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	Candidid	c2888176	5,341	wikipedia	https://en.wikipedia.org/wiki/Candidid	2021-01-18T18:44:55	{"umls": ["C2888176"], "icd-10": ["L30.2"], "wikidata": ["Q5031911"]}
A rare genetic multisystem disorder characterized by progressive pancytopenia with bone marrow failure, variable congenital malformations and predisposition to develop hematological or solid tumors. ## Epidemiology The expected prevalence at birth is at least 1/160,000. ## Clinical description The first signs of Fanconi anemia (FA) are typically non-hematological features. Limb anomalies typically affect the extremities, are unilateral or (usually asymmetric) bilateral. Minor anomalies can also be present such as low birth length and weight, microcephaly and/or microphthalmia. Skin pigmentation abnormalities (café-au-lait spots) and hypoplastic thenar eminence are frequent. Almost 20% of patients have ear malformations with or without hearing loss. Congenital malformations may involve other organ systems and vary within families. Short stature is syndromic and/or associated to endocrinopathies. Fertility is frequently impaired in males, and is highly disturbed in half of females. When congenital malformations are not prominent, diagnosis may be delayed until the onset of hematological anomalies. Bone marrow failure (BMF) occurs at a median age of 7 years, developing in 90% of patients by 40 years of age. The first manifestations are macrocytosis (very early) and thrombocytopenia. In patients with somatic mosaïcism, blood counts may stay normal until occurrence of hematological malignancy. In general, patients are highly predisposed to solid tumors (most frequently head and neck or anogenital regions). ## Etiology FA is genetically heterogeneous and the implicated variants are involved in DNA repair and genomic stability. More than 90% of patients have mutations within FANCA, FANCC, FANCG or FANCD2 genes. Mutations in genes with an upstream role in the FA-core complex are associated with classic FA. Some of ''Downstream'' variants (e.g.BRCA2) are associated with a very high risk of solid tumors in infancy and early childhood. ## Diagnostic methods Diagnosis relies on the evaluation of chromosomal breakage induced by diepoxybutane (DEB) or mitomycin C (MMC). This test may be normal in patients with somatic mosaicism; in which case, tests should be performed on fibroblasts. ## Differential diagnosis FA clinical manifestations overlap with many malformation syndromes (Dubowitz, Seckel, Holt-Oram, Baller-Gerold, thrombocytopenia-absent radius, Nijmegen breakage syndromes, VACTERL association, dyskeratosis congenital, Blackfan-Diamond anemia) and diagnosis of FA is often delayed until a patient develops BMF or malignancies. FA should be considered in the differential diagnosis of all young patients with BMF of unknown etiology, and in other cancer predisposition syndromes (Bloom, Rothmund-Thomson or Werner syndromes) or syndromes with either constitutional or acquired BMF. ## Antenatal diagnosis Prenatal diagnosis is feasible with a chromosomal breakage assay on fetal blood or, when the mutation is known, by genetic testing. ## Genetic counseling The disorder is usually autosomal recessive. Very rarely, X-linked (FANCB, < 1%) or autosomal dominant (FANCR, <1%) transmission may occur. If the variant is known, medical assisted reproduction should be offered to parents. ## Management and treatment Supportive care includes transfusions of packed red blood cells (RBC) or leucodepleted platelets but if regular transfusion is required, hematopoietic stem cell transplantation (HSCT) should be considered. Currently, the only curative treatment for hematologic manifestations is HSCT. Symptomatic treatment includes oral androgen administration, which improves blood counts in most patients but is associated with severe liver toxicity and does not suppress the leukemic risk. Administration of G-CSF, best after bone marrow aspirate, should be considered in patients with acute severe infections. Regular screening for hematological malignancies is recommended during childhood in non-transplanted patients; with the exception of 1q anomalies, identification of a clonal event should lead to transplantation. Screening for solid tumors should start in adolescence, especially in the post-transplant setting; risk may be higher in patients with chronic GVHD. Any suspect lesion should be biopsied. When malignancies develop, treatment is complicated by the sensitivity to radiation and chemotherapy of FA patients. ## Prognosis HSCT efficiently treats BMF. Solid tumors prevention and treatment are the main challenge for transplanted patients. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Fanconi anemia	c0015625	5,342	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=84	2021-01-23T18:39:33	{"gard": ["6425"], "mesh": ["D005199"], "omim": ["227645", "227646", "227650", "300514", "600901", "603467", "609053", "609054", "610832", "613390", "613951", "614082", "614083", "615272", "616435", "617243", "617244", "617247", "617883"], "umls": ["C0015625"], "icd-10": ["D61.0"], "synonyms": ["Fanconi pancytopenia"]}
Sexual fetishism relating to undergarments One type of underwear fetishism involves stockings. Underwear fetishism is a sexual fetishism relating to undergarments, and refers to preoccupation with the sexual excitement of certain types of underwear, including panties, stockings, pantyhose, bras, or other items. Some people can experience sexual excitement from wearing, while others get their excitement when observing, handling, or smelling the underwear worn by another, or watching somebody putting underwear on or taking it off. Underwear fetishism is not considered as paraphilia unless it causes distress or serious problems for the person or those associated with them. ## Contents * 1 Prevalence * 2 Panties * 2.1 Used panties * 3 Pantyhose * 3.1 Men wearing pantyhose * 4 Stockings * 5 Silk and satin * 6 Jockstraps * 7 See also * 8 References ## Prevalence To determine relative prevalences of different fetishes, Italian researchers obtained an international sample of 5,000 individuals from 381 fetish-themed discussion groups. The relative prevalences were estimated based on (a) the number of groups devoted to a particular fetish, (b) the number of individuals participating in the groups and (c) the number of messages exchanged. Within the sample population (a population of adults online involved in sexual discussion), 12% indicated a sexual preference for underwear.[1][2] In Singapore, there is a minority of males who appear to have a fetish for stealing women's underwear from outside their residences.[3] For example, in June 2020, a man was jailed for stealing underwear during the COVID-19 circuit breaker.[4] ## Panties A Japanese vending machine selling used panties for Burusera See also: Panty raid and panchira Panty fetishism is a fetish in which one eroticizes panties (or similar styles of underwear). Fetishistic behavior can involve sharing printed or electronic material depicting exposure of panties, usually of a softcore nature, or direct sight and physical contact with the panties. Some individuals have a paraphilia for a specific type of panty. For example, a common subclass of panty fetishism are panties that show the exposed buttocks (i.e. thongs and G-strings). Further, some individuals have the opposite preference, and are attracted to panties that cover the buttocks. ### Used panties One of the most common types of panty fetishes involves used panties. In this fetish, panties or other intimate clothing that have previously been worn are eroticized. With the advent of the Internet, a "used panty" industry has sprung up to cater to this fetish, consisting primarily of women or (on a much smaller scale) men selling their used undergarments through independent websites or panty seller groups. Sellers tend to charge for the number of days for which the panties or other garment are worn, and prices generally increase with time worn. In Japan, this industry has a long-established brick-and-mortar presence, known as burusera shops.[5][6][7] Outside Japan, such shops exist only on the internet and are generally run by individual women or men, as opposed to registered businesses. ## Pantyhose This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (May 2014) (Learn how and when to remove this template message) Pantyhose fetishism is a very common fetish involving women's pantyhose (known as "tights" in the UK). The sub-categories and degrees of pantyhose fetishism are too many to list and is in many cases combined with other fetishes or paraphilias of the fetishist (and often their partner too) so as to make an individual's preferences as with many other popular fetishes unique. A few typical examples of subcategories perhaps would be: * a focus on certain areas of the body while wearing pantyhose, e.g., feet, a variation of the very common foot fetishism, * wearing pantyhose with other specific garments, e.g. shoes, boots, or skirts, uniforms that usually include pantyhose (girl at work, secretary, flight attendant, policewoman, Hooters Girl waitress, girl next door, dream girl, French house maid, model, pinup women etc.), * certain styles e.g., sheer-to-waist, sandalfoot, reinforced toe, opaque, patterned or specific deniers; certain brands or shades, * tightlaced pantyhose, which places more emphasis on size of thighs and lace to give the rest of her legs the opaque style, * ripped pantyhose with a short skirt, this is to emphasize some roleplaying, the fashion or uniform roleplay may include (schoolgirl, emo, goth and alt), * simply admiring women who wear pantyhose (a mild form of voyeurism), * finding the wearing of them to be a primarily sensual comforting experience, rather than sexual. ### Men wearing pantyhose See also: Transvestic fetishism and Pantyhose for men Some males with a pantyhose fetish may wear them for some of the reasons mentioned above. Men who are discovered wearing women's pantyhose for fetishistic purposes may be labeled as transvestites by their partners, families, workmates, and society. A man who likes to wear pantyhose may be deeply anxious and worried about being associated with homosexuality or transvestism, and as such most will endeavour to keep the fetish private, commonly hiding it from their wives or partners (though some do have the ultimate trust and understanding of their partners) due to such enormous fears that are invariably completely out of context with such relatively mild desires. There is a small number of women, perhaps due to the nature of the garment who will also find them stimulating. ## Stockings A woman wearing a pulled up skirt, stockings and garters Some people experience sexual excitement from the look or feel of women's stockings. The attraction may be to the look or feel of the material, such as sheer nylon or silk, to the use of a garter belt, or to the act of a person donning or removing stockings. The attraction of stockings may include the perception that stockings and the associated use of garters, lace, high fashion, appliqué and the exposure of the thigh, are aesthetically pleasing or erotic. Stocking fetishism may include other feminine clothing which contributes to enhancing the fantasy. Some men find it arousing to collect and wear stockings, panties, and suspender belts. In some cases, this is done for the purpose of momentary sexual stimulation. Others wear such a complete combination under a pair of trousers or beneath a business suit on a regular daily basis.[8] The increasing acceptance with which modern societies have viewed this particular subject since the middle of the 1950s decade enabled many men to indulge in this practice to such an extent that it has been branded as a 20th-century social phenomenon.[citation needed] In contrast to conventional face-to-face purchasing, the growth of internet purchasing has enabled men to browse through many different assorted underwear offerings anonymously. Presently, many manufacturers and retailers specializing in lingerie and associated women’s apparel throughout the world cater to the need of an ever-growing population of men who usually invest significant amounts of effort and expense in order to acquire whatever intimate garments may suit their particular needs.[9] Such fetishists may also be divided into many subcategories relative to their attraction to certain types of stockings.[10] Some find fishnet stockings more arousing compared to other forms of stockings, for example. Other preferences include fully fashioned (seamed) stockings, seamless stockings, designer stockings, luxury stockings, reinforced heel and toe stockings (RHT), stay-ups, etc. Garter belts can be very tricky to attach to a lace welt, therefore it is much easier to start wearing garter belts with old-fashioned regular stockings that have a plain welt without any lace, designs, or silicon lining. Usually, garter belt fits around the waist or just a little lower, but it is not a good idea to have a garter belt too low on the hips because it may begin to slide down when walking as stockings tug on the straps.[original research?] In the Anime and Manga subculture, zettai ryōiki (絶対領域) (lit. Absolute Area/Domain/Region/Territory) refers to the bare skin between thigh-high stockings or socks and the skirt (though in some cases shorts also). Woman in a lace bra Silky full slip and stockings ## Silk and satin Some people experience sexual excitement from the look or feel of articles made of silk or satin fabric. Such interest is usually directed towards the person wearing silk or satin, but it can also be directed towards the garment itself, or to the feel of the garment when worn. The attraction can be to the physical properties of the garment, such as softness, smoothness, drape, and shine, and to its association with elegance, glamour, romance and opulence. The principal materials which are considered erotic are charmeuse silk (silk woven so that it has a sheen) and satins (such as acetate satin and rayon satin), but other materials with similar properties, such as spandex and polyester are also admired.[11][12] ## Jockstraps Jockstrap fetishism is the term applied to the sexual arousal from handling, wearing a jockstrap, watching another put one on, or sniffing a jockstrap. To quote on jockstrap sniffing, "jock[strap] sniffing specifically refers to the practice of inhaling odors from unlaundered jockstraps for the purpose of sexual stimulation. Practitioners, (usually male) are known as 'jock sniffers' and acquire unlaundered jockstraps either by swapping such garments with like-minded individuals or by swiping them from locker rooms, lockers or unattended gym bags".[13] Sexual arousal generally concerns the jockstrap itself and is why it is regarded as a paraphilia rather than a fetish. It is also regarded as a homosexual exclusive fetish even though straight males do often do this as well.[14][dead link][verification needed] ## See also * Clothing fetish * Cross-dressing * Rubber and PVC fetishism * Upskirt * Underwear as outerwear * Uniform fetishism ## References 1. ^ Scorolli C, Ghirlanda S, Enquist M, Zattoni S, Jannini EA (2007). "Relative prevalence of different fetishes". Int. J. Impot. Res. 19 (4): 432–7. doi:10.1038/sj.ijir.3901547. PMID 17304204. (Table 3) 2. ^ Dobson, Roger (2007). Heels are the world's No 1 fetish. The Independent Online Edition, "Archived copy". Archived from the original on 2008-05-20. Retrieved 2007-02-01.CS1 maint: archived copy as title (link), accessed February 2007. 3. ^ "Man arrested for series of underwear theft in Tampines: 2,500 undergarments seized by police". Stomp. 2020-04-03. Retrieved 2020-06-14. 4. ^ "Jail for serial bra thief who left house during circuit breaker to steal underwear". CNA. Retrieved 2020-06-14. 5. ^ "The economics of pricing used panties". April's Body. 13 January 2014. Archived from the original on 22 February 2014. Retrieved 16 February 2014. 6. ^ Natalie Paris (3 February 2014). "The world's weirdest vending machines". Telegraph. UK. 7. ^ Charles Waterstreet (21 June 2014). "Vending machines reveal cultural tolerance of abuse". The Sydney Morning Herald. 8. ^ Jeanette, Doris (2011). "Sexual Empowerment for Men: Love and Understanding for Men Who Wear Panties". drjeanette.com. Retrieved 31 December 2012. 9. ^ "Lingerie Tips for Men". HerRoom. Retrieved 31 December 2012. 10. ^ The Stocking Passion: Imagination and beyond (retrieved on May 9, 2007) 11. ^ Steele, Valerie (1985). Fashion and Eroticism: Ideals of Feminine Beauty from the Victorian Era to the Jazz Age. Oxford University Press, New York. ISBN 0-19-503530-5. 12. ^ Browne, Ray B. (1982). Objects of special devotion: fetishism in popular culture. Bowling Green University Popular Press. ISBN 0-87972-191-X. 13. ^ Pronger, Brian (May 15, 1992). The Arena of Masculinity. St. Martin's Griffin. ISBN 978-0312062934. 14. ^ "Understanding Male Sexuality". * Kunzle, David (2004). Fashion and Fetishism. Sutton. ISBN 0-7509-3808-0. * v * t * e Sexual fetishism Actions, states * Aquaphilia * Autassassinophilia * Coprophilia * Cuckold / Cuckquean * Emetophilia * Erotic hypnosis * Erotic lactation * Erotic spanking * Exhibitionism * Forced seduction * Gaining and feeding * Medical fetishism * Omorashi * Paraphilic infantilism (adult baby) * Pregnancy * Smoking * Tickling * Total enclosure * Transvestic * Tightlacing * Tamakeri * Urolagnia * Vorarephilia * Wet and messy fetishism Body parts * Armpit * Breast * Belly * Buttocks * Eyeball * Fat * Feet * Hands * Height * Hair * Legs * Navels * Noses Clothing * Boots * Ballet boots * Boot worship * Thigh-high boots * Clothing * Corset * Diapers * Gloves * Pantyhose * Latex * Rubber and PVC * Shoes * Spandex * Underwear * Uniforms Objects * Balloons * Dolls * Latex and PVC * Robots * Spandex Controversial / illegal * Lust murder * Necrophilia * Rape fantasy * Zoophilia Culture / media * Artists * Fetish art * Fetish clubs * Fashion * Magazines * Models Race * Asian sexual fetishism * Ethnic pornography * Sexual racism Related topics * BDSM * FetLife * International Fetish Day * Kink * Leather subculture * Leather Pride flag * Sexual roleplay * Book * Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Underwear fetishism	None	5,343	wikipedia	https://en.wikipedia.org/wiki/Underwear_fetishism	2021-01-18T19:06:23	{"wikidata": ["Q839072"]}
A rare mitochondrial disease characterized by a variable clinical phenotype with the core features of optic atrophy, ataxia, and hypotonia. Additional common manifestations include global developmental delay with or without regression, neuropathy, spasticity, and microcephaly, less frequently seizures, movement disorder, hearing loss, and respiratory failure. Brain imaging may show abnormalities of the corpus callosum, basal ganglia, and midbrain, cerebral or cerebellar atrophy, or white matter abnormalities. The condition is frequently fatal at an early age. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome	None	5,344	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=543470	2021-01-23T18:07:52	{"icd-10": ["G71.3"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Dilaceration" – news · newspapers · books · scholar · JSTOR (September 2014) (Learn how and when to remove this template message) Dilaceration SpecialtyDentistry Dilaceration is a developmental disturbance in shape of teeth. It refers to an angulation, or a sharp bend or curve, in the root or crown of a formed tooth. This disturbance is more likely to affect the maxillary incisors and occurs in permanent dentition.[1] Although this may seem more of an aesthetics issue, an impacted maxillary incisor will cause issues related to occlusion, phonetics, mastication, and psychology on young patients.[2] ## Contents * 1 Description * 2 Signs and Symptoms * 3 Cause * 4 Mechanism/ Pathophysiology * 5 Diagnosis * 6 Prevention/ Treatment * 7 Prognosis * 8 Epidemiology * 9 Research Directions * 10 See also * 11 References * 12 External links ## Description[edit] The condition is thought to be due to trauma or possibly a delay in tooth eruption relative to bone remodeling gradients during the period in which tooth is forming.[3] The result is that the position of the calcified portion of the tooth is changed and the remainder of the tooth is formed at an angle. The curve or bend may occur anywhere along the length of the tooth, sometimes at the cervical portion, at other times midway along the root or even just at the apex of the root, depending upon the amount of root formed when the injury occurred. Such an injury to a permanent tooth, resulting in dilaceration, often follows traumatic injury to the deciduous predecessor in which that tooth is driven apically into the jaw. ## Signs and Symptoms[edit] This image can be used as a reference point for dilaceration. As can be seen in this panorex image of a cleft palate, among the mixed dentition, all of the teeth remain to have straighter roots. Slight curves are common among the molars, however, there are no extreme curves or bends along the length of the teeth. Dilaceration would appear far more obviously in a radiograph Pressure or pain in the jaw area can be associated with dilaceration. Checking in with a general dentist and an endodontist should be done if a patient feels these symptoms.[4] Signs in radiographic imaging will indicate an bend in the tooth's root as opposed to a straight growth.[1] Dilaceration of the crown, the top part of the teeth that we see when we smile, can be visually seen for diagnosis. Crown dilaceration will present itself as a tooth that is angled to face outward or inward. It will be a non axial displacement and more of a longitudinal displacement.[5] ## Cause[edit] This image is used to orient on the formation of primary and permanent teeth. Focusing on the lower teeth in this xray, you may notice it seems that some small teeth are floating on top of larger more developed teeth. These floating teeth are primary teeth while the teeth with longer more developed roots are the permanent teeth. The etiology of dilaceration is not very commonly known. However, it is thought to be related to: * Traumatic injury that may have taken place to the deciduous teeth, also known as baby teeth.[1] * Idiopathic developmental disturbance, meaning it is unknown [1] * An ankylosed deciduous tooth, meaning a baby tooth that is permanently attached to the jaw bone [1] * And the presence of supernumerary teeth, meaning an individual that is born with extra teeth [1] * Smith-Magenis syndrome [6] * Axenfeld-Rieger syndrome [5] * Cysts[4][1] * Tumors[4][1] ## Mechanism/ Pathophysiology[edit] During the developmental stages, the permanent tooth germ, specifically of the maxillary incisor lies superior to the apex of the primary incisor.[5] If there is damage to the primary incisor, this will cause an impact on the permanent incisor as well as there is only about a 3mm space of thickness between the primary and permanent teeth.[5] In the human mouth, once the permanent teeth begin to develop, they remain underneath the primary teeth. Once they are ready to erupt they push upward eventually causing the primary teeth to fall out. There is essentially a small space between the permanent and primary teeth, roughly less than 3mm of spacing.[5] If a young child is to experience trauma to the mouth, this can cause developmental disorders to the permanent tooth that is still developing and lying direction underneath it. The impact from the primary tooth will be transferred to the permanent tooth that may have its roots formed, thus causing a bend or curvature of the permanent tooth root.[5] It is noted that rather than the force of the impact, the direction in which the impact occurs has a more significant effect on dilaceration formation.[5][7] Cysts or tumors can cause dilaceration as well. As a tumor or cyst forms it may cause impaction on the growth and development of the permanent teeth as well. This may cause crown or root dilaceration as the tooth tries to grow around the cysts or tumor causing dramatic angulation.[8] Similarly, patients present with supernumerary teeth, may have impacted the growth of underlying permanent teeth causing the abnormal root curvature growth.[1] An ankylosed deciduous tooth will not allow for proper growth the permanent tooth. Thus, the tooth may look for another path to erupt. This may cause dilaceration of root or may potentially impact neighboring teeth causing dilaceration to those teeth.[1] ## Diagnosis[edit] Dilaceration can be diagnosed with a simple radiograph of the affected teeth. However, if the bends are more lingual or facially present,[1] more advance imaging techniques may be necessary. In some cases a cone-bean CT scan may be useful to create a three dimensional view.[9] ## Prevention/ Treatment[edit] This radiograph shows a root canal treatment with no crown completed. This is a possible course of treatment for dilacerated teeth. The slight curves shown on these molar teeth are normal curves. Extreme curvature of roots are known to be dilaceration. There are currently no preventative measures to be taken for dilaceration as the etiology is not well known. However, there are some treatment options that may serve to be of use. A surgical method which involves the exposing the impacted tooth to meet with normal occlusion with the help of orthodontic traction.[2] Although this surgical method has proven to be of use in the past, it may not be the case for every patient with dilacerated teeth. Thus the degree of dilaceration is dependent on what kind of treatment can take place. In young children many cases of dilaceration occur due to some kind of trauma to the tooth, commonly causing dislocation of the tooth affecting its direction and growth.[10] Once a trauma has occurred dilaceration can be prevented by yearly visits to the dentist and maintaining radiographic images to note any changes that may occur. If changes do occur, treatment can be done through orthodontic treatment or the tooth may be completely extracted by a dentist to prevent impaction on permanent teeth.[10] Prevention for young children also includes avoiding injury to the mouth, especially during sporting activities, proper headgear and protective measures should be taken prior to engaging in recreational activities for the overall safety of the child.[4] Patients with supernumerary teeth may also be candidates for teeth extraction followed by orthodontic treatment to prevent dilaceration.[1] In some cases and Endodontist, a tooth root specialist, may be involved in treatment of dilaceration. Using radiographs to determine the extent of dilaceration, the endodontist may recommend a root canal treatment,[4] which is essentially cleaning out the nerve of the tooth and placing material inside the tooth to help maintain its structure. Since at this point the tooth with no nerve is essentially dead, further treatment from a general dentist to crown the tooth will be necessary. Crowning the tooth will prevent breakage of the tooth while still allowing functionality of the tooth. In order to achieve the best possible results, treatment should begin as soon as possible.[5] ## Prognosis[edit] The prognosis will vary from each patients case to case. In less severe cases, patients may face minor issues with aesthetics which orthodontic treatment can resolve. In more severe cases which are not as easily treatable patients may face more severe issues with occlusions and phonetics. In some cases young children may face psychological issues.[1] There is no death sentence associated with dilaceration. However, patients may face some difficulties as time progresses and if they are left untreated. Other teeth may become impacted and cause pain and soreness.[2] ## Epidemiology[edit] Most commonly affects patients in their permanent dentition.[9][1] It may also appear in primary teeth however, its incidence rate is significantly lower. Some studies indicate that dilaceration is not more common in any gender however, other studies indicate that incidence rate is more common in females than males with a ratio of 1:6.[5] There are reports of a 0.53% for this to occur on the two front teeth of the upper jaw. In a study conducted on the adult population in Croatia, the most common teeth to experience dilaceration were the lower jaw's 3rd molars with a whopping 24.1%.[11] Next was the upper jaw's first, second and third molars at 15.3%,11.4% and 8.1% incidence rate respectively.[11] ## Research Directions[edit] Although this disease is rare there has been a significant amount of research done on this. * A 2016 study was done to find reasoning behind dilacerated crowns and treatment options for different types of crown dilacerations. Researchers found that dental trauma should not be taken lightly as it is one of the most common caused for dilaceration. Researchers also concluded that if trauma has occurred to primary teeth, it should be followed up with the dentist on a regular basis due to the future complications that may arise. The main focus of treatment in this research was root canal therapy over surgical methods as it was less invasive and more conservative.[7] * A research review published in 2016 indicated that a multidisciplinary approach was more favorable in diagnosing and treatment of dilaceration. Researchers presented that although dilaceration of permanent teeth is rare, it can pose many issues. Therefore, rather than just simply having clinical follow ups and standard imaging conducted, to reach a proper diagnosis imaging tools such as a CBCT should be used. Additionally, treatment requires patient compliance as well as early treatment wherever possible. Treatment options may include exposure of the tooth followed by orthodontic treatment to bring the tooth to a corrected positioning.[5] * A 2014 case report indicated a young patient approached the pediatric dental department complaining of upper teeth that had still not come in yet. It was found that the patient had experienced a trauma, thus had completed extractions 6 years prior. Panoramic radiographs showed the tooth was impacted and potentially had a dilacerated root. A cone beam CT scan was done to gain a better idea of the relationship of the teeth. Treatment consisted of extractions followed by orthodontic bonding and extrusion of the tooth. This allowed for other teeth to come into better places as well.[9] * A research study conducted from 2005-2010 was conducted in South Iran to check for the presence of dilacerations. Records were compiled from the endodontic and periodontal departments of Shiraz University of Medical Science's dental school. All patients were Caucasian ranging from 12–75 years if age. Researchers found dilaceration in 0.3% of teeth among 7.2% of patients. Distribution was equal between the lower and upper jaw. Researchers concluded that root dilacerations mainly occur in posterior teeth.[12] ## See also[edit] * Tooth enamel * Turner's hypoplasia ## References[edit] 1. ^ a b c d e f g h i j k l m n "Dilaceration - an overview \| ScienceDirect Topics". www.sciencedirect.com. Retrieved 2020-11-12. 2. ^ a b c Deshpande, Anshula; Prasad, Sabrinath; Deshpande, Neeraj (April 2012). "Management of impacted dilacerated maxillary central incisor: A clinical case report". Contemporary Clinical Dentistry. 3 (Suppl1): S37–S40. doi:10.4103/0976-237X.95102. ISSN 0976-237X. PMC 3354783. PMID 22629064. 3. ^ [1] Standerwick RG. A possible etiology for the dilaceration and flexion of permanent tooth roots relative to bone remodeling gradients in alveolar bone. Dent Hypotheses [serial online] 2014 [cited 2014 Mar 3];5:7-10. Available from: http://www.dentalhypotheses.com/text.asp?2014/5/1/7/128105 4. ^ a b c d e "What Is Tooth Dilaceration?". www.colgate.com. Retrieved 2020-11-12. 5. ^ a b c d e f g h i j Walia, Pawanjit Singh; Rohilla, Ajit Kumar; Choudhary, Shweta; Kaur, Ravneet (2016). "Review of Dilaceration of Maxillary Central Incisor: A Mutidisciplinary Challenge". International Journal of Clinical Pediatric Dentistry. 9 (1): 90–98. doi:10.5005/jp-journals-10005-1341. ISSN 0974-7052. PMC 4890071. PMID 27274164. 6. ^ Tomona, Natalia; Smith, Ann C. M.; Guadagnini, Jean Pierre; Hart, Thomas C. (2006-12-01). "Craniofacial and dental phenotype of Smith-Magenis syndrome". American Journal of Medical Genetics. Part A. 140 (23): 2556–2561. doi:10.1002/ajmg.a.31371. ISSN 1552-4825. PMID 17001665. 7. ^ a b Bolhari, Behnam; Pirmoazen, Salma; Taftian, Ensieh; Dehghan, Somayeh (November 2016). "A Case Report of Dilacerated Crown of a Permanent Mandibular Central Incisor". Journal of Dentistry (Tehran, Iran). 13 (6): 448–452. ISSN 1735-2150. PMC 5318502. PMID 28243307. 8. ^ Neville, Brad W.; Damm, Douglas D.; Allen, Carl M.; Chi, Angela C. (2019-01-01), Neville, Brad W.; Damm, Douglas D.; Allen, Carl M.; Chi, Angela C. (eds.), "2 - Pathology of Teeth", Color Atlas of Oral and Maxillofacial Diseases, Philadelphia: Elsevier, pp. 41–78, ISBN 978-0-323-55225-7, retrieved 2020-12-18 9. ^ a b c R, Mahesh; IG, Kanimozhi; M, Sivakumar (May 2014). "Dilaceration and Eruption Disturbances in Permanent Teeth: A Sequelae of Trauma to Their Predecessors-Diagnosis and Treatment Using Cone Beam CT". Journal of Clinical and Diagnostic Research : JCDR. 8 (5): ZD10–ZD12. doi:10.7860/JCDR/2014/6657.4342. ISSN 2249-782X. PMC 4080075. PMID 24995254. 10. ^ a b Amorim, Camila Silva de; Americano, Gabriela Caldeira Andrade; Moliterno, Luiz Flávio Martins; Marsillac, Mirian de Waele Souchois de; Andrade, Márcia Rejane Thomas Canabarro; Campos, Vera (2018). "Frequency of crown and root dilaceration of permanent incisors after dental trauma to their predecessor teeth". Dental Traumatology. 34 (6): 401–405. doi:10.1111/edt.12433. ISSN 1600-9657. 11. ^ a b Malčić, Ana; Jukić, Silvana; Brzović, Valentina; Miletić, Ivana; Pelivan, Ivica; Anić, Ivica (2006-07-01). "Prevalence of root dilaceration in adult dental patients in Croatia". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 102 (1): 104–109. doi:10.1016/j.tripleo.2005.08.021. ISSN 1079-2104. 12. ^ Nabavizadeh, MR; Sedigh Shamsi, M; Moazami, F; Abbaszadegan, A (December 2013). "Prevalence of Root Dilaceration in Adult Patients Referred to Shiraz Dental School (2005-2010)". Journal of Dentistry. 14 (4): 160–164. ISSN 2345-6485. PMC 3977521. PMID 24724139. ## External links[edit] Classification D * ICD-10: K00.4 * ICD-9-CM: 520.4 * v * t * e Developmental tooth disease/tooth abnormality Quantity * Anodontia/Hypodontia * Hyperdontia Shape and size * Concrescence * Fusion * Gemination * Dens evaginatus/Talon cusp * Dens invaginatus * Enamel pearl * Macrodontia * Microdontia * Taurodontism * Supernumerary roots Formation * Dilaceration * Regional odontodysplasia * Turner's hypoplasia * Enamel hypoplasia * Ectopic enamel Other hereditary * Amelogenesis imperfecta * Dentinogenesis imperfecta * Dentin dysplasia * Regional odontodysplasia Other * Dental fluorosis * Tooth impaction [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Dilaceration	c0266048	5,345	wikipedia	https://en.wikipedia.org/wiki/Dilaceration	2021-01-18T19:03:33	{"umls": ["C0266048"], "icd-9": ["520.4"], "icd-10": ["K00.4"], "wikidata": ["Q5276656"]}
Congenital osteogenesis imperfecta-microcephaly-cataracts syndrome is characterised by multiple fractures in the prenatal period, microcephaly and bilateral cataracts. It has been described in three infants all of whom died in utero or a few hours after birth. The mode of inheritance appears to be autosomal recessive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Congenital osteogenesis imperfecta-microcephaly-cataracts syndrome	c1850184	5,346	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2772	2021-01-23T17:01:45	{"mesh": ["C537558"], "omim": ["259410"], "umls": ["C1850184"], "icd-10": ["Q78.0"]}
A number sign (#) is used with this entry because mutations in several genes in the mitochondrial glycine cleavage system have been found to cause glycine encephalopathy (GCE), also known as nonketotic hyperglycinemia (NKH). These include the genes encoding P protein (GLDC; 238300), T protein (AMT; 238310), and, in 1 patient, the H protein (GCSH; 238330). Most patients with GCE have a defect in the GLDC gene. Clinical Features ### Classic Neonatal Form Most patients with GCE have the neonatal phenotype, presenting in the first few days of life with lethargy, hypotonia, and myoclonic jerks, and progressing to apnea, and often to death. Those who regain spontaneous respiration develop intractable seizures and profound mental retardation. In the infantile form of GCE, patients present with seizures and have various degrees of mental retardation after a symptom-free interval and seemingly normal development for up to 6 months. In the mild-episodic form, patients present in childhood with mild mental retardation and episodes of delirium, chorea, and vertical gaze palsy during febrile illness. In the late-onset form, patients present in childhood with progressive spastic diplegia and optic atrophy, but intellectual function is preserved and seizures have not been reported (Hamosh and Johnston, 2001). See review by Tada and Hayasaka (1987). Unlike glycinemia with ketoacidosis and leukopenia, also known as propionic acidemia (606054), episodic ketoacidosis with vomiting, neutropenia, and thrombocytopenia does not occur in nonketotic hyperglycinemia. Glycine is the only amino acid elevated in serum and urine and the only amino acid harmful to these patients. Some have died in the newborn period after a course characterized by lethargy, weak cry, generalized hypotonia, absent reflexes, and periodic myoclonic jerks (Balfe et al., 1965). The few who attain an older age show severe mental retardation (Mabry and Karam, 1963; Gerritsen et al., 1965). Hayasaka et al. (1983) studied the glycine cleavage system in the liver and brain obtained at autopsy in 2 male infants with the typical form of nonketotic hyperglycinemia. In one a defect in the P protein was found; in the second, T protein was defective. The infant with the P protein defect was born of unrelated parents, was lethargic with a poor suck from birth, developed marked hypotonia, intermittent apnea, and poor responsiveness to stimuli, had mildly elevated blood ammonia and markedly elevated glycine in blood and cerebrospinal fluid, and died at age 12 days. Immunochemical analysis indicated absence of the enzyme P protein itself. The second infant appeared well at birth and nursed well the first day. He was hospitalized on the third day with 'lethargy, bordering on coma.' Despite ventilatory support, 7 exchange transfusions to lower blood glycine, and treatment with sodium benzoate and strychnine, he died on the twentieth day. T protein was undetectable in the brain and extremely low in liver. Autopsy in the first case, with P protein deficiency, showed absence of the corpus callosum and spinal cord hydromelia. The authors stated that they had seen a similar structural defect with deficiency of the pyruvate dehydrogenase complex (see 312170). Schutgens et al. (1986) reported a case with T protein deficiency. Cataltepe et al. (2000) reported 4 patients with nonketotic hyperglycinemia who developed pulmonary hypertension. Two patients had classic neonatal GCE and developed pulmonary hypertension in the newborn period; both died from pulmonary hypertension. The other 2 patients were sibs from Bangladesh with atypical GCE, the first of whom presented with pulmonary hypertension at the age of 6. His brother had documented pulmonary at the age of 4 years, which resolved spontaneously and then recurred in association with thiamine deficiency when he was 21 years old. Van Hove et al. (2000) reported 4 patients with typical neonatal-onset NKH who developed hydrocephalus requiring shunting in early infancy. Brain imaging revealed acute hydrocephalus, a megacisterna magna or posterior fossa cyst, pronounced atrophy of the white matter, and an extremely thin corpus callosum in all. The 3 older patients had profound developmental disabilities. Van Hove et al. (2000) concluded that the development of hydrocephalus in NKH is an additional poor prognostic sign. In cells derived from a deceased boy, born of unrelated Serbian parents, with GCE, Swanson et al. (2017) identified a homozygous missense mutation in the AMT gene (S117L; 238310.0009). In vitro functional expression studies showed that the mutant AMT protein was unstable and had only 9% residual enzymatic activity compared to controls. The patient was unusual because he had originally been reported as having D-glyceric aciduria (220120) caused by a homozygous frameshift mutation in the GLYCTK gene (610516.0001) (Brandt et al., 1974; Sass et al., 2010). Increased glycine in the patient had been thought to be secondary to the GLYCTK defect; however, the molecular findings confirmed that the patient had the unusual cooccurrence of 2 inborn errors of metabolism. Swanson et al. (2017) concluded that D-glyceric aciduria does not cause deficient glycine cleavage enzyme activity or nonketotic hyperglycinemia. ### Atypical Mild Form Unlike the classic neonatal form of the disorder, atypical or mild glycine encephalopathy is phenotypically heterogeneous and nonspecific, making diagnosis difficult (Flusser et al., 2005). Cole and Meek (1985) emphasized the occurrence of an expressive speech deficit and neurologic abnormalities during intercurrent infections as striking features of the milder form of the disease. The cases of Ando et al. (1978), Frazier et al. (1978), and Flannery et al. (1983) also fall into this category. Hayasaka et al. (1987) cited one patient with atypical GCE and features of progressive degeneration of the central nervous system. Dinopoulos et al. (2005) reported 3 unrelated adults with a mild form of glycine encephalopathy confirmed by genetic analysis (238300.0008; 238300.0009). All 3 patients showed hypotonia as infants and had developmental delay. One patient showed appendicular ataxia and choreoathetoid movements at age 4 years. Between ages 5 and 12 years, he had frequent outbursts of aggressiveness. He attended special education classes and graduated from high school. The second patient was hypotonic at birth and developed seizures during the first week of life. Aggressive behavior was noted at age 12 years; he was fully dependent on his family. The third patient developed hypotonia at age 6 months. He was diagnosed with attention deficit-hyperactivity disorder (ADHD) and had outbursts of aggression and impulsivity. Treatment with dextromethorphan was ineffective. He graduated from school in special education classes. Biochemical analysis showed residual GLDC activity ranging from 6 to 8%, which Dinopoulos et al. (2005) suggested may explain the milder clinical phenotype. The authors emphasized the clinical heterogeneity of the mild form of GCE. Flusser et al. (2005) reported a large consanguineous Israeli Bedouin kindred in which 9 members had atypical GCE confirmed by genetic analysis (238300.0010). Most patients presented during the first months of life with abnormal movements, including mild to moderate generalized hypotonia, lateral head nodding, choreoathetoid hand movements, and pill rolling. Seven patients had seizures with generalized spike and slow wave abnormalities in EEG; 2 had infantile spasms with hypsarrhythmia. All had delayed motor development, moderate mental retardation, and limited expressive language. The patients also showed irritability and restlessness as infants and later showed aggressive and destructive behavior. Treatment was ineffective. Yu et al. (2013) described 3 children from a consanguineous family who had autism spectrum disorder and who carried a homozygous mutation in the AMT gene. While individually nondiagnostic, the 3 affected children exhibited a range of neurologic symptoms that in aggregate were strongly suggestive of NKH. The eldest child was 12 years of age and had, in addition to a diagnosis of autism spectrum disorder, a history of severe epilepsy, with first seizures presenting at 10 months of age. The second child was 9 years of age and suffered from autism and epilepsy, but her seizures were milder. The third child was 2 years of age and had language and motor delays and carried a diagnosis of pervasive developmental disorder (PDD), but had had only 1 febrile seizure. Direct biochemical analysis of the mutation (ile308 to phe, I308F) demonstrated reduced activity. When compared to classical NKH-associated values, glycine cleavage activity of the mutated allele was at the mild end of the range of reported values, suggesting that the affected children in this family suffered from undiagnosed atypical NKH presenting as autism spectrum disorder and seizures. Plasma amino acid screening was normal in the 2 older children, a result that is typically seen in milder forms of NKH. ### Transient Neonatal Hyperglycinemia Transient neonatal hyperglycinemia (TNH) is characterized by elevated plasma and CSF glycine levels at birth that are normalized within 2 to 8 weeks. TNH is clinically and biochemically indistinguishable from typical nonketotic hyperglycinemia at onset. Applegarth and Toone (2001) reviewed 7 cases of transient NKH. Korman et al. (2004) reported 3 sibs from a consanguineous Muslim Palestinian family who had an unusual NKH phenotype. All 3 sibs were diagnosed with NKH within the first 3 days of life with characteristic elevated CSF and plasma glycine levels and elevated CSF-to-plasma glycine ratios. However, none of them developed neurologic symptoms, and all showed appropriate development, including good school performance in the 2 children of school age. The 2 older children showed persistent hyperglycinemia. A patient from a second unrelated family diagnosed with NKH had mild neurologic sequelae. In all 4 patients, Korman et al. (2004) identified a homozygous mutation in the GLDC gene (238300.0006), which was shown to retain 32% residual enzyme activity in vitro. The authors suggested that these patients exhibited a new phenotype of NKH. Inheritance Nonketotic hyperglycinemia is inherited as an autosomal recessive trait. Biochemical Features Gerritsen et al. (1965) described abnormally low oxalate excretion in the urine and postulated a defect in glycine oxidase. Ando et al. (1968) located the defect to glycine formiminotransferase. Tada et al. (1969) concluded that the primary lesion in hyperglycinemia of the nonketotic variety is in the glycine cleavage reaction. Baumgartner et al. (1969) showed that the nonketotic variety can have a fulminant early onset. The defect concerns the enzyme involved in the conversion of glycine to CO2, NH3 and hydroxymethyltetrahydrofolic acid. De Groot et al. (1970) described 2 affected sisters with consanguineous parents and presented evidence indicating that the defect lies in glycine decarboxylase, rather than in glycine oxidase. Pathogenesis Toone et al. (2003) performed a retrospective analysis of a group of NKH patients and found that greater than 50% had T protein (238310) mutations. The patients studied had 1 or more unusual biochemical findings: residual glycine cleavage system activity in liver, residual glycine cleavage system activity in lymphoblasts, and/or increased amniotic fluid glycine-to-serine ratio with a normal amniotic fluid glycine level in prenatal diagnosis. The selected patients had a much higher incidence of T-protein defects than expected in the general NKH patient population. Toone et al. (2003) reported 3 novel mutations and 5 polymorphisms of the T protein gene, PCR/restriction enzyme methods for 1 mutation and 2 polymorphisms, and an estimation of their frequency in normal controls. Population Genetics A high frequency of glycine encephalopathy has been found in Finland; the incidence has been estimated to be 1 in 55,000 newborns overall, and 1 in 12,000 in northern Finland (von Wendt and Simila, 1980; Boneh et al., 2005). High incidences have also been reported in British Columbia and in small Arab villages in Israel (Boneh et al., 2005). Diagnosis Applegarth and Toone (2001) reviewed the laboratory diagnosis of glycine encephalopathy and confirmed 9 mutations in the T protein and 8 mutations in the P protein. Tan et al. (2007) reported that they screened 733,527 babies over 8 years as part of the New South Wales Newborn Screening Program and subsequently diagnosed 9 babies with nonketotic hyperglycinemia. Two had newborn glycine levels above their cutoff and presented within 72 hours. The remaining patients could not have been diagnosed by newborn screening without an unacceptably high recall rate. Tan et al. (2007) concluded that babies with nonketotic hyperglycinemia were not usually identifiable by newborn screening strategies available at that time. ### Prenatal Diagnosis Hayasaka et al. (1990) described prenatal diagnosis of nonketotic hyperglycinemia by enzymatic analysis of the glycine cleavage system in chorionic villi. Toone et al. (1994) described their experience with direct assay of glycine cleavage enzyme in chorionic villus samples in 50 at-risk pregnancies. Applegarth et al. (2000) reported 3 false-negative prenatal diagnostic results using direct measurement of glycine cleavage enzyme activity in uncultured chorionic villus tissue from 290 pregnancies at risk for glycine encephalopathy. Because of these false negatives, Applegarth et al. (2000) counseled that there is a gray zone of uninterpretable activity where affected and normal enzyme values overlap, and suggested that there is an approximately 1% chance of a pregnancy with a normal chorionic villus sample activity resulting in an affected child. Kure et al. (1999) performed prenatal diagnosis for NKH by enzymatic analysis of chorionic villus samples in 28 families and by DNA analysis in 2 families. In 26 families, enzymatic analysis of the glycine cleavage system (GCS) yielded an unambiguous diagnosis; inconclusive results in 2 families were due to borderline GCS activity. A second chorionic sample was analyzed in both these families. In one case, GCS activity was normal in the second specimen and the baby did not have NKH. In the other case, Kure et al. (1999) again found extremely low GCS activity in a second specimen, but a healthy baby was born. The cause of this false-positive result was unknown. Kure et al. (1999) also reported the ability to obtain unambiguous prenatal diagnosis in both Finnish and Israeli Arab families due to prevalent mutations in those populations. The H42R mutation in the T protein (238310.0003) may lead to ambiguous enzymatic activity, suggesting an advantage for DNA analysis. Clinical Management Hamosh et al. (1992) reported clinical and electrophysiologic improvement in a child with GCE who was treated with dextromethorphan and sodium benzoate beginning with the twelfth day of life. Dextromethorphan is a noncompetitive antagonist of the NMDA type of glutamate receptor, which can be stimulated by glycine. Zammarchi et al. (1994) reported only transient improvement on the same regimen when the treatment was instituted at 65 hours of life. The child died at 5 months and 7 days of age in spite of increasing doses of dextromethorphan as high as 40 mg per kilogram per day. The enzymatic basis for the GCE in either the successfully or unsuccessfully treated infant was not specified. The authors speculated that the different responses may reflect genetic heterogeneity. Treatment of patients with GCE with high doses of benzoate can result in decreased CSF glycine levels and will improve seizure control and wakefulness (Hamosh et al., 1992), thus improving the quality of life in surviving infants, but even when started early, may not prevent the development of mental retardation (Zammarchi et al., 1994). Episodes of lethargy, coma, and increased seizures can be caused both by hyperglycinemia from underdosing benzoate, or by toxicity due to overdosing. Van Hove et al. (1995) found plasma carnitine deficiency in 3 of 4 patients with GCE treated with sodium benzoate, and benzoylcarnitine was identified in plasma, urine, and CSF. Treatment with L-carnitine normalized plasma-free carnitine. Close monitoring of glycine, benzoate and carnitine levels is advisable in patients receiving benzoate. Neuberger et al. (2000) reported a 6-month-old girl who presented with hypotonia and mild psychomotor retardation who was subsequently found to have NKH confirmed by decreased glycine cleavage system activity in the liver. After the patient developed hypsarrhythmia and had a single seizure, treatment with both sodium benzoate and dextromethorphan was started. During the following year, the girl was free of seizures with improvement of EEG activity and showed retarded but continuously progressing psychomotor development. At the age of 20 months she began to walk freely but had generalized muscular hypotonia and moderate mental retardation. Discontinuation of dextromethorphan after one year did not change the clinical or EEG status. However, after cessation of sodium benzoate, epileptic activity in the EEG and behavioral changes occurred. These changes disappeared promptly after sodium benzoate therapy was reinstituted. Korman et al. (2006) reported a patient with NKH caused by a homozygous mutation in the GLDC gene. He was born of first-cousin Palestinian Arabs. The patient was diagnosed prenatally and treated from birth with oral sodium benzoate and the NMDA receptor antagonist ketamine. Although neonatal hypotonia and apnea did not occur, the long-term outcome at age 11 months was poor, with intractable seizures and severe psychomotor retardation. Korman et al. (2006) noted that the plasma glycine level in this child was normal at birth, presumably reflecting placental clearance, whereas the CSF glycine level was markedly elevated, suggesting that the developing brain had been exposed prenatally to the potential toxicity of glycine. Nomenclature Nonketotic hyperglycinemia was originally named to distinguish it from ketotic hyperglycinemia, which is now known to be propionic acidemia (606054). Since the distinction is no longer required and clinical confusion between hyperglycinemia and hyperglycemia occurs, a more appropriate name for this disorder is glycine encephalopathy (Hamosh, 2001). INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Absent corpus callosum (variable) \- Lethargy \- Seizures \- Hiccups \- Hypotonia \- Hyporeflexia to hyperreflexia \- Myoclonic jerks \- Mental retardation \- Burst suppression pattern on neonatal EEG \- Expressive speech deficit Behavioral Psychiatric Manifestations \- Hyperactivity \- Impulsivity \- Aggressiveness \- Irritability \- Restlessness LABORATORY ABNORMALITIES \- Hyperglycinemia \- Hyperglycinuria \- Hepatic glycine cleavage defect \- Elevated CSF glycine \- Elevated CSF/plasma glycine ratio MISCELLANEOUS \- Death in infancy common for patients with the classic neonatal form \- Patients with atypical form have milder disease, with onset in the first months of life and increased survival MOLECULAR BASIS \- Caused by mutation in the glycine dehydrogenase gene (GLDC, 238300.0001 ) \- Caused by mutation in the glycine cleavage system H protein gene (GCSH, 238330.0001 ) \- Caused by mutation in the aminomethyltransferase gene (AMT, 238310.0001 ) ▲ 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	GLYCINE ENCEPHALOPATHY	c0751748	5,347	omim	https://www.omim.org/entry/605899	2019-09-22T16:10:52	{"doid": ["9268"], "mesh": ["D020158"], "omim": ["605899"], "icd-10": ["E72.51"], "orphanet": ["407", "289857", "289860", "289863"], "synonyms": ["Alternative titles", "HYPERGLYCINEMIA, NONKETOTIC"], "genereviews": ["NBK1357"]}
