Datasets:

findzebra
/

corpus

Dataset card Data Studio Files Files and versions Community

Split (1)

train · 30.7k rows

text stringlengths 297 230k	title stringlengths 4 145	cui stringlengths 4 10	idx int64 0 30.7k	source stringclasses 6 values	source_url stringlengths 33 155	retrieved_date timestamp[s]	classification_map stringlengths 2 1.45k
Shotelersuk et al. (2003) described a Thai sister and brother, born of healthy, unrelated parents, with a combination of features interpreted as representing a novel autosomal recessive multiple congenital anomalies/mental retardation (MCA/MR) syndrome. Both sibs had postnatal-onset growth deficiency, microcephaly with cortical dysplasia and cerebellar atrophy, bilateral lenticular cataracts, prominent supraorbital ridges, large joint contractures, severe osteoporosis, and mental retardation. The brother also had infrequent tonic-clonic seizures beginning at age 5 years, an arachnoid cyst in the right temporal area, bilateral ankle clonus, and upgoing plantar reflexes. Two other sibs were healthy. Shotelersuk et al. (2003) compared and contrasted the syndrome in these 2 sibs with other syndromes characterized by microcephaly, mental retardation, growth failure, and childhood cataracts. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Postnatal growth deficiency HEAD & NECK Head \- Microcephaly Face \- Prominent supraorbital ridges Eyes \- Cataracts, lenticular, bilateral SKELETAL \- Osteoporosis \- Contractures of the large joints NEUROLOGIC Central Nervous System \- Motor developmental delay, severe \- Mental retardation, severe \- No speech \- Cortical dysplasia \- Cerebellar atrophy \- Seizures, tonic-clonic ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	GROWTH FAILURE, MICROCEPHALY, MENTAL RETARDATION, CATARACTS, LARGE JOINT CONTRACTURES, OSTEOPOROSIS, CORTICAL DYSPLASIA, AND CEREBELLAR ATROPHY	c1842321	28,600	omim	https://www.omim.org/entry/608278	2019-09-22T16:08:02	{"mesh": ["C564264"], "omim": ["608278"]}
A number sign (#) is used with this entry because pycnodysostosis is caused by homozygous or compound heterozygous mutation in the cathepsin K gene (CTSK; 601105) on chromosome 1q21. Clinical Features The features of pycnodysostosis are deformity of the skull (including wide sutures), maxilla and phalanges (acroosteolysis), osteosclerosis, and fragility of bone. The disorder was first described and named by Maroteaux and Lamy (1962). Andren et al. (1962) simultaneously and independently delineated this syndrome. They found 11 patients reported under various designations and added the cases of monozygotic twins. Some of these cases have probably been diagnosed as osteopetrosis (see OPTB1, 259700), e.g., the case described by Seigman and Kilby (1950) in a black female whose parents were first or second cousins. Kajii et al. (1966) described a Japanese case in the daughter of a first-cousin marriage. From Portugal, Meneses de Almeida (1972) reported 7 cases in 4 families, of whom 3 had consanguineous parents. Kozlowski and Yu (1972) described a child who had hematologic features, hepatosplenomegaly and anemia, similar to those of osteopetrosis. The report by Mills and Johnston (1988) of 2 Scottish brothers, born in 1932 and 1944, described the late changes of the disorder, which included irregular resorption of the middle phalanges as well as the terminal phalanges. In a 24-year-old man with typical features of pycnodysostosis, Figueiredo et al. (1989) found large porencephalic cysts. A brother also had pycnodysostosis. The parents were not known to be related but were born in the same small village in Madeira. Edelson et al. (1992) examined 14 cases of pycnodysostosis in a small Arab village with 3,000 inhabitants. They pictured 4 affected sibs, including fraternal male twins. An extensive pedigree was presented. The features that they pointed out included stress fractures of the tibia and femur, spondylolysis of L4 and L5, healed hangman's fracture of C2 (fracture of the pedicle), and a double row of teeth resulting from persistence of deciduous teeth. Also