Psychosomatic condition For the film, see The Stendhal Syndrome. Stendhal syndrome, Stendhal's syndrome or Florence syndrome is a psychosomatic condition involving rapid heartbeat, fainting, confusion and even hallucinations,[1] allegedly occurring when individuals become exposed to objects, artworks, or phenomena of great beauty. [2] ## Contents * 1 History * 2 See also * 3 References * 4 External links ## History[edit] Stendhal syndrome was named after Marie-Henri Beyle (1783–1842), better known by his pen name, Stendhal. The affliction is named after the 19th-century French author Stendhal (pseudonym of Marie-Henri Beyle), who described his experience with the phenomenon during his 1817 visit to Florence in his book Naples and Florence: A Journey from Milan to Reggio. When he visited the Basilica of Santa Croce, where Niccolò Machiavelli, Michelangelo and Galileo Galilei are buried, he was overcome with profound emotion. Stendhal wrote: > I was in a sort of ecstasy, from the idea of being in Florence, close to the great men whose tombs I had seen. Absorbed in the contemplation of sublime beauty ... I reached the point where one encounters celestial sensations ... Everything spoke so vividly to my soul. Ah, if I could only forget. I had palpitations of the heart, what in Berlin they call 'nerves'. Life was drained from me. I walked with the fear of falling.[3] Although psychologists have long debated whether Stendhal syndrome exists, the apparent effects on some individuals are severe enough to warrant medical attention.[4] The staff at Florence's Santa Maria Nuova hospital are accustomed to tourists suffering from dizzy spells or disorientation after viewing the statue of David, the artworks of the Uffizi Gallery, and other historic relics of the Tuscan city.[1] Though there are numerous accounts of people fainting while taking in Florentine art, dating from the early 19th century, the syndrome was only named in 1979, when it was described by Italian psychiatrist Graziella Magherini, who observed over a hundred similar cases among tourists in Florence. There exists no scientific evidence to define Stendhal syndrome as a specific psychiatric disorder; however, there is evidence that the same cerebral areas involved in emotional responses are activated during exposure to art.[5] The syndrome is not listed as a recognised condition in the Diagnostic and Statistical Manual of Mental Disorders. A more recent account of the Stendhal syndrome was in 2018, where a visitor to the Uffizi Gallery in Florence suffered a heart attack while admiring Sandro Botticelli's The Birth of Venus.[6] ## See also[edit] * Double Rainbow * Jerusalem syndrome * Lisztomania * Paris syndrome * The Stendhal Syndrome, a psychological thriller film on the subject ## References[edit] 1. ^ a b Nick Squires (28 July 2010). "Scientists investigate Stendhal Syndrome – fainting caused by great art". The Daily Telegraph. London. Retrieved 1 October 2019. 2. ^ Nicholson, Timothy Richard Joseph; Pariante, Carmine; McLoughlin, Declan (2009). "Stendhal syndrome: A case of cultural overload". BMJ Case Reports. 2009: bcr0620080317. doi:10.1136/bcr.06.2008.0317. PMC 3027955. PMID 21686859. 3. ^ Chatzichristodoulou, Maria; Jefferies, Janis; Zerihan, Rachel, eds. (2009). Interfaces of Performance. Ashgate Publishing, Ltd. p. 196. ISBN 9781409486145. 4. ^ Clyde Haberman (15 May 1989). "Florence's Art Makes Some Go to Pieces". The New York Times. Retrieved 1 October 2019. 5. ^ Innocenti, Claudia; Fioravanti, Giulia; Spiti, Raffaello; Faravelli, Carlo (1 March 2014). "La sindrome di Stendhal fra psicoanalisi e neuroscienze" [The Stendhal syndrome between psychoanalysis and neuroscience]. Rivista di Psichiatria (in Italian). 49 (2): 61–66. doi:10.1708/1461.16139. ISSN 2038-2502. PMID 24770571. 6. ^ Jones, Jonathan (18 December 2018). "Stendhal syndrome: can art really be so beautiful it makes you ill?". The Guardian. Retrieved 27 November 2019. ## External links[edit] * Word Spy definition * Graziella Magherini. La Sindrome di Stendhal. Firenze, Ponte Alle Grazie, 1989. (in Italian) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Stendhal syndrome	None	5,348	wikipedia	https://en.wikipedia.org/wiki/Stendhal_syndrome	2021-01-18T18:54:13	{"wikidata": ["Q8363"]}
A number sign (#) is used with this entry because of evidence that platelet-type bleeding disorder-21 (BDPLT21) is caused by heterozygous mutation in the FLI1 gene (193067) on chromosome 11q24. One family with a homozygous mutation in the FLI1 gene has been reported. Heterozygous deletion of the FLI1 gene is believed to be responsible for the thrombocytopenia found in Paris-Trousseau type of thrombocytopenia (TCPT; 188025) and Jacobsen Syndrome (JBS; 147791), both of which are contiguous gene deletion syndromes. Description BDPLT21 is a hematologic disorder characterized by increased risk of bleeding resulting from a functional platelet defect. Platelets have decreased or even absent dense bodies and abnormally enlarged and fused alpha-granules, and they show defective secretion and aggregation responses to agonists. Platelets are usually enlarged, and some patients may have mild to moderate thrombocytopenia (summary by Saultier et al., 2017). Clinical Features Stockley et al. (2013) reported 7 patients from 3 unrelated families with BDPLT21. All patients had excessive bleeding associated with a significant reduction in platelet ATP secretion in response to all agonists tested, consistent with a defect in dense granule secretion. Three of the patients had mild thrombocytopenia. In 2 families, the platelet defect was associated with alopecia, eczema and/or psoriasis, and recurrent viral infections. Saultier et al. (2017) reported a father and son and an unrelated woman with BDPLT21 manifest as congenital macrothrombocytopenia. The father and son had not experienced significant bleeding episodes, whereas the 52-year-old woman had a history of excessive bleeding, predominantly gynecologic and obstetric, and involving the oral cavity. Patient platelets contained enlarged fused alpha-granules and almost complete absence of dense granules. Cultured patient-derived megakaryocytes were smaller and formed very few proplatelets compared to controls; patient megakaryocytes also had a lower percentage of mature markers compared to controls, suggesting impaired megakaryocyte differentiation. A small number (7-9%) of platelets from 2 patients showed glycogen-containing vacuoles, and a smaller number (3%) of platelets from 1 patient showed autophagosomes. The overall findings suggested a defect in vesicle biogenesis or trafficking. ### Autosomal Recessive BDPLT21 Stevenson et al. (2015) reported 2 adult sibs, born of consanguineous Caucasian parents, with a lifelong bleeding disorder characterized by moderate to severe mucosal bleeding and menorrhagia associated with thrombocytopenia and enlarged platelets. Patient platelets showed reduced aggregation in response to ADP and collagen, but normal response to arachidonic acid and ristocetin. Platelet electron microscopy showed some platelets with large, fused, and electron-dense alpha-granules characteristic of the defects observed in Paris-Trousseau thrombocytopenia. There were no other clinical features associated with Paris-Trousseau syndrome or Jacobsen Syndrome. The parents were unaffected. Inheritance The transmission pattern of BDPLT21 in the families reported by Stockley et al. (2013) and Saultier et al. (2017) was consistent with autosomal dominant inheritance. The transmission pattern of BDPLT21 in the family reported by Stevenson et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In affected members of 3 unrelated families with BDPLT21, Stockley et al. (2013) identified heterozygous mutations in the FLI1 gene (193067.0001-193067.0003). The mutations, which were found by next-generation sequencing analysis of candidate genes in 13 families with an inherited platelet disorder, were confirmed by Sanger sequencing. There were 2 missense mutations and 1 frameshift mutation. In vitro functional expression assays showed that the missense FLI1 variants were unable to bind to a transcription site in the promoter for GP6 (605546), one of the genes that is regulated by FLI1. Coexpression of the variants with wildtype FLI1 resulted in a significant reduction in transcriptional activity to 60% of wildtype alone. Patient platelets showed abnormal persistent expression of MYH10 (160776), suggesting that this may be a biomarker for FLI1 mutations. In 3 members of 2 unrelated families with BDPLT21, Saultier et al. (2017) identified heterozygous missense mutations in the FLI1 gene (193067.0004-193067.0005). In vitro functional expression studies using a luciferase reporter showed that both mutations resulted in reduced transcriptional activity compared to wildtype. The mutant proteins were unable to inhibit luciferase activity as well as the wildtype protein; however, cotransfection of mutant FLI1 and wildtype led to normal transcriptional activity. Western blot analysis and immunofluorescence staining showed that both mutant proteins were located primarily in the cytoplasm rather than the nucleus, suggesting altered subcellular localization. Flow cytometric studies of patient platelets showed abnormal persistent expression of MYH10. In 2 sibs, born of consanguineous parents, with autosomal recessive BDPLT21, Stevenson et al. (2015) identified a homozygous missense mutation in the FLI1 gene (R324W; 193067.0006). The mutation was found by Sanger sequencing and segregated with the disorder in the family. Western blot analysis and in vitro luciferase assays in HEK293 cells showed that the mutation caused a significant decrease in transcriptional activity compared to wildtype as well as decreased levels of platelet GP6, GP9 (173515), and GPIIb (ITGA2B, 607759)/GPIIIa (ITGB3, 173470), indicating a transcriptional defect affecting the promoter of known target genes. MYH10 was detected in the platelets of the probands. Stevenson et al. (2015) noted the unusual recessive inheritance pattern in this family and stated that neither parent had observable platelet defects or abnormal expression of MYH10, suggesting that the R324W mutant retains residual activity and is not a null allele. Other FLI1 mutations that cause disease in the heterozygous state are likely more damaging to protein function. INHERITANCE \- Autosomal dominant \- Autosomal recessive (1 family) HEAD & NECK Teeth \- Dental bleeding GENITOURINARY Internal Genitalia (Female) \- Menorrhagia \- Increased obstetric bleeding SKIN, NAILS, & HAIR Skin \- Eczema (in some patients) \- Psoriasis (in some patients) Hair \- Alopecia (in some patients) HEMATOLOGY \- Increased bleeding tendency \- Thrombocytopenia, mild (in some patients) \- Enlarged platelets \- Platelets have defective ATP secretion in response to agonists \- Platelet dense granule secretion defects \- Decreased or absent dense granules \- Enlarged alpha-granules \- Impaired platelet aggregation \- Defective megakaryocyte maturation and differentiation \- Decreased proplatelets IMMUNOLOGY \- Recurrent viral infections (in some patients) MISCELLANEOUS \- One family with autosomal recessive inheritance has been reported (last curated April 2017) MOLECULAR BASIS \- Caused by mutation in the friend leukemia virus integration 1 gene (FLI1, 193067.0001 ) ▲ 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	BLEEDING DISORDER, PLATELET-TYPE, 21	c1956093	5,349	omim	https://www.omim.org/entry/617443	2019-09-22T15:45:48	{"mesh": ["D054868"], "omim": ["617443"], "orphanet": ["851"]}
Cutis marmorata telangiectatica congenita (CMTC) is a birth defect involving the skin and blood vessels. It is characterized by patches of marbled-looking skin (cutis marmarota), small widened blood vessels under the skin (telangiectasia) and varicose veins (phlebectasia). The skin findings most often occur on the legs, but may also occur on the arms and trunk. The face is only rarely involved. CMTC usually only affects a specific area of the skin, although there have been a few cases of CMTC over the whole body. It may occasionally occur along with open sores (skin ulceration) or skin atrophy. The skin symptoms associated with CMTC generally improve with age. CMTC can occur alone or along with a variety of other birth defects, particularly those involving undergrowth or overgrowth of the same arm or leg. Most cases are thought to be sporadic (non-inherited), although rare cases have been observed in families. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Cutis marmorata telangiectatica congenita	c0345419	5,350	gard	https://rarediseases.info.nih.gov/diseases/6228/cutis-marmorata-telangiectatica-congenita	2021-01-18T18:01:00	{"mesh": ["C536226"], "omim": ["219250"], "umls": ["C0345419"], "orphanet": ["1556"], "synonyms": ["CMTC", "Hereditary cutis marmorata telangiectatica congenita", "Van Lohuizen syndrome"]}
Neurofaciodigitorenal syndrome is a rare multiple developmental anomalies syndrome characterized by neurological abnormalities (including megalencephaly, hypotonia, intellectual disability, abnormal EEG), dysmorphic facial features (high prominent forehead, grooved nasal tip, ptosis, ear anomalies) and acrorenal defects (such as triphalangism, broad halluces, unilateral renal agenesis). Additionally, intrauterine growth restriction, short stature and congenital heart defects may be associated. There have been no further descriptions in the literature since 1997. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Neurofaciodigitorenal syndrome	c0796088	5,351	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2673	2021-01-23T18:08:17	{"gard": ["3964"], "mesh": ["C537388"], "omim": ["256690"], "umls": ["C0796088"], "icd-10": ["Q87.8"], "synonyms": ["Freire Maia-Pinheiro-Opitz syndrome"]}
Prurigo pigmentosa SpecialtyDermatology Prurigo pigmentosa is a rare skin condition of unknown cause, characterized by the sudden onset of erythematous papules that leave a reticulated hyperpigmentation when they heal.[1]:57 The condition has been associated with a strict ketogenic diet in case reports in the medical literature.[2][3] It was first reported by Masaharu Nagashima in 1978.[4] ## See also[edit] * Pruritus * Skin lesion * Masaharu Nagashima ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. 2. ^ Michaels, Jason D.; Hoss, Elika; DiCaudo, David J.; Price, Harper (March 2015). "Prurigo Pigmentosa after a Strict Ketogenic Diet". Pediatric Dermatology. 32 (2): 248–251. doi:10.1111/pde.12275. PMID 24372546. 3. ^ "Prurigo Pigmentosa Induced by Ketosis: Resolution Through Dietary Modification". www.mdedge.com. Retrieved 2019-10-14. 4. ^ Nagashima, Masaji (April 1978). "Prurigo Pigmentosa". The Journal of Dermatology. 5 (2): 61–67. doi:10.1111/j.1346-8138.1978.tb01049.x. PMID 353107. ## External links[edit] Classification D * ICD-10: L28.2 (ILDS L28.226) * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji 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	Prurigo pigmentosa	c0406301	5,352	wikipedia	https://en.wikipedia.org/wiki/Prurigo_pigmentosa	2021-01-18T18:52:02	{"icd-10": ["L28.2"], "wikidata": ["Q7253114"]}
Ophthalmomandibulomelic dysplasia is characterized by complete blindness due to corneal opacities, difficult mastication due to temporomandibular fusion and anomalies of the arms. ## Epidemiology Three cases in one family have been described so far (two males, one female). ## Clinical description Micrognathia, shortening and bowing of the forearm, ulnar deviation and bowed radius, short fibula, genu valgum and coxa vara have been reported. Intelligence is normal. ## Etiology The causative gene has not yet been identified. ## Genetic counseling Autosomal dominant inheritance has been suggested. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Ophthalmomandibulomelic dysplasia	c1833872	5,353	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2741	2021-01-23T18:13:09	{"gard": ["4089", "4365"], "mesh": ["C563501"], "omim": ["164900"], "umls": ["C1833872"], "icd-10": ["Q87.8"], "synonyms": ["OMM syndrome", "Pillay syndrome"]}
A number sign (#) is used with this entry because Feingold syndrome-1 (FGLDS1) is caused by heterozygous mutation in the MYCN gene (164840) on chromosome 2p24. Description Feingold syndrome is an autosomal dominant disorder characterized by variable combinations of microcephaly, limb malformations, esophageal and duodenal atresias, and learning disability/mental retardation. Hand and foot abnormalities may include hypoplastic thumbs, clinodactyly of second and fifth fingers, syndactyly (characteristically between second and third and fourth and fifth toes), and shortened or absent middle phalanges. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described in a minority of patients (summary by Teszas et al., 2006). ### Genetic Heterogeneity of Feingold Syndrome Feingold syndrome-2 (FGLDS2; 614326) is caused by hemizygous deletion of the MIR17HG gene (609415) on chromosome 13q31.3. Clinical Features Feingold (1975) reported a father, son, and grandmother with microcephaly, hand abnormalities, tracheoesophageal fistula, duodenal atresia, and normal intelligence. Feingold (1978) reported a mother and daughter with similar findings except for the absence of tracheoesophageal fistula and duodenal atresia. Konig et al. (1990) described an affected mother and son with what they designated microcephaly, mesobrachyphalangy, and tracheoesophageal fistula (MMT) syndrome. Brunner and Winter (1991) reported 2 families with an autosomal dominant syndrome of abnormalities of the hands and feet with short palpebral fissures, variable microcephaly with learning disability, and esophageal/duodenal atresia. The hand anomalies included flexion deformity of the middle finger and clinodactyly of the second and fifth fingers. Foot anomalies included bilateral syndactyly of toes 2-3 and 4-5. In the first family, the mother and 2 sons were affected, and 8 other family members had the same abnormalities of the hands and feet; 3 of them had had operations in the neonatal period for esophageal or duodenal atresia or both. There were no instances of male-to-male transmission. In the second family, a mother and son and daughter were affected. There was no consanguinity in either family. The phenotype of the syndrome was similar to that observed with 13q22-qter deletion, but chromosome analysis detected no structural abnormality in these familial cases. Feingold et al. (1997) reported on 6 'new' families (12 patients) with this syndrome, updated the findings of the original families, and more clearly defined the syndrome. The most common findings were hand abnormalities, microcephaly, short and/or narrow palpebral fissures, broad nasal bridge, anteverted nostrils, ear abnormalities, and micrognathia. The features showed a significant amount of intrafamilial variability, especially as it related to the gastrointestinal findings. Although the first patients reported, who were very young, exhibited no developmental delay, they subsequently developed learning problems, and 87% of the 12 patients had mental retardation or learning difficulties. Typical hand findings, short second and fifth fingers, and clinodactyly and hypoplasia of the middle phalanx were pictured. Autosomal dominant inheritance was supported by the finding of male-to-male transmission in the family reported by Feingold (1975); in 8 of the 11 reported families, there was transmission through at least 2 generations. Innis et al. (1997) reported what appeared to be the same condition in a family with 6 and probably 8 affected members in 3 generations, including instances of male-to-male transmission. They referred to the condition as autosomal dominant microcephaly with normal intelligence, short palpebral fissures, and digital anomalies. Affected individuals consistently had microcephaly (OFC less than 3rd centile) and short palpebral fissures; however, there was considerable variability and individual asymmetry in the defects of the limbs. Major limb anomalies were hypoplasia, slender thumbs with limited flexion at the distal interphalangeal joints of thumbs and some fingers, thin proximal first metacarpals, and short middle phalanges of the index and fifth fingers. None of the affected persons had polyhydramnios or duodenal atresia, but 1 individual had a history of tracheoesophageal fistula. Taken together with previous reports, the risk for tracheoesophageal fistula and/or duodenal atresia in this disorder was 8 in 29, or approximately 28%. Frydman et al. (1997) described 4 families with what they considered to be the same disorder, which they called microcephaly-oculo-digito-esophageal-duodenal syndrome, or MODED. The phenotype is inherited as an autosomal dominant and includes microcephaly, type A brachydactyly, variable learning disabilities, short stature, duodenal atresia, patent ductus arteriosus (see 607411), hallux valgus, and a variety of digital anomalies. The authors reviewed previous reports, including their own observations. Penetrance of digital anomalies was almost complete. Microcephaly was present in 78% of known cases. Esophageal and duodenal atresias were found in 25% of known cases, but correction for ascertainment bias gave an estimate of 16.6%. Learning disabilities were seen in 31% of patients. Courtens et al. (1997) reported a seventh family with Feingold syndrome. The propositus was a male infant with esophageal and duodenal atresia, brachymesophalangy of the fifth fingers, bilateral syndactyly of toes 4-5 (and 2-3), relative microcephaly, and facial anomalies. His mother also had microcephaly, similar facial appearance, short fifth fingers with single flexion crease, syndactyly of toes 4-5, and learning disabilities. A sister and brother of the mother and her mother had the same phenotype. A review of the 7 families with Feingold syndrome demonstrated that intestinal (esophageal/duodenal) atresia/obstruction occurs in approximately one-third of patients with Feingold syndrome. Kawame et al. (1997) described 4 patients (2 boys and their mother and an unrelated girl) with microcephaly, normal intelligence, and digital abnormalities. The hand abnormalities were characterized by brachydactyly with radial clinodactyly of the fourth and fifth fingers, ulnar clinodactyly of the second fingers, and an increased space between the second and third fingers associated with an abnormal palmar crease that extended to the ulnar border. The foot abnormalities included short toes with syndactyly of the fourth and fifth toes. The mother had normal intelligence, and her sons and the unrelated girl had normal development. Kawame et al. (1997) noted similar findings in the patients reported by Feingold (1975) and Feingold et al. (1997), but suggested that the lack of gastrointestinal anomalies indicated that their 4 patients may have had a different autosomal dominant disorder. Buttiker et al. (2000) described a father and daughter with characteristic features of Feingold syndrome including microcephaly, short palpebral fissures, brachydactyly with clinodactyly of fifth fingers, and bilateral syndactyly of second to third and fourth to fifth toes. The infant presented with long-gap esophageal atresia without fistula. Her father, who had short stature and learning disabilities, had congenital imperforate anus with a rectovesical fistula. The authors thought that this was first report of distal intestinal atresia in Feingold syndrome. Shetty et al. (2000) described a 12-year-old girl with features of both the syndrome of microcephaly, mesobrachyphalangia, and tracheoesophageal fistula and Rett syndrome (312750). They suggested that this combination may constitute a new contiguous gene syndrome. However, the mapping of Rett syndrome to the X chromosome and the identification of the specific gene defect makes it unlikely that this was conventional Rett syndrome occurring as a contiguous gene syndrome with MMT syndrome, which maps to chromosome 2. Piersall et al. (2000) reported an additional family, a father and 2 sibs, with ODED syndrome, which associates microcephaly, abnormalities of the hands and feet, shortened palpebral fissures, tracheoesophageal fistula, and duodenal atresia. Vertebral anomalies were noted in this family. The sacral spine demonstrated a sagittal cleft at the body of S4 and absence of S5. His father had blocked vertebra of C5, 6, and 7 and neural arch fusion on the left of the 6th and 7th vertebrae. Shaw-Smith et al. (2005) and Shaw-Smith (2006) described a boy and his father with Feingold syndrome. They pictured short palpebral fissures and periorbital fullness, mild bilateral fifth finger clinodactyly, and in the father, bilateral clinodactyly of second and fifth fingers with brachymesophalangy of the second fingers. Shaw-Smith et al. (2005) observed short stature in the father and son and noted that of 18 cases of Feingold syndrome in the literature for which height was recorded, 4 had height at or below the 3rd centile, and 9 had height at or below the 10th centile; the authors suggested that short stature is likely to be a phenotypic feature of the syndrome. Teszas et al. (2006) reported a 4-year-old boy with classic features of Feingold syndrome associated with a pathogenic mutation in the MYCN gene (164840.0004). The patient's mother and grandmother both carried the mutation and had microcephaly, fifth finger clinodactyly, partial syndactyly of the toes, and normal intelligence, consistent with microcephaly and digital abnormalities with normal intelligence syndrome as defined by Kawame et al. (1997). The mother also had chronic nephritis, renal insufficiency, and hypertension. Teszas et al. (2006) suggested that microcephaly and digital abnormalities with normal intelligence represents a milder form of Feingold syndrome. Blaumeiser et al. (2008) reported monozygotic female twins with Feingold syndrome associated with a mutation in the MYCN gene (164840.0006). Both had the classic finger and toe malformations, hypertelorism, epicanthal folds, and developmental delay with occasional aggressive behavior. One sib had sensorineural deafness, and the other had duodenal atresia. Family history and genetic analysis showed that the mother and maternal grandfather also carried the mutation, but had only finger and toe anomalies. A maternal uncle of the twins also carried the mutation and had mental impairment, finger and toe anomalies, and structural renal problems. Blaumeiser et al. (2008) noted the wide phenotypic variability in this family. Kocak et al. (2009) reported a Turkish boy with Feingold syndrome confirmed by genetic analysis. He had microcephaly, frontal balding, upslanting and short palpebral fissures, choanal atresia, micrognathia, and large ears. He had bilateral hypoplastic middle phalanges of the second and fifth fingers, syndactyly of the second and third toes, and overriding of the fourth and fifth toes. He presented at age 3.5 months with seizures and vomiting. Family history revealed an older sib with esophageal atresia who died, as well as 3 other miscarriages. The father, who also carried the mutation, had a small head and severe digital anomalies, with brachydactyly, brachymesophalangy of all fingers, and partial skin syndactyly of the second and third toes. Inheritance Feingold syndrome is inherited in an autosomal dominant manner (Feingold et al., 1997; van Bokhoven et al., 2005). Mapping Celli et al. (2000) studied 4 pedigrees with ODED syndrome, including a 3-generation Dutch family with 11 affected members. Linkage analysis was initially aimed at chromosomal regions harboring candidate genes, and 12 different genomic regions covering 15 candidate genes were excluded. A subsequent nondirective mapping approach revealed evidence for linkage to marker D2S390 (maximum lod of 4.51 at theta of 0.0). A submicroscopic deletion in the fourth family provided independent confirmation of this genetic localization and narrowed the critical region to 7.3 cM in the 2p24-p23 region. These results showed that haploinsufficiency for a gene or genes in 2p24-p23 is associated with ODED syndrome. Tracheoesophageal fistula and esophageal atresia (TEF/EA) are common life-threatening conditions with multifactorial origins. Because these features occur in Feingold syndrome, this disorder may serve as a paradigm to identify genetic risk factors for TEF/EA. Van Bokhoven et al. (2005) carried out haplotype analysis in a previously unreported family with Feingold syndrome and confirmed linkage to the locus on chromosome 2 identified by Celli et al. (2003). Molecular Genetics In a previously unreported family with Feingold syndrome, van Bokhoven et al. (2005) found that affected members carried a microdeletion, which spanned a maximum interval of 1.2 Mb and encompassed the MYCN gene but no other known or predicted gene, making it an excellent candidate for Feingold syndrome. The MYCN gene had been shown to be activated by Sonic hedgehog (Shh; 600725) signaling and several lines of evidence suggest that the Shh pathway is disrupted in TEF/EA (Litingtung et al., 1998; Kenney et al., 2003; Oliver et al., 2003). In a cohort of 23 unrelated families with Feingold syndrome, van Bokhoven et al. (2005) sequenced the MYCN gene and identified 12 different heterozygous mutations in 15 families, including 3 different missense mutations at 2 adjacent arginine residues (164840.0001-164840.0003). Marcelis et al. (2008) analyzed the MYCN gene in 93 patients from 50 families with a strong clinical suspicion of Feingold syndrome and identified 16 heterozygous mutations in 17 families with a total of 26 patients, including mutations in exon 2, which had not previously been reported (see, e.g., 164840.0007). The authors reviewed the clinical features of the 77 mutation-positive patients reported to date and compared them with the largest previous overview (Celli et al., 2003), and found that digital anomalies involving brachymesophalangy and toe syndactyly were the most consistent features, present in 100% and 97% of patients, respectively, whereas small head circumference was present in 89% of cases. Gastrointestinal atresia was the most important major congenital anomaly (55%), but renal and cardiac anomalies were also frequent (18% and 15%, respectively). Marcelis et al. (2008) suggested that the presence of brachymesophalangy and toe syndactyly in combination with microcephaly is enough to justify MYCN analysis. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Microcephaly (79% of cases) \- Small anterior fontanelle \- Prominent occiput Face \- Micrognathia \- Triangular face \- Facial asymmetry Ears \- Posteriorly angulated ears \- Low-set ears \- Hearing loss Eyes \- Short palpebral fissures \- Narrow palpebral fissures \- Epicanthal folds \- Upslanting palpebral fissures Nose \- Broad nasal bridge \- Anteverted nostrils \- Flat nasal tip Mouth \- Prominent lips \- High-arched palate CARDIOVASCULAR Vascular \- Patent ductus arteriosus RESPIRATORY Larynx \- Vocal cord paralysis ABDOMEN Pancreas \- Annular pancreas Spleen \- Supernumerary spleen \- Congenital asplenia Gastrointestinal \- Tracheoesophageal fistula \- Esophageal atresia \- Duodenal atresia SKELETAL Hands \- Thumb symphalangism \- Absent/hypoplastic middle phalanx of 2nd finger \- Absent/hypoplastic middle phalanx of 5th finger Feet \- Syndactyly of toes 2-3 (56%) and 4-5 (86%) \- Short toes NEUROLOGIC Central Nervous System \- Mental retardation \- Learning disability (90% patients) PRENATAL MANIFESTATIONS Movement \- Decreased fetal movement Amniotic Fluid \- Polyhydramnios MOLECULAR BASIS \- Caused by mutations in the neuroblastoma-derived V-myc avian myelocytomatosis viral-related oncogene (MYCN, 164840.0001 ) ▲ 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	FEINGOLD SYNDROME 1	c0796068	5,354	omim	https://www.omim.org/entry/164280	2019-09-22T16:37:19	{"doid": ["0060464"], "mesh": ["C537734"], "omim": ["164280"], "orphanet": ["391641", "1305"], "synonyms": ["Digital anomalies with short palpebral fissures and atresia of esophagus or duodenum type 1", "Microcephaly-digital anomalies-normal intelligence syndrome type 1", "Microcephaly-intellectual disability-tracheoesophageal fistula syndrome type 1", "DIGITAL ANOMALIES WITH SHORT PALPEBRAL FISSURES AND ATRESIA OF ESOPHAGUS OR DUODENUM", "Microcephaly-oculo-digito-esophageal-duodenal syndrome syndrome type 1", "OCULODIGITOESOPHAGODUODENAL SYNDROME", "Oculo-digito-esophageal-duodenal syndrome type 1", "FGLDS1", "ODED SYNDROME", "MICROCEPHALY AND DIGITAL ABNORMALITIES WITH NORMAL INTELLIGENCE", "Brunner-Winter syndrome type 1", "MODED syndrome type 1", "MICROCEPHALY-OCULO-DIGITO-ESOPHAGEAL-DUODENAL SYNDROME", "FEINGOLD SYNDROME", "Alternative titles", "MICROCEPHALY, MENTAL RETARDATION, AND TRACHEOESOPHAGEAL FISTULA SYNDROME", "MMT type 1", "ODED syndrome type 1", "MMT SYNDROME", "FS1"], "genereviews": ["NBK7050", "NBK5192"]}
Neurogenic bladder dysfunction, or neurogenic bladder, refers to urinary bladder problems due to disease or injury of the central nervous system or peripheral nerves involved in the control of urination. There are multiple types of neurogenic bladder depending on the underlying cause and the symptoms. Symptoms include overactive bladder, urinary urgency, frequency, incontinence or difficulty passing urine. A range of diseases or conditions can cause neurogenic bladder including spinal cord injury, multiple sclerosis, stroke, brain injury, spina bifida, peripheral nerve damage, Parkinson's disease, or other neurodegenerative diseases. Neurogenic bladder can be diagnosed through a history and physical as well as imaging and more specialized testing. Treatment depends on underlying disease as well as symptoms and can be managed with behavioral changes, medications, surgeries, or other procedures. The symptoms of neurogenic bladder, especially incontinence, can have a significant impact on quality of life. ## Contents * 1 Classification * 1.1 Uninhibited * 1.2 Spastic * 1.3 Flaccid * 1.4 Mixed * 2 Signs and symptoms * 3 Causes * 3.1 Central nervous system * 3.2 Peripheral nervous system * 4 Diagnosis * 5 Treatment * 5.1 Catherization * 5.2 Medications * 5.3 Botulinum Toxin * 5.4 Neuromodulation * 5.5 Surgery * 6 Epidemiology * 7 Complications * 8 See also * 9 References * 10 External links ## Classification[edit] There are different types of neurogenic bladder depending on the underlying cause. Many of these types may have similar symptoms. Urinary bladder and urethra (red) with ureters (green) ### Uninhibited[edit] Uninhibited bladder is usually due to damage to the brain from a stroke or brain tumor. This can cause reduced sensation of bladder fullness, low capacity bladder and urinary incontinence. Unlike other forms of neurogenic bladder, it does not lead to high bladder pressures that can cause kidney damage.[1] ### Spastic[edit] In spastic neurogenic bladder (also known as upper motor neuron or hyper-reflexive bladder), the muscle of the bladder (detrusor) and urethral sphincter do not work together and are usually tightly contracted at the same time. This phenomenon is also called detrusor external sphincter dyssynergia (DESD). This leads to urinary retention with high pressures in the bladder that can damage the kidneys. The bladder volume is usually smaller than normal due to increased muscle tone in the bladder. Spastic neurogenic bladder is usually caused by damage to the spinal cord above the level of the 10th thoracic vertebrae (T10).[1][2] ### Flaccid[edit] In flaccid bladder (also known as lower motor neuron or hypotonic bladder), the muscles of the bladder lose ability to contract normally. This can cause the inability to void urine even if the bladder is full and cause a large bladder capacity. The internal urinary sphincter can contract normally, however urinary incontinence is common. This type of neurogenic bladder is caused by damage to the peripheral nerves that travel from the spinal cord to the bladder.[1] ### Mixed[edit] Mixed type of neurogenic bladder can cause a combination of the above presentations. In mixed type A, the bladder muscle is flaccid but the sphincter is overactive. This creates a large, low pressure bladder and inability to void, but does not carry as much risk for kidney damage as a spastic bladder. Mixed type B is characterized by a flaccid external sphincter and a spastic bladder causing problems with incontinence.[1] ## Signs and symptoms[edit] Neurogenic bladder can cause a range of urinary symptoms including urinary urgency, urinary incontinence or difficulty urinating (urinary retention.) The first sign of bladder dysfunction may be recurrent urinary tract infections (UTIs). ## Causes[edit] Urine storage and elimination (urination) requires coordination between the bladder emptying muscle (detrusor) and the external sphincter of the bladder. This coordination can be disrupted by damage or diseases of the central nervous system, peripheral nerves or autonomic nervous system.[3] This includes any condition that impairs bladder signaling at any point along the path from the urination center in the brain, spinal cord, peripheral nerves and the bladder. ### Central nervous system[edit] Damage to the brain or spinal cord is the most common cause of neurogenic bladder. Damage to the brain can be caused by stroke, brain tumors, multiple sclerosis, Parkinson's disease or other neurodegenerative conditions.[3] Bladder involvement is more likely if the damage is in the area of the pons. Damage to the spinal cord can be caused by traumatic injury, demyelinating disease, syringomyelia, cauda equina syndrome, or spina bifida. Spinal cord compression from herniated disks, tumor, or spinal stenosis can also result in neurogenic bladder.[1][3] ### Peripheral nervous system[edit] Damage to the nerves that travel from the spinal cord to the bladder (peripheral nerves) can cause neurogenic bladder, usually the flaccid type. Nerve damage can be caused by diabetes, alcoholism, and vitamin B12 deficiency. Peripheral nerves can also be damaged as a complication of major surgery of the pelvis, such as for removal of tumors.[1] ## Diagnosis[edit] Cystourethrograph showing bladder obstruction with dilation of urethra and bladder The diagnosis of neurogenic bladder is made based on a complete history and physical examination and may require imaging and specialized studies. History should include information on the onset, duration, triggers, severity, other medical conditions and medications (including anticholinergics, calcium channel blockers, diuretics, sedatives, alpha-adrenergic agonist, alpha 1 antagonists).[2][3] Urinary symptoms may include frequency, urgency, incontinence or recurrent urinary tract infections (UTIs). Questionnaires can be helpful in quantifying symptom burden.[2] In children it is important to obtain a prenatal and developmental history.[4] Ultrasound imaging can give information on the shape of the bladder, post-void residual volume, and evidence of kidney damage such as kidney size, thickness or ureteral dilation. A voiding cystourethrography study uses contrast dye to obtain images of the bladder both when it is full and after urination which can show changes in bladder shape consistent with neurogenic bladder.[4] Urodynamic studies are an important component of the evaluation for neurogenic bladder. Urodynamics refers to the measurement of the pressure-volume relationship in the bladder. The bladder usually stores urine at low pressure and urination can be completed without a dramatic pressure rise. Damage to the kidneys is probable if the pressure rises above 40 cm of water during filling.[2] Bladder pressure can be measured by cystometry, during which the bladder is artificially filled with a catheter and bladder pressures and detrusor activity are monitored. Patterns of involuntary detrusor activity as well as bladder flexibility, or compliance, can be evaluated. The most valuable test to test for detrusor sphincter dyssynergia (DESD) is to perform cystometry simultaneously with external sphincter electromyography (EMG).[3] Uroflowmetry is a less-invasive study that can measure urine flow rate and use it to estimate detrusor strength and sphincter resistance.[2][5] Urethral pressure monitoring is another less-invasive approach to assessing detrusor sphincter dyssynergia.[5] These studies can be repeated at regular intervals, especially if symptoms worsen or to measure response to therapies.[4] Evaluation of kidney function through blood tests such as serum creatinine should be obtained.[2] Imaging of the pelvis with CT scan or magnetic resonance imaging may be necessary, especially if there is concern for an obstruction such as a tumor. The inside of the bladder can be visualized by cystoscopy. ## Treatment[edit] Treatment depends on the type of neurogenic bladder and other medical problems. Treatment strategies include catheterization, medications, surgeries or other procedures. The goals of treatment is to keep bladder pressures in a safe range and eliminate residual urine in the bladder after urination (post-void residual volumes). ### Catherization[edit] Emptying the bladder with the use of a catheter is the most common strategy for managing urinary retention from neurogenic bladder. For most patients, this can be accomplished with intermittent catherization which involves no surgery or permanently attached appliances. Intermittent catheterization involves using straight catheters (which are usually disposable or single-use products) several times a day to empty the bladder.[3] This can be done independently or with assistance. For people who are unable to use disposable straight catheters, a Foley catheter allows continuous drainage of urine into a sterile drainage bag that is worn by the patient but are associated with higher rates of complications.[6] ### Medications[edit] Oxybutynin is a common anti-cholinergic medication used to reduce bladder contractions by blocking M3 muscarinic receptors in the detrusor.