see craniostenosis (123100) and acroosteolysis with osteoporosis and changes in skull and mandible (102500). Biochemical Features Soliman et al. (1996) reported defective growth hormone secretion in response to provocation and low insulin-like growth factor-1 (147440) concentration in 5 out of 6 patients with pycnodysostosis. Physiologic replacement with growth hormone increased IGF1 concentration and improved linear growth in these children. The IGF1 generation time ruled out significant resistance to growth hormone. Growth hormone treatment was used in 2 children. The normal TSH, free thyroxine, and 8-hour cortisol concentrations ruled out any significant abnormality of the hypothalamic-pituitary, thyroid, and adrenal axes in these patients. The normal sexual development, fertility, and serum gonadotropin and testosterone concentrations in the 2 affected adult males were evidence against any abnormality of the hypothalamic-pituitary-gonadal axis. Inheritance Sedano et al. (1968) found parental consanguinity in about 30% of reported cases, indicating autosomal recessive inheritance. Mapping In the inbred Arab kindred reported by Edelson et al. (1992), Gelb et al. (1995) demonstrated by linkage analysis that the pycnodysostosis locus is located on 1q21. Polymeropoulos et al. (1995) found the same linkage in an inbred Mexican kindred. In both cases, homozygosity mapping was used initially. In the Arab kindred, Gelb et al. (1995) found that 13 of 16 affected individuals were homozygous for the D1S305 allele, which had previously been assigned to the pericentromeric region of chromosome 1. Using markers flanking the centromere of chromosome 1, they localized the PKND locus to a region of about 4 cM between D1S442 and D1S305. D1S442 had previously been assigned to 1q21 by fluorescence in situ hybridization. They pointed to the interleukin-6 receptor (IL6R; 147880) and myeloid cell leukemia-1 (MCL1; 159552) as plausible candidate genes. IL6R induces the formation of osteoclasts and is highly expressed in osteoclasts from bone of patients with Paget disease (see 167250) and osteoarthritis. For the initial screening in the Mexican kindred, Polymeropoulos et al. (1995) used a pooling strategy in which DNA from affected individuals was pooled and genotyped. Using a total of 363 genetic markers, they compared the allelic ladders produced with those from a pool of unaffected heterozygous parents genotyped with the same markers. They noticed a reduction in the complexity of the number of alleles observed in the affected pool for markers D1S1595 and D1S534. Genetic linkage analysis was then performed in the family, confirming linkage for marker D1S1595 with a lod score of 4.11 at theta = 0.05, and for D1S534 with a lod score of 2.05 at theta = 0.08. Haplotype analysis in affected individuals placed the PKND gene in a 6-cM interval between markers D1S514 and D1S305. Polymeropoulos et al. (1995) suggested that macrophage colony-stimulating factor (CSF1; 120420) might be a candidate gene, but CSF1 maps to the proximal short arm of chromosome 1; indeed, they could demonstrate no mutations in the gene by SSCP analysis. They also suggested that one of the calcium-binding protein genes that are clustered at 1q21 may be the site of the mutation. Molecular Genetics Because cathepsin K (601105), a cysteine protease gene that is highly expressed in osteoclasts, maps to the same region as pycnodysostosis, Gelb et al. (1996) searched for mutations in the cathepsin K gene. They identified nonsense, missense, and stop codon mutations in patients (601105.0001-601105.0004). Transient expression of cDNA containing the stop codon mutation resulted in mRNA, but no immunologically detectable protein was present. The findings suggested to the authors that cathepsin K is a major protease in bone resorption, providing a possible rationale for the treatment of disorders such as osteoporosis and certain forms of arthritis. Bone resorption, a process mediated by osteoclasts, is characterized by the solubilization of inorganic mineral and subsequent proteolytic degradation of organic matrix, primarily type I collagen. In pycnodysostosis, osteoclast numbers are normal as are their ruffled borders and clear zones, but the region of demineralized bone surrounding individual osteoclasts is increased. Ultrastructural examination of these osteoclasts revealed large, abnormal cytoplasmic vacuoles containing bone collagen fibrils. These findings suggested that pycnodysostosis osteoclasts function normally in demineralizing bone, but do not adequately degrade the organic matrix. Cathepsin S (116845), which also maps to 1q, was ruled out as a candidate gene for pycnodysostosis (Gelb et al., 1996). Gelb et al. (1998) identified paternal uniparental disomy for chromosome 1 as the molecular basis of pycnodysostosis in a patient who had normal birth weight and height, had normal psychomotor development at age 7 years, and had only the usual features of pycnodysostosis. The patient represented the first case of paternal uniparental disomy of chromosome 1 and provided conclusive evidence that paternally derived genes on human chromosome 1 are not imprinted. The missense mutation in this case, inherited only from the father, was ala277 to val (601105.0004). In affected individuals from 8 unrelated families with pycnodysostosis, Hou et al. (1999) identified homozygosity for 8 different mutations in the cathepsin K gene. Animal Model For information on animal models of pycnodysostosis, see 601105. History Maroteaux and Lamy (1965) suggested that Toulouse-Lautrec (1864-1901) had pycnodysostosis. Features consistent with the disorder were dwarfing, parental consanguinity, bone fracture with relatively mild trauma, and probably large fontanels, prompting him to wear a hat much of the time. Maroteaux (1993) gave a charming and well-illustrated account of the case of Toulouse-Lautrec. Frey (1994) and Frey (1995) presented evidence suggesting that pycnodysostosis was not the diagnosis in the case of Toulouse-Lautrec. See the rebuttal by Maroteaux (1995) and the response to the rebuttal by Frey (1995). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature \- Adult height less than 150 cm HEAD & NECK Head \- Frontal and occipital prominence \- Persistent open anterior fontanelle Face \- Frontal bossing \- Micrognathia Nose \- Prominent nose Mouth \- Narrow palate Teeth \- Delayed eruption of deciduous teeth \- Persistence of deciduous teeth \- Delayed eruption of permanent teeth \- Hypodontia \- Caries CHEST Ribs Sternum Clavicles & Scapulae \- Aplasia of clavicle \- Hypoplasia of clavicle SKELETAL \- Osteosclerosis \- Susceptibility to fracture Skull \- Wormian bone \- Dense skull \- Delayed suture closure \- Absent frontal sinus \- Obtuse angle to mandible Spine \- Scoliosis \- Spondylolysis \- Spondylolisthesis Pelvis \- Narrow ilia Hands \- Brachydactyly \- Acro-osteolysis of distal phalanges SKIN, NAILS, & HAIR Skin \- Wrinkled skin over dorsa of fingers Nails \- Grooved nails \- Flattened nails MOLECULAR BASIS \- Caused by mutations in the cathepsin K gene (CTSK, 601105.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	PYCNODYSOSTOSIS	c0238402	28,601	omim	https://www.omim.org/entry/265800	2019-09-22T16:22:58	{"doid": ["0080038"], "mesh": ["D058631"], "omim": ["265800"], "orphanet": ["763"], "synonyms": ["Alternative titles", "PYKNODYSOSTOSIS", "PYCD"]}
Barber Say syndrome is a very rare condition characterized by the association of excessive hair growth (hypertrichosis), papery thin and fragile (atrophic) skin, outward turned eyelids (ectropion) and a large mouth (macrostomia). It has been described in less than 20 patients in the medical literature. Barber Say syndrome has a variable presentation, with reports of both mild and severe cases. Inheritance has been debated, with qualities suggestive of autosomal dominant and autosomal recessive. A recent study suggests that at least some cases of Barber Say syndrome are caused by dominant mutations in the TWIST2 gene. Treatment remains a challenge for both patients and doctors, and requires a multidisciplinary approach. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Barber Say syndrome	c1319466	28,602	gard	https://rarediseases.info.nih.gov/diseases/819/barber-say-syndrome	2021-01-18T18:01:53	{"mesh": ["C537908"], "omim": ["209885"], "umls": ["C1319466"], "orphanet": ["1231"], "synonyms": ["Hypertrichosis, atrophic skin, ectropion, and macrostomia", "Hypertrichosis atrophic skin ectropion macrostomia"]}