[6] Its use is limited by side effects such as dry mouth, constipation and decreased sweating. Tolterodine is a longer acting anticholinergic that may have fewer side effects.[4] For urinary retention, cholinergics (muscarinic agonists) like bethanechol can improve the squeezing ability of the bladder. Alpha blockers can also reduce outlet resistance and allow complete emptying if there is adequate bladder muscle function.[4] ### Botulinum Toxin[edit] Botulinum toxin (Botox) can be used through two different approaches. For spastic neurogenic bladder, the bladder muscle (detrusor) can be injected which will cause it to be flaccid for 6–9 months. This prevents high bladder pressures and intermittent catherization must be used during this time.[4] Botox can also be injected into the external sphincter to paralyze a spastic sphincter in patients with detrusor sphincter dyssynergia.[5] ### Neuromodulation[edit] There are various strategies to alter the interaction between the nerves and muscles of the bladder, including nonsurgical therapies (transurethral electrical bladder stimulation), minimally invasive procedures (sacral neuromodulation pacemaker), and operative (reconfiguration of sacral nerve root anatomy).[4] ### Surgery[edit] Surgical interventions may be pursued if medical approaches have been maximized. Surgical options depend on the type of dysfunction observed on urodynamic testing, and may include: * Urinary Diversion: Creation of a stoma (from the intestines, called "conduit") that bypasses the urethra to empty the bladder directly through a skin opening. Several techniques may be used. One technique is the Mitrofanoff stoma, where the appendixor a portion of the ileum (‘Yang-Monti’ conduit) are used to create the diversion.[4] The ileum and ascending colon can also be used to create a pouch accessible for catheterization (Indiana pouch). * Urethral stents or urethral sphincterotomy are other surgical approaches that can reduce bladder pressures but require use of an external urinary collection device.[5] * Urethral slings may be used in both adults and children [7][8][9] * Artificial Urinary Sphincters have shown good term outcomes in adults and pediatric patients.[10][8][11] One study on 97 patients followed for a mean duration of 4 years found that 92% percent were continent at day and night during follow up.[11] However, patients in this study who had intermediate-type bladders underwent adjuvant cystoplasty. * Bladder Neck Closure is a major surgical procedure which can be a last resort treatment for incontinence, a Mitrofanoff stoma is necessary to empty the bladder.[12] ## Epidemiology[edit] The overall prevalence of neurogenic bladder is limited due to the broad range of conditions that can lead to urinary dysfunction. Neurogenic bladder is common with spinal cord injury and multiple sclerosis.[5] Rates of some type of urinary dysfunction surpass 80% one year after spinal cord injury.[6] Among patients with multiple sclerosis, 20–25% will develop neurogenic bladder although the type and severity bladder dysfunction is variable.[5] ## Complications[edit] Neurogenic bladder can cause hydronephrosis (swelling of a kidney due to a build-up of urine), recurrent urinary tract infections, and recurrent kidney stones which may compromise kidney function.[6] This is especially significant in spastic neurogenic bladder that leads to high bladder pressures. Kidney failure was previously a leading cause of mortality in patients with spinal cord injury but is now dramatically less common due to improvements in bladder management.[6] ## See also[edit] * Spinal cord injury * Multiple sclerosis * Bladder sphincter dyssynergia * Urinary retention ## References[edit] 1. ^ a b c d e f Dorsher PT, McIntosh PM (2012). "Neurogenic bladder". Advances in Urology. 2012: 816274. doi:10.1155/2012/816274. PMC 3287034. PMID 22400020. 2. ^ a b c d e f Amarenco, Gerard; Sheikh Ismaël, Samer; Chesnel, Camille; Charlanes, Audrey; LE Breton, Frederique (Dec 2017). "Diagnosis and clinical evaluation of neurogenic bladder". European Journal of Physical and Rehabilitation Medicine. 53 (6): 975–980. doi:10.23736/S1973-9087.17.04992-9. ISSN 1973-9095. PMID 29072046. 3. ^ a b c d e f Bacsu, Chasta-Dawne; Chan, Lewis; Tse, Vincent (2012). "Diagnosing detrusor sphincter dyssynergia in the neurological patient". BJU International. 109 Suppl 3: 31–34. doi:10.1111/j.1464-410X.2012.11042.x. ISSN 1464-410X. PMID 22458490. 4. ^ a b c d e f g h Sripathi, Venkataramani; Mitra, Aparajita (2017-07-01). "Management of Neurogenic Bladder". The Indian Journal of Pediatrics. 84 (7): 545–554. doi:10.1007/s12098-017-2356-7. ISSN 0973-7693. PMID 28553689. 5. ^ a b c d e f Stoffel, John T. (2016). "Detrusor sphincter dyssynergia: a review of physiology, diagnosis, and treatment strategies". Translational Andrology and Urology. 5 (1): 127–135. doi:10.3978/j.issn.2223-4683.2016.01.08. ISSN 2223-4691. PMC 4739973. PMID 26904418. 6. ^ a b c d e Schurch, Brigitte; Tawadros, Cécile; Carda, Stefano (2015). "Dysfunction of lower urinary tract in patients with spinal cord injury". Handbook of Clinical Neurology. 130: 247–267. doi:10.1016/B978-0-444-63247-0.00014-6. ISBN 9780444632470. ISSN 0072-9752. PMID 26003248. 7. ^ Groen, LA; Spinoit, AF; Hoebeke, P; Van Laecke, E; De Troyer, B; Everaert, K (November 2012). "The AdVance male sling as a minimally invasive treatment for intrinsic sphincter deficiency in patients with neurogenic bladder sphincter dysfunction: a pilot study". Neurourology and urodynamics. 31 (8): 1284–7. doi:10.1002/nau.21256. PMID 22847896. 8. ^ a b Ludwikowski, Barbara M.; Bieda, Jan-Christoph; Lingnau, Anja; González, Ricardo (2019). "Surgical Management of Neurogenic Sphincter Incompetence in Children". Frontiers in Pediatrics. 7: 97. doi:10.3389/fped.2019.00097. ISSN 2296-2360. PMC 6448010. PMID 30984720. 9. ^ Myers, Jeremy B.; Mayer, Erik N.; Lenherr, Sara (February 2016). "Management options for sphincteric deficiency in adults with neurogenic bladder". Translational Andrology and Urology. 5 (1): 145–157. doi:10.3978/j.issn.2223-4683.2015.12.11. ISSN 2223-4691. PMC 4739985. PMID 26904420. 10. ^ Bersch, Ulf; Göcking, Konrad; Pannek, Jürgen (2009-03-01). "The Artificial Urinary Sphincter in Patients with Spinal Cord Lesion: Description of a Modified Technique and Clinical Results". European Urology. 55 (3): 687–695. doi:10.1016/j.eururo.2008.03.046. ISSN 0302-2838. PMID 18394784. 11. ^ a b Singh, G.; Thomas, D. G. (February 1996). "Artificial urinary sphincter in patients with neurogenic bladder dysfunction". British Journal of Urology. 77 (2): 252–255. doi:10.1046/j.1464-410x.1996.85515.x. ISSN 0007-1331. PMID 8800894. 12. ^ De Troyer, Bart; Van Laecke, Erik; Groen, Luitzen A.; Everaert, Karel; Hoebeke, Piet (2011-04-01). "A comparative study between continent diversion and bladder neck closure versus continent diversion and bladder neck reconstruction in children". Journal of Pediatric Urology. 7 (2): 209–212. doi:10.1016/j.jpurol.2010.03.011. ## External links[edit] Classification D * ICD-10: N31.9 * ICD-9-CM: 596.54 * MeSH: D001750 * DiseasesDB: 30837 External resources * MedlinePlus: 000754 * eMedicine: med/3176 * Patient UK: Neurogenic bladder dysfunction * v * t * e Diseases of the urinary tract Ureter * Ureteritis * Ureterocele * Megaureter Bladder * Cystitis * Interstitial cystitis * Hunner's ulcer * Trigonitis * Hemorrhagic cystitis * Neurogenic bladder dysfunction * Bladder sphincter dyssynergia * Vesicointestinal fistula * Vesicoureteral reflux Urethra * Urethritis * Non-gonococcal urethritis * Urethral syndrome * Urethral stricture * Meatal stenosis * Urethral caruncle Any/all * Obstructive uropathy * Urinary tract infection * Retroperitoneal fibrosis * Urolithiasis * Bladder stone * Kidney stone * Renal colic * Malakoplakia * Urinary incontinence * Stress * Urge * Overflow [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Neurogenic bladder dysfunction	c0005697	5,355	wikipedia	https://en.wikipedia.org/wiki/Neurogenic_bladder_dysfunction	2021-01-18T18:40:44	{"mesh": ["D001750"], "umls": ["C0005697"], "icd-10": ["N31.9"], "wikidata": ["Q2339038"]}
Lateral meningocele syndrome Other namesLehman syndrome[1] Lateral meningocele syndrome is inherited in an autosomal dominant manner The lateral meningocele syndrome is a very rare skeletal disorder with facial anomalies, hypotonia and meningocele-related neurologic dysfunction.[2] ## Contents * 1 Presentation * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 History * 6 References * 7 External links ## Presentation[edit] Facial features found in this syndrome include * dolichocephaly * hypertelorism * ptosis * microretrognathia * high arched palate * long flat philtrum * low set ears Non facial features of this syndrome include * hyperextensibility * hypotonia * lateral meningoceles The lateral meningoceles are a common finding in this syndrome. They may be associated with neurological abnormalities and result in bladder dysfunction and neuropathy. ## Genetics[edit] This syndrome appears to be inherited in an autosomal dominant fashion. Molecular analyses suggest that the causative mutations cause a truncation of the protein. These mutations result in the loss of PEST sequence in the protein. This loss is associated with a prolonged half life of the protein. Mutations in Notch 3 were found to be associated with this syndrome.[3] ## Diagnosis[edit] This section is empty. You can help by adding to it. (September 2017) ## Treatment[edit] This section is empty. You can help by adding to it. (September 2017) ## History[edit] This syndrome was first described by Lehman et al. in 1977.[4] This paper described a 14-year-old girl with a number of unusual findings. Her mother shared some of the same findings. Since then over a dozen additional cases have been reported. ## References[edit] 1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Lateral meningocele syndrome". www.orpha.net. Retrieved 20 October 2019. 2. ^ Pamir, M. Memet Ö̈zek, Giuseppe Cinalli, Wirginia J. Maixner; forewords by C. Sainte-Rose, C. di Rocco; preface by M. Necmettin, ed. (2008). Spina bifida : management and outcome. Milan: Springer. p. 432. ISBN 9788847006508. 3. ^ Gripp, K. W.; Robbins, K. M.; Sobreira, N. L.; Witmer, P. D.; Bird, L. M.; Avela, K; Makitie, O; Alves, D; Hogue, J. S.; Zackai, E. H.; Doheny, K. F.; Stabley, D. L.; Sol-Church, K (2014). "Truncating mutations in the last exon of NOTCH3 cause lateral meningocele syndrome". American Journal of Medical Genetics Part A. 167A (2): 271–81. doi:10.1002/ajmg.a.36863. PMC 5589071. PMID 25394726. 4. ^ Lehman RAW, Stears JC, Wesenberg RL, Nusbaum ED (1977) Familial osteosclerosis with abnormalities of the nervous system and meninges. J Pediat 90: 49-54 ## External links[edit] Classification D * ICD-10: Q87.5 * OMIM: 130720 * MeSH: C537878 External resources * Orphanet: 2789 This article about a congenital malformation is a stub. You can help Wikipedia by expanding it. * v * t * e This genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Lateral meningocele syndrome	c1851710	5,356	wikipedia	https://en.wikipedia.org/wiki/Lateral_meningocele_syndrome	2021-01-18T18:55:24	{"gard": ["9873"], "mesh": ["C537878"], "umls": ["C0344487", "C1851710"], "orphanet": ["2789"], "wikidata": ["Q18589160"]}
West Nile encephalitis is a form of West Nile virus that affects the neurological system. Signs and symptoms may include headache, fever, neck stiffness, disorientation, tremors, seizures, paralysis, or coma. West Nile virus is generally spread to humans by infected mosquitos. West Nile encephalitis, specifically, occurs when the virus crosses the blood-brain barrier and infects the central nervous system. Although West Nile encephalitis can affect anyone, people who are over age 60, have received an organ transplant, or are affected by certain medical conditions such as cancer, diabetes, hypertension, and kidney disease have the highest risk of developing the condition. Treatment is supportive and hospitalization may be required to address the associated symptoms. Recovery may take several weeks or months and some of the neurologic effects may be permanent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	West Nile virus encephalitis	c0751583	5,357	gard	https://rarediseases.info.nih.gov/diseases/9959/west-nile-virus-encephalitis	2021-01-18T17:57:06	{"mesh": ["D014901"], "umls": ["C0751583"], "synonyms": []}
Peters and Hovels (1960) described the familial nature of the syndrome. This is one of the first and second arch syndromes. It is easily confused with mandibulofacial dysostosis (154400). Its features are anterior-posterior shortening of the maxilla, antimongoloid-slanting of the palpebral fissures, minor malformation of the auricles, severe delay in speech, and nonfluent and inarticulate speech. Villaret and Desoille (1932) described 'primary familial hypoplasia of the maxilla' in grandfather, father and son. The mandible was relatively prognathic to a mild degree. Melnick and Eastman (1977) described affected mother and son. Eyes \- Antimongoloid slant of palpebral fissures Inheritance \- Autosomal dominant Neuro \- Severe speech delay \- Nonfluent and inarticulate speech Facies \- Anterior-posterior shortening of the maxilla \- Mandibular prognathism Ears \- Minor malformation of the auricles ▲ 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	MAXILLOFACIAL DYSOSTOSIS	c1835088	5,358	omim	https://www.omim.org/entry/155000	2019-09-22T16:38:31	{"mesh": ["C563599"], "omim": ["155000"]}
Splinter hemorrhage Splinter hemorrhage on a fingernail of the little finger Differential diagnosissubacute infective endocarditis, scleroderma, trichinosis, systemic lupus erythematosus (SLE), rheumatoid arthritis, psoriatic nails, antiphospholipid syndrome Splinter hemorrhages (or haemorrhages) are tiny blood clots that tend to run vertically under the nails. Splinter hemorrhages are not specific to any particular condition, and can be associated with subacute infective endocarditis, scleroderma, trichinosis, systemic lupus erythematosus (SLE), rheumatoid arthritis, psoriatic nails,[1] antiphospholipid syndrome,[2]:659 haematological malignancy, and trauma.[3] At first they are usually plum-colored, but then darken to brown or black in a couple of days. In certain conditions (in particular, infective endocarditis), clots can migrate from the affected heart valve and find their way into various parts of the body. If this happens in the finger, it can cause damage to the capillaries resulting in a splinter hemorrhage. There are a number of other causes for splinter hemorrhages. They could be due to hitting the nail (trauma), a sign of inflammation in blood vessels all around the body (systemic vasculitis), or they could be where a fragment of cholesterol has become lodged in the capillaries of the finger. Even if a patient does have infective endocarditis, roughly 1 in 10 patients have splinter hemorrhages.[4] ## Additional image[edit] Splinter hemorrhage under the microscope ## See also[edit] * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ Li, Cindy (29 March 2011). "Nail Psoriasis: Overview of Nail Psoriasis". Medscape. Retrieved 7 January 2012. 2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 4. ^ Hoen, Bruno (April 11, 2013). "Infective Endocarditis". New England Journal of Medicine. 368 (15): 1425–33. doi:10.1056/NEJMcp1206782. PMID 23574121. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Splinter hemorrhage	c0333286	5,359	wikipedia	https://en.wikipedia.org/wiki/Splinter_hemorrhage	2021-01-18T19:00:02	{"umls": ["C0333286"], "wikidata": ["Q7578579"]}
Hereditary cerebral amyloid angiopathy is a condition that can cause a progressive loss of intellectual function (dementia), stroke, and other neurological problems starting in mid-adulthood. Due to neurological decline, this condition is typically fatal in one's sixties, although there is variation depending on the severity of the signs and symptoms. Most affected individuals die within a decade after signs and symptoms first appear, although some people with the disease have survived longer. There are many different types of hereditary cerebral amyloid angiopathy. The different types are distinguished by their genetic cause and the signs and symptoms that occur. The various types of hereditary cerebral amyloid angiopathy are named after the regions where they were first diagnosed. The Dutch type of hereditary cerebral amyloid angiopathy is the most common form. Stroke is frequently the first sign of the Dutch type and is fatal in about one third of people who have this condition. Survivors often develop dementia and have recurrent strokes. About half of individuals with the Dutch type who have one or more strokes will have recurrent seizures (epilepsy). People with the Flemish and Italian types of hereditary cerebral amyloid angiopathy are prone to recurrent strokes and dementia. Individuals with the Piedmont type may have one or more strokes and typically experience impaired movements, numbness or tingling (paresthesias), confusion, or dementia. The first sign of the Icelandic type of hereditary cerebral amyloid angiopathy is typically a stroke followed by dementia. Strokes associated with the Icelandic type usually occur earlier than the other types, with individuals typically experiencing their first stroke in their twenties or thirties. Strokes are rare in people with the Arctic type of hereditary cerebral amyloid angiopathy, in which the first sign is usually memory loss that then progresses to severe dementia. Strokes are also uncommon in individuals with the Iowa type. This type is characterized by memory loss, problems with vocabulary and the production of speech, personality changes, and involuntary muscle twitches (myoclonus). Two types of hereditary cerebral amyloid angiopathy, known as familial British dementia and familial Danish dementia, are characterized by dementia and movement problems. Strokes are uncommon in these types. People with the Danish type may also have clouding of the lens of the eyes (cataracts) or deafness. ## Frequency The prevalence of hereditary cerebral amyloid angiopathy is unknown. The Dutch type is the most common, with over 200 affected individuals reported in the scientific literature. ## Causes Mutations in the APP gene are the most common cause of hereditary cerebral amyloid angiopathy. APP gene mutations cause the Dutch, Italian, Arctic, Iowa, Flemish, and Piedmont types of this condition. Mutations in the CST3 gene cause the Icelandic type. Familial British and Danish dementia are caused by mutations in the ITM2B gene. The APP gene provides instructions for making a protein called amyloid precursor protein. This protein is found in many tissues and organs, including the brain and spinal cord (central nervous system). The precise function of this protein is unknown, but researchers speculate that it may attach (bind) to other proteins on the surface of cells or help cells attach to one another. In the brain, the amyloid precursor protein plays a role in the development and maintenance of nerve cells (neurons). The CST3 gene provides instructions for making a protein called cystatin C. This protein inhibits the activity of enzymes called cathepsins that cut apart other proteins in order to break them down. Cystatin C is found in biological fluids, such as blood. Its levels are especially high in the fluid that surrounds and protects the brain and spinal cord (the cerebrospinal fluid or CSF). The ITM2B gene provides instructions for producing a protein that is found in all tissues. The function of the ITM2B protein is unclear. It is thought to play a role in triggering the self-destruction of cells (apoptosis) and keeping cells from growing and dividing too fast or in an uncontrolled way. Additionally, the ITM2B protein may be involved in processing the amyloid precursor protein. Mutations in the APP, CST3, or ITM2B gene lead to the production of proteins that are less stable than normal and that tend to cluster together (aggregate). These aggregated proteins form protein clumps called amyloid deposits that accumulate in certain areas of the brain and in its blood vessels. The amyloid deposits, known as plaques, damage brain cells, eventually causing cell death and impairing various parts of the brain. Brain cell loss in people with hereditary cerebral amyloid angiopathy can lead to seizures, movement abnormalities, and other neurological problems. In blood vessels, amyloid plaques replace the muscle fibers and elastic fibers that give the blood vessels flexibility, causing them to become weak and prone to breakage. A break in a blood vessel in the brain causes bleeding in the brain (hemorrhagic stroke), which can lead to brain damage and dementia. ### Learn more about the genes associated with Hereditary cerebral amyloid angiopathy * APP * CST3 * ITM2B ## Inheritance Pattern Hereditary cerebral amyloid angiopathy caused by mutations in the APP, CST3, or ITM2B gene is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. There is also a non-hereditary form of cerebral amyloid angiopathy that occurs in people with no history of the disorder in their family. The cause of this form of the condition is unknown. These cases are described as sporadic and are not inherited. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Hereditary cerebral amyloid angiopathy	c2931672	5,360	medlineplus	https://medlineplus.gov/genetics/condition/hereditary-cerebral-amyloid-angiopathy/	2021-01-27T08:25:24	{"gard": ["10266"], "mesh": ["C537944"], "omim": ["605714", "105150", "176500", "117300"], "synonyms": []}
Familial pancreatic cancer (FPC) is the occurrence of pancreatic cancer in two or more first-degree relatives (parent and child, or two siblings). It is sometimes referred to as FPC only when there is not a known hereditary cancer syndrome in an affected family. In familial cases, pancreatic cancer often occurs before age 50 (earlier than other forms of pancreatic cancer). In 60% of cases it occurs within the head of the pancreas. Symptoms of pancreatic cancer are generally non-specific and may include pain in the upper abdomen that radiates to the back; loss of appetite; significant weight loss; and jaundice due to bile duct obstruction. Pancreatic cancer often goes undetected until the advanced stages of the disease, and rapid tumor growth and metastasis are common. A specific genetic cause of FPC (in the absence of a known syndrome) has not been identified. Familial cases of pancreatic cancer due to hereditary conditions may be caused by mutations in any of several genes. Individuals who carry a mutation in one of these genes are often at an increased risk of other types of cancers as well. Currently, only 10-20% of families with FPC will have a mutation identified by genetic testing. Hereditary cancer syndromes and other inherited conditions associated with pancreatic cancer include: * BRCA1 hereditary breast and ovarian cancer syndrome * BRCA2 hereditary breast and ovarian cancer syndrome * Peutz-Jeghers syndrome * FAMMM syndrome * Lynch syndrome * Hereditary pancreatitis In many cases, inheritance of FPC is autosomal dominant; in some cases, is may be multifactorial. It is important to note that pancreatic cancer itself is not inherited, but a genetic predisposition to developing cancer is inherited. Treatment may include surgical resection, chemotherapy, and/or radiotherapy. Resection is the only potential cure, but most patients have advanced, non-resectable tumors by the time of diagnosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Familial pancreatic cancer	c2931038	5,361	gard	https://rarediseases.info.nih.gov/diseases/4206/familial-pancreatic-cancer	2021-01-18T18:00:33	{"mesh": ["C535837"], "umls": ["C2931038"], "orphanet": ["1333"], "synonyms": ["Hereditary pancreatic carcinoma", "Familial pancreatic carcinoma", "Hereditary pancreatic cancer"]}
A number sign (#) is used with this entry because of evidence that some cases of Martsolf syndrome are caused by homozygous mutation in the gene encoding the noncatalytic subunit of RAB3 GTPase-activating protein (RAB3GAP2; 609275) on chromosome 1q41. Warburg Micro syndrome-2 (WARBM2; 614225), a clinically overlapping but more severe disorder, is also caused by mutation in the RAB3GAP2 gene. Clinical Features Martsolf et al. (1978) described a family in which 2 brothers had severe mental retardation, cataracts, short stature, primary hypogonadism, and minor digital and cephalic abnormalities. The parents were first cousins of Polish-Jewish descent and had 1 normal daughter. There are several mental retardation syndromes associated with cataracts, with or without short stature. These were reviewed by Cuendet et al. (1976). The association of mental retardation, cataracts, and primary hypogonadism is more rare. Sanchez et al. (1985) described this syndrome in 2 brothers of Sephardic Jewish ancestry. Strisciuglio et al. (1988) reported a non-Jewish case. Hennekam et al. (1988) described an affected brother and sister of Dutch or Belgian ancestry. Harbord et al. (1989) described a syndrome of microcephaly, mental retardation, cataracts, and hypogonadism in a brother and sister with consanguineous parents of Pakistani origin. One sib had cardiomyopathy while the other had cardiac failure. Cardiac features had not previously been described in Martsolf syndrome. Aligianis et al. (2006) described a consanguineous Pakistani family with 3 affected sibs. The first child had cataracts, microphthalmia, micropenis, and cryptorchidism at birth. Spastic diplegia was noted at the age of 3.5 years. At age 11 years, he had mild learning difficulties, was microcephalic, and walked with a walker. The sister of the proband likewise had dense bilateral cataracts, microphthalmia, and microcephaly at birth. Hypotonia was noted in infancy, and she later developed spastic diplegia. She had global developmental delay. At age 5 years, she had moderate learning difficulties and required special schooling, but she was bilingual in English and Punjabi. The third sib had congenitally corrected transposition of the great vessels with micropenis, bilateral cryptorchidism, congenital cataracts, and microphthalmia. Cardiac arrest of unknown cause occurred immediately after cataract surgery at the age of 2 months and, following resuscitation, he was found to have severe hypoxic ischemic encephalopathy with convulsions. Ehara et al. (2007) reported a Japanese brother and sister with clinical features consistent with Martsolf syndrome. They were 31 and 24 years of age, respectively, at the time of the report. As children, both showed delayed motor development, short stature, cataracts, thoracic scoliosis, and severe mental retardation. Both also developed skeletal abnormalities of the femoral neck, including metaphyseal broadening and fragmentation consistent with Legg-Calve-Perthes disease (150600). The sister was found to have Klipper-Feil malformation (118100). Laboratory evaluations showed growth hormone deficiency and lack of response to GnRH stimulation suggesting hypothalamic-pituitary insufficiency. Brain MRI showed enlarged Sylvian fissures, mildly dilated ventricles, and mild cerebral atrophy. Other features included brachycephaly, short philtrum, low posterior hairline, scoliosis, talipes valgus, flat feet, and lax finger joints. Bora et al. (2007) described a 7-year-old Turkish boy, born of first-cousin parents and whose great-grandparents were also first cousins, who had severe psychomotor retardation, microcephaly, microphthalmia with a myotic pupil, bilateral congenital cataracts (for which he had surgery in infancy), maxillary retrusion, dysplastic low-set ears, long philtrum, micropenis, cryptorchidism, and pes planus and equinovarus. Neurologic examination revealed hypotonia, 1- to 2-beat clonus, and diminished deep tendon reflexes; the boy had difficulties in walking and speaking, and his overall developmental age was 20 months. Laboratory studies were normal including cholesterol; cranial MRI showed high-intensity signals in the deep periventricular white matter. Handley et al. (2013) studied 2 Gambian sisters and a Mexican Hispanic boy with Martsolf syndrome. All 3 were described as having postnatal growth retardation, postnatal microcephaly, axial hypotonia, and moderate mental retardation; speech was delayed in the boy, whereas both sisters had preserved speech and were bilingual. By 3 years of age, the boy exhibited spasticity of the lower limbs; the sisters, who were 14 and 17 years of age, showed general pyramidal signs with knee contractures, absence of knee reflex, and peripheral neuropathy. Nerve conduction studies in the sisters showed demyelinating polyneuropathy with motor predominance and distal secondary axonal neuropathy. Brain MRI in all 3 patients showed bilateral polymicrogyria, involving the parietal and occipital lobes in the sisters and the supratentorial cortex in the boy. All 3 exhibited bilateral microphthalmia, microcornea, and cataracts; the sisters had optic nerve atrophy, whereas the boy had pale optic nerves. Other features in the boy included cryptorchidism and micropenis. Molecular Genetics In a consanguineous Pakistani family with microphthalmia, congenital cataracts, hypogonadism, and mild mental retardation, Aligianis et al. (2006) identified a homozygous missense mutation in the noncatalytic subunit of RAB3GAP (RAB3GAP2) that resulted in abnormal splicing (609725.0001). Mutations in the catalytic subunit of RAB3GAP1 (602536) cause the Warburg micro syndrome (600118), a severe neurodevelopmental condition with clinical features overlapping those of Martsolf syndrome. RAB3GAP is a heterodimeric protein that consists of a catalytic subunit and a noncatalytic subunit encoded by RAB3GAP1 and RAB3GAP2, respectively. In mRNA expression studies of the orthologs of these 2 genes in zebrafish embryos, Aligianis et al. (2006) demonstrated that, whereas developmental expression of Rab3gap1 was generalized similar to that reported in mice, Rab3gap2 expression was restricted to the central nervous system. These findings were consistent with RAB3GAP2 having a key role in neurodevelopment. In 2 Gambian sisters and a Mexican Hispanic boy with Martsolf syndrome, Handley et al. (2013) identified homozygosity for a missense mutation in the RAB3GAP2 gene (R426C; 609275.0003). Heterogeneity In the sibs with Martsolf syndrome reported by Hennekam et al. (1988), Aligianis et al. (2006) found no mutation in the RAB3GAP2 gene, indicating genetic heterogeneity. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature \- Height less than 5th percentile Weight \- Weight less than 5th percentile HEAD & NECK Head \- Brachycephaly \- Microcephaly Face \- Maxillary hypoplasia, mild \- Micrognathia \- Short philtrum Ears \- Prominent antitragus \- Posteriorly rotated ears Eyes \- Cataracts \- Epicanthal folds \- Downslanting palpebral fissures Nose \- Low nasal bridge \- Broad nasal tip Mouth \- Pouty lower lip \- High palate Teeth \- Malaligned teeth CARDIOVASCULAR Heart \- Cardiomyopathy \- Cardiac failure RESPIRATORY \- Recurrent respiratory infections Airways \- Tracheomalacia CHEST Ribs Sternum Clavicles & Scapulae \- Pectus carinatum \- Pectus excavatum Breasts \- Prominent nipples ABDOMEN Gastrointestinal \- Feeding problems (infancy) GENITOURINARY External Genitalia (Male) \- Small penis Internal Genitalia (Male) \- Cryptorchidism SKELETAL Spine \- Lumbar hyperlordosis Limbs \- Thin limbs \- Slender radii \- Slender ulnae Hands \- Short palms \- Broad fingertips \- Finger joint laxity \- Short metacarpals \- Short phalanges Feet \- Metatarsus varus \- Short toes \- Clubfoot \- Talipes valgus SKIN, NAILS, & HAIR Nails \- Abnormal toenails NEUROLOGIC Central Nervous System \- Mental retardation, severe ENDOCRINE FEATURES \- Hypogonadotropic hypogonadism MOLECULAR BASIS \- Caused by mutation in the RAB3 GTPase-activating protein subunit 2 gene (RAB3GAP2, 609275.0001 ) ▲ 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	MARTSOLF SYNDROME	c0796037	5,362	omim	https://www.omim.org/entry/212720	2019-09-22T16:30:03	{"mesh": ["C536028"], "omim": ["212720"], "orphanet": ["1387"], "synonyms": ["Alternative titles", "CATARACT-MENTAL RETARDATION-HYPOGONADISM"], "genereviews": ["NBK475670"]}
A number sign (#) is used with this entry because of evidence that combined oxidative phosphorylation deficiency-29 (COXPD29) is caused by homozygous mutation in the TXN2 gene (609063) on chromosome 22q12.3. One such patient has been reported. For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). Clinical Features Holzerova et al. (2016) reported a 16-year-old boy, born of unrelated German parents, with a severe early-onset neurodegenerative disorder. The patient was born with microcephaly and showed decreased activity. Brain imaging showed global brain atrophy, abnormal hippocampal shape, subependymal cysts, and abnormal T2-weighted signals in the cerebellum. Serum and CSF lactate levels were increased. He subsequently showed severely delayed psychomotor development with disturbed muscle tone, spasticity, dystonia, and incoordination. No specific dysmorphic features were noted. Muscle biopsy showed reduced activities of mitochondrial respiratory complexes I and III and decreased ATP production. Additional features included severe drug-resistant epilepsy, optic neuropathy and retinopathy, poor feeding necessitating a gastrostomy tube, and peripheral neuropathy with axonal degeneration. Subsequent brain imaging showed rapid progression of the cerebellar atrophy, as well as delayed myelination. Treatment with coenzyme Q10 resulted in some clinical improvement. Inheritance The transmission pattern of COXPD29 in the family reported by Holzerova et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In a German boy with COXPD29, Holzerova et al. (2016) identified a homozygous truncating mutation in the TXN2 gene (W24X; 609063.0001). The mutation was found by whole-exome sequencing and segregated with the disorder in the family. Patient fibroblasts showed absence of TXN2 protein, increased levels of reactive oxygen species levels, impaired survival against oxidative stress, and oxidative phosphorylation dysfunction, all of which could be restored with wildtype TXN2. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly Eyes \- Optic atrophy \- Retinopathy ABDOMEN Gastrointestinal \- Poor feeding MUSCLE, SOFT TISSUES \- Hypotonia \- Abnormal muscles tone \- Decreased activities of mitochondrial respiratory complexes I and III seen on skeletal muscle biopsy NEUROLOGIC Central Nervous System \- Global developmental delay, severe \- Seizures, refractory \- Spasticity \- Dystonia \- Incoordinated movements \- Autonomic neuropathy \- Global brain atrophy \- Cerebellar atrophy \- Subependymal cysts \- Abnormal hippocampal shape \- Delayed myelination Peripheral Nervous System \- Peripheral neuropathy \- Axonal degeneration LABORATORY ABNORMALITIES \- Increased serum lactate \- Increased CSF lactate MISCELLANEOUS \- Onset at birth \- Progressive disorder \- Favorable response to treatment with coenzyme Q10 \- One patient with unrelated German parents has been reported (last curated February 2016) MOLECULAR BASIS \- Caused by mutation in the thioredoxin 2 gene (TXN2, 609063.0001 ) ▲ 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	COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 29	c4225200	5,363	omim	https://www.omim.org/entry/616811	2019-09-22T15:47:51	{"omim": ["616811"]}
Pierre Robin sequence Other namesPierre Robin syndrome, Pierre Robin malformation, Pierre Robin anomaly, Pierre Robin anomalad[1] SpecialtyMedical genetics SymptomsMicrognathia, glossoptosis, obstruction of the upper airway, sometimes cleft palate Usual onsetDuring gestation, present at birth Causesintrauterine compression of fetal mandible or de-novo mutations (on chromosomes 2, 4, 11, or 17) Diagnostic methodPhysical examination TreatmentCraniofacial surgery, oral and maxillofacial surgery Frequency1 in 8,500 to 14,000 people[2] Pierre Robin sequence[a] (/pjɛər rɔːˈbæ̃/;[3] abbreviated PRS) is a congenital defect observed in humans which is characterized by facial abnormalities. The three main features are micrognathia (abnormally small mandible), which causes glossoptosis (downwardly displaced or retracted tongue), which in turn causes breathing problems due to obstruction of the upper airway. A wide, U-shaped cleft palate is commonly also present. PRS is not merely a syndrome, but rather it is a sequence—a series of specific developmental malformations which can be attributed to a single cause.[4] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Mechanical basis * 2.2 Genetic basis * 3 Diagnosis * 4 Management * 5 Prognosis * 6 Epidemiology * 7 History * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] PRS is characterized by an unusually small mandible, posterior displacement or retraction of the tongue, and upper airway obstruction. Cleft palate (incomplete closure of the roof of the mouth) is present in the majority of patients. Hearing loss and speech difficulty are often associated with PRS.[citation needed] ## Causes[edit] ### Mechanical basis[edit] The physical craniofacial deformities of PRS may be the result of a mechanical problem in which intrauterine growth of certain facial structures is restricted, or mandibular positioning is altered.[4] One theory for the etiology of PRS is that, early in the first trimester of gestation, some mechanical factor causes the neck to be abnormally flexed such that the tip of the mandible becomes compressed against the sternoclavicular joint. This compression of the chin interferes with development of the body of the mandible, resulting in micrognathia. The concave space formed by the body of the hypoplastic mandible is too small to accommodate the tongue, which continues to grow unimpeded. With nowhere else to go, the base of the tongue is downwardly displaced, which causes the tip of the tongue to be interposed between the left and right palatal shelves. This in turn may result in failure of the left and right palatal shelves to fuse in the midline to form the hard palate.[1] This condition manifests as a cleft palate. Later in gestation (at around 12 to 14 weeks), extension of the neck of the fetus releases the pressure on the mandible, allowing it to grow normally from this point forward. At birth, however, the mandible is still much smaller (hypoplastic) than it would have been with normal development. After the child is born, the mandible continues to grow until the child reaches maturity.[citation needed] ### Genetic basis[edit] Alternatively, PRS may also be caused by a genetic disorder. In the case of PRS which is due to a genetic disorder, a hereditary basis has been postulated, but it usually occurs due to a de-novo mutation. Specifically, mutations at chromosome 2 (possibly at the GAD1 gene), chromosome 4, chromosome 11 (possibly at the PVRL1 gene), or chromosome 17 (possibly at the SOX9 gene or the KCNJ2 gene) have all been implicated in PRS.[5] Some evidence suggests that genetic dysregulation of the SOX9 gene (which encodes the SOX-9 transcription factor) and/or the KCNJ2 gene (which encodes the Kir2.1 inward-rectifier potassium channel) impairs the development of certain facial structures, which can lead to PRS.[6][7] PRS may occur in isolation, but it is often part of an underlying disorder or syndrome.[8] Disorders associated with PRS include Stickler syndrome, DiGeorge syndrome, fetal alcohol syndrome, Treacher Collins syndrome, and Patau syndrome.[9] ## Diagnosis[edit] PRS is generally diagnosed clinically shortly after birth. The infant usually has respiratory difficulty, especially when supine. The palatal cleft is often U-shaped and wider than that observed in other people with cleft palate.[citation needed] ## Management[edit] The goals of treatment in infants with PRS focus upon breathing and feeding, and optimizing growth and nutrition despite the predisposition for breathing difficulties. If there is evidence of airway obstruction (snorty breathing, apnea, difficulty taking a breath, or drops in oxygen), then the infant should be placed in the sidelying or prone position, which helps bring the tongue base forward in many children. One study of 60 infants with PRS found that 63% of infants responded to prone positioning.[10] Fifty-three percent of the infants in this study required some form of feeding assistance, either nasogastric tube or gastrostomy tube feedings (feeding directly into the stomach). In a separate study of 115 children with the clinical diagnosis of PRS managed at two different hospitals in Boston,[11] respiratory distress was managed successfully in 56% without an operation (either by prone positioning, short-term intubation, or placement of a nasopharyngeal airway). In this study, gastrostomy tube feeding were placed in 42% of these infants due to feeding difficulties.[citation needed] Gastroesophageal reflux (GERD) seems to be more prevalent in children with PRS.[12] Because reflux of acidic contents in the posterior pharynx and upper airway can intensify the symptoms of PRS, specifically by worsening airway obstruction, it is important to maximize treatment for GER in children with PRS and reflux symptoms. Treatment may include upright positioning on a wedge (a tucker sling may be needed if the baby is in the prone position), small and frequent feedings (to minimize vomiting), and/or pharmacotherapy (such as proton pump inhibitors).[citation needed] In nasopharyngeal cannulation (or placement of the nasopharyngeal airway or tube), the infant is fitted with a blunt-tipped length of surgical tubing (or an endotracheal tube fitted to the child), which is placed under direct visualization with a laryngoscope, being inserted into the nose and down the pharynx (or throat), ending just above the vocal cords. Surgical threads fitted through holes in the outside end of the tube are attached to the cheek with a special skin-like adhesive material called 'stomahesive', which is also wrapped around the outside end of the tube (but not over the opening at the end) to keep the tube in place. This tube or cannula, which itself acts as an airway, primarily acts as a sort of "splint" which maintains patency of the airway by keeping the tongue from falling back on the posterior pharyngeal wall and occluding the airway, therefore preventing airway obstruction, hypoxia and asphyxia. Nasopharyngeal airways are not available at every center; however, when available, nasopharyngeal cannulation should be favored over the other treatments mentioned in this article, as it is far less invasive; it allows the infant to feed without the further placement of a nasogastric tube. This treatment may be utilized for multiple months, until the jaw has grown enough so that the tongue assumes a more normal position in the mouth and airway (at birth, the jaws of some infants are so underdeveloped that only the tip of the tongue can be seen when viewed in the throat). Some institutions discharge the infant home with a nasopharyngeal tube in place.[13] Distraction osteogenesis (DO), also called a "Mandibular Distraction", can be used to correct abnormal smallness of one or both jaws seen in patients with PRS. Enlargement of the lower jaw brings the tongue forward, preventing it from obstructing the upper airway. The process of DO begins with preoperative assessment. Doctors use three-dimensional imaging to identify the parts of the patient's facial skeleton that need repositioning and determine the magnitude and direction of distraction. They may then select the most appropriate distraction device or sometimes have custom devices fabricated. When possible, intraoral devices are used. DO surgery starts with an osteotomy (surgical division or sectioning of bone) followed by the distraction device being placed under the skin and across the osteotomy. A few days later, the two ends of the bone are very gradually pulled apart through continual adjustments that are made to the device by the parents at home. The adjustments are made by turning a small screw that protrudes through the skin, usually at a rate of 1 mm per day. This gradual distraction leads to formation of new bone between the two ends. After the process is complete, the osteotomy is allowed to heal over a period of six to eight weeks. A small second surgery is then performed to remove the device. The cleft palate is generally repaired between the ages of 6½ months and 2 years by a plastic surgeon, an oromaxillofacial surgeon, or an otorhinolaryngologist (ENT surgeon). In many centres there is now a cleft lip and palate team comprising these specialties, as well as a coordinator, a speech and language therapist, an orthodontist, sometimes a psychologist or other mental health specialist, an audiologist, and nursing staff. The glossoptosis and micrognathism generally do not require surgery, as they improve to some extent unaided, though the mandibular arch remains significantly smaller than average. In some cases jaw distraction is needed to aid in breathing and feeding. Lip-tongue attachment is performed in some centres, though its efficacy has been recently questioned. A cleft palate (PRS or not) makes it difficult for individuals to articulate speech sounds, which may be due to the physical nature of cleft palate or the hearing loss that is associated with the condition.[14] This is typically why a speech language pathologist and/or audiologist is involved with the patient. Hearing should be checked by an audiologist regularly and can be treated with hearing amplification such as hearing aids. Because middle ear effusion is found in many patients with PRS, tympanostomy (ventilation) tubes are often a treatment option.[15] One study with children showed that patients with PRS displayed a moderate and severe hearing loss most frequently.[15] Planigraphs of temporal bones in these patients displayed an underdeveloped pneumatization of the mastoid bone in all PRS patients and in most patients with cleft palate (without PRS).[15] There were no abnormalities of the inner or middle ear anatomy in patients with PRS.[15] ## Prognosis[edit] Children affected with PRS usually reach full development and size. However, it has been found internationally that children with PRS are often slightly below average size, raising concerns of incomplete development due to chronic hypoxia related to upper airway obstruction as well as lack of nutrition due to early feeding difficulties or the development of an oral aversion. However, the general prognosis is quite good once the initial breathing and feeding difficulties are overcome in infancy. Most PRS babies grow to lead a healthy and normal adult life. The most important medical problems are difficulties in breathing and feeding. Affected infants very often need assistance with feeding, for example needing to stay in a lateral (on the side) or prone (on the tummy) position which helps bring the tongue forward and opens up the airway. Babies with a cleft palate will need a special cleft feeding device (such as the Haberman Feeder). Infants who are unable to take in enough calories by mouth to ensure growth may need supplementation with a nasogastric tube. This is related to the difficulty in forming a vacuum in the oral cavity related to the cleft palate, as well as to breathing difficulty related to the posterior position of the tongue. Given the breathing difficulties that some babies with PRS face, they may require more calories to grow (as working of breathing is somewhat like exercising for an infant). Infants, when moderately to severely affected, may occasionally need nasopharyngeal cannulation, or placement of a nasopharyngeal tube to bypass the airway obstruction at the base of the tongue. in some places, children are discharged home with a nasopharyngeal tube for a period of time, and parents are taught how to maintain the tube. Sometimes endotracheal intubation or tracheostomy may be indicated to overcome upper respiratory obstruction. In some centers, a tongue lip adhesion is performed to bring the tongue forward, effectively opening up the airway. Mandibular distraction can be effective by moving the jaw forward to overcome the upper airway obstruction caused by the posterior positioning of the tongue. Given that some children with PRS will have Stickler syndrome, it is important that children with PRS be evaluated by an optometrist or ophthalmologist. Because the retinal detachment that sometimes accompanies Stickler syndrome is a leading cause of blindness in children, it is very important to recognize this diagnosis.[citation needed] ## Epidemiology[edit] The prevalence of PRS is estimated to be 1 in 8,500 to 14,000 people.[2] Hearing loss has a higher incidence in those with cleft palate versus non-cleft palate. One study showed hearing loss in PRS at an average of 83%, versus an average of 60% of individuals with cleft without PRS.[16] Another study with children showed that hearing loss was found more frequently with PRS (73.3%) compared to those with cleft and no PRS (58.1%).[15] Hearing loss with PRS typically is a bilateral, conductive loss (affecting the outer/middle portion of the ear).[16] ## History[edit] The condition is named for the French dental surgeon Pierre Robin.[17][18] It is likely that Noel Rosa, one of the most famous and influential artists in the history of Brazilian music, had PRS.[19] ## See also[edit] * Andersen–Tawil syndrome * First arch syndrome * Weissenbacher–Zweymüller syndrome ## References[edit] 1. ^ Formerly known as Pierre Robin syndrome, Pierre Robin malformation, Pierre Robin anomaly or Pierre Robin anomalad.[1] 1. ^ a b c Edwards, JR; Newall, DR (1985). "The Pierre Robin syndrome reassessed in the light of recent research". British Journal of Plastic Surgery. 38 (3): 339–42. doi:10.1016/0007-1226(85)90238-3. PMID 4016420. 2. ^ a b "Isolated Pierre Robin sequence". Genetics Home Reference. Bethesda, Maryland: United States National Library of Medicine. 2019. Retrieved May 11, 2019. 3. ^ "merriam-webster.com – Pierre Robin syndrome". Retrieved 30 June 2019. 4. ^ a b Gangopadhyay, N; Mendonca, DA; Woo, AS (2012). "Pierre Robin Sequence". Seminars in Plastic Surgery. 26 (2): 76–82. doi:10.1055/s-0032-1320065. PMC 3424697. PMID 23633934. 5. ^ Jakobsen, LP; Knudsen, MA; Lespinasse, J; García Ayuso, C; Ramos, C; Fryns, JP; Bugge, M; Tommerup, N (2006). "The genetic basis of the Pierre Robin Sequence". The Cleft Palate-Craniofacial Journal. 43 (2): 155–9. doi:10.1597/05-008.1. PMID 16526920. S2CID 25888887. 6. ^ Selvi, R; Mukunda Priyanka, A (2013). "Role of SOX9 in the Etiology of Pierre-Robin Syndrome". Iranian Journal of Basic Medical Sciences. 16 (5): 700–4. PMC 3700045. PMID 23826492. 7. ^ Jakobsen, LP; Ullmann, R; Christensen, SB; Jensen, KE; Mølsted, K; Henriksen, KF; Hansen, C; Knudsen, MA; Larsen, LA; Tommerup, N; Tümer, Z (2007). "Pierre Robin sequence may be caused by dysregulation of SOX9 and KCNJ2". Journal of Medical Genetics. 44 (6): 381–6. doi:10.1136/jmg.2006.046177. PMC 2740883. PMID 17551083. 8. ^ van den Elzen AP, Semmekrot BA, Bongers EM, Huygen PL, Marres HA (2001). "Diagnosis and treatment of the Pierre Robin sequence: results of a retrospective clinical study and review of the literature". Eur. J. Pediatr. 160 (1): 47–53. doi:10.1007/s004310000646. PMID 11195018. S2CID 35802241. Archived from the original on 2001-03-09. 9. ^ Jaiswal, SK; Sukla, KK; Gupta, V; Rai, AK (December 2014). "Overlap of Patau and Pierre Robin syndromes along with abnormal metabolism: an interesting case study" (PDF). Journal of Genetics. 93 (3): 865–8. doi:10.1007/s12041-014-0452-2. PMID 25572249. S2CID 12421132. 10. ^ Smith and Senders, 2006, Int J Pediatr Oto 11. ^ Evans et al., 2006, In J Pediatr Oto 12. ^ Dudkiewicz, March 2000, CPCJ 13. ^ KD Anderson, May 2007, CPCJ 14. ^ Pierre Robin Syndrome - Birth Defect Fact Sheet, 2020 15. ^ a b c d e Handžić-Ćuk, 2007 16. ^ a b Handžić et al, 1995 17. ^ synd/1291 at Who Named It? 18. ^ Pierre Robin. La glossoptose. Son diagnostic, ses consequences, son traitement. Bulletin de l’Académie nationale de médecine, Paris, 1923, 89: 37. Journal de médecine de Paris, 1923, 43: 235-237 19. ^ "Noel Rosa 100 anos". O Página Cultural. Archived from the original on April 2, 2015. Retrieved March 1, 2015. Handžić-Ćuk, J., Ćuk, V., Rišavi, R., Katić, V., Katušić, D., Bagatin, M., … Gortan, D. (2007, June 29). Pierre Robin syndrome: characteristics of hearing loss, effect of age on hearing level and possibilities in therapy planning: The Journal of Laryngology & Otology. Retrieved from https://www.cambridge.org/core/journals/journal-of-laryngology-and-otology/article/pierre-robin-syndrome-characteristics-of-hearing-loss-effect-of-age-on-hearing-level-and-possibilities-in-therapy-planning/6DD871B7BD583AD124C1EE0A3538FCCD Handzic, J., Bagatin, M., & Subotic, R. (1995, February). Hearing Levels in Pierre Robin Syndrome. Retrieved March 11, 2020, from https://www.researchgate.net/publication/15470673_Hearing_Levels_in_Pierre_Robin_Syndrome Pierre Robin Syndrome - Birth Defect Fact Sheet. (2020, March 11). Retrieved from https://www.birthdefects.org/pierre-robin-syndrome Pierre Robin Sequence (PRS). (2020). Retrieved from http://craniofacialteamtexas.com/pierre-robin-sequence-prs/ ## External links[edit] Classification D * ICD-10: Q87.0 * ICD-9-CM: 756.0 * OMIM: 261800 * MeSH: D010855 * DiseasesDB: 29413 External resources * MedlinePlus: 001607 * eMedicine: ped/2680 ent/150 * Patient UK: Pierre Robin sequence * http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=718 * v * t * e Congenital malformations and deformations of musculoskeletal system / musculoskeletal abnormality Appendicular limb / dysmelia Arms clavicle / shoulder * Cleidocranial dysostosis * Sprengel's deformity * Wallis–Zieff–Goldblatt syndrome hand deformity * Madelung's deformity * Clinodactyly * Oligodactyly * Polydactyly Leg hip * Hip dislocation / Hip dysplasia * Upington disease * Coxa valga * Coxa vara knee * Genu valgum * Genu varum * Genu recurvatum * Discoid meniscus * Congenital patellar dislocation * Congenital knee dislocation foot deformity * varus * Club foot * Pigeon toe * valgus * Flat feet * Pes cavus * Rocker bottom foot * Hammer toe Either / both fingers and toes * Polydactyly / Syndactyly * Webbed toes * Arachnodactyly * Cenani–Lenz syndactylism * Ectrodactyly * Brachydactyly * Stub thumb reduction deficits / limb * Acheiropodia * Ectromelia * Phocomelia * Amelia * Hemimelia multiple joints * Arthrogryposis * Larsen syndrome * RAPADILINO syndrome Axial Skull and face Craniosynostosis * Scaphocephaly * Oxycephaly * Trigonocephaly Craniofacial dysostosis * Crouzon syndrome * Hypertelorism * Hallermann–Streiff syndrome * Treacher Collins syndrome other * Macrocephaly * Platybasia * Craniodiaphyseal dysplasia * Dolichocephaly * Greig cephalopolysyndactyly syndrome * Plagiocephaly * Saddle nose Vertebral column * Spinal curvature * Scoliosis * Klippel–Feil syndrome * Spondylolisthesis * Spina bifida occulta * Sacralization Thoracic skeleton ribs: * Cervical * Bifid sternum: * Pectus excavatum * Pectus carinatum * v * t * e Congenital abnormality syndromes Craniofacial * Acrocephalosyndactylia * Apert syndrome * Carpenter syndrome * Pfeiffer syndrome * Saethre–Chotzen syndrome * Sakati–Nyhan–Tisdale syndrome * Bonnet–Dechaume–Blanc syndrome * Other * Baller–Gerold syndrome * Cyclopia * Goldenhar syndrome * Möbius syndrome Short stature * 1q21.1 deletion syndrome * Aarskog–Scott syndrome * Cockayne syndrome * Cornelia de Lange syndrome * Dubowitz syndrome * Noonan syndrome * Robinow syndrome * Silver–Russell syndrome * Seckel syndrome * Smith–Lemli–Opitz syndrome * Snyder–Robinson syndrome * Turner syndrome Limbs * Adducted thumb syndrome * Holt–Oram syndrome * Klippel–Trénaunay–Weber syndrome * Nail–patella syndrome * Rubinstein–Taybi syndrome * Gastrulation/mesoderm: * Caudal regression syndrome * Ectromelia * Sirenomelia * VACTERL association Overgrowth syndromes * Beckwith–Wiedemann syndrome * Proteus syndrome * Perlman syndrome * Sotos syndrome * Weaver syndrome * Klippel–Trénaunay–Weber syndrome * Benign symmetric lipomatosis * Bannayan–Riley–Ruvalcaba syndrome * Neurofibromatosis type I Laurence–Moon–Bardet–Biedl * Bardet–Biedl syndrome * Laurence–Moon syndrome Combined/other, known locus * 2 (Feingold syndrome) * 3 (Zimmermann–Laband syndrome) * 4/13 (Fraser syndrome) * 8 (Branchio-oto-renal syndrome, CHARGE syndrome) * 12 (Keutel syndrome, Timothy syndrome) * 15 (Marfan syndrome) * 19 (Donohue syndrome) * Multiple * Fryns syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Pierre Robin sequence	c0031900	5,364	wikipedia	https://en.wikipedia.org/wiki/Pierre_Robin_sequence	2021-01-18T18:41:01	{"gard": ["4347"], "mesh": ["D010855"], "icd-9": ["756.0"], "icd-10": ["Q87.0"], "orphanet": ["718"], "wikidata": ["Q1756040"]}
For a general phenotypic description and a discussion of genetic heterogeneity of episodic kinesigenic dyskinesia (EKD), also referred to as paroxysmal kinesigenic choreoathetosis (PKC), see EKD1 (128200). Clinical Features Valente et al. (2000) reported a large Indian kindred in which 13 individuals received a definite diagnosis of PKC. Family history indicated that 4 deceased individuals had been affected. The male:female ratio was 1.8:1. Age at onset ranged from 7 to 13 years, and all had brief attacks of up to 2 minutes consisting of dystonic or choreic movements precipitated by sudden movements, with a frequency of 1 to 20 episodes per day. None of the affected patients had a history of benign infantile convulsions. However, 5 family members, including 2 with PKC, had sporadic episodes of generalized tonic-clonic seizures in their teenage years that spontaneously resolved. Incomplete (75%) penetrance was reported. Spacey et al. (2002) reported further details of the Indian family. Six patients experienced sensory aura in the form of paresthesias involving the same part of the body. Nine of 17 affected members had spontaneous remission at an average age of 23.3 years. Mapping By linkage and haplotype analysis of large Indian family with PKC, Valente et al. (2000) identified a 15.8-cM candidate region, referred to as EKD2, between markers D16S685 and D16S503, on chromosome 16q13-q22.1 (maximum lod score of 3.66 at D16S419). The region was distinct from and telomeric to the EKD1 locus identified in Japanese families with PKC (Tomita et al., 1999) and the ICCA locus (602066), but overlapped with a region identified in an African American family with PKC (Bennett et al., 2000). Epilepsy did not segregate with the EKD haplotype, suggesting that it is not part of the phenotype. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Dyskinesia, episodic \- Choreic movements, episodic \- Dystonia, episodic \- Abnormal involuntary movements \- Episodes last up to 2 minutes \- Frequency of 1 to 20 episodes per day \- Sensory aura may occur MISCELLANEOUS \- Onset in childhood or adolescence \- Male-to-female ratio, 1.8 to 1 \- Symptoms precipitated by sudden movements \- Favorable response to anticonvulsants \- Symptoms often decrease or remit with age \- Genetic heterogeneity, see EKD1 ( 128200 ) ▲ 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	EPISODIC KINESIGENIC DYSKINESIA 2	c1868682	5,365	omim	https://www.omim.org/entry/611031	2019-09-22T16:03:44	{"doid": ["0090054"], "omim": ["611031"], "orphanet": ["98809"], "synonyms": ["Alternative titles", "DYSTONIA 19"]}
Distal trisomy 19q is a rare chromosomal anomaly syndrome characterized by low birth weight, developmental delay, intellectual disability, short stature, craniofacial dysmorphism (incl. microcephaly, midface hypoplasia, hypertelorism, flat nasal bridge, ear anomalies, short philtrum, downturned corners of the mouth, micrognathia) and a short neck with redundant skin folds. Additional features may include hypotonia, skeletal anomalies (e.g. clino/camptodactyly), seizures and congenital cardiac, urogenital and gastrointestinal malformations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Distal trisomy 19q	c4707664	5,366	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1717	2021-01-23T18:15:19	{"icd-10": ["Q92.3"], "synonyms": ["Distal duplication 19q", "Telomeric duplication 19q", "Trisomy 19qter"]}
A number sign (#) is used with this entry because of evidence that Joubert syndrome-33 (JBTS33) is caused by homozygous or compound heterozygous mutation in the PIBF1 gene (607532) on chromosome 13q21. Description Joubert syndrome represents a classic ciliopathy characterized by hypotonia, ataxia, cognitive impairment, and a distinctive brain malformation, the 'molar tooth sign.' In addition, retinal dystrophy, cystic kidney disease, liver fibrosis, and polydactyly occur in a subset of patients (summary by Wheway et al., 2015). For a discussion of genetic heterogeneity of Joubert syndrome, see JBTS1 (213300). Clinical Features Wheway et al. (2015) reported 6 children with Joubert syndrome from 4 Hutterite families, designated H1 to H4. The 5 patients for whom clinical information was available showed mild to moderate developmental delay, and 4 also exhibited ataxia. Brain MRI was performed in 5 patients, of whom 3 exhibited the molar tooth sign and 2 did not. Other features seen on MRI included mild to moderate vermian hypoplasia, dysplasia of superior cerebellum, thickening of superior cerebellar peduncles, and deep interpeduncular fossa. Molecular Genetics By whole-exome sequencing in 2 brothers with Joubert syndrome from a family of Schmiedeleut Hutterite descent (family H1), who were negative for mutations in known JBTS-associated genes, Wheway et al. (2015) identified homozygosity for a missense mutation in the PIBF1 gene (D637A; 607532.0001) for which their parents were heterozygous. Homozygosity for the D637A mutation was also detected in 3 affected children from 2 more Hutterite families (H2 and H3), suggesting a founder effect. In a fourth Hutterite family (H4), the unaffected parents and an unaffected child were heterozygous for D637A; mutation status was not reported for the proband, who died at 15 days of life. Analysis of an additional 643 Joubert families negative for mutation in known JBTS-associated genes identified 2 in which affected individuals were compound heterozygous for mutations in the PIBF1 gene: in both families, 1 of the mutations was an R405Q substitution (607532.0002), whereas the second mutation was a different truncating mutation in each family (see, e.g., 607532.0003). INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Oculomotor apraxia RESPIRATORY \- Cyanotic episodes in infancy \- Irregular breathing \- Apneic episodes NEUROLOGIC Central Nervous System \- Developmental delay, mild to moderate \- Ataxia, axial \- Ataxia, appendicular (in some patients) \- Molar tooth sign \- Vermian hypoplasia \- Dysplasia of superior cerebellum \- Thickened superior cerebellar peduncles \- Deep interpeduncular fossa MOLECULAR BASIS \- Caused by mutation in the progesterone-induced blocking factor-1 gene (PIBF, 607532.0001 ) ▲ 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	JOUBERT SYNDROME 33	c4540389	5,367	omim	https://www.omim.org/entry/617767	2019-09-22T15:44:53	{"omim": ["617767"]}
Portal vein thrombosis Portal vein thrombosis seen with computed tomography. SpecialtyAngiology Portal vein thrombosis (PVT) is a vascular disease of the liver that occurs when a blood clot occurs in the hepatic portal vein, which can lead to increased pressure in the portal vein system and reduced blood supply to the liver. The mortality rate is approximately 1 in 10.[1] An equivalent clot in the vasculature that exits the liver carrying deoxygenated blood to the right atrium via the inferior vena cava, is known as hepatic vein thrombosis or Budd-Chiari syndrome.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] See also: Portal hypertension § Signs and symptoms Portal vein thrombosis causes upper abdominal pain, possibly accompanied by nausea and an enlarged liver and/or spleen; the abdomen may be filled with fluid (ascites).[3] A persistent fever may result from the generalized inflammation.[1] While abdominal pain may come and go if the thrombus forms suddenly, long-standing clot build-up can also develop without causing symptoms, leading to portal hypertension before it is diagnosed.[4][2] Other symptoms can develop based on the cause. For example, if portal vein thrombosis develops due to liver cirrhosis, bleeding or other signs of liver disease may be present. If portal vein thrombosis develops due to pylephlebitis, signs of infection such as fever, chills, or night sweats may be present. ## Causes[edit] Slowed blood flow due to underlying cirrhosis or congestive heart failure is often implicated. The prevalence of PVT in patients with cirrhosis is unclear, with a wide variety of incidence claimed by various researchers (estimated to be 1 in 100 by some while others believe it affects nearly 1 in 4).[5] Thrombophilia (including inherited conditions such as factor V Leiden deficiency, protein C or S deficiency, or antiphospholipid antibody syndrome) is another common cause.[3] Nearly one-third of patients have a myeloproliferative disorder (e.g. polycythemia vera[6] or primary thrombocytosis), most commonly due to a Janus kinase 2 (JAK2) gene mutation.[1] Oral contraceptive use or pregnancy are other non-inherited tendencies for thrombosis. Alternatively, the portal vein may be injured as a result of pancreatitis, diverticulitis, cholangiocarcinoma, hepatocellular carcinoma (HCC), or abdominal surgery/trauma.[3] Red flags for cancerous growth as a cause are elevated alpha fetoprotein levels, portal vein diameter greater than 2.3cm, pulsatility on Doppler ultrasound imaging, or hyperintense hepatic arterial phase (HAP) on CT scan with contrast.[1] PVT is also a known complication of surgical removal of the spleen.[7] During the last several years, myeloproliferative neoplasms (MPNs) have emerged as a leading systemic cause of splanchnic vein thromboses (includes PVT). ## Mechanism[edit] The main portal vein is formed by the union of the splenic vein and superior mesenteric vein (SMV). It is responsible for approximately three-fourths of the liver’s blood flow, transported from much of the gastrointestinal system as well as the pancreas, gallbladder, and spleen.[3] Cirrhosis alters bleeding pathways thus patients are simultaneously at risk of uncontrolled bleeding and forming clots.[3] A long-standing hindrance in flow as in chronic PVT, also known as portal cavernoma, can cause an increase in the hepatic venous pressure gradient (portal hypertension) and increased blood flow through subsidiary veins.[1] This may lead to ascites or bleeding from varices.[6] An infected thrombus may become septic, known as pylephlebitis; if blood cultures are positive for growth at this time, the most common organism is Bacteroides.[1] ## Diagnosis[edit] Portal vein thrombosis on computed tomography (left) and cavernous transformation of the portal vein after 1 year (right) The diagnosis of portal vein thrombosis is usually made with imaging confirming a clot in the portal vein; ultrasound is the least invasive method and the addition of Doppler technique shows a filling defect in blood flow. PVT may be classified as either occlusive or nonocclusive based on evidence of blood flow around the clot.[5] An alternative characterization based on site can be made: Type 1 is limited to the main portal vein, Type 2 involves only a portal vein branch (2a, or 2b if both branches are affected), and Type 3 if clot is found throughout both areas.[8] Determination of condition severity may be derived via computed tomography (CT) with contrast, magnetic resonance imaging (MRI), or MR angiography (MRA). Those with chronic PVT may undergo upper endoscopy (esophagogastroduodenoscopy, EGD) to evaluate the presence of concurrent dilated veins (varices) in the stomach or esophagus.[3] Other than perhaps slightly elevated transaminases, laboratory tests to evaluate liver function are typically normal.[1] D-dimer levels in the blood may be elevated as a result of fibrin breakdown. ## Treatment[edit] Treatment is aimed at opening the blocked veins to minimize complications; the duration of clot (acute versus chronic) affects treatment. Unless there are underlying reasons why it would be harmful, anticoagulation (low molecular weight heparin, followed by warfarin) is often initiated and maintained in patients who do not have cirrhosis. Anticoagulation for patients with cirrhosis who experience portal vein thrombosis is usually not advised unless they have chronic PVT 1) with thrombophilia, 2) with clot burden in the mesenteric veins, or 3) inadequate blood supply to the bowels.[3] In more severe instances, shunts or a liver transplant may be considered. If blood flow to the gastrointestinal tract has been compromised chronically, surgery may be required to remove dead intestine.[1] Different considerations are made in the management of PVT in pediatric patients or those who have already received a liver transplant.[1] ## See also[edit] * Pylephlebitis * Budd–Chiari syndrome ## References[edit] 1. ^ a b c d e f g h i DeLeve LD, Valla DC, Garcia-Tsao G (2009). "Vascular disorders of the liver". Hepatology. 49 (5): 1729–64. doi:10.1002/hep.22772. PMC 6697263. PMID 19399912.CS1 maint: multiple names: authors list (link) 2. ^ a b O’Mara SR, Wiesner L. "Hepatic Disorders". In Tintinalli JE, Ma O, Yealy DM, Meckler GD, Stapczynski J, Cline DM, Thomas SH (eds.). Tintinalli's Emergency Medicine: A Comprehensive Study Guide (9 ed.). New York, NY: McGraw-Hill. 3. ^ a b c d e f g Simonetto DA, Singal AK, Garcia-Tsao G, Caldwell, SH, Ahn J, Kamath PS (January 3, 2020). "ACG Clinical Guideline: Disorders of the Hepatic and Mesenteric Circulation". Am J Gastroenterol. 115 (1): 18–40. doi:10.14309/ajg.0000000000000486. PMID 31895720. 4. ^ Hall TC, Garcea G, Metcalfe M, Bilku D, Dennison AR (November 2011). "Management of acute non-cirrhotic and non-malignant portal vein thrombosis: a systematic review". World Journal of Surgery. 35 (11): 2510–20. doi:10.1007/s00268-011-1198-0. PMID 21882035. 5. ^ a b Nery F, Chevret S, Condat B, de Raucourt E, Boudaoud L, Rautou P, Plessier A, Roulot D, Chaffaut C, Bourcier V, Trinchet J, Valla D (February 2015). "Causes and Consequences of Portal Vein Thrombosis in 1,243 Patients With Cirrhosis: Results of a Longitudinal Study". Hepatology. 61 (2): 660–667. doi:10.1002/hep.27546. PMID 25284616. 6. ^ a b Bacon BR. "Cirrhosis and Its Complications". In Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J (eds.). Harrison's Principles of Internal Medicine (20 ed.). New York, NY: McGraw-Hill. 7. ^ Ali Cadili, Chris de Gara, "Complications of Splenectomy", The American Journal of Medicine, 2008, pp 371-375. 8. ^ Friedman LS (2020). "Noncirrhotic Portal Hypertension". In Papadakis MA, McPhee SJ, Rabow MW (eds.). Current Medical Diagnosis and Treatment 2020. McGraw-Hill. ## External links[edit] Wikimedia Commons has media related to Portal vein thrombosis. * Merck Classification D * ICD-10: I81 * ICD-9-CM: 452 External resources * eMedicine: radio/571 * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Portal vein thrombosis	c0155773	5,368	wikipedia	https://en.wikipedia.org/wiki/Portal_vein_thrombosis	2021-01-18T18:32:31	{"umls": ["C0155773"], "orphanet": ["854"], "wikidata": ["Q1704044"]}
A number sign (#) is used with this entry because of evidence that pyogenic sterile arthritis, pyoderma gangrenosum, and acne is caused by heterozygous mutation in the PSTPIP1 gene (606347) on chromosome 15q24. Clinical Features Lindor et al. (1997) described a multigeneration family with transmission of an autosomal dominant disorder characterized by pyogenic arthritis, pyoderma gangrenosum, and severe cystic acne. Ten affected family members manifested variable expression of pauciarticular, nonaxial, destructive, corticosteroid-responsive arthritis that began in childhood; pyoderma gangrenosum; and severe cystic acne in adolescence and beyond. Other less commonly associated features included adult-onset insulin-dependent diabetes mellitus, proteinuria, abscess formation at the site of parenteral injections, and cytopenias attributable to sulfonamide medications. Genetic studies excluded linkage to the major histocompatibility complex. Mapping Yeon et al. (2000) used linkage mapping to locate the PAPAS gene on chromosome 15q (maximum 2-point lod score of 5.83 with recombination fraction = 0 at D15S206). Under the assumption of complete penetrance, haplotype analysis of recombination events defined a disease interval of 10 cM between D15S1023 and D15S979. They indicated that the gene is in the same region as the IL16 gene (603035) and the CRABP1 gene (180230) (incorrectly stated to be the CRABP2 gene), which map to 15q26.1 and 15q24, respectively. In a 3-generation family in which 9 members had been diagnosed with juvenile idiopathic arthritis (604302), Wise et al. (2000) demonstrated linkage to chromosome 15q22-q24. In this family the disease was of very early onset and included episodic inflammation leading to eventual destruction of joints, muscle, and skin. The authors treated this disorder as a distinct clinical entity which they called familial recurrent arthritis (FRA). The proband in the family reported by Wise et al. (2000) presented at the age of 5 years with a history of recurrent joint swelling and cystic skin lesions since infancy. Arthritis was characteristically intermittent and migratory and led to the accumulation of sterile pyogenic material within the joint space if left untreated. It followed a monarticular pattern (rarely more than 1 joint affected during flares). It involved primarily the elbows, knees, and ankles, although small joints were occasionally affected. The father, 2 brothers (who were twins), a paternal aunt, and 2 cousins were also affected. The father reported that he had experienced marked improvement in the joint symptoms after puberty, with subsequent appearance of severe acne. In their discussion, Wise et al. (2000) stated that familial recurrent arthritis and PAPA syndrome are likely to be the same disorder. They pointed to a patient reported by Jacobs and Goetzl (1975) who may have had the same disorder, although no information was provided. Molecular Genetics Wise et al. (2002) identified missense mutations in the PSTPIP1 gene (606347) gene in 2 reported families with this disorder. PSTPIP1 and its murine ortholog are adaptor proteins known to interact with PEST-type PTPs such as PTPN12 (600079). Yeast 2-hybrid assays demonstrated severely reduced binding between PTPN12 and the E250Q (606347.0001) and A230T (606347.0002) mutant proteins of PSTPIP1. Previous evidence supported the integral role of CD2BP1 (alternative symbol for PSTPIP1) and its interacting proteins in actin reorganization during cytoskeletal-mediated events. The authors hypothesized that the disease-causing mutations identified compromise physiologic signaling necessary for the maintenance of a proper inflammatory response. INHERITANCE \- Autosomal dominant ABDOMEN Gastrointestinal \- Irritable bowel syndrome SKELETAL \- Intermittent sterile, pauciarticular, peripheral erosive arthritis (elbow, knee, ankle) \- Synovial tissue biopsy shows polymorphonuclear infiltrate without presence of immunoglobulin or complement deposits SKIN, NAILS, & HAIR Skin \- Pyoderma gangrenosum \- Severe cystic acne \- Sterile abscesses at site of parenteral injection HEMATOLOGY \- Normocytic pancytopenia following sulfa use MISCELLANEOUS \- PAPA syndrome is an acronym for Pyogenic sterile Arthritis, Pyoderma gangrenosum, Acne \- Onset of arthritis in early childhood \- Onset of acne in adolescence, persists into adulthood MOLECULAR BASIS \- Caused by mutation in the proline/serine/threonine phosphatase-interacting protein 1 (PSTPIP1, 606347.0001 ) ▲ 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	PYOGENIC STERILE ARTHRITIS, PYODERMA GANGRENOSUM, AND ACNE	c1858361	5,369	omim	https://www.omim.org/entry/604416	2019-09-22T16:11:58	{"doid": ["0080519"], "mesh": ["C536253"], "omim": ["604416"], "icd-10": ["M04.8"], "orphanet": ["69126"], "synonyms": ["Alternative titles", "PAPA SYNDROME", "FAMILIAL RECURRENT ARTHRITIS"]}
Chronic phase chronic myelogenous leukemia is a phase of chronic myelogenous leukemia in which 5% or fewer of the cells in the blood and bone marrow are blast cells (immature blood cells). This phase may last from several months to several years, and there may be no symptoms of leukemia. ## References[edit] * Chronic phase chronic myelogenous leukemia entry in the public domain NCI Dictionary of Cancer Terms This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms". This oncology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Chronic phase chronic myelogenous leukemia	c0023474	5,370	wikipedia	https://en.wikipedia.org/wiki/Chronic_phase_chronic_myelogenous_leukemia	2021-01-18T18:54:23	{"mesh": ["D015466"], "wikidata": ["Q5113990"]}
Fox-Fordyce disease is a chronic skin disease most common in women aged 13-35 years. It is characterized by the development of intense itching in the underarm area, the pubic area, and around the nipple of the breast as a result of perspiration which becomes trapped in the sweat gland and surrounding areas. The cause is unknown, but heat, humidity, and stress may play a role. Treatment may include the use of retinoids, antibiotics, and immunosuppressants. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Fox-Fordyce disease	c0016632	5,371	gard	https://rarediseases.info.nih.gov/diseases/6462/fox-fordyce-disease	2021-01-18T18:00:26	{"mesh": ["D005588"], "umls": ["C0016632"], "synonyms": ["Miliaria, apocrine", "Apocrine miliaria", "Fox-Fordyce syndrome"]}
This article is about the memory error. In everyday speech, "confabulation" may refer to a conversation. In psychology, confabulation is a memory error defined as the production of fabricated, distorted, or misinterpreted memories about oneself or the world. People who confabulate present incorrect memories ranging from "subtle alterations to bizarre fabrications",[1] and are generally very confident about their recollections, despite contradictory evidence.[2] ## Contents * 1 Description * 1.1 Distinctions * 2 Signs and symptoms * 3 Theories * 3.1 Neuropsychological theories * 3.2 Self-identity theory * 3.3 Temporality theory * 3.4 Monitoring theory * 3.5 Strategic retrieval account theory * 3.6 Executive control theory * 3.7 In the context of delusion theories * 3.8 Fuzzy-trace theory * 3.9 Epistemic theory * 4 Presentation * 4.1 Associated neurological and psychological conditions * 4.2 Location of brain lesions * 4.3 Developmental differences * 4.4 Provoked versus spontaneous confabulations * 4.5 Confidence in false memories * 4.6 Among normal subjects * 5 Diagnosis and treatment * 5.1 Deese–Roediger–McDermott lists * 5.2 Recognition tasks * 5.3 Free recall tasks * 5.4 Treatment * 6 Research * 7 See also * 8 References * 9 Further reading * 10 External links ## Description[edit] Confabulation is distinguished from lying as there is no intent to deceive and the person is unaware the information is false.[3] Although individuals can present blatantly false information, confabulation can also seem to be coherent, internally consistent, and relatively normal.[3] Most known cases of confabulation are symptomatic of brain damage or dementias, such as aneurysm, Alzheimer's disease, or Wernicke–Korsakoff syndrome (a common manifestation of thiamine deficiency caused by alcoholism).[4] Additionally confabulation often occurs in people who are suffering from anticholinergic toxidrome when interrogated about bizarre or irrational behaviour. Confabulated memories of all types most often occur in autobiographical memory and are indicative of a complicated and intricate process that can be led astray at any point during encoding, storage, or recall of a memory.[2] This type of confabulation is commonly seen in Korsakoff's syndrome.[5] ### Distinctions[edit] Two types of confabulation are often distinguished: * Provoked (momentary, or secondary) confabulations represent a normal response to a faulty memory, are common in both amnesia and dementia,[6] and can become apparent during memory tests.[7] * Spontaneous (or primary) confabulations do not occur in response to a cue[7] and seem to be involuntary.[8] They are relatively rare, more common in cases of dementia, and may result from the interaction between frontal lobe pathology and organic amnesia.[6] Another distinction is that between:[8] * Verbal confabulations- spoken false memories, most common type * Behavioral confabulations- occur when an individual acts on their false memories ## Signs and symptoms[edit] Confabulation is associated with several characteristics: 1. Typically verbal statements but can also be non-verbal gestures or actions. 2. Can include autobiographical and non-personal information, such as historical facts, fairy-tales, or other aspects of semantic memory. 3. The account can be fantastic or coherent. 4. Both the premise and the details of the account can be false. 5. The account is usually drawn from the patient's memory of actual experiences, including past and current thoughts. 6. The patient is unaware of the accounts' distortions or inappropriateness, and is not concerned when errors are pointed out. 7. There is no hidden motivation behind the account. 8. The patient's personality structure may play a role in his/her readiness to confabulate.[3] ## Theories[edit] Theories of confabulation range in emphasis. Some theories propose that confabulations represent a way for memory-disabled people to maintain their self-identity.[7] Other theories use neurocognitive links to explain the process of confabulation.[9] Still other theories frame confabulation around the more familiar concept of delusion.[10] Other researchers frame confabulation within the fuzzy-trace theory.[11] Finally, some researchers call for theories that rely less on neurocognitive explanations and more on epistemic accounts.[12] ### Neuropsychological theories[edit] The most popular theories of confabulation come from the field of neuropsychology or cognitive neuroscience.[9] Research suggests that confabulation is associated with dysfunction of cognitive processes that control the retrieval from long-term memory. Frontal lobe damage often disrupts this process, preventing the retrieval of information and the evaluation of its output.[13][14] Furthermore, researchers argue that confabulation is a disorder resulting from failed "reality monitoring/source monitoring" (i.e. deciding whether a memory is based on an actual event or whether it is imagined).[15] Some neuropsychologists suggest that errors in retrieval of information from long-term memory that are made by normal subjects involve different components of control processes than errors made by confabulators.[16] Kraepelin distinguished two subtypes of confabulation, one of which he called simple confabulation, caused partly by errors in the temporal ordering of real events. The other variety he called fantastic confabulation, which was bizarre and patently impossible statements not rooted in true memory. Simple confabulation may result from damage to memory systems in the medial temporal lobe. Fantastic confabulations reveal a dysfunction of the Supervisory System,[17] which is believed to be a function of the frontal cortex. ### Self-identity theory[edit] Some argue confabulations have a self-serving, emotional component in those with memory deficits that aids to maintain a coherent self-concept.[7] In other words, people who confabulate are motivated to do so, because they have gaps in their memory that they want to fill in and cover up. ### Temporality theory[edit] Support for the temporality account suggests that confabulations occur when an individual is unable to place events properly in time.[7] Thus, an individual might correctly state an action he/she performed, but say he/she did it yesterday, when he/she did it weeks ago. In the Memory, Consciousness, and Temporality Theory, confabulation occurs because of a deficit in temporal consciousness or awareness.[18] ### Monitoring theory[edit] Along a similar notion are the theories of reality and source monitoring theories.[8] In these theories, confabulation occurs when individuals incorrectly attribute memories as reality, or incorrectly attribute memories to a certain source. Thus, an individual might claim an imagined event happened in reality, or that a friend told him/her about an event he/she actually heard about on television. ### Strategic retrieval account theory[edit] Supporters of the strategic retrieval account suggest that confabulations occur when an individual cannot actively monitor a memory for truthfulness after its retrieval.[8] An individual recalls a memory, but there is some deficit after recall that interferes with the person establishing its falseness. ### Executive control theory[edit] Still others propose that all types of false memories, including confabulation, fit into a general memory and executive function model.[19] In 2007, a framework for confabulation was proposed that stated confabulation is the result of two things: Problems with executive control and problems with evaluation. In the executive control deficit, the incorrect memory is retrieved from the brain. In the evaluative deficit, the memory will be accepted as a truth due to an inability to distinguish a belief from an actual memory.[7] ### In the context of delusion theories[edit] Recent models of confabulation have attempted to build upon the link between delusion and confabulation.[10] More recently, a monitoring account for delusion, applied to confabulation, proposed both the inclusion of conscious and unconscious processing. The claim was that by encompassing the notion of both processes, spontaneous versus provoked confabulations could be better explained. In other words, there are two ways to confabulate. One is the unconscious, spontaneous way in which a memory goes through no logical, explanatory processing. The other is the conscious, provoked way in which a memory is recalled intentionally by the individual to explain something confusing or unusual.[20] ### Fuzzy-trace theory[edit] Fuzzy-trace theory, or FTT, is a concept more commonly applied to the explanation of judgement decisions.[11] According to this theory, memories are encoded generally (gist), as well as specifically (verbatim). Thus, a confabulation could result from recalling the incorrect verbatim memory or from being able to recall the gist portion, but not the verbatim portion, of a memory. FTT uses a set of five principles to explain false-memory phenomena. Principle 1 suggests that subjects store verbatim information and gist information parallel to one another. Both forms of storage involve the surface content of an experience. Principle 2 shares factors of retrieval of gist and verbatim traces. Principle 3 is based on dual-opponent processes in false memory. Generally, gist retrieval supports false memory, while verbatim retrieval suppresses it. Developmental variability is the topic of Principle 4. As a child develops into an adult, there is obvious improvement in the acquisition, retention, and retrieval of both verbatim and gist memory. However, during late adulthood, there will be a decline in these abilities. Finally, Principle 5 explains that verbatim and gist processing cause vivid remembering. Fuzzy-trace Theory, governed by these 5 principles, has proved useful in explaining false memory and generating new predictions about it.[21] ### Epistemic theory[edit] However, not all accounts are so embedded in the neurocognitive aspects of confabulation. Some attribute confabulation to epistemic accounts.[12] In 2009, theories underlying the causation and mechanisms for confabulation were criticized for their focus on neural processes, which are somewhat unclear, as well as their emphasis on the negativity of false remembering. Researchers proposed that an epistemic account of confabulation would be more encompassing of both the advantages and disadvantages of the process. ## Presentation[edit] ### Associated neurological and psychological conditions[edit] Confabulations are often symptoms of various syndromes and psychopathologies in the adult population including: Korsakoff's syndrome, Alzheimer's disease, schizophrenia, and traumatic brain injury. Wernicke–Korsakoff syndrome is a neurological disorder typically characterized by years of chronic alcohol abuse and a nutritional thiamine deficiency.[22] Confabulation is one salient symptom of this syndrome.[23][24] A study on confabulation in Korsakoff's patients found that they are subject to provoked confabulation when prompted with questions pertaining to episodic memory, not semantic memory, and when prompted with questions where the appropriate response would be "I don’t know."[25] This suggests that confabulation in these patients is "domain-specific." Korsakoff's patients who confabulate are more likely than healthy adults to falsely recognize distractor words, suggesting that false recognition is a "confabulatory behavior." Alzheimer's disease is a condition with both neurological and psychological components. It is a form of dementia associated with severe frontal lobe dysfunction. Confabulation in individuals with Alzheimer's is often more spontaneous than it is in other conditions, especially in the advanced stages of the disease. Alzheimer's patients demonstrate comparable abilities to encode information as healthy elderly adults, suggesting that impairments in encoding are not associated with confabulation.[26] However, as seen in Korsakoff's patients, confabulation in Alzheimer's patients is higher when prompted with questions investigating episodic memory. Researchers suggest this is due to damage in the posterior cortical regions of the brain, which is a symptom characteristic of Alzheimer's Disease. Schizophrenia is a psychological disorder in which confabulation is sometimes observed. Although confabulation is usually coherent in its presentation, confabulations of schizophrenic patients are often delusional[27] Researchers have noted that these patients tend to make up delusions on the spot which are often fantastic and become increasingly elaborate with questioning.[28] Unlike patients with Korsakoff's and Alzheimer's, patients with schizophrenia are more likely to confabulate when prompted with questions regarding their semantic memories, as opposed to episodic memory prompting.[29] In addition, confabulation does not appear to be related to any memory deficit in schizophrenic patients. This is contrary to most forms of confabulation. Also, confabulations made by schizophrenic patients often do not involve the creation of new information, but instead involve an attempt by the patient to reconstruct actual details of a past event. Traumatic brain injury (TBI) can also result in confabulation. Research has shown that patients with damage to the inferior medial frontal lobe confabulate significantly more than patients with damage to the posterior area and healthy controls.[30] This suggests that this region is key in producing confabulatory responses, and that memory deficit is important but not necessary in confabulation. Additionally, research suggests that confabulation can be seen in patients with frontal lobe syndrome, which involves an insult to the frontal lobe as a result of disease or traumatic brain injury (TBI).[31][32][33] Finally, rupture of the anterior or posterior communicating artery, subarachnoid hemorrhage, and encephalitis are also possible causes of confabulation.[13][34] ### Location of brain lesions[edit] Confabulation is believed to be a result of damage to the right frontal lobe of the brain.[3] In particular, damage can be localized to the ventromedial frontal lobes and other structures fed by the anterior communicating artery (ACoA), including the basal forebrain, septum, fornix, cingulate gyrus, cingulum, anterior hypothalamus, and head of the caudate nucleus.[35][36] ### Developmental differences[edit] While some recent literature has suggested that older adults may be more susceptible than their younger counterparts to have false memories, the majority of research on forced confabulation centers around children.[37] Children are particularly susceptible to forced confabulations based on their high suggestibility.[38][39] When forced to recall confabulated events, children are less likely to remember that they had previously confabulated these situations, and they are more likely than their adult counterparts to come to remember these confabulations as real events that transpired.[40] Research suggests that this inability to distinguish between past confabulatory and real events is centered on developmental differences in source monitoring. Due to underdeveloped encoding and critical reasoning skills, children's ability to distinguish real memories from false memories may be impaired. It may also be that younger children lack the meta-memory processes required to remember confabulated versus non-confabulated events.[41] Children's meta-memory processes may also be influenced by expectancies or biases, in that they believe that highly plausible false scenarios are not confabulated.[42] However, when knowingly being tested for accuracy, children are more likely to respond, "I don’t know" at a rate comparable to adults for unanswerable questions than they are to confabulate.[43][44] Ultimately, misinformation effects can be minimized by tailoring individual interviews to the specific developmental stage, often based on age, of the participant.[45] ### Provoked versus spontaneous confabulations[edit] There is evidence to support different cognitive mechanisms for provoked and spontaneous confabulation.[46] One study suggested that spontaneous confabulation may be a result of an amnesic patient's inability to distinguish the chronological order of events in their memory. In contrast, provoked confabulation may be a compensatory mechanism, in which the patient tries to make up for their memory deficiency by attempting to demonstrate competency in recollection. ### Confidence in false memories[edit] Confabulation of events or situations may lead to an eventual acceptance of the confabulated information as true.[47] For instance, people who knowingly lie about a situation may eventually come to believe that their lies are truthful with time.[48] In an interview setting, people are more likely to confabulate in situations in which they are presented false information by another person, as opposed to when they self-generate these falsehoods.[49] Further, people are more likely to accept false information as true when they are interviewed at a later time (after the event in question) than those who are interviewed immediately or soon after the event.[50] Affirmative feedback for confabulated responses is also shown to increase the confabulator's confidence in their response.[51] For instance, in culprit identification, if a witness falsely identifies a member of a line-up, he will be more confident in his identification if the interviewer provides affirmative feedback. This effect of confirmatory feedback appears to last over time, as witnesses will even remember the confabulated information months later.[52] ### Among normal subjects[edit] On rare occasions, confabulation can also be seen in normal subjects.[16] It is currently unclear how completely healthy individuals produce confabulations. It is possible that these individuals are in the process of developing some type of organic condition that is causing their confabulation symptoms. It is not uncommon, however, for the general population to display some very mild symptoms of provoked confabulations. Subtle distortions and intrusions in memory are commonly produced by normal subjects when they remember something poorly. ## Diagnosis and treatment[edit] Spontaneous confabulations, due to their involuntary nature, cannot be manipulated in a laboratory setting.[8] However, provoked confabulations can be researched in various theoretical contexts. The mechanisms found to underlie provoked confabulations can be applied to spontaneous confabulation mechanisms. The basic premise of researching confabulation comprises finding errors and distortions in memory tests of an individual. ### Deese–Roediger–McDermott lists[edit] Confabulations can be detected in the context of the Deese–Roediger–McDermott paradigm by using the Deese–Roediger–McDermott lists.[53] Participants listen to audio recordings of several lists of words centered around a theme, known as the critical word. The participants are later asked to recall the words on their list. If the participant recalls the critical word, which was never explicitly stated in the list, it is considered a confabulation. Participants often have a false memory for the critical word. ### Recognition tasks[edit] Confabulations can also be researched by using continuous recognition tasks.[8] These tasks are often used in conjunction with confidence ratings. Generally, in a recognition task, participants are rapidly presented with pictures. Some of these pictures are shown once; others are shown multiple times. Participants press a key if they have seen the picture previously. Following a period of time, participants repeat the task. More errors on the second task, versus the first, are indicative of confusion, representing false memories. ### Free recall tasks[edit] Confabulations can also be detected using a free recall task, such as a self-narrative task.[8] Participants are asked to recall stories (semantic or autobiographical) that are highly familiar to them. The stories recalled are encoded for errors that could be classified as distortions in memory. Distortions could include falsifying true story elements or including details from a completely different story. Errors such as these would be indicative of confabulations. ### Treatment[edit] Treatment for confabulation is somewhat dependent on the cause or source, if identifiable. For example, treatment of Wernicke–Korsakoff syndrome involves large doses of vitamin B in order to reverse the thiamine deficiency.[54] If there is no known physiological cause, more general cognitive techniques may be used to treat confabulation. A case study published in 2000 showed that Self-Monitoring Training (SMT)[55] reduced delusional confabulations. Furthermore, improvements were maintained at a three-month follow-up and were found to generalize to everyday settings. Although this treatment seems promising, more rigorous research is necessary to determine the efficacy of SMT in the general confabulation population. ## Research[edit] Although significant gains have been made in the understanding of confabulation in recent years, there is still much to be learned. One group of researchers in particular has laid out several important questions for future study. They suggest more information is needed regarding the neural systems that support the different cognitive processes necessary for normal source monitoring. They also proposed the idea of developing a standard neuro-psychological test battery able to discriminate between the different types of confabulations. And there is a considerable amount of debate regarding the best approach to organizing and combining neuro-imaging, pharmacological, and cognitive/behavioral approaches to understand confabulation.[56] In a recent review article, another group of researchers contemplate issues concerning the distinctions between delusions and confabulation. They question whether delusions and confabulation should be considered distinct or overlapping disorders and, if overlapping, to what degree? They also discuss the role of unconscious processes in confabulation. Some researchers suggest that unconscious emotional and motivational processes are potentially just as important as cognitive and memory problems. Finally, they raise the question of where to draw the line between the pathological and the nonpathological. Delusion-like beliefs and confabulation-like fabrications are commonly seen in healthy individuals. What are the important differences between patients with similar etiology who do and do not confabulate? Since the line between pathological and nonpathological is likely blurry, should we take a more dimensional approach to confabulation? Research suggests that confabulation occurs along a continuum of implausibility, bizarreness, content, conviction, preoccupation, and distress, and impact on daily life.[57] ## See also[edit] * Anosognosia * Confabulation (neural networks) * Cryptomnesia * False memory * Gaslighting * Hindsight bias * Misinformation effect * Revelation ## References[edit] 1. ^ "Truth about Confabulation". Archived from the original on 2013-01-03. Retrieved 2013-03-23. 2. ^ a b Nalbantian, edited by Suzanne; Matthews, Paul M.; McClelland, James L. (2010). The memory process : neuroscientific and humanistic perspectives. Cambridge, Massachusetts: MIT Press. ISBN 978-0-262-01457-1.CS1 maint: extra text: authors list (link) 3. ^ a b c d Moscovitch M. 1995. "Confabulation". In (Eds. Schacter D.L., Coyle J.T., Fischbach G.D., Mesulum M.M. & Sullivan L.G.), Memory Distortion. pp. 226–51. Cambridge, Massachusetts: Harvard University Press. 4. ^ Sivolap IuP Damulin IV (2013). "[Wernicke encephalopathy and Korsakoff's psychosis: clinical-pathophysiological correlation, diagnostics and treatment]". Zh Nevrol Psikhiatr Im S S Korsakova. 113 (6 Pt 2): 20–26. PMID 23887463. 5. ^ Kopelman, M. D.; Thomson, A. D.; Guerrini, I; Marshall, E. J. (2009). "The Korsakoff Syndrome: Clinical Aspects, Psychology and Treatment". Alcohol and Alcoholism. 44 (2): 148–54. doi:10.1093/alcalc/agn118. PMID 19151162. 6. ^ a b Kopelman, M. D. (1987). "Two types of confabulation". Journal of Neurology, Neurosurgery, and Psychiatry. 50 (11): 1482–87. doi:10.1136/jnnp.50.11.1482. PMC 1032561. PMID 3694207. 7. ^ a b c d e f Metcalf, Kasey; Langdon, Robyn; Coltheart, Max (1 February 2007). "Models of confabulation: A critical review and a new framework". Cognitive Neuropsychology. 24 (1): 23–47. doi:10.1080/02643290600694901. PMID 18416482. S2CID 45885109. 8. ^ a b c d e f g Gilboa, A. (13 April 2006). "Mechanisms of spontaneous confabulations: a strategic retrieval account". Brain. 129 (6): 1399–1414. doi:10.1093/brain/awl093. PMID 16638795. 9. ^ a b Glowinski, Remy; Payman, Vahid; Frencham, Kate (2008). "Confabulation: a spontaneous and fantastic review". Australian and New Zealand Journal of Psychiatry. 42 (11): 932–40. doi:10.1080/00048670802415335. PMID 18941957. S2CID 23586700. 10. ^ a b Kopelman, Michael D. (2010). "Varieties of confabulation and delusion". 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"Memorial consequences of forced confabulation: Age differences in susceptibility to false memories". Developmental Psychology. 34 (6): 1358–72. doi:10.1037/0012-1649.34.6.1358. PMID 9823517. 41. ^ Ghetti, Simona; Castelli, Paola; Lyons, Kristen E. (2010). "Knowing about not remembering: developmental dissociations in lack-of-memory monitoring". Developmental Science. 13 (4): 611–21. doi:10.1111/j.1467-7687.2009.00908.x. PMID 20590725. 42. ^ Ghetti, Simona; Alexander, Kristen Weede (2004). ""If It Happened, I Would Remember It": Strategic Use of Event Memorability in the Rejection of False Autobiographical Events". Child Development. 75 (2): 542–61. doi:10.1111/j.1467-8624.2004.00692.x. PMID 15056205. 43. ^ Roebers, Claudia; Fernandez, Olivia (2002). "The Effects of Accuracy Motivation on Children's and Adults' Event Recall, Suggestibility, and Their Answers to Unanswerable Questions". 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"False memories and confabulation". Trends in Cognitive Sciences. 2 (4): 137–45. doi:10.1016/S1364-6613(98)01152-8. PMID 21227110. S2CID 10033853. 57. ^ Langdon, R.; Turner, M (2010), "Delusion and confabulation: Overlapping or distinct distortions in reality?", Cognitive Neuropsychiatry, 15 (1): 1–13, doi:10.1080/13546800903519095, PMID 20043251, S2CID 35177831 ## Further reading[edit] * Hirstein, William (2005), Brain Fiction: Self-deception and the riddle of confabulation, Cambridge, Massachusetts: MIT Press, ISBN 978-0-262-08338-6, retrieved 21 March 2012 * Sacks, Oliver (1985), "The Man Who Mistook His Wife for a Hat", The British Journal of Psychiatry : The Journal of Mental Science, New York: Perennial Library, 166 (1): 130–1, doi:10.1192/bjp.166.1.130, ISBN 978-0-06-097079-6, PMID 7894870 ## External links[edit] Classification D * v * t * e Human memory Basic concepts * Encoding * Storage * Recall * Attention * Consolidation * Neuroanatomy Types Sensory * Echoic * Eidetic * Eyewitness * Haptic * Iconic * Motor learning * Visual Short-term * "The Magical Number Seven, Plus or Minus Two" * Working memory Intermediate * Long-term * Active recall * Autobiographical * Explicit * Declarative * Episodic * Semantic * Flashbulb * Hyperthymesia * Implicit * Meaningful learning * Personal-event * Procedural * Rote learning * Selective retention * Tip of the tongue Forgetting * Amnesia * anterograde * childhood * post-traumatic * psychogenic * retrograde * transient global * Decay theory * Forgetting curve * Interference theory * Memory inhibition * Motivated forgetting * Repressed memory * Retrieval-induced forgetting * Selective amnesia * Weapon focus Memory errors * Confabulation * False memory * Hindsight bias * Imagination inflation * List of memory biases * Memory conformity * Mere-exposure effect * Misattribution of memory * Misinformation effect * Source-monitoring error * Wernicke–Korsakoff syndrome Research * Art of memory * Memory and aging * Deese–Roediger–McDermott paradigm * Exceptional memory * Indirect tests of memory * Lost in the mall technique * Memory disorder * Memory implantation * Methods used to study memory * The Seven Sins of Memory * Effects of exercise on memory In society * Collective memory * Cultural memory * False memory syndrome * Memory and social interactions * Memory sport * Politics of memory * Shas Pollak * World Memory Championships Related topics * Absent-mindedness * Atkinson–Shiffrin memory model * Context-dependent memory * Childhood memory * Cryptomnesia * Effects of alcohol * Emotion and memory * Exosomatic memory * Flashbacks * Free recall * Involuntary memory * Levels-of-processing effect * Memory and trauma * Memory improvement * Metamemory * Mnemonic * Muscle memory * Priming * Intertrial * Prospective memory * Recovered-memory therapy * Retrospective memory * Sleep and memory * State-dependent memory * Transactive memory People * Robert A. 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Shimamura * Andriy Slyusarchuk * Larry Squire * Susumu Tonegawa * Anne Treisman * Endel Tulving * Robert Stickgold * Clive Wearing * Psychology portal * Philosophy 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	Confabulation	c0233800	5,372	wikipedia	https://en.wikipedia.org/wiki/Confabulation	2021-01-18T18:51:23	{"umls": ["C0233800"], "wikidata": ["Q1082351"]}
A uniparental disomy of maternal origin that does not seem to have an adverse impact on the phenotype of an individual. There is a possibility of homozygosity for a recessive disease mutation for which the mother is a carrier and specific phenotype depends on the inherited disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Maternal uniparental disomy of chromosome X	None	5,373	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261519	2021-01-23T18:01:40	{"icd-10": ["Q99.8"], "synonyms": ["UPD(X)mat"]}
Vinotherapy, also written "Vinotherapie" describes a beauty therapy process where the residue of wine making (the pips and pulp) are rubbed into the skin. The pulp is said to have excellent exfoliating qualities and help reduce the problems associated with ageing. ## History[edit] The concept of vinotherapy was expanded by Mathilde and Bertrand Thomas. The French couple learned about the impact of grape seeds from the leading expert on grape and grapevine polyphenols Dr. Vercauteren.[1] In 1995, Mathilde and Bertrand launched a line of Vinothérapie skincare products made from grape derived ingredients: Caudalie. Vinotherapie makes use of the benefits from the grape and the vine extracts to provide effective skincare treatments, with anti-ageing action. Caudalíe was the first to stabilized and patent (Patent n° WO9429404) the extraction of Grape Seed Polyphenols (OPC), and use them in dermocosmetics. There is a "Vinothérapie" spa hotel at La Rioja in Spain.[2] ## References[edit] 1. ^ Mathilde Cathiard-Thomas, La santé par le raisin 2. ^ "Vinotherapy: all the benefits of wine without the health risks?". Guardian. 1 March 2013. Retrieved 31 March 2015. ## External links[edit] Look up vinotherapy in Wiktionary, the free dictionary. This wine-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Vinotherapy	None	5,374	wikipedia	https://en.wikipedia.org/wiki/Vinotherapy	2021-01-18T18:43:01	{"wikidata": ["Q2436654"]}
Inborn errors of renal tubular transport SpecialtyObstetrics and gynaecology, urology, medical genetics, endocrinology Inborn errors of renal tubular transport are metabolic disorders which lead to impairment in the ability of solutes, such as salts or amino acids, to be transported across the brush border of the renal tubule. This results in disruptions of renal reabsorption. Examples of these disorders include Iminoglycinuria, renal tubular acidosis and Gitelman syndrome. ## References[edit] ## External links[edit] Classification D * MeSH: D015499 * 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 Kidney disease Glomerular disease * See Template:Glomerular disease Tubules * Renal tubular acidosis * proximal * distal * Acute tubular necrosis * Genetic * Fanconi syndrome * Bartter syndrome * Gitelman syndrome * Liddle's syndrome Interstitium * Interstitial nephritis * Pyelonephritis * Balkan endemic nephropathy Vascular * Renal artery stenosis * Renal ischemia * Hypertensive nephropathy * Renovascular hypertension * Renal cortical necrosis General syndromes * Nephritis * Nephrosis * Renal failure * Acute renal failure * Chronic kidney disease * Uremia Other * Analgesic nephropathy * Renal osteodystrophy * Nephroptosis * Abderhalden–Kaufmann–Lignac syndrome * Diabetes insipidus * Nephrogenic * Renal papilla * Renal papillary necrosis * Major calyx/pelvis * Hydronephrosis * Pyonephrosis * Reflux nephropathy This article about an endocrine, nutritional, or metabolic disease is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Inborn errors of renal tubular transport	c0035091	5,375	wikipedia	https://en.wikipedia.org/wiki/Inborn_errors_of_renal_tubular_transport	2021-01-18T18:35:29	{"mesh": ["D015499"], "umls": ["C0035091"], "wikidata": ["Q6013986"]}
Gemignani syndrome is a rare neurodegenerative disease characterized by slowly progressive ataxia, amyotrophy of the hands and distal arms, spastic paraplegia, progressive sensorineural hearing loss, hypogonadism and short stature. Additional features include generalized cerebellar atrophy and peripheral nervous system anomalies. Small cervical spinal cord, intellectual/language disability and localized vitiligo have also been reported. There have been no further descriptions in the literature since 1989. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Gemignani syndrome	c2931587	5,376	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2074	2021-01-23T18:54:50	{"gard": ["2451"], "mesh": ["C537678"], "umls": ["C2931587"], "synonyms": ["Spinocerebellar ataxia-amyotrophy-deafness syndrome", "Spinocerebellar ataxia-amyotrophy-hearing loss syndrome"]}
A number sign (#) is used with this entry because of evidence that ichthyosis vulgaris is caused by heterozygous mutation in the filaggrin gene (FLG; 135940) on chromosome 1q21. Patients with homozygous or compound heterozygous mutations in this gene have a more severe phenotype. Clinical Features Ichthyosis is one of the most frequent single-gene disorders in humans. The most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy English schoolchildren (Wells and Kerr, 1966). The phenotypic characteristics of ichthyosis vulgaris include palmar hyperlinearity, keratosis pilaris, and a fine scale that is most prominent over the lower abdomen, arms, and legs. Wells and Kerr (1965) suggested that dominant ichthyosis vulgaris is distinguishable clinically from the X-linked variety (308100). In the dominant form, the first skin involvement is usually noted after the first 3 months of life and less of the body surface is affected. Lesions are rarely observed in the axillae or antecubital and popliteal fossae but the palms and soles often show increased markings. There are some histologic differences also. A considerable proportion of patients with dominant ichthyosis have asthma, eczema, or hay fever. For a useful classification and discussion of the various forms of ichthyosis, see Schnyder (1970). Mevorah et al. (1978) described ichthyosis in a mother and 6 of her sons. A seventh son and 2 daughters were normal. The disorder in the mother was clinically and histologically of the dominant type, whereas the affected sons showed features of both the autosomal dominant and X-linked recessive forms. The authors concluded that the mother was heterozygous for both forms. Biochemical Features Anton-Lamprecht (1978) pointed out that electron microscopy is particularly revealing in dominant disorders in which structural abnormality of a protein is likely to be found, whereas biochemistry is more likely to be revealing in recessive disorders. The examples he used from dermatology to illustrate electron microscopic abnormalities were structural defects of tonofibrils in hystrix-like ichthyoses, of the anchoring fibrils in dominant dystrophic epidermolysis bullosa of Pasini, and of keratohyalin in autosomal dominant ichthyosis vulgaris. In skin fibroblasts from patients with autosomal dominant ichthyosis vulgaris, Meyer et al. (1982) found elevation of arylsulfatase C activity using 4-methylumbelliferylsulfate. This may correspond to the f isoform (ARSC2; 301780) (see Chang et al. (1986, 1990)). However, Meyer et al. (1982) found that steroid sulfatase (STS; 300747) activity using 3-dehydroepiandrosteronsulfate was normal. In leukocytes, both activities were the same in patients and controls. Ichthyosis vulgaris is characterized histologically by absent or reduced keratohyalin granules in the epidermis and mild hyperkeratosis. Keratohyalin contains a histidine-rich protein which is the precursor form (profilaggrin) of filaggrin (FLG; 135940), a keratin filament-aggregating protein. Using an antiserum, Sybert et al. (1985) demonstrated that profilaggrin and filaggrin were reduced or absent in 5 patients from 2 kindreds with ichthyosis vulgaris. The biochemical abnormality correlated with the morphologic reduction in amount of keratohyalin. Nirunsuksiri et al. (1998) presented evidence that profilaggrin mRNA in keratinocytes cultured from subjects with ichthyosis vulgaris is intrinsically unstable and has a shorter half-life compared with that in normal cells. When ichthyosis vulgaris-affected keratinocytes were treated with the protein synthesis inhibitor cycloheximide, the steady-state level of profilaggrin mRNA was increased due to stabilization of the transcript. The number of filaggrin repeats (10 to 12) in individuals with ichthyosis vulgaris did not differ from that of unaffected subjects. Expression of the gene was biallelic and coequal in both control and affected individuals. The results of Nirunsuksiri et al. (1998) suggested a model in which a labile ribonuclease and a stabilizing factor may modulate the profilaggrin mRNA steady-state level in normal cells, whereas the stabilizing factor may be absent or functionally inactive in ichthyosis vulgaris-affected keratinocytes. Mapping By linkage analysis, Zhong et al. (2003) identified a locus for ichthyosis vulgaris on chromosome 1q22 with a maximum 2-point lod score of 2.47 at marker D1S1653 with a recombination fraction of 0.00. The epidermal differentiation complex (EDC; see 152445) comprises 3 gene families that are functionally related and mapped to 1q21. Zhong et al. (2003) stated that there was no overlap between the EDC region and the ichthyosis vulgaris locus on 1q22. However, only 4 Mb of genomic DNA separated EDC from D1S1653. In an American family, Compton et al. (2002) showed linkage between ichthyosis vulgaris associated with a histologically absent granular layer and markers in the EDC on 1q21. The EDC is a dense cluster of genes encoding scores of epidermal structural proteins including filaggrin, loricrin (LOR; 152445), involucrin (IVL; 147360), trichohyalin (THH; 190370), and others. Molecular Genetics Smith et al. (2006) analyzed the filaggrin gene in 7 unrelated ichthyosis vulgaris patients and 8 sporadic cases, based on linkage and histologic evidence presented by Compton et al. (2002) and Zhong et al. (2003). In 1 family they identified a homozygous mutation, R501X (135940.0001), near the start of repeat 1 in exon 3 of the FLG gene. Further studies showed this mutation in the other 14 ichthyosis vulgaris kindreds studied. The mutation created a new restriction enzyme site which could be used to confirm the mutation and screen populations. By this means, they found the mutation to be present in relatively high allele frequencies in Irish, Scottish, and European American populations (combined frequency, 0.027). In 3 families, Smith et al. (2006) found that ichthyosis vulgaris patients with a very pronounced phenotype were homozygous for R501X. In other families, they found individuals with the marked ichthyosis vulgaris phenotype to be heterozygous for R501X. Further sequencing in these cases showed the existence of a second mutation, 2282del4 (135940.0002), in exon 3 of the FLG gene. The 2282del4 mutation leads to a premature termination codon 107 bp downstream and, like R501X, stops protein translation within the first filaggrin repeat. This mutation also created a restriction enzyme site which could be used to screen ichthyosis vulgaris families and populations. The 2282del4 mutation segregated in 10 of the ichthyosis vulgaris families. Of the 8 'sporadic' cases of clinically significant ichthyosis vulgaris in which family history was not available, 4 were homozygous for R501X and the remaining 4 were R501X/2282del4 compound heterozygotes. Restudy of the family reported by Compton et al. (2002) showed that severely affected individuals were compound heterozygotes for these 2 mutations. The association of ichthyosis vulgaris with atopic diathesis is well established; 37 to 50% of people with ichthyosis vulgaris have atopic diseases, and roughly 8% of patients with atopic dermatitis (603165) have classic features of ichthyosis vulgaris. Nomura et al. (2007) sequenced the entire FLG gene in 7 Japanese patients with ichthyosis vulgaris from 4 unrelated families who were negative for the R501X and 2282del4 mutations, and identified heterozygosity for 2 novel mutations, S2554X (135940.0003) and 3321delA (135940.0004), respectively. The older sister of 1 proband, who had a more severe presentation of the disease, was found to be homozygous for the S2554X mutation. Noting that the R501X and 2282del4 mutations were absent from a total of 253 Japanese individuals, including their patients with ichthyosis vulgaris and atopic dermatitis, Nomura et al. (2007) concluded that FLG mutations in Japan are different from those found in European-origin populations. Inheritance In 1 family studied by Smith et al. (2006), the semidominant mode of inheritance of ichthyosis vulgaris was exemplified by multiple examples of patients with very mild presentation as well as by R501X homozygotes and R501X/2282del4 compound heterozygotes with the full ichthyosis vulgaris phenotype. In their series of families studied by Smith et al. (2006), there were only 2 individuals who were heterozygous for a null mutation, namely R501X, and had no obvious phenotype. On the basis of these small numbers, Smith et al. (2006) calculated the penetrance in heterozygotes to be about 90%. Animal Model Presland et al. (2000) demonstrated that 'flaky tail' (ft) mice express an abnormal profilaggrin (135940) polypeptide that does not form normal keratohyalin F-granules and is not proteolytically processed to filaggrin. This autosomal recessive trait maps to the central region of mouse chromosome 3, in the vicinity of the epidermal differentiation complex. Affected homozygous ft/ft mice exhibit large, disorganized scales on tail and paw skin, marked attenuation of the epidermal granular layer, mild acanthosis, and orthokeratotic hyperkeratosis. Cultured ft/ft keratinocytes synthesized reduced amounts of profilaggrin mRNA and protein, demonstrating that the defect in profilaggrin expression is intrinsic to epidermal cells. Presland et al. (2000) proposed that the absence of filaggrin, and in particular the hygroscopic, filaggrin-derived amino acids that are thought to function in epidermal hydration, underlies the dry, scaly skin characteristic of ft/ft mice. Inheritance \- Autosomal dominant Misc \- Onset usually after 3 months age \- Lesions rare in the axillae, antecubital or popliteal fossae \- Palms and soles often show increased markings \- Frequent asthma, eczema or hay fever Skin \- Ichthyosis vulgaris \- Ichthyosis simplex ▲ 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	ICHTHYOSIS VULGARIS	c0079584	5,377	omim	https://www.omim.org/entry/146700	2019-09-22T16:39:39	{"doid": ["1702"], "mesh": ["D016112"], "omim": ["146700"], "icd-10": ["Q80.0"], "synonyms": ["Alternative titles", "ICHTHYOSIS SIMPLEX"]}
Typical posture of a person with Parkinson's disease, illustration by Sir William Richard Gowers, from A Manual of Diseases of the Nervous System (1886) Parkinsonian gait (or festinating gait, from Latin festinare [to hurry]) is the type of gait exhibited by patients suffering from Parkinson's disease (PD).[1] It is often described by people with Parkinson's as feeling like being stuck in place, when initiating a step or turning, and can increase the risk of falling.[2] This disorder is caused by a deficiency of dopamine in the basal ganglia circuit leading to motor deficits. Gait is one of the most affected motor characteristics of this disorder although symptoms of Parkinson's disease are varied. Parkinsonian gait is characterized by small shuffling steps and a general slowness of movement (hypokinesia), or even the total loss of movement (akinesia) in the extreme cases.[3][4][5] Patients with PD demonstrate reduced stride length, walking speed during free ambulation and cadence rate, while double support duration is increased.[6][7][8][9] The patient has difficulty starting, but also has difficulty stopping after starting. This is due to muscle hypertonicity.[10] ## Contents * 1 Abnormal gait characteristics * 1.1 Heel to toe characteristics * 1.2 Vertical ground reaction force * 1.3 Falls and freezing of gait * 1.4 Postural sway * 1.5 Electromyographic studies * 2 Gait improvement strategies * 2.1 Drugs * 2.2 Auditory and visual cues * 2.3 Deep brain stimulation * 2.4 Other treatments strategies * 3 Comparison with other gait disorders * 4 Socio-economic impact * 5 References * 6 External links ## Abnormal gait characteristics[edit] Parkinson's disease patient showing a flexed walking posture pictured in 1892, from Nouvelle Iconographie de la Salpètrière, vol. 5. Patients with Parkinson's disease exhibit gait characteristics that are markedly different from normal gait. While the list of abnormal gait characteristics given below is the most discussed, it is certainly not exhaustive. ### Heel to toe characteristics[edit] Whereas in normal gait, the heel strikes the ground before the toes (also called heel-to-toe walking), in Parkinsonian gait, motion is characterised by flat foot strike (where the entire foot is placed on the ground at the same time)[11] or less often and in the more advanced stages of the disease by toe-to-heel walking (where the toes touch the ground before the heel). In addition, PD patients have reduced foot lifting during the swing phase of gait, which produces smaller clearance between the toes and the ground.[12] Patients with Parkinson's disease have reduced impact at heel strike and this mechanism has been found to be related to the disease severity with impact decreasing as the disease progresses. Also, Parkinson patients show a trend towards higher relative loads in the forefoot regions combined with a load shift towards medial foot areas. This load shift is believed to help in compensating for postural imbalance. The intra-individual variability in foot strike pattern is found to be surprisingly lower in PD patients compared with normal people.[13] ### Vertical ground reaction force[edit] In normal gait, the vertical ground reaction force (GRF) plot has two peaks – one when the foot strikes the ground and the second peak is caused by push-off force from the ground. The shape of the vertical GRF signal is abnormal in PD.[14][15] In the earlier stages of the disease, reduced forces (or peak heights) are found for heel contact and the push-off phase resembling that of elderly subjects. In the more advanced stages of the disorder where gait is characterized by small shuffling steps, PD patients show only one narrow peak in the vertical GRF signal. ### Falls and freezing of gait[edit] Falls and freezing of gait are two episodic phenomena that are common in Parkinsonian gait. Falls and freezing of gait in PD are generally thought to be closely intertwined for several reasons, most importantly : both symptoms are common in the advanced stages of the disease and are less common in the earlier stages, with freezing of gait leading to falls in many instances. Both symptoms often respond poorly and sometimes paradoxically to treatment with dopaminergic medication, perhaps pointing to a common underlying pathophysiology.[16] Freezing of Gait: Freezing of Gait (FOG) is typically a transient episode – lasting less than a minute, in which gait is halted and the patient complains that his/her feet are glued to the ground. When the patient overcomes the block, walking can be performed relatively smoothly. The most common form of FOG is 'start hesitation' (which happens when the patient wants to start walking) followed in frequency by 'turning hesitation'[17][18] FOG can also be experienced in narrow or tight quarters such as a doorway, whilst adjusting one’s steps when reaching a destination, and in stressful situations such as when the telephone or the doorbell rings or when the elevator door opens. As the disease progresses, FOG can appear spontaneously even in an open runway space.[16] It is proven that psychological interventions can help reduce negative effect of psychosocial factors, like anxiety or depression, that can worsen freezing of gait or tremor in Parkinson's patients.[19] Based on that, every patient could benefit from psychological intervention, not only to reduce anxiety, depression, pain, and insomnia, but also to reduce effect of psychosocial factors in worsening of motor symptoms. Falls: Falls, like FOG are rare in the earlier stages of the disorder and becomes more frequent as the disease progresses. Falls result mainly due to sudden changes in posture, in particular turning movements of the trunk, or attempts to perform more than one activity simultaneously with walking or balancing. Falls are also common during transfers, such as rising from a chair or bed. PD patients fall mostly forward (45% of all falls) and about 20% fall laterally.[16] ### Postural sway[edit] Postural instability in upright stance is common in end-stage PD and compromises the ability to maintain balance during everyday tasks such as walking, turning and standing up from sitting. An inability to adequately balance the body's center of mass over the base of support combined with inflexibility in body movements (due to increased rigidity) causes patients with advanced PD to fall. Whereas postural sway in normal stance usually increases in patients with balance disorders arising from stroke, head injury and cerebellar ataxia it is often reduced in patients with PD. The reason for this because in PD the problem appears to be a lack of flexibility in shifting postural responses. This inflexibility increases the tendency to fall in these patients.[20][21] ### Electromyographic studies[edit] Electromyographic (EMG) studies of the leg muscles in PD patients have shown an extreme reduction in the activation of the tibialis anterior muscle in the early stance and in the early and late swing phases, and a reduction in triceps surae muscle bursting at push-off. The quadriceps and hamstring muscles on the other hand, show prolonged activation in the stance phase of gait.[22] This implies that PD patients have higher passive stiffness of ankle joints, show larger background EMG activity and more co-contraction of leg muscles in stance. Stiffer joints lead to abnormal postural sway in the PD patients.[23][24] ## Gait improvement strategies[edit] ### Drugs[edit] L-dopa(activates D1 receptor) most widely used drug for Parkinson's treatment The most widely used form of treatment is L-dopa in various forms. L-dopa is able to pass the blood–brain barrier as a prodrug and is decarboxylated in the brain to the neurotransmitter dopamine by the enzyme aromatic-L-amino-acid decarboxylase. In this way, L-DOPA can replace some of the deficit in dopamine seen in Parkinsonism. Due to feedback inhibition, L-dopa results in a reduction in the endogenous formation of L-dopa, and so eventually becomes counterproductive. Effect on gait parameters: The stride length and the kinematic parameters (swing velocity, peak velocity) related to the energy are Dopa-sensitive. Temporal parameters (stride and swing duration, stride duration variability), related to rhythm, are Dopa-resistant.[25] Effect on falls and freezing of gait: Levodopa treatment decreases the frequency and the akinetic type of FOG, with a tendency for shorter FOG episodes. Results indicate that this is primarily because L-dopa increases the threshold for FOG to occur but the fundamental pathophysiology for FOG did not change.[26] It has also been shown that other dopamine agonists like ropinirole, pramipexole and pergolide that have a strong affinity to D2 receptors (as opposed to L-dopa which has a strong D1 receptor affinity) increase the frequency of FOGs.[27] Effects on postural sway: Parkinson’s disease have abnormal postural sway in stance and treatment with levodopa increases postural sway abnormalities.[28] During movement, it has been shown that early autonomic postural disturbances are only partially corrected while the later occurring postural corrections are not affected by dopamine. These results indicate that non-dopaminergic lesions play a role in postural imbalance in PD patients.[29] Metronome used to deliver rhythmic auditory cues for Parkinsons disease patients Metronome sound used as auditory cues ### Auditory and visual cues[edit] Basal ganglia dysfunction in PD causes it to stop acting as an internal cue for gait in Parkinson's patients. Hence various external sensory cues like auditory and visual cues have been developed to bypass the basal ganglia's cueing functions. Visual cues: The visual cues are commonly transverse lines or rods on the floor (floor markers). Such cues have been shown to improve stride length and velocity in Parkinsonian gait by substituting kinaesthetic feedback with visual feedback for regulating movement amplitude.[30] In addition gait initiation has been shown to be significantly improved in PD patients compared with auditory cues.[31] Virtual reality glasses have also been developed recently to aid walking in PD patients.[32] Auditory cues: The auditory cues are commonly rhythmic cues generated by a metronome or equivalent, sometimes embedded in music, set at or slightly above the subject’s usual cadence. Rhythmic auditory cues have been associated with increases in velocity and cadence and sometimes stride after gait has been initiated. Auditory cues have been shown to have little or no effect in gait initiation.[31] ### Deep brain stimulation[edit] Deep Brain Stimulation on a Parkinson's patient. The picture shows the process of implantation of a DBS electrode into a patients brain. Deep brain stimulation (DBS) in the pedunculopontine nucleus, a part of the brainstem involved in motor planning,[33] has been shown to improve gait function in patients with Parkinson's disease.[34] DBS in the subthalamic nucleus (STN) and the globus pallidus have also been shown to have positive effects on gait abnormalities presented by Parkinson's Disease patients. DBS in the STN has been reported to reduce freezing of gait significantly at 1 and 2 year follow up.[35] Contradictory results have been reported on the effects on DBS on postural stability [28][36] The results seem to be highly location specific. The studies which do report positive effects suggest that the effectiveness of DBS in improving postural stability is due to its ability to affect non-dopaminergic pathways (in addition to dopaminergic pathways) which are believed to cause postural sway in PD patients.[28] Several studies suggest that STN stimulation with low frequencies (60–80 Hz) better alleviates gait deficits than with the commonly used high frequencies (>130 Hz).[37] ### Other treatments strategies[edit] Attention strategies: By consciously paying more attention to walking and rehearsing each step before actually making it, PD patients have shown to improve their gait. Sometimes, a companion walking alongside reminds the patient to concentrate on gait or they create a visual cue to step over by putting a foot in front of the person with PD over which the person must step. This causes the patient to focus their attention on the stepping action, thus making this a voluntary action and hence bypassing the faulty basal ganglia pathway (which is responsible for involuntary actions like walking). Avoidance of dual tasks that require motor attention or cognitive attention has also been shown to normalize gait in the PD patients.[38][39] Exercise: Physical therapy and exercise have been shown to have positive effects on gait parameters in PD patients.[40] Physiotherapists may help improve gait by creating training programs to lengthen a patient's stride length, broaden the base of support, improve the heel-toe gait pattern, straighten out a patient's posture, and increase arm swing patterns.[41] Research has shown gait training combining an overhead harness with walking on a treadmill has shown to improve both walking speed and stride length.[42] The harness assists the patient in maintaining an upright posture by eliminating the need to use a mobility aid, a practice which normally promotes a forward flexed posture.[41] It is believed the activation of the central pattern generator leads to the improvement in gait pattern.[41] Improving trunk flexibility, along with strengthening of the core muscles and lower extremities has been associated with increased balance and an improvement in gait pattern.[43] Aerobic exercises such as tandem bicycling and water aerobics are also crucial in improving strength and overall balance.[43] Due to PD’s progressive nature it is important to sustain an exercise routine to maintain its benefits.[43] Strategies such as using a vertical walking pole can also help to improve upright postural alignment. The therapist may also use tiles or footprints on the ground to improve foot placement and widen the patient's base of support.[41] Creative visualization of walking with a more normalized gait pattern, and mentally rehearsing the desired movement has also shown to be effective.[43] The patient should also be challenged by walking on a variety of surfaces such as tile, carpet, grass, or foamed surfaces will also benefit the individual’s progress towards normalizing their gait pattern.[41] ## Comparison with other gait disorders[edit] Subcortical arteriosclerotic encephalopathy (SAE), also called lower-body parkinsonism, and cerebellar ataxia are two other gait disorders whose symptoms seem to closely resemble that of Parkinson's. However, through regression analysis studies have revealed that in Parkinson's, increasing the velocity of walking changes the stride length linearly (which resembles that of controls). However, in SAE and cerebellar ataxia stride length had a disproportionate contribution to increasing velocity, indicating that SAE and cerebellar ataxia have common underlying mechanisms different from those of Parkinson's.[35] ## Socio-economic impact[edit] Mobility issues associated with falls and freezing of gait have a devastating impact in the lives of PD patients. Fear of falling in itself can have an incapacitating effect in PD patients and can result in social seclusion leaving patients largely isolated leading to depression. Immobility can also lead to osteoporosis which in-turn facilitates future fracture development. This then becomes a vicious circle with falls leading to immobility and immobility facilitating future falls. Hip fractures from falls are the most common form of fracture among PD patients. Fractures increase treatment costs associated with health care expenditures in PD.[16] Also, when gait is affected it often heralds the onset of Lewy body dementia.[44][45][46] ## References[edit] 1. ^ "Definition: festinating gait from Online Medical Dictionary". 2. ^ "Movement Symptoms". Parkinson's Foundation. Retrieved 11 November 2019. 3. ^ Morris M.; Iansek R.; Matyas T.; Summers J. (1998). "Abnormalities in the stride length-cadence relation in Parkinsonian gait". Mov Disord. 13 (1): 61–69. doi:10.1002/mds.870130115. PMID 9452328. 4. ^ Aita J.F. (1982). "Why patients with Parkinson's disease fall". JAMA. 247 (4): 515–516. doi:10.1001/jama.247.4.515. 5. ^ Koller W.C.; Glatt S.; Vetere-Overfield B.; Hassanein R. (1989). "Falls and Parkinson's disease". Clin Neuropharmacol. 12 (2): 98–105. doi:10.1097/00002826-198908000-00006. PMID 2720700. 6. ^ M.E. Morris, R. Iansek, T.A. Matyas and J.J. Summers "Stride length regulation in Parkinson's disease. Normalization strategies and underlying mechanisms. Brain 1996; 119 7. ^ Hausdorff J.M.; Cudkowicz M.E.; Firtion R.; Wei J.Y.; Goldberger A.L. (1998). "Gait variability and basal ganglia disorders: stride-to-stride variations of gait cycle timing in Parkinson's disease and Huntington's disease". Mov Disord. 13 (3): 428–437. doi:10.1002/mds.870130310. PMID 9613733. 8. ^ Vieregge P.; Stolze H.; Klein C.; Heberlein I. (1997). "Gait quantitation in Parkinson's disease – locomotor disability and correlation to clinical rating scales". J Neural Transm. 104 (2–3): 237–248. doi:10.1007/bf01273184. PMID 9203085. 9. ^ W. Zijlstra, A.W. Rutgers and T.W. Van Weerden, Voluntary and involuntary adaptation of gait in parkinson's disease. Gait & Posture 7 (1998), pp. 53–63 10. ^ Saint, Sanjay; Wiese, Jeff; Bent, Stephen (2006). Clinical clerkships: the answer book. Hagerstown, MD: Lippincott Williams & Wilkins. p. 218. ISBN 978-0-7817-3754-8. 11. ^ Hughes J.R.; Bowes S.G.; Leeman A.L.; O'Neill C.J.; Deshmukh A.A.; Nicholson P.W.; et al. (1990). "Parkinsonian abnormality of foot strike: a phenomenon of ageing and/or one responsive to levodopa therapy?". Br J Clin Pharmacol. 29 (2): 179–186. doi:10.1111/j.1365-2125.1990.tb03617.x. PMC 1380081. PMID 2306409. 12. ^ Murray M.P.; Sepic S.B.; Gardner G.M.; Downs W.J. (1978). "Walking patterns of men with Parkinsonism". Am J Phys Med. 57: 278–294. PMID 742658. 13. ^ Stefan Kimmeskamp, Ewald M. Hennig "Heel to toe motion characteristics in Parkinson patients during free walking". Clinical Biomechanics, Volume 16, Issue 9, November 2001, Pages 806–812 14. ^ Koozekanani S.H.; Balmaseda Jr M.T.; Fatehi M.T.; Lowney E.D. (1987). "Ground reaction forces during ambulation in Parkinsonism: pilot study". Arch Phys Med Rehabil. 68 (1): 28–30. PMID 3800620. 15. ^ Ueno E.; Yanagisawa N.; Takami M. (1993). "Gait disorders in Parkinsonism a study with floor reaction forces and EMG". Adv Neurol. 60: 414–418. PMID 8420164. 16. ^ a b c d Bloem BR, Hausdorff JM, Visser JE, Giladi N (2004). "Falls and freezing of gait in Parkinson's disease: a review of two interconnected, episodic phenomena". Mov. Disord. 19 (8): 871–84. doi:10.1002/mds.20115. PMID 15300651. 17. ^ Giladi N, McMahoon D, Przedborski S, et al. (1992). "Motor blocks in Parkinson's disease". Neurology. 42 (2): 333–339. doi:10.1212/wnl.42.2.333. PMID 1736161. 18. ^ Giladi N, Treves TA, Simon ES, et al. (2001). "Freezing of gait in patients with advanced Parkinson's disease". J Neural Transm. 108 (1): 53–61. doi:10.1007/s007020170096. PMID 11261746. 19. ^ Zečević, Ivan (20 March 2020). "Clinical Practice Guidelines Based on Evidence for Cognitive‐Behavioral Therapy in Parkinson's Disease Comorbidities: A Literature Review". Clinical Psychology & Psychotherapy. doi:10.1002/cpp.2448. PMID 32196842. 20. ^ Morris ME, Iansek R, Smithson F, Huxham F (2000). "Postural instability in Parkinson's disease: a comparison with and without a concurrent task". Gait & Posture. 12 (3): 205–216. doi:10.1016/s0966-6362(00)00076-x. PMID 11154931. 21. ^ Horak FB, Nutt JG, Nashner LM (1992). "Postural inflexibility in Parkinsonian subjects". J Neurol Sci. 111 (1): 46–58. doi:10.1016/0022-510x(92)90111-w. PMID 1402997. 22. ^ Cioni M, Richards CL, Malouin F, Bedard PJ, Lemieux R (1997). "Characteristics of the electromyographic patterns of lower limb muscles during gait in patients with PARKINSON's disease when OFF and ON L-DOPA treatment". Ital J Neurol Sci. 18 (4): 195–208. doi:10.1007/bf02080464. PMID 9323513. 23. ^ Robertson LT, Horak FB, Anderson VC, et al. (2001). "Assessments of axial motor control during deep brain stimulation in Parkinsonian patients". Neurosurgery. 48 (3): 544–551. doi:10.1097/00006123-200103000-00017. PMID 11270544. 24. ^ Dietz V, Zijlstra W, Assaiante C, et al. (1993). "Balance control in Parkinson's disease". Gait & Posture. 1 (2): 77–84. doi:10.1016/0966-6362(93)90018-v. 25. ^ Blin O.; Ferrandez A. M.; Pailhous J.; Serratrice G. (1991). "Dopa-sensitive and dopa-resistant gait parameters in Parkinson's disease". J. Neurol. Sci. 103 (1): 51–54. doi:10.1016/0022-510x(91)90283-d. PMID 1865232. 26. ^ Schaafsma JD, Balash Y, Gurevich T, et al. (2003). "Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson's disease". Eur J Neurol. 10 (4): 391–398. doi:10.1046/j.1468-1331.2003.00611.x. PMID 12823491. 27. ^ Arnt J, Bogeso KP, Hyttel J, Meier E (1988). "Relative dopamine D1 and D2 receptors affinity and efficacy determine whether dopamine agonists induce hyperactivity or oral stereotypy in rats". Pharmacol Toxicol. 62 (3): 121–130. doi:10.1111/j.1600-0773.1988.tb01859.x. PMID 3259694. 28. ^ a b c Rocchi L, Chiari L, Horak FB (2002). "Effects of deep brain stimulation and levodopa on postural sway in Parkinson's disease". J Neurol Neurosurg Psychiatry. 73 (3): 267–274. doi:10.1136/jnnp.73.3.267. PMC 1738049. PMID 12185157. 29. ^ Bloem BR, Beckley DJ, van Dijk JG, Zwinderman AH, Remler MP, Roos RA (1996). "Influence of dopaminergic medication on automatic postural responses and balance impairment in Parkinson's disease". Mov Disord. 11 (5): 509–521. doi:10.1002/mds.870110506. PMID 8866492. 30. ^ Lewis G, Byblow WD, Walt S (2000). "Stride length regulation in Parkinson's disease: the use of extrinsic, visual cues". Brain. 123 (10): 2077–2090. doi:10.1093/brain/123.10.2077. PMID 11004125. 31. ^ a b Jiang Y, Norman KE (2006). "Effects of visual and auditory cues on gait initiation in people with Parkinson's disease". Clin Rehabil. 20 (1): 36–45. doi:10.1191/0269215506cr925oa. PMID 16502748. 32. ^ McAuley JH, Daly PM, Curtis CR (August 2009). "A preliminary investigation of a novel design of visual cue glasses that aid gait in Parkinson's disease". Clin Rehabil. 23 (8): 687–695. doi:10.1177/0269215509104170. PMID 19403552. 33. ^ Tattersall T. L.; et al. (2014). "Imagined gait modulates neuronal network dynamics in the human pedunculopontine nucleus" (PDF). Nature Neuroscience. 17 (3): 449–454. doi:10.1038/nn.3642. PMID 24487235. 34. ^ Thevathasan W.; et al. (2012). "A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation". Brain. 135 (5): 1446–1454. doi:10.1093/brain/aws039. PMC 3338924. PMID 22396391. 35. ^ a b Freezing of gait after bilateral subthalamic nucleus stimulation for Parkinson's disease Clinical Neurology and Neurosurgery, Volume 108, Issue 5, Pages 461-464. 36. ^ Yokoyama T, Sugiyama K, Nishizawa S, Yokota N, Ohta S, Uemura K (1999). "Subthalamic nucleus stimulation for gait disturbance in Parkinson's disease". Neurosurgery. 45: 41–49. doi:10.1227/00006123-199907000-00011. 37. ^ Feng, Tao; Zhou, Junhong; Ma, Huizi; Liu, Genliang; Wang, Xuemei; Wang, Zhan; Liu, Yuye; Hu, Wanli; Chen, Huimin (2018-09-27). "Frequency-dependent effects of subthalamic deep brain stimulation on motor symptoms in Parkinson's disease: a meta-analysis of controlled trials". Scientific Reports. 8 (1): 14456. Bibcode:2018NatSR...814456S. doi:10.1038/s41598-018-32161-3. ISSN 2045-2322. PMC 6160461. PMID 30262859. 38. ^ Yogev G, Giladi N, Peretz C, Springer S, Simon ES, Hausdorff JM: Dual tasking, gait rhythmicity, and Parkinson's disease: which aspects of gait are attention demanding? Eur J Neurosci 2005 39. ^ O'Shea S.; Morris M.E.; Iansek R. (2002). "Dual task interference during gait in people with Parkinson disease: effects of motor versus cognitive secondary tasks". Phys. Ther. 82 (9): 888–897. doi:10.1093/ptj/82.9.888. 40. ^ De Goede CJ, Keus SH, Kwakkel G, et al. (2001). "The effects of physical therapy in Parkinson's disease: a research synthesis". Arch Phys Med Rehabil. 82 (4): 509–515. doi:10.1053/apmr.2001.22352. PMID 11295012. 41. ^ a b c d e O'Sullivan, S.O. (2007). Parkinson's Disease: Physical Therapy Intervention. In S.B. O'Sullivan, & T.J. Schmitz (Eds.), Physical Rehabilitation (5th ed., pp.853-893). Philadelphia: E.A. Davis Company. 42. ^ Protas E.; Mitchell K.; Williams A.; Qureshy H.; Caroline K.; Lai E. (2005). "Gait and step training to reduce falls in Parkinson's disease". NeuroRehabilitation. 20 (3): 183–190. doi:10.3233/NRE-2005-20305. 43. ^ a b c d Morris M.; Martin C.; Schenkman M. (2010). "Striding out with Parkinson Disease: Evidence-Based Physical Therapy for Gait Disorders". Physical Therapy. 90 (2): 280–8. doi:10.2522/ptj.20090091. PMC 2816030. PMID 20022998. 44. ^ Alves, Guido; Larsen, Jan Petter; Emre, Murat; Wentzel-Larsen, Tore; Aarsland, Dag (August 2006). "Changes in motor subtype and risk for incident dementia in Parkinson's disease". Movement Disorders. 21 (8): 1123–1130. doi:10.1002/mds.20897. PMID 16637023. 45. ^ Burn, DJ; Rowan, EN; Allan, LM; Molloy, S; O'Brien, JT; McKeith, IG (May 2006). "Motor subtype and cognitive decline in Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies". Journal of Neurology, Neurosurgery, and Psychiatry. 77 (5): 585–9. doi:10.1136/jnnp.2005.081711. PMC 2117449. PMID 16614017. 46. ^ Factor, SA; Steenland, NK; Higgins, DS; Molho, ES; Kay, DM; Montimurro, J; Rosen, AR; Zabetian, CP; Payami, H (May 2011). "Postural instability/gait disturbance in Parkinson's disease has distinct subtypes: an exploratory analysis". Journal of Neurology, Neurosurgery, and Psychiatry. 82 (5): 564–8. doi:10.1136/jnnp.2010.222042. PMC 4646086. PMID 20884673. ## External links[edit] * Auditory Cues for Parkinson's * Visual Cues for Parkinson's * Medfriendly: Festinating gait * About Physical Therapy * GP Notebook * v * t * e Symptoms and signs relating to movement and gait Gait * Gait abnormality * CNS * Scissor gait * Cerebellar ataxia * Festinating gait * Marche à petit pas * Propulsive gait * Stomping gait * Spastic gait * Magnetic gait * Truncal ataxia * Muscular * Myopathic gait * Trendelenburg gait * Pigeon gait * Steppage gait * Antalgic gait Coordination * Ataxia * Cerebellar ataxia * Dysmetria * Dysdiadochokinesia * Pronator drift * Dyssynergia * Sensory ataxia * Asterixis Abnormal movement * Athetosis * Tremor * Fasciculation * Fibrillation Posturing * Abnormal posturing * Opisthotonus * Spasm * Trismus * Cramp * Tetany * Myokymia * Joint locking Paralysis * Flaccid paralysis * Spastic paraplegia * Spastic diplegia * Spastic paraplegia * Syndromes * Monoplegia * Diplegia / Paraplegia * Hemiplegia * Triplegia * Tetraplegia / Quadruplegia * General causes * Upper motor neuron lesion * Lower motor neuron lesion Weakness * Hemiparesis Other * Rachitic rosary * Hyperreflexia * Clasp-knife response [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Parkinsonian gait	c0427160	5,378	wikipedia	https://en.wikipedia.org/wiki/Parkinsonian_gait	2021-01-18T18:56:27	{"wikidata": ["Q3743995"]}
A rare autosomal recessive axonal hereditary motor and sensory neuropathy characterized by infantile onset of recurrent episodes of acute liver failure (resulting in chronic liver fibrosis and hepatosplenomegaly), delayed motor development, cerebellar dysfunction presenting as gait disturbances and intention tremor, neurogenic stuttering, and motor and sensory neuropathy with muscle weakness especially in the lower legs, and numbness. Mild intellectual disability was reported in some patients. MRI of the brain shows non-progressive atrophy of the cerebellar vermis and thinning of the optic nerve. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome	c4225236	5,379	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=466794	2021-01-23T18:37:07	{"omim": ["616719"], "icd-10": ["G11.0"], "synonyms": ["Autosomal recessive spinocerebellar ataxia type 21", "SCAR21"]}
Radial dysplasia Other namesRadial longitudinal deficiency Radial club hand with thumb missing Radial dysplasia, also known as radial club hand or radial longitudinal deficiency, is a congenital difference occurring in a longitudinal direction resulting in radial deviation of the wrist and shortening of the forearm. It can occur in different ways, from a minor anomaly to complete absence of the radius, radial side of the carpal bones and thumb.[1] Hypoplasia of the distal humerus may be present as well and can lead to stiffness of the elbow.[2] Radial deviation of the wrist is caused by lack of support to the carpus, radial deviation may be reinforced if forearm muscles are functioning poorly or have abnormal insertions.[3] Although radial longitudinal deficiency is often bilateral, the extent of involvement is most often asymmetric.[1] The incidence is between 1:30,000 and 1:100,000 and it is more often a sporadic mutation rather than an inherited condition.[1][3] In case of an inherited condition, several syndromes are known for an association with radial dysplasia, such as the cardiovascular Holt-Oram syndrome, the gastrointestinal VATER syndrome and the hematologic Fanconi anemia and TAR syndrome.[1] Other possible causes are an injury to the apical ectodermal ridge during upper limb development,[2] intrauterine compression, or maternal drug use (thalidomide).[3] ## Contents * 1 Classification * 2 Treatment * 2.1 Splinting and stretching * 2.2 Centralization * 2.3 Radialization * 2.4 Vascularized metatarsophalangeal (MTP)-joint transfer * 3 References ## Classification[edit] Classification of radial dysplasia is practised through different models. Some only include the different deformities or absences of the radius, where others also include anomalies of the thumb and carpal bones. The Bayne and Klug classification discriminates four different types of radial dysplasia.[4] A fifth type was added by Goldfarb et al. describing a radial dysplasia with participation of the humerus.[4] In this classification only anomalies of the radius and the humerus are taken in consideration. James and colleagues expanded this classification by including deficiencies of the carpal bones with a normal distal radius length as type 0 and isolated thumb anomalies as type N.[4] Type N: Isolated thumb anomaly Type 0: Deficiency of the carpal bones Type I: Short distal radius Type II: Hypoplastic radius in miniature Type III: Absent distal radius Type IV: Complete absent radius Type V: Complete absent radius and manifestations in the proximal humerus The term absent radius can refer to the last 3 types. ## Treatment[edit] ### Splinting and stretching[edit] In cases of a minor deviation of the wrist, treatment by splinting and stretching alone may be a sufficient approach in treating the radial deviation in RD. Besides that, the parent can support this treatment by performing passive exercises of the hand. This will help to stretch the wrist and also possibly correct any extension contracture of the elbow. Furthermore, splinting is used as a postoperative measure trying to avoid a relapse of the radial deviation.[3] ### Centralization[edit] More severe types (Bayne type III en IV) of radial dysplasia can be treated with surgical intervention. The main goal of centralization is to increase hand function by positioning the hand over the distal ulna, and stabilizing the wrist in straight position. Splinting or soft-tissue distraction may be used preceding the centralization. In classic centralization central portions of the carpus are removed to create a notch for placement of the ulna.[5] A different approach is to place the metacarpal of the middle finger in line with the ulna with a fixation pin.[1][3] If radial tissues are still too short after soft-tissue stretching, soft tissue release and different approaches for manipulation of the forearm bones may be used to enable the placement of the hand onto the ulna. Possible approaches are shortening of the ulna by resection of a segment, or removing carpal bones.[6] If the ulna is significantly bent, osteotomy may be needed to straighten the ulna.[1] After placing the wrist in the correct position, radial wrist extensors are transferred to the extensor carpi ulnaris tendon, to help stabilize the wrist in straight position.[2] If the thumb or its carpometacarpal joint is absent, centralization can be followed by pollicization. Postoperatively, a long arm plaster splinter has to be worn for at least 6 to 8 weeks. A removable splint is often worn for a long period of time.[3] Radial angulation of the hand enables patients with stiff elbows to reach their mouth for feeding; therefore treatment is contraindicated in cases of extension contracture of the elbow.[2][3] A risk of centralization is that the procedure may cause injury to the ulnar physis, leading to early epiphyseal arrest of the ulna, and thereby resulting in an even shorter forearm.[1][3] Sestero et al. reported that ulnar growth after centralization reaches from 48% to 58% of normal ulnar length, while ulnar growth in untreated patients reaches 64% of normal ulnar length.[7] Several reviews note that centralization can only partially correct radial deviation of the wrist and that studies with longterm follow-up show relapse of radial deviation.[6][8] ### Radialization[edit] Buck-Gramcko described another operation technique, for treatment of radial dysplasia, which is called radialization. During radialization the metacarpal of the index finger is pinned onto the ulna and radial wrist extensors are attached to the ulnar side of the wrist, causing overcorrection or ulnar deviation. This overcorrection is believed to make relapse of radial deviation less likely.[1] ### Vascularized metatarsophalangeal (MTP)-joint transfer[edit] Villki reported a different approach in During this procedure a vascularised MTP-joint of the second toe is transferred to the radial side of ulna, creating a platform that provides radial support for the wrist. The graft is vascularised and therefore maintains its ability to join the growth of the supporting ulna.[6] Prior to the actual transfer of the MTP-joint of the second toe soft-tissue distraction of the wrist is required to create enough space to place the MTP joint. When after several weeks enough space has been created through distraction, the actual transfer of the MTP joint can be initiated. During this surgical intervention the wrist and the second toe are prepared for transfer at the same time. The ipsilateral second toe MTP joint, together with its metatarsal arteries, its extensor and flexor tendons and its dorsal nerves to the skin, is harvested for transfer. The distal and middle phalanx of the toe are removed. The transferred toe, consisting of the metatarsal and proximal phalanx, is fixed between the physis of the ulna and the second metacarpal, or the scaphoid. The tendons of the toe are attached to those of the radial flexor and extensors muscles of the wrist to create more stability to the MTP joint. K-wires are placed to fixate the bones in the desired position. Once the bones are secured anastomosis are made between the vessels of the toe and the vessels of the forearm. After revascularization of the toe, the skin paddle is placed and the skin is closed.[9] Vilkki et al. have conducted a study on 19 forearms treated with vascularized MTP-joint transfer with a mean follow-up of 11 years which reports an ulnar length of 67% compared to the contralateral side.[9] De Jong et al. described in a review that compared to study outcomes on centralization, Vilkki reported a smaller deviation postoperatively and a lower severity of the relapse.[6] ## References[edit] 1. ^ a b c d e f g h Bednar MS, James MA, Light TR (2009). "Congenital longitudinal deficiency". J Hand Surg. 34 (9): 1739–47. doi:10.1016/j.jhsa.2009.09.002. PMID 19896016. 2. ^ a b c d Bates SJ, Hansen SL, Jones NF (2009). "Reconstruction of congenital differences of the hand". Plast Reconstr Surg. 124 (1): 128e–143e. doi:10.1097/PRS.0b013e3181a80777. PMID 19568146. 3. ^ a b c d e f g h Netscher DT, Baumholtz MA (2007). "Treatment of congenital upper extremity problems". Plast Reconstr Surg. 119 (5): 101e–129e. doi:10.1097/01.prs.0000258535.31613.43. PMID 17415231. 4. ^ a b c Goldfarb CA, Manske PR, Busa R, Mills J, Carter P, Ezaki M (2005). "Upper-extremity phocomelia reexamined: a longitudinal dysplasia". J Bone Joint Surg Am. 87 (12): 2639–48. doi:10.2106/JBJS.D.02011. PMID 16322613. 5. ^ Lamb DW. (1991). "The treatment of longitdunal radial deficiency". Prosthet Orthot Int. 15 (2): 100–3. doi:10.3109/03093649109164642. PMID 1923709. 6. ^ a b c d de Jong JP, Moran SL, Vilkki SK (2012). "Changing Paradigms in the Treatment of Radial Club Hand: Microvascular Joint Transfer for Correction of Radial Deviation and Preservation of Long-term Growth". Clin Orthop Surg. 4 (1): 36–44. doi:10.4055/cios.2012.4.1.36. PMC 3288493. PMID 22379554. 7. ^ Sestero AM, Van Heest A, Agel J (2006). "Ulnar growth patterns in radial longitudinal deficiency". J Hand Surg Am. 31 (6): 960–7. doi:10.1016/j.jhsa.2006.03.016. PMID 16843156. 8. ^ Manske PR, Goldfarb CA (2009). "Congenital failure of formation of the upper limb". Hand Clin. 25 (2): 157–70. doi:10.1016/j.hcl.2008.10.005. PMID 19380058. 9. ^ a b Vilkki SK. (2008). "Vascularized metatarsophalangeal joint transfer for radial hypoplasia". Semin Plast Surg. 22 (3): 195–212. doi:10.1055/s-2008-1081403. PMC 2884879. PMID 20567714. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Radial dysplasia	c4025414	5,380	wikipedia	https://en.wikipedia.org/wiki/Radial_dysplasia	2021-01-18T18:41:09	{"gard": ["225"], "icd-10": ["Q71.4"], "orphanet": ["93321"], "synonyms": ["Congenital longitudinal deficiency of the radius", "Radial clubhand", "Radial longitidinal meromelia", "Radial ray agenesis"], "wikidata": ["Q1776603"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (July 2011) Plum syndrome Other namesOculocerebroosseous syndrome Plum syndrome is a very rare genetic disorder. It is characterized by retinal non-attachment, colobomata, odd facies, eyes set wide, flat face, dislocated hip, abnormal big toe, contractures of the extremities, cleft lip and mono-segmented leucocytes. There may be associated learning difficulties.[1][2] Named by Dr. C. M. Plum.[citation needed] ## References[edit] 1. ^ Metabolic and Pediatric Ophthalmology, 1979, vol./is. 3/2-4(149-155), 0191-2771 (1979) 2. ^ http://www.checkorphan.org/disease/plum-syndrome accessed 5 July 2011 ## External links[edit] Classification D External resources * Orphanet: 2708 This genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Plum syndrome	None	5,381	wikipedia	https://en.wikipedia.org/wiki/Plum_syndrome	2021-01-18T18:59:33	{"orphanet": ["2708"], "wikidata": ["Q7205365"]}
Male infertility SpecialtyUrology Male infertility refers to a male's inability to cause pregnancy in a fertile female.[1] In humans it accounts for 40–50% of infertility.[2][3][4] It affects approximately 7% of all men.[5] Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.[6] ## Contents * 1 Causes * 1.1 Immune infertility * 1.1.1 Other * 1.2 Pre-testicular causes * 1.2.1 Varicocele * 1.2.2 Tobacco smoking * 1.2.3 DNA damage * 1.2.4 Epigenetic * 1.3 Post-testicular causes * 2 Diagnosis * 2.1 Medical history * 2.2 Physical examination * 2.3 Sperm sample * 2.3.1 Semen sample obtaining * 2.3.2 Special obtaining * 2.4 Blood sample * 2.5 Ultrasonography * 3 Prevention * 4 Treatment[43] * 4.1 Hormonal therapy * 5 Future potential treatments * 6 Global trends * 7 Society and culture * 8 See also * 9 References * 10 External links ## Causes[edit] Factors relating to male infertility include:[7] ### Immune infertility[edit] Antisperm antibodies (ASA) have been considered as infertility cause in around 10–30% of infertile couples.[8] ASA production are directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, inhibiting capacitation and acrosome reaction, impaired fertilization, influence on the implantation process, and impaired growth and development of the embryo. Risk factors for the formation of antisperm antibodies in men include the breakdown of the blood‑testis barrier, trauma and surgery, orchitis, varicocele, infections, prostatitis, testicular cancer, failure of immunosuppression and unprotected receptive anal or oral sex with men.[8][9] Genetics Chromosomal anomalies and genetic mutations account for nearly 10–15% of all male infertility cases.[10] Klinefelter syndrome One of the most commonly known causes of infertility is Klinefelter syndrome, affecting 1 out of 500–1000 newborn males[11] Klinefelter syndrome is a chromosomal defect that occurs during gamete formation due to a non-disjunction error during cell division. Resulting in males having smaller testes, reducing the amount of testosterone and sperm production.[12] Males with this syndrome carry an extra X chromosome (XXY), meaning they have 47 chromosomes compared to the normal 46 in each cell. This extra chromosome directly affects sexual development before birth and during puberty (links to learning disabilities and speech development have also been shown to be affected). There are varieties in Klinefelter syndrome, where some cases may have the extra X chromosome in some cells but not others, referred to as mosaic Klinefelter syndrome, or where individuals have the extra X chromosome in all cells. The reduction of testosterone in the male body normally results in an overall decrease in the production of viable sperm for these individuals thereby forcing them to turn to fertility treatments to father children.[11] Y chromosome deletions Y chromosomal infertility is a direct cause of male infertility due to its effects on sperm production, occurring in 1 out of every 2000 males.[13] Usually affected men show no sign of symptoms other than at times can exhibit smaller teste size. Men with this condition can exhibit azoospermia (no sperm production), oligozoospermia (small number of sperm production), or they will produce abnormally shaped sperm (teratozoospermia).[13] This case of infertility occurs during the development of gametes in the male, where a normal healthy male will produce both X and a Y chromosome, affected males have genetic deletions in the Y chromosome. These deletions affect protein production that is vital for spermatogenesis. Studies have shown that this is an inherited trait; if a male is fathered by a man who also exhibited y chromosome deletions then this trait will be passed down. These individuals are thereby “Y-linked”, although daughters are not affected due to the lack of the Y chromosome. #### Other[edit] * Age group 12-49 (see also: Paternal age effect) * Abnormal set of chromosomes * Centriole[14] * Neoplasm, e.g. seminoma * Idiopathic failure * Cryptorchidism * Trauma * Hydrocele * Hypopituitarism in adults, and hypopituitarism untreated in children (resulting in growth hormone deficiency and proportionate dwarfism.) * Mumps[15] * Malaria * Testicular cancer * Defects in USP26 in some cases[16] * Acrosomal defects affecting egg penetration * Idiopathic oligospermia \- unexplained sperm deficiencies account for 30% of male infertility.[17] ### Pre-testicular causes[edit] Pre-testicular factors refer to conditions that impede adequate support of the testes and include situations of poor hormonal support and poor general health including: #### Varicocele[edit] Varicocele is a condition of swollen testicle veins.[18] It is present in 15% of normal men and in about 40% of infertile men. It is present in up to 35% of cases of primary infertility and 69–81% of secondary infertility.[19] * Hypogonadotropic hypogonadism due to various causes * Obesity increases the risk of hypogonadotropic hypogonadism.[20] Animal models indicate that obesity causes leptin insensitivity in the hypothalamus, leading to decreased Kiss1 expression, which, in turn, alters the release of gonadotropin-releasing hormone (GnRH).[20] * Undiagnosed and untreated coeliac disease (CD). Coeliac men may have reversible infertility. Nevertheless, CD can present with several non-gastrointestinal symptoms that can involve nearly any organ system, even in the absence of gastrointestinal symptoms. Thus, the diagnosis may be missed, leading to a risk of long-term complications.[21] In men, CD can reduce semen quality and cause immature secondary sex characteristics, hypogonadism and hyperprolactinaemia, which causes impotence and loss of libido.[22] The giving of gluten free diet and correction of deficient dietary elements can lead to a return of fertility.[21][22] It is likely that an effective evaluation for infertility would best include assessment for underlying celiac disease, both in men and women.[23] * Drugs, alcohol * Strenuous riding (bicycle riding,[24] horseback riding) * Medications, including those that affect spermatogenesis such as chemotherapy, anabolic steroids, cimetidine, spironolactone; those that decrease FSH levels such as phenytoin; those that decrease sperm motility such as sulfasalazine and nitrofurantoin * Genetic abnormalities such as a Robertsonian translocation #### Tobacco smoking[edit] See also: Smoking and pregnancy There is increasing evidence that the harmful products of tobacco smoking may damage the testicles[25] and kill sperm,[26][27] but their effect on male fertility is not clear.[28] Some governments require manufacturers to put warnings on packets. Smoking tobacco increases intake of cadmium, because the tobacco plant absorbs the metal. Cadmium, being chemically similar to zinc, may replace zinc in the DNA polymerase, which plays a critical role in sperm production. Zinc replaced by cadmium in DNA polymerase can be particularly damaging to the testes.[29] #### DNA damage[edit] Common inherited variants in genes that encode enzymes employed in DNA mismatch repair are associated with increased risk of sperm DNA damage and male infertility.[30] As men age there is a consistent decline in semen quality, and this decline appears to be due to DNA damage.[31] The damage manifests by DNA fragmentation and by the increased susceptibility to denaturation upon exposure to heat or acid, the features characteristic of apoptosis of somatic cells.[32] These findings suggest that DNA damage is an important factor in male infertility. #### Epigenetic[edit] See also: DNA methylation An increasing amount of recent evidence has been recorded documenting abnormal sperm DNA methylation in association with abnormal semen parameters and male infertility.[33][34] Until recently, scientists have thought that epigenetic markers only affect the individual and are not passed down due to not changing the DNA.[35] New studies suggest that environmental factors that changed an individual's epigenetic markers can be seen in their grandchildren, one such study demonstrating this through rats and fertility disruptors.[35] Another study bred rats exposed to an endocrine disruptor, observing effects up to generation F5 including decreased sperm motility and decreased sperm count.[36] These studies suggest that environmental factors that influence fertility can be felt for generations even without changing the DNA. ### Post-testicular causes[edit] Post-testicular factors decrease male fertility due to conditions that affect the male genital system after testicular sperm production and include defects of the genital tract as well as problems in ejaculation: * Vas deferens obstruction * Lack of Vas deferens, often related to genetic markers for cystic fibrosis * Infection, e.g. prostatitis * Retrograde ejaculation * Ejaculatory duct obstruction * Hypospadias * Impotence ## Diagnosis[edit] The diagnosis of infertility begins with a medical history and physical exam by a physician, physician assistant, or nurse practitioner. Typically two separate semen analyses will be required. The provider may order blood tests to look for hormone imbalances, medical conditions, or genetic issues. ### Medical history[edit] The history should include prior testicular or penile insults (torsion, cryptorchidism, trauma), infections (mumps orchitis, epididymitis), environmental factors, excessive heat, radiation, medications, and drug use (anabolic steroids, alcohol, smoking). Sexual habits, frequency and timing of intercourse, use of lubricants, and each partner's previous fertility experiences are important. Loss of libido and headaches or visual disturbances may indicate a pituitary tumor. The past medical or surgical history may reveal thyroid or liver disease (abnormalities of spermatogenesis), diabetic neuropathy (retrograde ejaculation), radical pelvic or retroperitoneal surgery (absent seminal emission secondary to sympathetic nerve injury), or hernia repair (damage to the vas deferens or testicular blood supply). A family history may reveal genetic problems. ### Physical examination[edit] Usually, the patient disrobes completely and puts on a gown. The physician, physician assistant, or nurse practitioner will perform a thorough examination of the penis, scrotum, testicles, I vas deferens, spermatic cords, ejaculatory ducts, urethra, urinary bladder, anus and rectum. An orchidometer can measure testicular volume, which in turn is tightly associated with both sperm and hormonal parameters.[5] A physical exam of the scrotum can reveal a varicocele, but the impact of detecting and surgically correct a varicocele on sperm parameters or overall male fertility is debated.[5] ### Sperm sample[edit] #### Semen sample obtaining[edit] Semen sample obtaining is the first step in spermiogram. The optimal sexual abstinence for semen sample obtaining is of 2–7 days. The first way to obtain the semen sample is through masturbation, and the best place to obtain it is in the same clinic, as this way temperature changes during transport can be avoided, which can be lethal for some spermatozoa. A single semen sample is not determining for disease diagnosis, so two different samples have to be analyzed with an interval between them of seven days to three months, as sperm production is a cyclic process. It is prudent to ask about possible sample loss, as that could mask true results of spermiogram. To obtain the sample, a sterile plastic recipient is put directly inside, always no more than one hour before being studied. Conventional preservatives shouldn't be used, as they have chemical substances as lubricants or spermicides that could damage the sample. If preservatives have to be used, for cases of religious ethics in which masturbation is forbidden, a preservative with holes is used. In case of paraplegia it is possible to use mechanic tools or electroejaculation. The sample should never be obtained through coitus interruptus for several reasons: * Some part of ejaculation could be lost. * Bacterial contamination could happen. * The acid vaginal pH could be deleterious for sperm motility. Also is very important to label the sample correctly the recipient with patient identification, date, hour, abstinence days, among other data required to be known. Main article: Semen analysis Further information: Semen quality The volume of the semen sample, approximate number of total sperm cells, sperm motility/forward progression, and % of sperm with normal morphology are measured. This is the most common type of fertility testing.[37][38] Semen deficiencies are often labeled as follows: * Oligospermia or oligozoospermia – decreased number of spermatozoa in semen * Aspermia – complete lack of semen * Hypospermia – reduced seminal volume * Azoospermia – absence of sperm cells in semen * Teratospermia – increase in sperm with abnormal morphology * Asthenozoospermia – reduced sperm motility * Necrozoospermia – all sperm in the ejaculate are dead * Leucospermia – a high level of white blood cells in semen * Normozoospermia or normospermia – It is a result of semen analysis that shows normal values of all ejaculate parameters by WHO but still there are chances of being infertile. This is also called as unexplained Infertility[citation needed] There are various combinations of these as well, e.g. Teratoasthenozoospermia, which is reduced sperm morphology and motility. Low sperm counts are often associated with decreased sperm motility and increased abnormal morphology, thus the terms "oligoasthenoteratozoospermia" or "oligospermia" can be used as a catch-all. #### Special obtaining[edit] * Psychological inhibition \- Psychotherapy \- Intercourses with special preservatives without lubricants or spermicides. In case of religion limitations we should use a SCD, or Seminal Collection Device, such us preservatives with holes. \- Drug stimulation \- Percutaneous spermatozoa obtaining directly from epididymis, testes, etc. * Neurological injury \- Vibro-stimulation \- Electro-stimulation * Retrograde ejaculation This type of ejaculation happens when there is a defect on prostate, so the sample is not ejaculated outside but to the bladder. So, in that case, what we have to do to obtain the sample is: \- Intake bicarbonate, about 25 grams, the night before and the morning of the sample obtaining. This will neutralize acidic urine and will turn it alkaline, near semen’s pH, so spermatozoa can survive. \- Before masturbation we have to urinate to empty the bladder. This must go to the first recipient. \- Just after that, the subject has to masturbate and ejaculate, obtaining then a new urine sample with ejaculation that will be stored on the second recipient. \- Finally we have to obtain the next urine, 2nd urine, for potential ejaculation fraction, which will be stored in the third recipient. This may contain the most important fraction. ### Blood sample[edit] Common hormonal test include determination of FSH and testosterone levels. A blood sample can reveal genetic causes of infertility, e.g. Klinefelter syndrome, a Y chromosome microdeletion, or cystic fibrosis. ### Ultrasonography[edit] Scrotal ultrasonography is useful when there is a suspicion of some particular diseases. It may detect signs of testicular dysgenesis, which is often related to an impaired spermatogenesis and to a higher risk of testicular cancer.[5] Scrotum ultrasonography may also detect testicular lesions suggestive of malignancy. A decreased testicular vascularization is characteristic of testicular torsion, whereas hyperemia is often observed in epididymo-orchitis or in some malignant conditions such as lymphoma and leukemia.[5] Doppler ultrasonography useful in assessing venous reflux in case of a varicocele, when palpation is unreliable or in detecting recurrence or persistence after surgery, although the impact of its detection and surgical correction on sperm parameters and overall fertility is debated.[5] Dilation of the head or tail of the epididymis is suggestive of obstruction or inflammation of the male reproductive tract.[5] Such abnormalities are associated with abnormalities in sperm parameters, as are abnormalities in the texture of the epididymis.[5] Scrotal and transrectal ultrasonography (TRUS) are useful in detecting uni- or bilateral congenital absence of the vas deferens (CBAVD), which may be associated with abnormalities or agenesis of the epididymis, seminal vesicles or kidneys, and indicate the need for testicular sperm extraction.[5] TRUS plays a key role in assessing azoospermia caused by obstruction, and detecting distal CBAVD or anomalies related to obstruction of the ejaculatory duct, such as abnormalities within the duct itself, a median cyst of the prostate (indicating a need for cyst aspiration), or an impairment of the seminal vesicles to become enlarged or emptied.[5] ## Prevention[edit] Some strategies suggested or proposed for avoiding male infertility include the following: * Avoiding smoking[39] as it damages sperm DNA * Avoiding heavy marijuana and alcohol use.[40] * Avoiding excessive heat to the testes.[40] * Maintaining optimal frequency of coital activity: sperm counts can be depressed by daily coital activity[40] and sperm motility may be depressed by coital activity that takes place too infrequently (abstinence 10–14 days or more).[40] * Wearing a protective cup and jockstrap to protect the testicles, in any sport such as baseball, football, cricket, lacrosse, hockey, softball, paintball, rodeo, motorcross, wrestling, soccer, karate or other martial arts or any sport where a ball, foot, arm, knee or bat can come into contact with the groin. * Diet: Healthy diets (i.e. the Mediterranean diet[41]) rich in such nutrients as omega-3 fatty acids, some antioxidants and vitamins, and low in saturated fatty acids (SFAs) and trans-fatty acids (TFAs) are inversely associated with low semen quality parameters. In terms of food groups, fish, shellfish and seafood, poultry, cereals, vegetables and fruits, and low-fat dairy products have been positively related to sperm quality. However, diets rich in processed meat, soy foods, potatoes, full-fat dairy products, coffee, alcohol and sugar-sweetened beverages and sweets have been inversely associated with the quality of semen in some studies. The few studies relating male nutrient or food intake and fecundability also suggest that diets rich in red meat, processed meat, tea and caffeine are associated with a lower rate of fecundability. This association is only controversial in the case of alcohol. The potential biological mechanisms linking diet with sperm function and fertility are largely unknown and require further study.[42] ## Treatment[43][edit] Treatments vary according to the underlying disease and the degree of the impairment of the male's fertility. Further, in an infertility situation, the fertility of the female needs to be considered. Pre-testicular conditions can often be addressed by medical means or interventions. Testicular-based male infertility tends to be resistant to medication. Usual approaches include using the sperm for intrauterine insemination (IUI), in vitro fertilization (IVF), or IVF with intracytoplasmatic sperm injection (ICSI). With IVF-ICSI even with a few sperm pregnancies can be achieved. Obstructive causes of post-testicular infertility can be overcome with either surgery or IVF-ICSI. Ejaculatory factors may be treatable by medication, or by IUI therapy or IVF. Vitamin E helps counter oxidative stress,[44] which is associated with sperm DNA damage and reduced sperm motility.[45][46] A hormone-antioxidant combination may improve sperm count and motility.[47][46] Giving oral antioxidants to men in couples undergoing in vitro fertilisation for male factor or unexplained subfertility may lead to an increase in the live birth rate but overall the risk of adverse effects is unclear.[48] ### Hormonal therapy[edit] See also: Spermatogenesis § Hormonal control Administration of luteinizing hormone (LH) (or human chorionic gonadotropin) and follicle-stimulating hormone (FSH) is very effective in the treatment of male infertility due to hypogonadotropic hypogonadism.[49] Although controversial,[50] off-label clomiphene citrate, an antiestrogen, may also be effective by elevating gonadotropin levels.[49] Though androgens are absolutely essential for spermatogenesis and therefore male fertility, exogenous testosterone therapy has been found to be ineffective in benefiting men with low sperm count.[51] This is thought to be because very high local levels of testosterone in the testes (concentrations in the seminiferous tubules are 20- to 100-fold greater than circulating levels)[52] are required to mediate spermatogenesis, and exogenous testosterone therapy (which is administered systemically) cannot achieve these required high local concentrations (at least not without extremely supraphysiological dosages).[51] Moreover, exogenous androgen therapy can actually impair or abolish male fertility by suppressing gonadotropin secretion from the pituitary gland, as seen in users of androgens/anabolic steroids (who often have partially or completely suppressed sperm production).[49][51] This is because suppression of gonadotropin levels results in decreased testicular androgen production (causing diminished local concentrations in the testes)[49][51] and because FSH is independently critical for spermatogenesis.[53][54] In contrast to FSH, LH has little role in male fertility outside of inducing gonadal testosterone production.[55] Estrogen, at some concentration, has been found to be essential for male fertility/spermatogenesis.[56][57] However, estrogen levels that are too high can impair male fertility by suppressing gonadotropin secretion and thereby diminishing intratesticular androgen levels.[51] As such, clomiphene citrate (an antiestrogen) and aromatase inhibitors such as testolactone or anastrozole have shown effectiveness in benefiting spermatogenesis.[51] Low-dose estrogen and testosterone combination therapy may improve sperm count and motility in some men,[58] including in men with severe oligospermia.[59] ## Future potential treatments[edit] Researchers at Münster University developed in vitro culture conditions using a three-dimensional agar culture system which induces mouse testicular germ cells to reach the final stages of spermatogenesis, including spermatozoa generation.[60] If reproduced in humans, this could potentially enable infertile men to father children with their own sperm.[61][62] Researchers from Montana State University developed precursors of sperm from skin cells of infertile men.[63][64][65] Sharpe et al. comment on the success of intracytoplasmic sperm injection (ICSI) in women saying, "[t]hus, the woman carries the treatment burden for male infertility, a fairly unique scenario in medical practice. Ironically, ICSI's success has effectively diverted attention from identifying what causes male infertility and focused research onto the female, to optimize the provision of eggs and a receptive endometrium, on which ICSI's success depends."[66][67] ## Global trends[edit] Currently, there are no solid numbers on how many couples worldwide experience infertility, but the World Health Organization estimates between 60 and 80 million couples are affected. The population in different regions suffer from varying amounts of infertility. Starting in the late 20th century, scientists have expressed concerns about the declining semen quality in men. A study was done in 1992 with men who had never suffered from infertility showed that the amount of sperm in semen had declined by 1% per year since 1938.[68][69] Further research a few years later also confirmed the decline in sperm count and also seminal volume.[70] Various studies in Finland, Southern Tunisia, and Argentina also showed a decline in sperm count, motility, morphology, and seminal volume. Males from India suffered a 30.3% decline in sperm count, 22.9% decline in sperm motility, and a 51% decrease in morphology over a span of a decade. Doctors in India disclosed that the sperm count of a fertile Indian male had decreased by a third over a span of three decades.[71] Some factors may include exposure to high temperatures at places such as factories. A 1 degree increase in temperature will reduce 14% of spermatogenesis.[72] Researchers in Calcutta conducted a study between 1981 and 1985 that also showed a decrease in sperm motility and seminal volume, but no change in sperm concentration.[73] ## Society and culture[edit] There are a variety of social stigmas that surround male infertility throughout the world. A lot of research has pointed to the relationship between infertility and emasculation.[74][75][76] In places like Egypt,[75] Zimbabwe,[74] and Mexico,[77] erectile dysfunction also known as impotence, is considered a determinant of infertility. When stereotypical ideals of manhood are virility and strength, men sharing problems of infertility can face feelings of inadequacy, unworthiness, and have thoughts of suicide.[78] In many cases, a variety of socio-economic interventions come in play to determine penile activity. For the Shona people, since impotence is linked to infertility, an examination to check on the penile function spans from infancy to post marriage.[74] At infancy, there are daily check-ups by the mothers on the son's erection and urine quality.[74] When the son reaches puberty, they are asked to ejaculate in river banks and for their male elders to examine sperm quality.[74] The traditions last until post-marriage, when the family of the bride take part to check on consummation and the groom's sperm quality.[74] ## See also[edit] * Female infertility * Fertility preservation * Fertility testing * Infertility * Male accessory gland infection (MAGI) * Meiosis * Oncofertility * Paternal age effect * Spermatogenesis ## References[edit] 1. ^ Leslie, Stephen W.; Siref, Larry E.; Khan, Moien AB (2020), "Male Infertility", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 32965929, retrieved 2020-11-26 2. ^ "Men's Health - Male Factor Infertility". 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ESHRE Monographs. 2008 (1): 34–41. doi:10.1093/humrep/den143. ISSN 1477-741X. 77. ^ Inhorn, Marcia C.; Wentzell, Emily A. (November 2011). "Embodying emergent masculinities: Men engaging with reproductive and sexual health technologies in the Middle East and Mexico". American Ethnologist. 38 (4): 801–815. doi:10.1111/j.1548-1425.2011.01338.x. ISSN 0094-0496. 78. ^ Smith, James F.; Walsh, Thomas J.; Shindel, Alan W.; Turek, Paul J.; Wing, Holly; Pasch, Lauri; Katz, Patricia P. (September 2009). "Sexual, Marital, and Social Impact of a Man's Perceived Infertility Diagnosis". The Journal of Sexual Medicine. 6 (9): 2505–2515. doi:10.1111/j.1743-6109.2009.01383.x. ISSN 1743-6095. PMC 2888139. PMID 19619144. ## External links[edit] Classification D * ICD-10: N46 * ICD-9-CM: 606 * MeSH: D007248 * DiseasesDB: 7772 External resources * MedlinePlus: 001191 * eMedicine: med/3535 med/1167 * Patient UK: Male infertility * v * t * e Male diseases of the pelvis and genitals Internal Testicular * Orchitis * Hydrocele testis * Testicular cancer * Testicular torsion * Male infertility * Aspermia * Asthenozoospermia * Azoospermia * Hyperspermia * Hypospermia * Oligospermia * Necrospermia * Teratospermia Epididymis * Epididymitis * Spermatocele * Hematocele Prostate * Prostatitis * Acute prostatitis * Chronic bacterial prostatitis * Chronic prostatitis/chronic pelvic pain syndrome * Asymptomatic inflammatory prostatitis * Benign prostatic hyperplasia * Prostate cancer Seminal vesicle * Seminal vesiculitis External Penis * Balanoposthitis / Balanitis * Balanitis plasmacellularis * Pseudoepitheliomatous keratotic and micaceous balanitis * Phimosis * Paraphimosis * Priapism * Sexual dysfunction * Erectile dysfunction * Peyronie's disease * Penile cancer * Penile fracture * Balanitis xerotica obliterans Other * Hematospermia * Retrograde ejaculation * Postorgasmic illness syndrome * v * t * e Assisted reproductive technology Infertility * Female * Male * Fertility clinic * Fertility testing * Fertility tourism * Male infertility crisis Fertility medication * Estrogen antagonists * aromatase inhibitor * clomifene * FSH * GnRH agonists * Gonadotropins * menotropins * hCG In vitro fertilisation (IVF) and expansions * Assisted zona hatching * Autologous endometrial coculture * Cytoplasmic transfer * Embryo transfer * Gestational carrier * In vitro maturation * Intracytoplasmic sperm injection * Oocyte selection * Ovarian hyperstimulation * Preimplantation genetic diagnosis * Transvaginal ovum retrieval * Zygote intrafallopian transfer Other methods * Artificial insemination * Ovulation induction * Cryopreservation * embryos * oocyte * ovarian tissue * semen * Gamete intrafallopian transfer * Reproductive surgery * Vasectomy reversal * Selective reduction * Sex selection * Surrogacy Donation * Donor registration * Donor Sibling Registry * Egg donation * Embryo * Sperm * Semen collection * Sperm bank * Ova bank Ethics * Accidental incest * Genetic diagnosis of intersex * Religious response to ART * Mitochondrial donation * Sex selection In fiction * See subsection in sperm donation * Reproduction and pregnancy in speculative fiction [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Male infertility	c0021364	5,382	wikipedia	https://en.wikipedia.org/wiki/Male_infertility	2021-01-18T18:37:28	{"mesh": ["D007248"], "umls": ["C0021364"], "wikidata": ["Q280156"]}
A rare multiple congenital anomalies syndrome characterized by cutaneous mastocytosis, microcephaly, microtia and/or hearing loss, hypotonia and skeletal anomalies (e.g. clinodactyly, camptodactyly, scoliosis). Additional common features are short stature, intellectual disability and difficulties. Facial dysmorphism may include upslanted palpebral fissures, highly arched palate and micrognathia. Rarely, seizures and asymmetrically small feet have 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	Hennekam-Beemer syndrome	c3151493	5,383	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2135	2021-01-23T18:14:16	{"gard": ["3409"], "omim": ["248910"], "icd-10": ["Q82.2"], "synonyms": ["Mastocytosis-short stature-deafness syndrome", "Mastocytosis-short stature-hearing loss syndrome"]}
Blister containing purulent fluid For other uses, see Pimple (disambiguation). Pimple Other namesZit, spot A pimple (center) evolved into the pustule stage SpecialtyDermatology A pimple is a kind of comedo that results from excess sebum and dead skin cells getting trapped in the pores of the skin. In its aggravated state, it may evolve into a pustule or papules.[1] Pimples can be treated by acne medications, antibiotics, and anti-inflammatories prescribed by a physician, or various over the counter remedies purchased at a pharmacy. ## Contents * 1 Causes * 2 Treatment * 2.1 Over-the-counter medications * 2.2 Prescription medication * 2.3 Expression * 3 References * 4 External links ## Causes Sebaceous glands inside the pore of the skin produce sebum. When the outer layers of skin shed (a natural and continuous process, normally), dead skin and oily sebum left behind may bond together and form a blockage of the sebaceous gland at the base of the skin. This is most common when the skin becomes thicker at puberty.[2] The sebaceous gland continues to produce sebum, which builds up behind the blockage, allowing bacteria to grow in the area, including the species Staphylococcus aureus and Cutibacterium acnes, which causes inflammation and infection. Other causes of pimples include family history, stress, fluctuations in hormone levels, hair and skincare products, medication side effects, and un-diagnosed or underlying medical conditions.[3] Pimples can be part of the presentation of rosacea.[4] The American Academy of Dermatology recommends that adults with acne use products labeled as "non-comedogenic", "non-acnegenic", "oil-free" or "won’t clog pores", as they are "least likely" to cause skin irritation or acne.[3] * Sebaceous filaments are commonly mistaken for blackheads. Sebaceous Filaments, however, are completely harmless and are a natural part of the skin for people with oily skin.[5] * Some more severe pimples can lead to significant swelling and may appear on the back and chest. ## Treatment See also: Acne vulgaris § Management ### Over-the-counter medications Common over-the-counter medications for pimples are benzoyl peroxide, salicylic acid, adapalene, and antibacterial agents such as triclosan. These topical medications, which can be found in many creams and gels used to treat acne (acne vulgaris), induce skin to slough off more easily, helping to remove bacteria faster. Before application, the face should be washed with warm water or a topical cleanser and then dried. A regimen of keeping the affected skin area clean plus the regular application of these topical medications is usually enough to keep acne under control, if not at bay altogether. The most common product is a topical treatment of benzoyl peroxide, which has minimal risk apart from minor skin irritation that may present similar as a mild allergy.[6] Recently nicotinamide (vitamin B3), applied topically, has been shown to be more effective in treatment of pimples than antibiotics such as clindamycin.[7] Nicotinamide is not an antibiotic and has no side effects typically associated with antibiotics. It has the added advantage of reducing skin hyperpigmentation which results in pimple scars.[8] An emerging treatment for pimples is toothpaste, which contains anti-microbial agents that are associated with reducing pimples.[9] ### Prescription medication Severe acne usually indicates the necessity of prescription medication to treat the pimples. Prescription medications used to treat acne and pimples include isotretinoin, which is a retinoid, anti-seborrheic medications, anti-androgen medications, hormonal treatments, alpha hydroxy acid, azelaic acid, and keratolytic soaps.[10] Historically, antibiotics such as tetracyclines and erythromycin were prescribed. While they were more effective than topical applications of benzoyl peroxide, the bacteria eventually grew resistant to the antibiotics and the treatments became less and less effective. Also, antibiotics had more side effects than topical applications, such as stomach cramps and severe discoloration of teeth. Common antibiotics prescribed as of 2001 by dermatologists included doxycycline and minocycline.[11] Isotretinoin is used primarily for severe cystic acne and acne that has not responded to other treatments.[12][13][14][15] Many dermatologists also support its use for treatment of lesser degrees of acne that prove resistant to other treatments, or that produce physical or psychological scarring.[16] It is teratogenic, and requires strict prevention of pregnancy during its use. ### Expression Expression, the manual bursting of pimples which have evolved into whiteheads with one's fingers, can allow bacteria to be introduced into the open wound this creates. This can result in infection and permanent scarring. Thus expression is generally recommended against by dermatologists and estheticians in favour of allowing pimples to run through their natural lifespans.[17][18][19][20][21] Some dermatologists offer incision and drainage services to sterilely drain the pimple.[22] ## References 1. ^ "pimple" at Dorland's Medical Dictionary 2. ^ Anderson, Laurence. 2006. Looking Good, the Australian guide to skin care, cosmetic medicine and cosmetic surgery. AMPCo. Sydney. ISBN 0-85557-044-X. 3. ^ a b "Adult acne! American Academy of Dermatology". www.aad.org. Retrieved 1 August 2019. 4. ^ Tüzün Y, Wolf R, Kutlubay Z, Karakuş O, Engin B (2014). "Rosacea and rhinophyma". Clinics in Dermatology. 32 (1): 35–46. doi:10.1016/j.clindermatol.2013.05.024. PMID 24314376. 5. ^ Plewig, Gerd; Melnik, Bodo; WenChieh, Chen (8 June 2019). Plewig and Kligman's Acne and Rosacea. Springer. p. 64. ISBN 978-3-319-49274-2. 6. ^ "Understanding Benzoyl Peroxide". Archived from the original on 23 February 2012. 7. ^ Siegle RJ, Fekety R, Sarbone PD, Finch RN, Deery HG, Voorhees JJ (August 1986). "Effects of topical clindamycin on intestinal microflora in patients with acne". Journal of the American Academy of Dermatology. 15 (2 Pt 1): 180–5. doi:10.1016/S0190-9622(86)70153-9. PMID 2943760. 8. ^ Handfield-Jones S, Jones S, Peachey R (May 1988). "High dose nicotinamide in the treatment of necrobiosis lipoidica". The British Journal of Dermatology. 118 (5): 693–6. doi:10.1111/j.1365-2133.1988.tb02572.x. PMID 2969260. 9. ^ Dharmik, Preeti; Gomashe, Ashok (June 2014). "Anti-Acne Activity of Toothpaste An Emerging Pimple Treatment". International Journal of Chemical and Pharmaceutical Analysis. 1 (4): 149–53. doi:10.21276/ijcpa. 10. ^ Ramos-e-Silva M, Carneiro SC (March 2009). "Acne vulgaris: review and guidelines". Dermatology Nursing. 21 (2): 63–8, quiz 69. PMID 19507372. 11. ^ Morrison A, O'Loughlin S, Powell FC (February 2001). "Suspected skin malignancy: a comparison of diagnoses of family practitioners and dermatologists in 493 patients". International Journal of Dermatology. 40 (2): 104–7. doi:10.1046/j.1365-4362.2001.01159.x. PMID 11328390. 12. ^ Merritt B, Burkhart CN, Morrell DS (June 2009). "Use of isotretinoin for acne vulgaris". Pediatric Annals. 38 (6): 311–20. doi:10.3928/00904481-20090512-01. PMID 19588674. 13. ^ Layton A (May 2009). "The use of isotretinoin in acne". Dermato-Endocrinology. 1 (3): 162–9. doi:10.4161/derm.1.3.9364. PMC 2835909. PMID 20436884. 14. ^ "Roaccutane 20mg Soft Capsules - Summary of Product Characteristics". UK Electronic Medicines Compendium. 1 July 2015. 15. ^ US Label (PDF) (Report). FDA. 22 October 2010 [January 2010]. Retrieved 1 June 2017. See FDA Index page for NDA 018662 for updates 16. ^ Strauss JS, Krowchuk DP, Leyden JJ, Lucky AW, Shalita AR, Siegfried EC, Thiboutot DM, Van Voorhees AS, Beutner KA, Sieck CK, Bhushan R (April 2007). "Guidelines of care for acne vulgaris management". Journal of the American Academy of Dermatology. 56 (4): 651–63. doi:10.1016/j.jaad.2006.08.048. PMID 17276540. 17. ^ "What to Know Before You Pop a Pimple". WebMD. Retrieved 3 April 2017. 18. ^ "The 10 Most Satisfying Pimple Popping Videos Of 2016". Men's Health. 29 December 2016. Retrieved 3 April 2017. 19. ^ "Should I Pop My Pimple?". kidshealth.org. Retrieved 3 April 2017. 20. ^ Merlin, Design: Wolfgang (www.1-2-3-4.info)/Modified. "A14. What should I do after popping a pimple?Skinacea.com". www.skinacea.com. Retrieved 3 April 2017. 21. ^ "How to Pop a Pimple - Instructions from Acne.org". www.acne.org. Retrieved 3 April 2017. 22. ^ "Pimple popping: Why only a dermatologist should do it \| American Academy of Dermatology". www.aad.org. Retrieved 3 August 2019. ## External links Listen to this article (1.6 megabytes) This audio file was created from a revision of this article dated 26 April 2010 (2010-04-26), and does not reflect subsequent edits. (Audio help · More spoken articles) * The dictionary definition of pimple at Wiktionary Classification D * ICD-10: R23.8 * ICD-9-CM: 709.8 * v * t * e Bacterial skin disease Gram +ve Firmicutes * Staphylococcus * Staphylococcal scalded skin syndrome * Impetigo * Toxic shock syndrome * Streptococcus * Impetigo * Cutaneous group B streptococcal infection * Streptococcal intertrigo * Cutaneous Streptococcus iniae infection * Erysipelas / Chronic recurrent erysipelas * Scarlet fever * Corynebacterium * Erythrasma * Listeriosis * Clostridium * Gas gangrene * Dermatitis gangrenosa * Mycoplasma * Erysipeloid of Rosenbach Actinobacteria * Mycobacterium-related: Aquarium granuloma * Borderline lepromatous leprosy * Borderline leprosy * Borderline tuberculoid leprosy * Buruli ulcer * Erythema induratum * Histoid leprosy * Lepromatous leprosy * Leprosy * Lichen scrofulosorum * Lupus vulgaris * Miliary tuberculosis * Mycobacterium avium-intracellulare complex infection * Mycobacterium haemophilum infection * Mycobacterium kansasii infection * Papulonecrotic tuberculid * Primary inoculation tuberculosis * Rapid growing mycobacterium infection * Scrofuloderma * Tuberculosis cutis orificialis * Tuberculosis verrucosa cutis * Tuberculous cellulitis * Tuberculous gumma * Tuberculoid leprosy * Cutaneous actinomycosis * Nocardiosis * Cutaneous diphtheria infection * Arcanobacterium haemolyticum infection * Group JK corynebacterium sepsis Gram -ve Proteobacteria * α: Endemic typhus * Epidemic typhus * Scrub typhus * North Asian tick typhus * Queensland tick typhus * Flying squirrel typhus * Trench fever * Bacillary angiomatosis * African tick bite fever * American tick bite fever * Rickettsia aeschlimannii infection * Rickettsialpox * Rocky Mountain spotted fever * Human granulocytotropic anaplasmosis * Human monocytotropic ehrlichiosis * Flea-borne spotted fever * Japanese spotted fever * Mediterranean spotted fever * Flinders Island spotted fever * Verruga peruana * Brill–Zinsser disease * Brucellosis * Cat-scratch disease * Oroya fever * Ehrlichiosis ewingii infection * β: Gonococcemia/Gonorrhea/Primary gonococcal dermatitis * Melioidosis * Cutaneous Pasteurella hemolytica infection * Meningococcemia * Glanders * Chromobacteriosis infection * γ: Pasteurellosis * Tularemia * Vibrio vulnificus * Rhinoscleroma * Haemophilus influenzae cellulitis * Pseudomonal pyoderma / Pseudomonas hot-foot syndrome / Hot tub folliculitis / Ecthyma gangrenosum / Green nail syndrome * Q fever * Salmonellosis * Shigellosis * Plague * Granuloma inguinale * Chancroid * Aeromonas infection * ε: Helicobacter cellulitis Other * Syphilid * Syphilis * Chancre * Yaws * Pinta * Bejel * Chlamydia infection * Leptospirosis * Rat-bite fever * Lyme disease * Lymphogranuloma venereum Unspecified pathogen * Abscess * Periapical abscess * Boil/furuncle * Hospital furunculosis * Carbuncle * Cellulitis * Paronychia / Pyogenic paronychia * Perianal cellulitis * Acute lymphadenitis * Pilonidal cyst * Pyoderma * Folliculitis * Superficial pustular folliculitis * Sycosis vulgaris * Pimple * Ecthyma * Pitted keratolysis * Trichomycosis axillaris * Necrotizing fascitis * Gangrene * Chronic undermining burrowing ulcers * Fournier gangrene * Elephantiasis nostras * Blistering distal dactylitis * Botryomycosis * Malakoplakia * Gram-negative folliculitis * Gram-negative toe web infection * Pyomyositis * Blastomycosis-like pyoderma * Bullous impetigo * Chronic lymphangitis * Recurrent toxin-mediated perineal erythema * Tick-borne lymphadenopathy * Tropical ulcer * v * t * e Symptoms and signs relating to skin and subcutaneous tissue Disturbances of skin sensation * Hypoesthesia * Paresthesia * Formication * Hyperesthesia * Hypoalgesia * Hyperalgesia Circulation * Cyanosis * Pallor * Livedo * Livedo reticularis * Flushing * Petechia * Blanching Edema * Peripheral edema * Anasarca Other * Rash * Desquamation * Induration * Diaphoresis * Mass * Neck mass Skin * Asboe-Hansen sign * Auspitz's sign * Borsari's sign * Braverman's sign * Crowe sign * Dennie–Morgan fold * Darier's sign * Fitzpatrick's sign * Florid cutaneous papillomatosis * Gottron's sign * Hutchinson's sign * Janeway lesion * Kerr's sign * Koebner's phenomenon * Koplik's spots * Leser-Trelat sign * Nikolsky's sign * Pastia's sign * Russell's sign * Wickham striae * Wolf's isotopic response * Munro's microabscess Nails * Aldrich-Mees' lines * Beau's lines * Muehrcke's lines * Terry's nails [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Pimple	c0241157	5,384	wikipedia	https://en.wikipedia.org/wiki/Pimple	2021-01-18T18:36:12	{"umls": ["C0241157"], "icd-9": ["709.8709.8"], "icd-10": ["R23.823.8"], "wikidata": ["Q1172159"]}
Condition of having an additional breast Accessory breast A woman with several accessory breasts Pronunciation * no information SpecialtyMedical genetics Accessory breasts, also known as polymastia, supernumerary breasts, or mammae erraticae, is the condition of having an additional breast. Extra breasts may appear with or without nipples or areolae. It is a condition and a form of atavism which is most prevalent in male humans, and often goes untreated as it is mostly harmless. In recent years, many affected women have had a plastic surgery operation to remove the additional breasts, for purely aesthetic reasons. A related condition, in which extra nipples form, is called "supernumerary nipple" or "polythelia". ## Contents * 1 Presentation * 2 Cause * 3 See also * 4 References * 5 External links ## Presentation[edit] In some cases, the accessory breast may not be visible at the surface. In these cases, it may be possible to distinguish their appearance from normal breast tissue with MRI.[1] In other cases, accessory breasts have been known to lactate, as illustrated in a woodcut showing a child nursing at ectopic breast tissue on the lateral thigh.[2] There is some evidence that the condition may be more common in Native American populations.[3] ## Cause[edit] Polymastia typically occurs in the womb during the development. During normal development, breast tissue will develop along the milk line, and additional tissue will disintegrate and be absorbed into the body. Polymastia occurs when the additional tissue doesn’t disintegrate before birth. This condition can be inherited and run in families. ## See also[edit] * Artemis § As the Lady of Ephesus (fertility goddess with many breasts) * Fleischer's syndrome ## References[edit] 1. ^ Laor T, Collins MH, Emery KH, Donnelly LF, Bove KE, Ballard ET (2004). "MRI appearance of accessory breast tissue: a diagnostic consideration for an axillary mass in a peripubertal or pubertal girl". AJR Am J Roentgenol. 183 (6): 1779–81. doi:10.2214/ajr.183.6.01831779. PMID 15547228. 2. ^ Grossl, Norman A. (2000). "Supernumerary Breast Tissue". Southern Medical Journal. 93: 29–32. doi:10.1097/00007611-200093010-00005. Retrieved Dec 30, 2008. 3. ^ Emsen IM (2006). "Treatment with ultrasound-assisted liposuction of accessory axillary breast tissues". Aesthetic Plast Surg. 30 (2): 251–2. doi:10.1007/s00266-005-0160-7. PMID 16547633. S2CID 21813839. * A Paper on the Appearance of Multiple Mammaries in Humans, R. Eghardt, Oxford University Press (1923) * Weird Diseases, B. Hargreaves and M. Wallette, Emu Publishing (2007) ## External links[edit] Classification D * ICD-10: Q83.1 * ICD-9-CM: 757.6 * OMIM: 163700 External resources * eMedicine: derm/735 * v * t * e Congenital malformations and deformations of the breast Breast * Amastia * Polymastia * Micromastia * Symmastia Nipple * Athelia * Polythelia Authority control * TA98: A16.0.02.003 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Accessory breast	c0266010	5,385	wikipedia	https://en.wikipedia.org/wiki/Accessory_breast	2021-01-18T18:56:25	{"umls": ["C0266010"], "icd-9": ["757.6"], "icd-10": ["Q83.1"], "orphanet": ["180182"], "wikidata": ["Q2701591"]}
A rare otorhinolaryngological malformation characterized by recurrent infections, swelling, pain, discharge and abscess formation in the defect area. The anomaly results from incomplete fusion of the ventral part of the first and second branchial arch, presenting as either a fistula, sinus or cyst occurring anywhere between the external auditory canal and the mandibular angle, including parotid gland. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	First branchial cleft anomaly	c3874320	5,386	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141013	2021-01-23T18:20:36	{"icd-10": ["Q18.0"], "synonyms": ["First branchial cleft cyst", "First branchial cleft fistula"]}
A number sign (#) is used with this entry because of evidence that familial hypertrophic cardiomyopathy-27 (CMH27) is caused by homozygous mutation in the ALPK3 gene (617608) on chromosome 15q25. Description CMH27 is a severe, early-onset cardiomyopathy with morphologic features of both dilated and hypertrophic disease, characterized by biventricular involvement and atypical distribution of hypertrophy. Heterozygotes are at increased risk of developing cardiomyopathy (Almomani et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of hypertrophic cardiomyopathy, see CMH1 (192600). An oligogenic form of hypertrophic cardiomyopathy, involving heterozygous mutations in the ALPK3, TTN (188840), and MYL3 (160790) genes has also been reported in 1 family. Clinical Features Almomani et al. (2016) studied 3 families with pediatric cardiomyopathy. The proband in family A, a male infant born of Dutch parents who were sixth-degree cousins, had severe left ventricular dilation with markedly reduced contractility of both ventricles, and mitral and tricuspid regurgitation, and he died of progressive heart failure at 5 days. Postmortem examination showed severe cardiomegaly with biventricular dilation; microscopically, there was subendocardial fibroelastosis without fatty replacement in both ventricles, fragmented elastin fibers, and myxoid degeneration of the stroma. Immunohistochemistry showed absence of the desmosomal proteins plakoglobin (JUP; 173325) and desmoplakin (DSP; 125647) at intercalated discs. In family B, there were 3 affected sibs born of first-cousin Moroccan parents. The first affected sib died in utero with generalized hydrops fetalis and cardiomegaly with reduced contractility. In the second affected sib, prenatal ultrasound at 20 and 26 weeks showed an enlarged heart with reduced contractility, thickened myocardium with spongy appearance, and tricuspid regurgitation; by 30 weeks, marked hydrops fetalis had developed, and the female infant died 2 hours after birth with severe cardiac hypertrophy and biventricular dilation. Postmortem microscopic examination revealed focal hypertrophy of cardiomyocytes and extensive subendocardial fibroelastosis without fatty infiltration, but no myocyte disarray. The third affected sib had an unaffected dizygotic twin sister; neither twin showed abnormalities on prenatal ultrasound, but echocardiography 4 days after birth revealed severe concentric cardiac hypertrophy in 1 of the twins. Her disease remained stable, and examination at age 10 years showed increased thickness of the interventricular septum and left ventricular posterior wall with biventricular diastolic dysfunction; there were repolarization abnormalities, but no ventricular arrhythmias. In family C, the proband was a boy born of consanguineous Turkish parents, who was diagnosed with severe hypertrophic cardiomyopathy (CMH) at age 4 years, with subsequent slow disease progression. At age 7, he underwent cardiac arrest and received an implantable cardioverter-defibrillator (ICD), after which experienced several appropriate ICD shocks. Examination at age 11 years showed severe concentric left ventricular hypertrophy, moderate right ventricular hypertrophy, and repolarization abnormalities. His father and a paternal uncle were diagnosed with CMH at 27 and 29 years of age; imaging showed concentric left ventricular hypertrophy with septal involvement and right ventricular hypertrophy. His asymptomatic mother underwent echocardiographic screening that showed no abnormalities. Phelan et al. (2016) reported affected first cousins from a consanguineous Pakistani pedigree who presented in infancy with left ventricular dilation that progressed over a period of months to CMH. Electrocardiography in the female proband showed a prolonged QT interval, inferolateral ST depression, biatrial enlargement, and large ventricular voltages, consistent with left ventricular hypertrophy. Echocardiography and cardiac MRI demonstrated hypertrophic cardiomyopathy with thickening of the left ventricular free wall and interventricular septum; there was no evidence of left ventricular noncompaction or fibrosis. She underwent placement of an ICD at 18 years of age. Both affected individuals also exhibited multiple pterygia with skeletal muscle underdevelopment. The authors noted that the patients described by Almomani et al. (2016) who died before age 5 days displayed predominantly dilated cardiomyopathy (CMD) or a mixed CMD/CMH phenotype, whereas the patients who lived beyond the first decade of life had severe CMH. Caglayan et al. (2017) described a 2.5-year-old Turkish boy who was diagnosed in utero with dilated cardiomyopathy, which progressed to hypertrophic cardiomyopathy after birth. He also exhibited mild facial dysmorphism, with low-set ears and high-arched palate. His asymptomatic parents, who were not known to be consanguineous but came from the same small village, had normal echocardiogram results. In a previous pregnancy, a male fetus had died at 30 weeks' gestation due to cardiac abnormalities. Mapping In 2 families with pediatric cardiomyopathy (families A and B), Almomani et al. (2016) performed homozygosity mapping and identified a 3.1-Mb region of homozygosity at chromosome 15q25 that overlapped between the affected individuals in both families. In a consanguineous Pakistani pedigree with pediatric cardiomyopathy that initially presented as CMD but progressed to CMH, Phelan et al. (2016) performed linkage analysis and identified a single linkage region that approached genomewide significance (lod = 2.9) at chromosome 15q25.1-q26.1. Molecular Genetics By exome sequencing in 2 unrelated families with severe early-onset cardiomyopathy mapping to chromosome 15q25, Almomani et al. (2016) identified homozygosity for mutations in the ALPK3 gene that segregated with disease: a nonsense mutation (R1261X; 617608.0001) in 3 affected sibs from a Moroccan family (family B), and a splice site mutation (617608.0002) in a Dutch proband (family A). Analysis of 46 known cardiomyopathy-related genes revealed no other pathogenic variants in the Moroccan family. Sanger sequencing of the ALPK3 gene in a cohort of 60 probands with childhood-onset CMH or dilated cardiomyopathy (CMD) revealed a Turkish boy (family C) with CMH who was homozygous for a nonsense mutation (W1765X; 617608.0003). His father and a paternal uncle, who both developed CMH in the third decade of life and were negative for mutation in 48 known cardiomyopathy genes, were heterozygous for the W1765X mutation in ALPK3; his unaffected mother was also heterozygous for W1765X. The authors suggested that ALPK3 mutations carriers have an increased risk of developing cardiomyopathy and that periodic screening should be considered. In the proband from a Pakistani pedigree with CMH mapping to chromosome 15q25.1-q26.1, Phelan et al. (2016) performed whole-exome sequencing and identified homozygosity for a nonsense mutation in the ALPK3 gene (W1264X; 617608.0004). Sanger sequencing confirmed that the mutation was homozygous in both affected cousins and heterozygous in their parents. The mutation was not found in more than 200 in-house exomes or in public variant databases. The affected individuals, who presented in infancy with CMD that progressed over a period of months to CMH, also exhibited congenital pterygia. The authors suggested the pterygia might have resulted from impaired skeletal muscle development or function, thus potentially expanding the ALPK3-associated phenotype. In a Turkish boy who was diagnosed in utero with CMD, which progressed CMH after birth, Caglayan et al. (2017) performed whole-exome sequencing and identified homozygosity for a 1-bp deletion (c.2018delC) in the ALPK3 gene, for which his unaffected parents were heterozygous. The authors noted that homozygous variants segregating with disease also were detected in 6 additional genes. ### Oligogenicity In a mother and 2 children, diagnosed with CMH in the fifth to seventh decades of life, Li et al. (2017) performed whole-exome sequencing and found shared heterozygosity for 145 pathogenic variants in 139 genes, including 2 cardiomyopathy-associated genes, TTN (188840) and ALPK3 (617608). In contrast to their mother's mild phenotype, the sibs had a severe CMH phenotype with left ventricular outflow obstruction; they also shared heterozygosity for the pathogenic MYL2 variant A13T (160781.0001), which was not present in their mother. Their father, who carried only the MYL2 variant, had mild left ventricular hypertrophy attributed to severe aortic stenosis, with postoperative resolution of symptoms after valve replacement and single-vessel coronary artery bypass surgery. One of the sibs had an asymptomatic 7-year-old son who also carried all 3 variants, but had normal electrocardiography and echocardiography. The authors suggested that a subset of CMH might be oligogenic, caused by multiple pathogenic variants that do not perfectly cosegregate with the phenotype. INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Cardiomegaly \- Biventricular dilation \- Biatrial enlargement \- Mitral regurgitation \- Tricuspid regurgitation \- Reduced ventricular contractility \- Concentric hypertrophy \- Septal hypertrophy \- Repolarization abnormalities \- Prolonged QT interval \- Thickened myocardium \- Spongy appearance of myocardium \- Subendocardial fibroelastosis \- Fragmented elastin fibers \- Myxoid degeneration of stroma \- Focal hypertrophy of cardiomyocytes \- Sarcomere disorganization \- Unstructured intercalated discs \- Prolonged field potential intervals \- Increased irregular Ca(2+) transients PRENATAL MANIFESTATIONS \- Hydrops fetalis MISCELLANEOUS \- Death in utero or shortly after birth (in some patients) \- An initial phenotype of dilated cardiomyopathy may progress to a hypertrophic phenotype (in some patients) \- Patients are at risk for potentially fatal ventricular arrhythmias \- Heterozygotes are at increased risk for developing later-onset hypertrophic cardiomyopathy MOLECULAR BASIS \- Caused by mutation in the alpha kinase-3 gene (ALPK3, 617608.0001 ) ▲ 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	CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC 27	None	5,387	omim	https://www.omim.org/entry/618052	2019-09-22T15:43:51	{"omim": ["618052"]}
Short head due to premature fusion of the coronal sutures For brachycephalic animal breeds, see Cephalic index in animal breeding. For the condition in animals, see Brachycephalic airway obstructive syndrome. Brachycephaly Other namesBrachyceplalic Brachicephaly and dolichocephaly SpecialtyMedical genetics Brachycephaly (derived from the Ancient Greek βραχύς, "short" and κεφαλή, "head") is the shape of a skull shorter than typical for its species. It is perceived as a desirable trait in some domesticated dog and cat breeds, notably the pug and Persian, and can be normal or abnormal in other animal species. In humans, the cephalic disorder is known as flat head syndrome, and results from premature fusion of the coronal sutures, or from external deformation. The coronal suture is the fibrous joint that unites the frontal bone with the two parietal bones of the skull. The parietal bones form the top and sides of the skull. This feature can be seen in Down syndrome. In anthropology, human populations have been characterized as either dolichocephalic (long headed), mesaticephalic (moderate headed), or brachycephalic (short headed). The usefulness of the cephalic index was questioned by Giuseppe Sergi, who argued that cranial morphology provided a better means to model racial ancestry.[1] There are also cases of brachycephaly associated with plagiocephaly. Brachycephaly with plagiocephaly is positional and has become more prevalent since the "Back to Sleep" campaign. The Back to Sleep campaign began in 1994 as a way to educate parents about ways to reduce the risk for sudden infant death syndrome (SIDS). The campaign was named for its recommendation to place healthy babies on their backs to sleep. Placing babies on their backs to sleep reduces the risk for SIDS, also known as "cot death" or "crib death." This campaign has been successful in promoting infant back sleeping and other risk-reduction strategies to parents, family members, child care providers, health professionals, and all other caregivers of infants, at a cost of increasing the incidence of this deformation of the head.[2] It is considered a cosmetic problem.[3][4] Many pediatricians remain unaware of the issue and possible treatments. Treatments include regular prone repositioning of babies ("tummy time").[5] Brachycephaly also describes a developmentally normal type of skull with a high cephalic index, such as in snub-nosed breeds of dog such as pugs, Shih Tzus, and bulldogs or cats such as the Persian, Exotic and Himalayan. The term is from Greek roots meaning "short" and "head".[6] ## Contents * 1 Diagnosis * 2 Treatment * 3 See also * 4 References * 5 External links ## Diagnosis[edit] This section is empty. You can help by adding to it. (December 2017) ## Treatment[edit] Brachycephaly can be corrected with a cranial remolding orthoses (helmet) which provide painless total contact over the prominent areas of the skull and leave voids over the flattened areas to provide a pathway for more symmetrical skull growth. Treatment generally takes 3–4 months, but varies depending on the infant's age and severity of the cranial asymmetry. However studies by scientists in the Netherlands have found there was no significant difference over time between infants treated with helmets and infants left untreated. All parents of infants treated with helmets confirmed negative side effects including skin irritation and sweating.[7][8] This study focused only on patients with mild to moderate cases, the participation rate was only 21%, and there was a 73% reporting of fitting issues,[9] calling into question the validity of the study. Incorrectly fit devices cannot be expected to yield results. Additionally, independent published research that examined the effectiveness of helmet therapy conclude that as many as 95% of patients demonstrate an improvement in head shape symmetry following helmet therapy, and the American Orthotics and Prosthetics Association (AOPA) has serious concerns about the relevance and validity of this study.[10] ## See also[edit] * Artificial cranial deformation * Cephalic index * Craniosynostosis * Dolichocephaly * Plagiocephaly * Safe to Sleep ## References[edit] 1. ^ K. Killgrove (2005). "Bioarchaeology in the Roman World" (PDF). M.A. Thesis, UNC Chapel Hill. Archived from the original (PDF) on 28 March 2012. Cite journal requires `\|journal=` (help) 2. ^ John Persing; et al. (1 July 2003). "Prevention and Management of Positional Skull Deformities in Infants". Pediatrics. 112 (1): 199–202. doi:10.1542/peds.112.1.199. PMID 12837890. 3. ^ "Plagiocephaly and brachycephaly (flat head syndrome)". NHS. 13 February 2012. 4. ^ Matthew L. Speltz; et al. (15 February 2010). "Case-Control Study of Neurodevelopment in Deformational Plagiocephaly". Pediatrics. 125 (3): e537–e542. doi:10.1542/peds.2009-0052. PMC 3392083. PMID 20156894. "Although DP is considered a purely aesthetic problem by many practitioners, several studies have challenged this view." 5. ^ Di Rocco, Federico; Ble, Valeria; Beuriat, Pierre-Aurelien; Szathmari, Alexandru; Lohkamp, Laura Nanna; Mottolese, Carmine (30 April 2019). "Prevalence and severity of positional plagiocephaly in children and adolescents". Acta Neurochirurgica. 161 (6): 1095–1098. doi:10.1007/s00701-019-03924-2. PMID 31041593. S2CID 141503557. 6. ^ Chisholm, Hugh, ed. (1911). "Brachycephalic" . Encyclopædia Britannica (11th ed.). Cambridge University Press. 7. ^ "Baby helmets 'have no added value', study finds". BBC News. 2 May 2014. 8. ^ Van Wijk, R. M.; Van Vlimmeren, L. A.; Groothuis-Oudshoorn, C. G. M.; Van Der Ploeg, C. P. B.; Ijzerman, M. J.; Boere-Boonekamp, M. M. (1 May 2014). "Helmet therapy in infants with positional skull deformation: randomised controlled trial". BMJ. British Medical Journal. 348: g2741. doi:10.1136/bmj.g2741. PMC 4006966. PMID 24784879. 9. ^ British Medical Journal. Retrieved 2 May 2014. 10. ^ "AOPA Response to British Medical Journal Study" (PDF). ## External links[edit] * NINDS - Cephalic Disorders Overview * Brachycephalic Official Website Classification D * ICD-9-CM: 756.0 * DiseasesDB: 29893 * v * t * e Congenital malformations and deformations of musculoskeletal system / musculoskeletal abnormality Appendicular limb / dysmelia Arms clavicle / shoulder * Cleidocranial dysostosis * Sprengel's deformity * Wallis–Zieff–Goldblatt syndrome hand deformity * Madelung's deformity * Clinodactyly * Oligodactyly * Polydactyly Leg hip * Hip dislocation / Hip dysplasia * Upington disease * Coxa valga * Coxa vara knee * Genu valgum * Genu varum * Genu recurvatum * Discoid meniscus * Congenital patellar dislocation * Congenital knee dislocation foot deformity * varus * Club foot * Pigeon toe * valgus * Flat feet * Pes cavus * Rocker bottom foot * Hammer toe Either / both fingers and toes * Polydactyly / Syndactyly * Webbed toes * Arachnodactyly * Cenani–Lenz syndactylism * Ectrodactyly * Brachydactyly * Stub thumb reduction deficits / limb * Acheiropodia * Ectromelia * Phocomelia * Amelia * Hemimelia multiple joints * Arthrogryposis * Larsen syndrome * RAPADILINO syndrome Axial Skull and face Craniosynostosis * Scaphocephaly * Oxycephaly * Trigonocephaly Craniofacial dysostosis * Crouzon syndrome * Hypertelorism * Hallermann–Streiff syndrome * Treacher Collins syndrome other * Macrocephaly * Platybasia * Craniodiaphyseal dysplasia * Dolichocephaly * Greig cephalopolysyndactyly syndrome * Plagiocephaly * Saddle nose Vertebral column * Spinal curvature * Scoliosis * Klippel–Feil syndrome * Spondylolisthesis * Spina bifida occulta * Sacralization Thoracic skeleton ribs: * Cervical * Bifid sternum: * Pectus excavatum * Pectus carinatum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Brachycephaly	c0221356	5,388	wikipedia	https://en.wikipedia.org/wiki/Brachycephaly	2021-01-18T18:38:32	{"mesh": ["D003398"], "umls": ["C0221356"], "icd-9": ["756.0"], "wikidata": ["Q42649"]}
This syndrome is characterised by total or partial anosmia at birth. So far, 15 patients have been described. The anosmia is caused by a defect in the development of the olfactory bulbs or by replacement of the olfactory epithelium by respiratory epithelium. The mode of transmission appears to be autosomal dominant with incomplete penetrance. Isolated congenital anosmia is found in some parents of individuals with Kallman syndrome (see this term). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Isolated congenital anosmia	c0393778	5,389	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=88620	2021-01-23T17:27:29	{"gard": ["9486"], "mesh": ["C535983"], "omim": ["107200"], "umls": ["C0393778"], "icd-10": ["Q07.8"]}
Hepatorenal syndrome is a form of impaired kidney function that occurs in individuals with advanced chronic liver disease. As many as 40% of individuals with cirrhosis and ascites will develop hepatorenal syndrome. Symptoms may include fatigue, abdominal pain, and a general feeling of ill health (malaise). There are two distinct types of hepatorenal syndrome. Type I progresses quickly (within days), leading to kidney failure. Individuals with type I typically have dramatically reduced urine output, edema, and jaundice, and often suffer from hepatic encephalopathy. Type II progresses more slowly, over weeks or months, and the symptoms are less severe. The cause of hepatorenal syndrome is unknown. A contributing factor seems to be a narrowing of the blood vessels that connect into the kidneys. This causes a decrease in blood flow to the kidneys, impairing their function. In some cases, triggers or precipitating factors (infections, blood loss from the gastrointestinal tract, low blood pressure) are involved. Treatment is aimed at helping the liver work better and maintaining kidney function. In many cases, a liver transplant is needed. In some cases, individuals also need a kidney transplant. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Hepatorenal syndrome	c0019212	5,390	gard	https://rarediseases.info.nih.gov/diseases/6610/hepatorenal-syndrome	2021-01-18T18:00:05	{"mesh": ["D006530"], "synonyms": ["Hepato-renal syndrome"]}
Ependymoblastoma is a rare type of primitive neuroectodermal tumor (PNET) that usually occurs in young children under the age of 2 and is histologically distinguished by the production of ependymoblastic rosettes. It is associated with an aggressive course and 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	Ependymoblastoma	c0700367	5,391	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251880	2021-01-23T18:47:10	{"mesh": ["D018242"], "umls": ["C0700367"], "icd-10": ["C71.9"]}
Eosinophilic pustular folliculitis (EPF) is a skin disorder characterized by recurring itchy, red or skin-colored bumps and pustules (bumps containing pus). The condition is named after the fact that skin biopsies of this disorder find eosinophils (a type of immune cell) around hair follicles. The papules mostly appear on the face, scalp, neck and trunk and may persist for weeks or months. EPF affects males more than females. There are several variants of EPF including classic eosinophilic pustular folliculitis (mainly occurring in adults in Japan); HIV-associated EPF, also referred to as immunosuppression-associated EPF; and infantile EPF (with onset from birth or within the first year of life). Whether these are distinct disorders rather than variants of one disorder is controversial, partly because the underlying cause of EFP is not known. Several treatments have been described with variable results, including various oral or topical medications and phototherapy. In patients with HIV-associated disease, antiretroviral therapy tends to greatly diminish symptoms or even eliminate 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	Eosinophilic pustular folliculitis	c0406305	5,392	gard	https://rarediseases.info.nih.gov/diseases/8534/eosinophilic-pustular-folliculitis	2021-01-18T18:00:41	{"mesh": ["C535953"], "umls": ["C0406305"], "synonyms": ["Ofuji's disease", "Ofuji disease", "Eosinophilic folliculitis, pustular", "EPF", "Eosinophilic folliculitis"]}
Abortion in the Solomon Islands is only legal if the abortion will save the mother's life.[1] In the Solomon Islands, if an abortion is performed on a woman for any other reason, the violator is subject to a life sentence in prison.[1] A woman who performs a self-induced abortion may also be imprisoned for life.[1] Any approved abortion requires consent from two physicians as well as the woman's husband or next of kin.[1] ## References[edit] 1. ^ a b c d Abortion Policies: Oman to Zimbabwe. United Nations Publications. 2001. ISBN 9789211513653. Retrieved 23 November 2014. * v * t * e Abortion in Oceania Sovereign states * Australia * Federated States of Micronesia * Fiji * Kiribati * Marshall Islands * Nauru * New Zealand * Palau * Papua New Guinea * Samoa * Solomon Islands * Tonga * Tuvalu * Vanuatu Associated states of New Zealand * Cook Islands * Niue Dependencies and other territories * American Samoa * Christmas Island * Cocos (Keeling) Islands * Easter Island * French Polynesia * Guam * Hawaii * New Caledonia * Norfolk Island * Northern Mariana Islands * Pitcairn Islands * Tokelau * Wallis and Futuna * v * t * e Abortion Main topics * Definitions * History * Methods * Abortion debate * Philosophical aspects * Abortion law Movements * Abortion-rights movements * Anti-abortion movements Issues * Abortion and mental health * Beginning of human personhood * Beginning of pregnancy controversy * Abortion-breast cancer hypothesis * Anti-abortion violence * Abortion under communism * Birth control * Crisis pregnancy center * Ethical aspects of abortion * Eugenics * Fetal rights * Forced abortion * Genetics and abortion * Late-term abortion * Legalized abortion and crime effect * Libertarian perspectives on abortion * Limit of viability * Malthusianism * Men's rights * Minors and abortion * Natalism * One-child policy * Paternal rights and abortion * Prenatal development * Reproductive rights * Self-induced abortion * Sex-selective abortion * Sidewalk counseling * Societal attitudes towards abortion * Socialism * Toxic abortion * Unsafe abortion * Women's rights By country Africa * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde * Central African Republic * Chad * Egypt * Ghana * Kenya * Namibia * Nigeria * South Africa * Uganda * Zimbabwe Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Brunei * Cambodia * China * Cyprus * East Timor * Georgia * India * Iran * Israel * Japan * Kazakhstan * South Korea * Malaysia * Nepal * Northern Cyprus * Philippines * Qatar * Saudi Arabia * Singapore * Turkey * United Arab Emirates * Vietnam * Yemen Europe * Albania * Andorra * Austria * Belarus * Belgium * Bosnia and Herzegovina * Bulgaria * Croatia * Czech Republic * Denmark * Estonia * Finland * France * Germany * Greece * Hungary * Iceland * Ireland * Italy * Kazakhstan * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Moldova * Monaco * Montenegro * Netherlands * North Macedonia * Norway * Poland * Portugal * Romania * Russia * San Marino * Serbia * Slovakia * Slovenia * Spain * Sweden * Switzerland * Ukraine * United Kingdom North America * Belize * Canada * Costa Rica * Cuba * Dominican Republic * El Salvador * Guatemala * Mexico * Nicaragua * Panama * Trinidad and Tobago * United States Oceania * Australia * Micronesia * Fiji * Kiribati * Marshall Islands * New Zealand * Papua New Guinea * Samoa * Solomon Islands * Tonga * Tuvalu * Vanuatu South America * Argentina * Bolivia * Brazil * Chile * Colombia * Ecuador * Guyana * Paraguay * Peru * Suriname * Uruguay * Venezuela Law * Case law * Constitutional law * History of abortion law * Laws by country * Buffer zones * Conscientious objection * Fetal protection * Heartbeat bills * Informed consent * Late-term restrictions * Parental involvement * Spousal consent Methods * Vacuum aspiration * Dilation and evacuation * Dilation and curettage * Intact D&X * Hysterotomy * Instillation * Menstrual extraction * Abortifacient drugs * Methotrexate * Mifepristone * Misoprostol * Oxytocin * Self-induced abortion * Unsafe abortion Religion * Buddhism * Christianity * Catholicism * Hinduism * Islam * Judaism * Scientology * Category This abortion-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Abortion in the Solomon Islands	None	5,393	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_the_Solomon_Islands	2021-01-18T19:10:49	{"wikidata": ["Q19568865"]}
Progressive supranuclear palsy Other namesSteele–Richardson–Olszewski syndrome, frontotemporal dementia with parkinsonism SpecialtyNeurology SymptomsImpaired balance, slowed movements, difficulty moving eyes, dementia Usual onset60–70 years CausesUnknown Differential diagnosisParkinson's disease, corticobasal degeneration, FTDP-17, Alzheimer's disease TreatmentMedication, physical therapy, occupational therapy MedicationLevodopa, amantadine Prognosis7–10 years after diagnosis. Frequency6 per 100,000 Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain.[1][2] The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and dementia.[1] PSP may be mistaken for other neurodegenerative diseases such as Parkinson's and Alzheimer's. The cause of the condition is uncertain, but involves accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases.[1] PSP affects about six people per 100,000.[1] The first symptoms typically occur in persons aged 60–70 years. Males are slightly more likely to be affected than females.[1] No association has been found between PSP and any particular race, location, or occupation.[1] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Pathophysiology * 4 Diagnosis * 4.1 Types * 4.2 Differential diagnosis * 5 Current management * 5.1 Rehabilitation * 6 Experimental treatments * 7 Prognosis * 8 History * 9 Societies * 10 In popular culture * 11 See also * 12 References ## Signs and symptoms[edit] The initial symptoms in two-thirds of cases are loss of balance, lunging forward when mobilizing, fast walking, bumping into objects or people, and falls.[3][citation needed] Dementia symptoms are also initially seen in about one in five cases.[4] Other common early symptoms are changes in personality, general slowing of movement, and visual symptoms. The most common behavioural symptoms in patients with PSP include apathy, disinhibition, anxiety, and dysphoria.[4] Later symptoms and signs are dementia (typically including loss of inhibition and ability to organize information), slurring of speech, difficulty swallowing, and difficulty moving the eyes, particularly in the vertical direction. The latter accounts for some of the falls experienced by these patients, as they are unable to look up or down.[citation needed] Some of the other signs are poor eyelid function, contracture of the facial muscles, a backward tilt of the head with stiffening of the neck muscles, sleep disruption, urinary incontinence, and constipation.[citation needed] The visual symptoms are of particular importance in the diagnosis of this disorder. Patients typically complain of difficulty reading due to the inability to look down well. Notably, the ophthalmoparesis experienced by these patients mainly concerns voluntary eye movement and the inability to make vertical saccades, which is often worse with downward saccades. Patients tend to have difficulty looking down (a downgaze palsy) followed by the addition of an upgaze palsy. This vertical gaze paresis will correct when the examiner passively rolls the patient's head up and down as part of a test for the oculocephalic reflex. Involuntary eye movement, as elicited by Bell's phenomenon, for instance, may be closer to normal. On close inspection, eye movements called "square-wave jerks" may be visible when the patient fixes at distance. These are fine movements, that can be mistaken for nystagmus, except that they are saccadic in nature, with no smooth phase. Although healthy individuals also make square-wave jerk movements, PSP patients make slower square-wave jerk movements, with smaller vertical components.[5] Assessment of these square-wave jerks and diminished vertical saccades is especially useful for diagnosing progressive supranuclear palsy, because these movements set PSP patients apart from other parkinsonian patients.[5] Difficulties with convergence (convergence insufficiency), where the eyes come closer together while focusing on something near, like the pages of a book, is typical. Because the eyes have trouble coming together to focus at short distances, the patient may complain of diplopia (double vision) when reading.[citation needed] A characteristic facial appearance known as “procerus sign”, with a wide-eye stare, furrowing of forehead with a frowning expression and deepening of other facial creases is diagnostic of PSP.[6] Cardinal manifestations:[citation needed] * Supranuclear ophthalmoplegia * Neck dystonia * Parkinsonism * Pseudobulbar palsy * Behavioral and cognitive impairment * Imbalance and walking difficulty * Frequent falls ## Cause[edit] The cause of PSP is unknown. Fewer than 1% of those with PSP have a family member with the same disorder. A variant in the gene for tau protein called the H1 haplotype, located on chromosome 17 (rs1800547), has been linked to PSP.[7] Nearly all people with PSP received a copy of that variant from each parent, but this is true of about two-thirds of the general population. Therefore, the H1 haplotype appears to be necessary but not sufficient to cause PSP. Other genes, as well as environmental toxins, are being investigated as other possible contributors to the cause of PSP.[citation needed] Additionally, the H2 haplotype, combined with vascular dysfunction, seems to be a factor of progressive supranuclear palsy.[8] Besides tauopathy, mitochondrial dysfunction seems to be a factor involved in PSP. Especially, mitochondrial complex I inhibitors (such as acetogenins and quinolines contained in Annonaceae, as well as rotenoids) are implicated in PSP-like brain injuries.[9] ## Pathophysiology[edit] The affected brain cells are both neurons and glial cells. The neurons display neurofibrillary tangles (NFTs), which are clumps of tau protein, a normal part of a brain cell's internal structural skeleton. These tangles are often different from those seen in Alzheimer's disease, but may be structurally similar when they occur in the cerebral cortex.[10] Their chemical composition is usually different, however, and is similar to that of tangles seen in corticobasal degeneration.[11] Tufts of tau protein in astrocytes, or tufted astrocytes, are also considered diagnostic. Unlike globose NFTs, they may be more widespread in the cortex.[12] Lewy bodies are seen in some cases, but whether this is a variant or an independent co-existing process is not clear, and in some cases, PSP can coexist with corticobasal degeneration, Parkinson's, and/or Alzheimer's disease, particularly with older patients.[13][14][15][16][17] The principal areas of the brain affected are the:[citation needed] * basal ganglia, particularly the subthalamic nucleus, substantia nigra, and globus pallidus * brainstem, particularly the portion of the midbrain where "supranuclear" eye movement resides, as well as dopaminergic nuclei. * cerebral cortex, particularly that of the frontal lobes and the limbic system (similarly to frontotemporal degeneration) * dentate nucleus of the cerebellum * spinal cord, particularly the area where some control of the bladder and bowel resides Some consider PSP, corticobasal degeneration, and frontotemporal dementia to be variations of the same disease.[18][19] Others consider them separate diseases.[20][21][22] PSP has been shown occasionally to co-exist with Pick's disease.[23] ## Diagnosis[edit] Person with progressive dementia, ataxia, and incontinence. A clinical diagnosis of normal-pressure hydrocephalus was entertained. Imaging did not support this, however, and on formal testing, abnormal nystagmus and eye movements were detected. A sagittal view of the CT/MRI scan shows atrophy of the midbrain, with preservation of the volume of the pons. This appearance has been called the "hummingbird sign" or "penguin sign". Also, atrophy of the tectum is seen, particularly the superior colliculi. These findings suggest the diagnosis of progressive supranuclear palsy.[24] MRI is often done to diagnose PSP. MRI may show atrophy in the midbrain with preservation of the pons giving a "hummingbird" sign appearance and Mickey Mouse sign.[25] ### Types[edit] Based on the pathological findings in confirmed cases of PSP, it is divided into the following categories: * classical Richardson syndrome (PSP-RS)[citation needed] * PSP-parkinsonism (PSP-P) and PSP-pure akinesia with gait freezing (PSP-PAGF)[citation needed] * frontal PSP, PSP-corticobasal syndrome (PSP-CBS), PSP-behavioural variant of frontotemporal dementia (PSP-bvFTD) and PSP-progressive non-fluent aphasia (PSP-PNFA)[26] * PSP-C * PSP induced by Annonaceae[27] Richardson syndrome is characterized by the typical features of PSP. In PSP-P features of Parkinson’s Disease overlap with the clinical presentation of PSP and follows a more benign course. In both PSP-P and PSP- PAGF distribution of abnormal tau is relatively restricted to the brain stem. Frontal PSP initially presents with behavioral and cognitive symptoms, with or without ophthalmoparesis and then evolve into typical PSP.[6] The phenotypes of PSP-P and PSP-PAGF are sometimes referred as the ‘brain stem’ variants of PSP, as opposed to the ‘cortical’ variants which present with predominant cortical features including PSP-CBS, PSP-bvFTD, and PSP-PNFA.[28] Cerebellar ataxia as the predominant early presenting feature is increasingly recognized as a very rare subtype of PSP (PSP-C) which is associated with severe neuronal loss with gliosis and higher densities of coiled bodies in the cerebellar dentate nucleus.[29] ### Differential diagnosis[edit] PSP is frequently misdiagnosed as Parkinson's disease because they both involve slowed movements and gait difficulty, with PSP being one of a collection of diseases referred to as Parkinson plus syndromes. Both Parkinson's and PSP have an onset in late middle age and involve slowing and rigidity of movement. However, several distinguishing features exist. Tremor is very common with Parkinson's, but rare with PSP. Speech and swallowing difficulties are more common and severe with PSP and the abnormal eye movements of PSP are essentially absent with PD.[30] A poor response to levodopa along with symmetrical onset can also help differentiate PSP from PD.[31] Patients with the Richardson variant of PSP tend to have an upright posture or arched back, as opposed to the stooped-forward posture of other Parkinsonian disorders, although PSP-Parkinsonism (see below) can demonstrate a stooped posture.[32] Early falls are also more common with PSP, especially with Richardson syndrome.[33] PSP can also be misdiagnosed as Alzheimer's disease because of the behavioral changes.[34] Chronic traumatic encephalopathy shows many similarities with PSP.[citation needed] ## Current management[edit] Supportive therapies No cure for PSP is known, and management is primarily supportive. PSP cases are often split into two subgroups, PSP-Richardson, the classic type, and PSP-Parkinsonism, where a short-term response to levodopa can be obtained.[35] Dyskinesia is an occasional but rare complication of treatment.[36] Amantadine is also sometimes helpful.[37] After a few years the Parkinsonian variant tends to take on Richardson features.[38] Other variants have been described.[39][40][41][42] Botox can be used to treat neck dystonia and blepharospasm, but this can aggravate dysphagia.[43] Two studies have suggested that rivastigmine may help with cognitive aspects, but the authors of both studies have suggested a larger sampling be used.[44][45] There is some evidence that the hypnotic zolpidem may improve motor function and eye movements, but only from small-scale studies.[46][47] ### Rehabilitation[edit] Patients with PSP usually seek or are referred to occupational therapy, speech-language pathology for motor speech changes typically a spastic-ataxic dysarthria, and physical therapy for balance and gait problems with reports of frequent falls.[48] Evidence-based approaches to rehabilitation in PSP are lacking and, currently, the majority of research on the subject consists of case reports involving only a small number of patients.[citation needed] Case reports of rehabilitation programs for patients with PSP generally include limb-coordination activities, tilt-board balancing, gait training, strength training with progressive resistive exercises, and isokinetic exercises and stretching of the neck muscles.[48] While some case reports suggest that physiotherapy can offer improvements in balance and gait of patients with PSP, the results cannot be generalized across all PSP patients, as each case report only followed one or two patients.[48] The observations made from these case studies can be useful, however, in helping to guide future research concerning the effectiveness of balance and gait training programs in the management of PSP.[citation needed] Individuals with PSP are often referred to occupational therapists to help manage their condition and to help enhance their independence. This may include being taught to use mobility aids.[49][50] Due to their tendency to fall backwards, the use of a walker, particularly one that can be weighted in the front, is recommended over a cane.[49] The use of an appropriate mobility aid helps to decrease the individual’s risk of falls and makes them safer to ambulate independently in the community.[50] Due to their balance problems and irregular movements, individuals need to spend time learning how to safely transfer in their homes and in the community.[49] This may include rising from and sitting in chairs safely.[50] Due to the progressive nature of this disease, all individuals eventually lose their ability to walk and will need to progress to using a wheelchair.[49] Severe dysphagia often follows, and at this point death is often a matter of months.[35] ## Experimental treatments[edit] Drugs targeting the tau protein offer a promising avenue for therapeutic intervention. The growth factor davunetide was recently trialed in patients to prevent hyperphosphorylated, insoluble forms of tau, however it was unable to show efficacy possibly due insufficient CNS penetration.[51] Antisense therapy has shown efficacy in several other human neurodegenerative disorders and has recently been shown to substantially extend lifespan in animals with PSP.[52] Biogen and Ionis Pharmaceuticals currently are investigating a tau-lowering antisense therapy for Alzheimer's disease and frontotemporal dementia which could also have applicability to PSP.[53] ## Prognosis[edit] No effective treatment or cure has been found for PSP, although some of the symptoms can respond to nonspecific measures. The poor prognosis is predominantly attributed to the serious impact this condition has on the quality of life.[3] The average age at symptoms onset is 63 and survival from onset averages seven years with a wide variance.[54] Pneumonia is a frequent cause of death.[55] ## History[edit] In 1877, Charcot described a 40-year-old woman who had rigid-akinetic parkinsonism, neck dystonia, dysarthria, and eye-movement problems. Chavany and others reported the clinical and pathologic features of a 50-year-old man with a rigid and akinetic form of parkinsonism with postural instability, neck dystonia, dysarthria, and staring gaze in 1951. Progressive supranuclear palsy was first described as a distinct disorder by neurologists John Steele, John Richardson, and Jerzy Olszewski in 1963.[1][56][57][58] They recognized the same clinical syndrome in 8 patients and described the autopsy findings in 6 of them in 1963.[citation needed] Progressive supranuclear palsy was not a “new” disease in 1963, as 22 well-documented case reports had been identified in the neurologic literature between 1877 and 1963.[59] The unique frontal lobe cognitive changes of progressive supranuclear palsy (apathy, loss of spontaneity, slowing of thought processes, and loss of executive functions) were first described by Albert and colleagues in 1974.[60] ## Societies[edit] There are several organizations around the world that support PSP patients and the research into PSP and related diseases, such as corticobasal degeneration (CBD) and multiple system atrophy (MSA). * Canada: PSP Society of Canada, a federally registered non-profit organization which serves patients and families dealing with PSP, CBD and MSA, set up in 2017 through the help of CurePSP in the USA[61] * France: Association PSP France, a nonprofit patient association set up in 1996 through the help of PSPA in the UK. It also gives support to French speaking patients in Quebec, Morocco, Algeria, Belgium and Lebanon[62] * UK: PSPA, a national charity for information, patient support and research of PSP and CBD, set up in 1995[63] * Ireland: PSPAI, a body which aims to get PSP better known[64] * US: CurePSP, a nonprofit organization for promoting awareness, care and research of PSP, CBD, MSA "and other prime of life neurodegenerative diseases"[65] ## In popular culture[edit] In the 2020 American musical comedy-drama television series, Zoey's Extraordinary Playlist, the title character's father (Mitch Clarke, played by Peter Gallagher) has PSP and dies in the final episode of the first season.[66] American singer Linda Ronstadt was diagnosed with PSP in 2019, subsequent to an initial diagnosis of Parkinson's disease in 2014.[67] ## See also[edit] * Lytico-bodig disease (Parkinsonism-Dementia Complex of Guam) * Annonacin ## References[edit] 1. ^ a b c d e f g Golbe LI (April 2014). 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Classification D * ICD-10: G23.1 * ICD-9-CM: 333.0 * OMIM: 601104 * MeSH: D013494 * DiseasesDB: 10723 External resources * MedlinePlus: 000767 * eMedicine: neuro/328 * Patient UK: Progressive supranuclear palsy * Orphanet: 683 * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Progressive supranuclear palsy	c0038868	5,394	wikipedia	https://en.wikipedia.org/wiki/Progressive_supranuclear_palsy	2021-01-18T18:28:53	{"gard": ["7471"], "mesh": ["D013494"], "umls": ["C0038868"], "orphanet": ["683"], "wikidata": ["Q945930"]}
A number sign (#) is used with this entry because of evidence that osteogenesis imperfecta X (OI10) is caused by homozygous mutation in the SERPINH gene (600943) on chromosome 11q13. Description Osteogenesis imperfecta (OI) comprises a group of connective tissue disorders characterized by bone fragility and low bone mass. The disorder is clinically and genetically heterogeneous. OI type X is an autosomal recessive form characterized by multiple bone deformities and fractures, generalized osteopenia, dentinogenesis imperfecta, and blue sclera (Christiansen et al., 2010). Clinical Features Christiansen et al. (2010) reported a child with a severe deforming form of OI who was born to a clinically normal consanguineous Saudi Arabian couple and was the only affected member in the extended family. At birth he was noted to have a triangular face, relative macrocephaly, bitemporal narrowing, blue sclerae, micrognathia, and relatively short limbs with bowing at the thighs. Radiographs of the chest showed thin ribs with healing fractures, a fracture of the right humerus, a healing fracture of the left humerus, and platyspondyly. A skeletal survey at the age of 1 month was consistent with the diagnosis of osteogenesis imperfecta. There were multiple bone deformities and fractures that involved the upper and lower extremities and ribs and generalized osteopenia. When he was 1 year old, bilateral renal stones were noticed with left pelviureteric junction obstruction that ultimately required left nephrectomy because of hydronephrosis and loss of renal function. He had chronic lung disease of unclear etiology and from the age of 1.5 years he required continuous oxygen by nasal cannula to maintain adequate oxygenation. He had small opalescent teeth consistent with dentinogenesis imperfecta. At age 3 years and 6 months he had sudden unexplained respiratory distress at home and died soon after arrival at the hospital. No autopsy was performed. Duran et al. (2015) studied a consanguineous family in which a sister and brother (cases R92-020A and B, International Skeletal Dysplasia Registry) were diagnosed with a moderately severe form of OI at ages 4 years and 6 months, respectively. No fractures occurred during their first few months of life, but radiographs showed generalized osteopenia, large anterior fontanel and wormian bones in the skull, coxa valga, mild femoral bowing, reduced thorax size, and scoliosis with compression fractures in the vertebrae. Hyperextensibility was noted in the fingers, knees, and hips. Blue sclerae were not observed, nor was there dentinogenesis imperfecta or hearing loss. Molecular Genetics Because the SERPINH1 gene encodes a collagen-binding protein that functions as a chaperone in the endoplasmic reticulum, Christiansen et al. (2010) screened for mutations in this gene in individuals with OI whose cells did not produce overmodified type I collagen. In a Saudi Arabian patient with severe deforming OI X, they identified a homozygous missense mutation (L78P; 600943.0002). Using DNA from a 4-year-old girl with a moderately severe form of OI, Duran et al. (2015) analyzed the exon sequences of 9 known OI-associated genes and identified homozygosity for a missense mutation in the SERPINH1 gene (M237T; 600943.0003). Her unaffected third-cousin parents were heterozygous carriers of the mutation; DNA from her affected brother was not available. In experiments using cultured patient dermal fibroblasts, the authors demonstrated that protein levels of both HSP47 and FKBP65 (FKBP10, 607063; see OI11, 610968) were reduced and mislocalized, and proximity ligation assays indicated that the proteins interact in subcellular compartments. Duran et al. (2015) suggested that the similarity in phenotype between OI10 and OI11 might be explained by the similar consequences on type I procollagen synthesis. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Weight \- Weight less than 5th centile HEAD & NECK Head \- Macrocephaly, relative \- Bitemporal narrowing \- Open anterior fontanel \- High forehead \- Prominent forehead Face \- Triangular face \- Midface hypoplasia Eyes \- Blue sclera (patient A) \- Shallow orbits (patient A) Mouth \- Micrognathia Teeth \- Dentinogenesis imperfecta (patient A) RESPIRATORY Lung \- Chronic lung disease (patient A) CHEST External Features \- Narrow chest Ribs Sternum Clavicles & Scapulae \- Thin ribs \- Broad ribs ABDOMEN Gastrointestinal \- Pyloric stenosis (patient A) GENITOURINARY Internal Genitalia (Male) \- Inguinal hernia, bilateral (patient A) Kidneys \- Renal stones, bilateral (patient A) SKELETAL \- Bone fractures, multiple \- Osteopenia, generalized \- Bone deformities, multiple Spine \- Platyspondyly \- Vertebral compression fractures \- Scoliosis Limbs \- Short limbs, relative \- Bowing of long bones \- Genu valgum \- Joint laxity, generalized NEUROLOGIC Central Nervous System \- Hypotonia, generalized (patient A) VOICE \- High-pitched voice (patient A) MISCELLANEOUS \- Based on 2 sibs and an unrelated patient (patient A) (last curated October 2016) MOLECULAR BASIS \- Caused by mutation in the serpin peptidase inhibitor, clade H, member 1 (SERPINH1, 600943.0002 ) ▲ 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	OSTEOGENESIS IMPERFECTA, TYPE X	c0268362	5,395	omim	https://www.omim.org/entry/613848	2019-09-22T15:57:15	{"doid": ["0110346"], "mesh": ["C536044"], "omim": ["613848"], "orphanet": ["216812", "666"], "synonyms": ["Alternative titles", "OI, TYPE X"]}
Zunich–Kaye syndrome Other namesZunich neuroectodermal syndrome Zunich–Kaye syndrome has an autosomal recessive pattern of inheritance. Zunich–Kaye syndrome, also known as Zunich neuroectodermal syndrome, is a rare congenital ichthyosis first described in 1983.[1] It is also referred to as CHIME syndrome, after its main symptoms (colobomas, heart defects, ichthyosiform dermatosis, intellectual disability, and either ear defects or epilepsy).[2] It is a congenital[3] syndrome with only a few cases studied and published.[2] ## Contents * 1 Symptoms and signs * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 Bibliography * 8 External links ## Symptoms and signs[edit] Associated symptoms range from things such as colobomas of the eyes, heart defects, ichthyosiform dermatosis, intellectual disability, and ear abnormalities. Further symptoms that may be suggested include characteristic facies, hearing loss, and cleft palate.[citation needed] ## Genetics[edit] Zunich–Kay syndrome is considered to have an autosomal recessive inheritance pattern. This means the defective gene is located on an autosome, and two copies of the gene, one from each parent, are required to inherit the disorder. The parents of an individual with autosomal recessive disorder both carry one copy of the defective gene, but usually do not have the disorder.[citation needed] ## Diagnosis[edit] This section is empty. You can help by adding to it. (May 2017) ## Treatment[edit] Treatment with isotretinoin may induce substantial resolution of skin lesions, but the risk of secondary infection remains.[2] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Zunich J, Kaye CI (1983). "New syndrome of congenital ichthyosis with neurologic abnormalities". Am. J. Med. Genet. 15 (2): 331–3, 335. doi:10.1002/ajmg.1320150217. PMID 6192719. 2. ^ a b c OrphaNet entry 3. ^ Birth Disorder Information Directory - Z ## Bibliography[edit] * Schnur RE, Greenbaum BH, Heymann WR, Christensen K, Buck AS, Reid CS (1997). "Acute lymphoblastic leukemia in a child with the CHIME neuroectodermal dysplasia syndrome". Am. J. Med. Genet. 72 (1): 24–9. doi:10.1002/(SICI)1096-8628(19971003)72:1<24::AID-AJMG5>3.0.CO;2-V. PMID 9295069. * Shashi V, Zunich J, Kelly TE, Fryburg JS (1995). "Neuroectodermal (CHIME) syndrome: an additional case with long term follow up of all reported cases". J. Med. Genet. 32 (6): 465–9. doi:10.1136/jmg.32.6.465. PMC 1050487. PMID 7666399. * Zunich J, Esterly NB, Holbrook KA, Kaye CI (1985). "Congenital migratory ichthyosiform dermatosis with neurologic and ophthalmologic abnormalities". Arch Dermatol. 121 (9): 1149–56. doi:10.1001/archderm.121.9.1149. PMID 4037840. * Zunich J, Esterly NB, Kaye CI (1988). "Autosomal recessive transmission of neuroectodermal syndrome". Arch Dermatol. 124 (8): 1188–9. doi:10.1001/archderm.124.8.1188. PMID 3041916. * Zunich J, Kaye CI (1984). "Additional case report of new neuroectodermal syndrome". Am. J. Med. Genet. 17 (3): 707–10. doi:10.1002/ajmg.1320170324. PMID 6711621. ## External links[edit] Classification D * ICD-10: GroupMajor.minor * ICD-9-CM: xxx * OMIM: 280000 * MeSH: C536729 * DiseasesDB: 32624 * SNOMED CT: 720639008 * v * t * e Congenital malformations and deformations of integument / skin disease Genodermatosis Congenital ichthyosis/ erythrokeratodermia AD * Ichthyosis vulgaris AR * Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis * Lamellar ichthyosis * Harlequin-type ichthyosis * Netherton syndrome * Zunich–Kaye syndrome * Sjögren–Larsson syndrome XR * X-linked ichthyosis Ungrouped * Ichthyosis bullosa of Siemens * Ichthyosis follicularis * Ichthyosis prematurity syndrome * Ichthyosis–sclerosing cholangitis syndrome * Nonbullous congenital ichthyosiform erythroderma * Ichthyosis linearis circumflexa * Ichthyosis hystrix EB and related * EBS * EBS-K * EBS-WC * EBS-DM * EBS-OG * EBS-MD * EBS-MP * JEB * JEB-H * Mitis * Generalized atrophic * JEB-PA * DEB * DDEB * RDEB * related: Costello syndrome * Kindler syndrome * Laryngoonychocutaneous syndrome * Skin fragility syndrome Ectodermal dysplasia * Naegeli syndrome/Dermatopathia pigmentosa reticularis * Hay–Wells syndrome * Hypohidrotic ectodermal dysplasia * Focal dermal hypoplasia * Ellis–van Creveld syndrome * Rapp–Hodgkin syndrome/Hay–Wells syndrome Elastic/Connective * Ehlers–Danlos syndromes * Cutis laxa (Gerodermia osteodysplastica) * Popliteal pterygium syndrome * Pseudoxanthoma elasticum * Van der Woude syndrome Hyperkeratosis/ keratinopathy PPK * diffuse: Diffuse epidermolytic palmoplantar keratoderma * Diffuse nonepidermolytic palmoplantar keratoderma * Palmoplantar keratoderma of Sybert * Meleda disease * syndromic * connexin * Bart–Pumphrey syndrome * Clouston's hidrotic ectodermal dysplasia * Vohwinkel syndrome * Corneodermatoosseous syndrome * plakoglobin * Naxos syndrome * Scleroatrophic syndrome of Huriez * Olmsted syndrome * Cathepsin C * Papillon–Lefèvre syndrome * Haim–Munk syndrome * Camisa disease * focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis * Focal palmoplantar and gingival keratosis * Howel–Evans syndrome * Pachyonychia congenita * Pachyonychia congenita type I * Pachyonychia congenita type II * Striate palmoplantar keratoderma * Tyrosinemia type II * punctate: Acrokeratoelastoidosis of Costa * Focal acral hyperkeratosis * Keratosis punctata palmaris et plantaris * Keratosis punctata of the palmar creases * Schöpf–Schulz–Passarge syndrome * Porokeratosis plantaris discreta * Spiny keratoderma * ungrouped: Palmoplantar keratoderma and spastic paraplegia * desmoplakin * Carvajal syndrome * connexin * Erythrokeratodermia variabilis * HID/KID Other * Meleda disease * Keratosis pilaris * ATP2A2 * Darier's disease * Dyskeratosis congenita * Lelis syndrome * Dyskeratosis congenita * Keratolytic winter erythema * Keratosis follicularis spinulosa decalvans * Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome * Keratosis pilaris atrophicans faciei * Keratosis pilaris Other * cadherin * EEM syndrome * immune system * Hereditary lymphedema * Mastocytosis/Urticaria pigmentosa * Hailey–Hailey see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder Developmental anomalies Midline * Dermoid cyst * Encephalocele * Nasal glioma * PHACE association * Sinus pericranii Nevus * Capillary hemangioma * Port-wine stain * Nevus flammeus nuchae Other/ungrouped * Aplasia cutis congenita * Amniotic band syndrome * Branchial cyst * Cavernous venous malformation * Accessory nail of the fifth toe * Bronchogenic cyst * Congenital cartilaginous rest of the neck * Congenital hypertrophy of the lateral fold of the hallux * Congenital lip pit * Congenital malformations of the dermatoglyphs * Congenital preauricular fistula * Congenital smooth muscle hamartoma * Cystic lymphatic malformation * Median raphe cyst * Melanotic neuroectodermal tumor of infancy * Mongolian spot * Nasolacrimal duct cyst * Omphalomesenteric duct cyst * Poland anomaly * Rapidly involuting congenital hemangioma * Rosenthal–Kloepfer syndrome * Skin dimple * Superficial lymphatic malformation * Thyroglossal duct cyst * Verrucous vascular malformation * Birthmark [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Zunich–Kaye syndrome	c1848392	5,396	wikipedia	https://en.wikipedia.org/wiki/Zunich%E2%80%93Kaye_syndrome	2021-01-18T18:48:51	{"gard": ["310"], "mesh": ["C536729"], "umls": ["C1848392"], "orphanet": ["3474"], "wikidata": ["Q8075299"]}
## Summary ### Clinical characteristics. Amish lethal microcephaly is characterized by severe congenital microcephaly and highly elevated 2-ketoglutarate or lactic acidosis. The occipitofrontal circumference is typically more than two standard deviations (occasionally >6 SD) below the mean; anterior and posterior fontanels are closed at birth and facial features are distorted. The average life span of an affected infant is between five and six months among the Lancaster Amish, although an affected Amish-Mennonite child was reported to be living with severe developmental delay at age seven years. ### Diagnosis/testing. The diagnosis of Amish lethal microcephaly is established in a proband with typical clinical findings and/or identification of biallelic pathogenic variants in SLC25A19 by molecular genetic testing. All affected individuals within the Old Order Amish population are homozygous for the same single-base pair substitution. ### Management. Treatment of manifestations: Treatment is supportive only. Phenobarbital has been used to treat a few children with seizures. Physical therapy may alleviate contractures or other secondary neurologic manifestations. Infectious illnesses are managed to minimize acidosis. ### Genetic counseling. Amish lethal microcephaly is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing or preimplantation diagnosis for pregnancies at increased risk are possible once the pathogenic variants have been identified in the family. ## Diagnosis ### Suggestive Findings Amish lethal microcephaly should be suspected in individuals with the following findings: * Severe microcephaly: * Present at birth * Occipitofrontal circumference typically >2 SD (occasionally >6 SD) below the mean * Highly elevated (≥10-fold increased) levels of the urinary organic acid 2-ketoglutarate OR lactic acidosis Note that the clinical criteria for this disorder are based solely on the manifestations in the Old Order Amish kindreds from southeastern Pennsylvania and a single non-Amish patient clinical report. The spectrum of the disorder may be larger than currently appreciated. ### Establishing the Diagnosis The diagnosis of Amish lethal microcephaly is established in a proband with typical clinical findings and/or identification of biallelic pathogenic variants in SLC25A19 by molecular genetic testing (see Table 1). Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing: * Single-gene testing. Sequence analysis of SLC25A19 is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found. Note: No deletions or duplications involving SLC25A19 as causative of Amish lethal microcephaly have been reported. Targeted analysis for the c.530G>C pathogenic variant can be performed first in individuals of Amish ancestry. * A multigene panel that includes SLC25A19 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Amish Lethal Microcephaly View in own window Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method SLC25A19Sequence analysis 3100% 4 Gene-targeted deletion/duplication analysis 5Unknown 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. To date, all individuals with Amish microcephaly have the c.530G>C variant. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. No data on detection rate of gene-targeted deletion/duplication analysis are available. ## Clinical Characteristics ### Clinical Description Amish lethal microcephaly (MCPHA) is a distinct disorder with little variability in its presentation, at least among the Old Order Amish from Lancaster County, Pennsylvania [Kelley et al 2002] and the single reported patient from outside of this area [Siu et al 2010]. Microcephaly. Affected infants have severe microcephaly at birth. * The cranial vault is extremely underdeveloped as a result of the small brain size. * Anterior and posterior fontanels are closed, and ridging from premature sutural fusion may be evident. * MRI imaging has not been done in most affected individuals; partial absence of the corpus callosum and closed spinal dysraphism were identified by imaging in the individual reported by Siu et al [2010]. * The facial features are distorted as a result of the profound microcephaly. * Many affected infants have difficulty maintaining body temperature. * The Amish individuals died quite young. The single affected individual described by Siu et al [2010] had irritability and profound developmental delay. The Amish patients were able to breast/bottle feed early on, but developed severe irritability and seizures. Non-CNS physical anomalies * Moderate micrognathia is seen. * Mild hepatomegaly has been observed in several affected individuals, usually during acute illnesses associated with metabolic acidosis. * 2-ketoglutaric acidosis has been demonstrated in a number of Amish infants with this disorder (a variable finding). Prognosis. After the first two or three months of life, increasing irritability of unknown causes commonly develops [Kelley et al 2002]. Although no changes in physical or neurologic examination accompany the irritability, the Lancaster Amish children are more likely to die within 24-48 hours of developing their next viral illness. The average life span of an affected infant is between five and six months among the Lancaster Amish; the affected Amish-Mennonite child reported by Siu et al [2010] was alive (albeit with severe developmental delay) at age seven years. Neuropathology. A partial autopsy of an affected infant age four months gave insight into the neuropathology of the disorder [Strauss et al 2002]. The severity of the malformation was more pronounced in the anterior portion of the brain. Frontal lobes are smooth and rudimentary. Increasing convolution and lamination progress occipitotemporally. Regions that are most hypoplastic are most disorganized histologically. No pathology on the case reported by Siu et al [2010] has been available. ### Genotype-Phenotype Correlations With a single pathogenic variant identified in all known individuals with MCPHA and little variation in clinical presentation, no conclusions about genotype-phenotype correlation can be made at this time. ### Prevalence MCPHA has been found primarily in the Old Order Amish who have ancestors in Lancaster County, Pennsylvania. At least 61 affected infants have been born to 33 nuclear families in the past 40 years. In this population, incidence is approximately one in 500 births. There are typically three or more births of infants with MCPHA per year in this population. The report of Siu et al [2010] shows that the phenotype is not limited to the Old Order Amish population, although prevalence is difficult to estimate. ## Differential Diagnosis Microcephaly has a wide variety of causative factors. It can be syndromic or isolated, environmental or genetic, congenital or acquired [Battaglia & Carey 2003]. A metabolic screen (including urine organic acids, plasma amino acids, lactate, pyruvate, and electrolytes) is indicated for all children with congenital microcephaly. Further specific evaluations are performed as indicated based on the results of this screen. Elevated alpha-ketoglutarate may be seen in other disorders as well. Microcephaly. The differential diagnosis for isolated congenital microcephaly includes single-gene disorders inherited in an autosomal recessive manner. Primary autosomal recessive microcephalies are a group of nonsyndromic disorders characterized by a small-sized brain which are not associated with gross anomalies of brain architecture or malformations in other organ systems. Associated genes include ASPM, CDK5RAP2, CENPJ, CEP152, MCPH1, STIL, and WDR62. The degree of microcephaly is much greater in Amish lethal microcephaly than in any of these other genetically defined microcephaly syndromes. Additionally, 2-ketoglutaric aciduria has not been reported as a finding with these disorders. Microcephaly may also be inherited in an autosomal dominant manner and possibly in an X-linked manner, though most of the causative genes have not been identified [Battaglia & Carey 2003]. Members of a three-generation family with microcephaly were found to have a heterozygous pathogenic variant in WDFY3 [Kadir et al 2016]. Alpha-ketoglutarate. Elevated levels of urinary alpha-ketoglutarate may also be seen in individuals with pathogenic variants in the alpha-ketoglutarate dehydrogenase complex, but this phenotype does not typically present with microcephaly [Dunckelmann et al 2000]. Increased levels of urinary 2-ketoglutarate are common in a wide variety of disorders of mitochondrial dysfunction, including those caused by mutation of both mtDNA and nuclear DNA genes. Among other genetic malformation syndromes, a similar level of urinary 2-ketoglutarate is also characteristic of the autosomal recessive form of DOORS (deafness, onychodystrophy, osteodystrophy, intellectual disability [formerly known as mental retardation] seizures) syndrome, associated with biallelic pathogenic variants in TBC1D24 (see TBC1D24-Related Disorders). ## Management ### Evaluation Following Initial Diagnosis To establish the extent of disease in an individual diagnosed with Amish lethal microcephaly (MCPHA), the following evaluations are recommended if they have not already been completed: * Appropriate imaging studies. Given that the fontanels are typically closed or overriding, MRI is more useful than ultrasound. Computed tomography can be used, but has lower resolution. * Consultation with a clinical geneticist, biochemical geneticist, and/or genetic counselor. Care coordination is important in managing affected infants as it is necessary to provide appropriate comfort care given the uniformly poor prognosis. ### Treatment of Manifestations This disorder is fatal within the first year of life in children of the Old Order Amish of Lancaster County, Pennsylvania. No intervention – including mitochondrial vitamin treatment – has shown promise for treatment or amelioration in this population. However, most experience with this disorder is based on the Old Order Amish; therefore, most clinical experience is based on a single allele. It is now known that this same allele can manifest in a more mild form [Siu et al 2010]. In this case, it was shown that a ketogenic diet improved the acidosis. Seizures have occurred in some affected infants; the few children who were treated responded well to phenobarbital. Physical therapy may be considered if the affected child develops contractures or other secondary neurologic manifestations. The patients respond to benzodiazepine anxiolytics. Support and respite for the family may be needed during the stressful terminal irritability phase of the disease, which can last for several weeks. In general, a palliative approach to care is appropriate. Within the Old Order Amish, care within the extended family is sufficient. Non-Amish patients may be considered for pediatric hospice care. ### Prevention of Primary Manifestations Routine childhood illnesses should be managed to minimize the acidosis associated with acute illnesses. Many affected infants in the Lancaster Amish population have died during metabolic exacerbations associated with an intercurrent infectious illness. ### Agents/Circumstances to Avoid Good handwashing and avoidance of contact with individuals with communicable respiratory diseases is appropriate. ### Evaluation of Relatives at Risk Prior to genetic testing, or while it is under way, urine and plasma amino acids and pyruvate and lactate levels should be considered. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Amish Lethal Microcephaly	c1846648	5,397	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1365/	2021-01-18T21:43:05	{"mesh": ["C538247"], "synonyms": ["Amish Microcephaly", "MCPHA"]}
A rare hemorrhagic disorder due to an acquired coagulation factor defect characterized by sudden, spontaneous, and often severe bleeding, manifesting with skin, muscle and mucuous membrane hemorrhages, in persons without a previous bleeding tendency. Additional symptoms may include epistaxis, gastrointestinal and/or urogenital bleeding, spontaneous bruising, melena, and hematuria. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Acquired hemophilia	c1096116	5,398	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=73274	2021-01-23T18:49:27	{"gard": ["10350"], "umls": ["C1096116"], "icd-10": ["D68.4"]}
Syndrome characterized by acute brain damage and liver function problems Reye syndrome Other namesReye's syndrome Appearance of a liver from a child who died of Reye syndrome as seen with a microscope. Hepatocytes are pale-staining due to intracellular fat droplets. Pronunciation * /raɪ ˈsɪndroʊm/ rye SIN-drohm SpecialtyPediatrics SymptomsVomiting, personality changes, confusion, seizures, loss of consciousness[1] ComplicationsPersistent vegetative state, coma CausesUnknown[2] Risk factorsAspirin use in children, viral infection[1][2] TreatmentSupportive care[1] MedicationMannitol[2] Prognosis1⁄3rd long term disability[2][3] FrequencyLess than one in a million children a year[2] Deaths~30% chance of death[2][3] Reye syndrome is a rapidly worsening brain disease.[2] Symptoms may include vomiting, personality changes, confusion, seizures, and loss of consciousness.[1] Even though liver toxicity typically occurs, jaundice usually does not.[2] Death occurs in 20–40% of those affected and about a third of those who survive are left with a significant degree of brain damage.[2][3] The cause of Reye syndrome is unknown.[2] It usually begins shortly after recovery from a viral infection, such as influenza or chickenpox.[1] About 90% of cases in children are associated with aspirin (salicylate) use.[2] Inborn errors of metabolism are also a risk factor.[3] Changes on blood tests may include a high blood ammonia level, low blood sugar level, and prolonged prothrombin time.[2] Often the liver is enlarged.[2] Prevention is typically by avoiding the use of aspirin in children.[1] When aspirin was withdrawn for use in children a decrease of more than 90% in rates of Reye syndrome was seen.[2] Early diagnosis improves outcomes.[1] Treatment is supportive.[1] Mannitol may be used to help with the brain swelling.[2] The first detailed description of Reye syndrome was in 1963 by Douglas Reye, an Australian pathologist.[4] Children are most commonly affected.[2] It affects fewer than one in a million children a year.[2] The general recommendation to use aspirin in children was withdrawn because of Reye syndrome, with use of aspirin only recommended in Kawasaki disease.[3] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Aspirin * 3 Diagnosis * 3.1 Differential diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 History * 8 References * 9 External links ## Signs and symptoms[edit] Reye syndrome progresses through five stages:[5][6][7] * Stage I * Rash on palms of hands and feet * Persistent, heavy vomiting that is not relieved by not eating * Generalized lethargy * Confusion * Nightmares * No fever usually present[8] * Headaches * Stage II * Stupor * Hyperventilation * Fatty liver (found on biopsy) * Hyperactive reflexes * Stage III * Continuation of Stage I and II symptoms * Possible coma * Possible cerebral edema * Rarely, respiratory arrest * Stage IV * Deepening coma * Dilated pupils with minimal response to light * Minimal but still present liver dysfunction * Stage V * Very rapid onset following stage IV * Deep coma * Seizures * Multiple organ failure[9] * Flaccidity * Hyperammonemia (above 300 mg/dL of blood) * Death ## Causes[edit] The cause of Reye syndrome is unknown.[2] It usually begins shortly after recovery from a viral infection, such as influenza or chickenpox.[1] About 90% of cases in children are associated with aspirin (salicylate) use.[2] Inborn errors of metabolism are also a risk factor.[3] The association with aspirin has been shown through epidemiological studies. The diagnosis of "Reye Syndrome" greatly decreased in the 1980s, when genetic testing for inborn errors of metabolism was becoming available in developed countries.[10] A retrospective study of 49 survivors of cases diagnosed as "Reye's Syndrome" showed that the majority of the surviving patients had various metabolic disorders, particularly a fatty-acid oxidation disorder medium-chain acyl-CoA dehydrogenase deficiency.[11] ### Aspirin[edit] There is an association between taking aspirin for viral illnesses and the development of Reye syndrome,[12] but no animal model of Reye syndrome has been developed in which aspirin causes the condition.[10] The serious symptoms of Reye syndrome appear to result from damage to cellular mitochondria,[13] at least in the liver, and there is a number of ways that aspirin could cause or exacerbate mitochondrial damage. A potential increased risk of developing Reye syndrome is one of the main reasons that aspirin has not been recommended for use in children and teenagers, the age group for which the risk of lasting serious effects is highest.[citation needed] In some countries, oral mouthcare product Bonjela (not the form specifically designed for teething) has labeling cautioning against its use in children, given its salicylate content. There have been no cases of Reye syndrome following its use, and the measure is a precaution.[14] Other medications containing salicylates are often similarly labeled as a precaution.[citation needed] The Centers for Disease Control and Prevention (CDC), the U.S. Surgeon General, the American Academy of Pediatrics (AAP) and the Food and Drug Administration (FDA) recommend that aspirin and combination products containing aspirin not be given to children under 19 years of age during episodes of fever-causing illnesses. Hence, in the United States, it is advised that the opinion of a doctor or pharmacist should be obtained before anyone under 19 years of age is given any medication containing aspirin (also known on some medicine labels as acetylsalicylate, salicylate, acetylsalicylic acid, ASA, or salicylic acid).[citation needed] Current advice in the United Kingdom by the Committee on Safety of Medicines is that aspirin should not be given to those under the age of 16 years, unless specifically indicated in Kawasaki disease or in the prevention of blood clot formation.[15] ## Diagnosis[edit] ### Differential diagnosis[edit] Causes for similar symptoms include[citation needed] * Various inborn metabolic disorders * Viral encephalitis * Drug overdose or poisoning * Head trauma * Liver failure due to other causes * Meningitis * Kidney failure * Shaken baby syndrome ## Treatment[edit] Treatment is supportive.[1] Mannitol may be used to help with the brain swelling.[2] ## Prognosis[edit] Documented cases of Reye syndrome in adults are rare. The recovery of adults with the syndrome is generally complete, with liver and brain function returning to normal within two weeks of onset.[citation needed] In children, mild to severe permanent brain damage is possible, especially in infants. Over thirty percent of the cases reported in the United States from 1981 through 1997 resulted in fatality.[citation needed] ## Epidemiology[edit] Reye syndrome occurs almost exclusively in children. While a few adult cases have been reported over the years, these cases do not typically show permanent neural or liver damage. Unlike in the United Kingdom, the surveillance for Reye syndrome in the United States is focused on people under 18 years of age.[citation needed] In 1980, after the CDC began cautioning physicians and parents about the association between Reye syndrome and the use of salicylates in children with chickenpox or virus-like illnesses, the incidence of Reye syndrome in the United States began to decline, prior to the FDA's issue of warning labels on aspirin in 1986.[10] In the United States between 1980 and 1997, the number of reported cases of Reye syndrome decreased from 555 cases in 1980 to about two cases per year since 1994. During this time period 93% of reported cases for which racial data were available occurred in whites and the median age was six years. In 93% of cases a viral illness had occurred in the preceding three-week period. For the period 1991–1994, the annual rate of hospitalizations due to Reye syndrome in the United States was estimated to be between 0.2 and 1.1 per million population less than 18 years of age.[citation needed] During the 1980s, a case-control study carried out in the United Kingdom also demonstrated an association between Reye syndrome and aspirin exposure.[16] In June 1986, the United Kingdom Committee on Safety of Medicines issued warnings against the use of aspirin in children under 12 years of age and warning labels on aspirin-containing medications were introduced. United Kingdom surveillance for Reye syndrome documented a decline in the incidence of the illness after 1986. The reported incidence rate of Reye syndrome decreased from a high of 0.63 per 100,000 population less than 12 years of age in 1983–1984 to 0.11 in 1990–1991.[citation needed] From November 1995 to November 1996 in France, a national survey of pediatric departments for children under 15 years of age with unexplained encephalopathy and a threefold (or greater) increase in serum aminotransferase and/or ammonia led to the identification of nine definite cases of Reye syndrome (0.79 cases per million children). Eight of the nine children with Reye syndrome were found to have been exposed to aspirin. In part because of this survey result, the French Medicines Agency reinforced the international attention to the relationship between aspirin and Reye syndrome by issuing its own public and professional warnings about this relationship.[17] ## History[edit] The syndrome is named after Douglas Reye, who, along with fellow physicians Graeme Morgan and Jim Baral, published the first study of the syndrome in 1963 in The Lancet.[18] In retrospect, the occurrence of the syndrome may have first been reported in 1929. Also in 1964, George Johnson and colleagues published an investigation of an outbreak of influenza B that described 16 children who developed neurological problems, four of whom had a profile remarkably similar to Reye syndrome. Some investigators refer to this disorder as Reye-Johnson syndrome, although it is more commonly called Reye syndrome. In 1979, Karen Starko and colleagues conducted a case-control study in Phoenix, Arizona, and found the first statistically-significant link between aspirin use and Reye syndrome.[19] Studies in Ohio and Michigan soon confirmed her findings[20] pointing to the use of aspirin during an upper respiratory tract or chickenpox infection as a possible trigger of the syndrome. Beginning in 1980, the CDC cautioned physicians and parents about the association between Reye syndrome and the use of salicylates in children and teenagers with chickenpox or virus-like illnesses. In 1982 the U.S. Surgeon General issued an advisory, and in 1986 the Food and Drug Administration required a Reye syndrome-related warning label for all aspirin-containing medications.[21] ## References[edit] 1. ^ a b c d e f g h i j "NINDS Reye's Syndrome Information Page". NINDS. September 25, 2009. Archived from the original on August 1, 2016. Retrieved August 8, 2016. 2. ^ a b c d e f g h i j k l m n o p q r s t Pugliese, A; Beltramo, T; Torre, D (October 2008). "Reye's and Reye's-like syndromes". Cell Biochemistry and Function. 26 (7): 741–6. doi:10.1002/cbf.1465. PMID 18711704. S2CID 22361194. 3. ^ a b c d e f Schrör, K (2007). "Aspirin and Reye syndrome: a review of the evidence". Paediatric Drugs. 9 (3): 195–204. doi:10.2165/00148581-200709030-00008. PMID 17523700. S2CID 58727745. 4. ^ McMillan, Julia A.; Feigin, Ralph D.; DeAngelis, Catherine; Jones, M. Douglas (2006). Oski's Pediatrics: Principles & Practice. Philadelphia: Lippincott Williams & Wilkins. p. 2306. ISBN 9780781738941. Archived from the original on August 15, 2016. 5. ^ Knight, J. (2009). "Reye's Syndrome". Healthy Child Care. 12 (4). Archived from the original on May 22, 2013. 6. ^ Boldt, D.W. (February 2003). "Reye Syndrome". University of Hawaii John A. Burns School of Medicine. Archived from the original on March 6, 2013. 7. ^ "What is Reye's Syndrome?". National Reye's Syndrome Foundation. 1974. Archived from the original on May 11, 2013. 8. ^ "Reye's Syndrome". KidsHealth.org. Nemour Foundation. Archived from the original on February 6, 2015. Retrieved February 6, 2015. 9. ^ Ku AS, Chan LT (April 1999). "The first case of H5N1 avian influenza infection in a human with complications of adult respiratory distress syndrome and Reye's syndrome". Journal of Paediatrics and Child Health. 35 (2): 207–9. doi:10.1046/j.1440-1754.1999.t01-1-00329.x. PMID 10365363. 10. ^ a b c Orlowski JP, Hanhan UA, Fiallos MR (2002). "Is aspirin a cause of Reye's syndrome? A case against". Drug Safety. 25 (4): 225–31. doi:10.2165/00002018-200225040-00001. PMID 11994026. S2CID 20552758. 11. ^ Orlowski JP (August 1999). "Whatever happened to Reye's syndrome? Did it ever really exist?". Critical Care Medicine. 27 (8): 1582–7. doi:10.1097/00003246-199908000-00032. PMID 10470768. 12. ^ Hurwitz, E. S. (1989). "Reye's syndrome". Epidemiologic Reviews. 11: 249–253. doi:10.1093/oxfordjournals.epirev.a036043. PMID 2680560. 13. ^ Gosalakkal JA, Kamoji V (September 2008). "Reye syndrome and reye-like syndrome". Pediatric Neurology. 39 (3): 198–200. doi:10.1016/j.pediatrneurol.2008.06.003. PMID 18725066. 14. ^ "New advice on oral salicylate gels in under 16s" (Press release). Medicines and Healthcare products Regulatory Agency. April 23, 2009. Archived from the original on April 26, 2009. Retrieved May 1, 2009. 15. ^ "2.9 Antiplatelet drugs". British National Formulary for Children. British Medical Association and Royal Pharmaceutical Society of Great Britain. 2007. p. 151. 16. ^ Hall SM, Plaster PA, Glasgow JF, Hancock P (1988). "Preadmission antipyretics in Reye's syndrome". Arch. Dis. Child. 63 (7): 857–66. doi:10.1136/adc.63.7.857. PMC 1779086. PMID 3415311. 17. ^ Autret-Leca E, Jonville-Béra AP, Llau ME, et al. (2001). "Incidence of Reye's syndrome in France: a hospital-based survey". Journal of Clinical Epidemiology. 54 (8): 857–62. doi:10.1016/S0895-4356(00)00366-8. PMID 11470397. 18. ^ Reye RD, Morgan G, Baral J (1963). "Encephalopathy and fatty degeneration of the viscera. A Disease entity in childhood". Lancet. 2 (7311): 749–52. doi:10.1016/S0140-6736(63)90554-3. PMID 14055046. 19. ^ Starko KM, Ray CG, Dominguez LB, Stromberg WL, Woodall DF (December 1980). "Reye's syndrome and salicylate use". Pediatrics. 66 (6): 859–864. PMID 7454476. 20. ^ Mortimor, Edward A. Jr.; et al. (June 1, 1980). "Reye Syndrome-Ohio, Michigan". Morbidity and Mortality Weekly Report. 69 (29): 532, 810–2. PMID 7079050. Archived from the original on June 11, 2008. 21. ^ "Aspirin Labels to Warn About Reye Syndrome". The New York Times. Associated Press. March 8, 1986. Archived from the original on March 5, 2016. ## External links[edit] * NINDS Reye's Syndrome Information Page Classification D * ICD-10: G93.7 * ICD-9-CM: 331.81 * MeSH: D012202 * DiseasesDB: 11463 * SNOMED CT: 74351001 External resources * MedlinePlus: 001565 * eMedicine: emerg/399 * Patient UK: Reye syndrome * Orphanet: 3096 * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis Authority control * LCCN: sh85113551 * NDL: 00576410 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid	Reye syndrome	c0035400	5,399	wikipedia	https://en.wikipedia.org/wiki/Reye_syndrome	2021-01-18T18:28:02	{"gard": ["7570"], "mesh": ["D012202"], "umls": ["C0035400"], "orphanet": ["3096"], "wikidata": ["Q826103"]}

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