A number sign (#) is used with this entry because of evidence that developmental delay, intellectual disability, obesity, and dysmorphism (DIDOD) is caused by heterozygous mutation in the PHIP gene (612870) on chromosome 6q14. Description DIDOD is a disorder characterized by global developmental delay apparent from infancy, intellectual disability or learning difficulties, behavioral abnormalities, dysmorphic features, and obesity. The severity of the phenotype and additional features are variable (summary by Jansen et al., 2018). Clinical Features De Ligt et al. (2012) reported a girl with moderate gross motor delay, broad-based gait, severe speech delay, and intellectual disability. She had dysmorphic features, including straight eyebrows, strabismus, blepharophimosis, ptosis, a long philtrum and full lips, tapered fingers, clinodactyly of fifth fingers, and long toes. Brain imaging was normal. Jansen et al. (2018) reported follow-up of this patient (patient 8), noting that she also had stereotypic behavior and anxiety. Jansen et al. (2018) stated that brain MRI of this patient showed slightly enlarged gyri and sulci and atypical large cavum septum pellucidum. Webster et al. (2016) reported 2 unrelated girls with a developmental disorder characterized by global developmental delay, intellectual disability, anxiety, hypotonia, poor balance, obesity, and dysmorphic features. Both girls had normal weight at birth but became obese later in childhood, with weight and body mass index (BMI) above the 97th percentile. Patient 1 was a 14-year-old girl who also had insulin resistance and polycystic ovary syndrome, and patient 2 was an 8-year-old girl with behavioral issues, including aggression. Dysmorphic features in patient 2 included fleshy ears, small nose, deep-set eyes, short philtrum, micrognathia, round face, and upturned upper lip. Brain imaging was normal in both girls. Jansen et al. (2018) reported 21 patients, including 2 sets of sib pairs and the patient reported by de Ligt et al. (2012) (patient 8), with DIDOD associated with point mutations in the PHIP gene. Two additional patients had gross chromosomal abnormalities, including a translocation (patient 13) and a large deletion encompassing several genes (patient 14). Three patients (patients 3, 9, and 17) carried variants of uncertain significance in another gene in addition to mutation in PHIP, although the PHIP mutations were considered to be responsible for the neurologic phenotype. The patients had global developmental delay, variable intellectual disability or learning difficulties, and behavioral problems, such as autistic features, attention deficit-hyperactivity disorder (ADHD), anxiety, aggression, poor impulse control, and mood disorders. Most had obesity and dysmorphic features, including high forehead, full eyebrows/synophrys, full fleshy ears, upturned nose with thick alae nasi, long philtrum, and thin lips. Additional features included hypotonia, easy fatigability, tapered fingers, clinodactyly, and skin syndactyly of the second and third toes. More variable features included high palate, hypertelorism, upslanting palpebral fissures, epicanthal folds, strabismus, cryptorchidism, joint hypermobility, cafe-au-lait spots, hypermetropia, and nystagmus. Most patients had normal brain imaging, but some had nonspecific mild abnormalities. Molecular Genetics In a girl with DIDOD, de Ligt et al. (2012) identified a de novo heterozygous nonsense mutation in the PHIP gene (Y1149X; 612870.0001). The patient was ascertained from a cohort of 100 patients with severe intellectual disability who underwent exome sequencing. Functional studies of the variant were not performed. In 2 unrelated girls with DIDOD, Webster et al. (2016) identified different de novo heterozygous mutation in the PHIP gene (F17S, 612870.0002 and c.779delT, 612870.0003). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Functional studies of the variants and studies of patient cells were not performed, but Webster et al. (2016) postulated haploinsufficiency as a mechanism, since 1 of the mutations was predicted to result in a frameshift and premature termination. The patients were part of a cohort of 2,522 patients with developmental delay or intellectual disability who underwent whole-exome sequencing. In 20 patients with DIDOD, Jansen et al. (2018) identified heterozygous point mutations in the PHIP gene (see, e.g., 612870.0004-612870.0007). Most of the mutations occurred de novo, but parental DNA was not available for all patients. There were 2 sets of affected sibs, including 2 sisters (patients 18 and 19) who inherited a mutation from their mildly affected father, and a brother and sister (patients 6 and 7) whose mother did not carry the mutation and whose father was not available for testing, suggesting either paternal inheritance or germline mosaicism. The first 5 individuals with loss-of-function point mutations in the PHIP gene were ascertained from a cohort of 3,275 patients with intellectual disability collected through international collaboration who underwent targeted resequencing of 24 candidate genes. The remaining individuals were collected from data-sharing resources. Functional studies of the variants and studies of patient cells were not performed, but Jansen et al. (2018) concluded that the mutations resulted in haploinsufficiency of PHIP as the underlying cause of the phenotype. INHERITANCE \- Autosomal dominant GROWTH Weight \- Obesity HEAD & NECK Face \- High forehead \- Micrognathia \- Round face \- Short philtrum \- Long philtrum Ears \- Large ears \- Thick helices \- Thick earlobes Eyes \- Thick eyebrows \- Synophrys \- Hypertelorism \- Upslanting palpebral fissures \- Epicanthal folds \- Strabismus \- Hypermetropia \- Nystagmus Nose \- Small nose \- Upturned nose \- Thick alae nasi Mouth \- High palate \- Thin lips GENITOURINARY External Genitalia (Male) \- Cryptorchidism SKELETAL \- Joint hypermobility Hands \- Tapering fingers \- Clinodactyly Feet \- Skin syndactyly of the second and third toes SKIN, NAILS, & HAIR Skin \- Cafe au lait spots MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Global developmental delay \- Intellectual disability \- Learning disabilities Behavioral Psychiatric Manifestations \- Anxiety \- Aggression \- Autistic features \- Impulsivity \- Mood disorders \- Attention deficit-hyperactivity disorder (ADHD) MISCELLANEOUS \- Onset in infancy \- Variable features and severity \- Most mutations occur de novo MOLECULAR BASIS \- Caused by mutation in the pleckstrin homology domain-interacting protein gene (PHIP, 612870.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	DEVELOPMENTAL DELAY, INTELLECTUAL DISABILITY, OBESITY, AND DYSMORPHISM	c4693860	28,603	omim	https://www.omim.org/entry/617991	2019-09-22T15:44:08	{"omim": ["617991"]}
A number sign (#) is used with this entry because autosomal dominant cutis laxa-1 (ADCL1) is caused by heterozygous mutations in the elastin gene (ELN; 130160) on chromosome 7q11. Description Cutis laxa is a collection of disorders that are typified by loose and/or wrinkled skin that imparts a prematurely aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The skin lacks elastic recoil, in marked contrast to the hyperelasticity apparent in classic Ehlers-Danlos syndrome (see 130000). These properties are nearly always attributable to loss, fragmentation, or severe disorganization of dermal elastic fibers (summary by Davidson and Giro, 2002). Autosomal dominant congenital cutis laxa (ADCL) is genetically heterogeneous and shows clinical variability. The characteristic loose skin may be accompanied by gastrointestinal diverticula, hernia, and genital prolapse. Rare manifestations are pulmonary artery stenosis, aortic aneurysm, bronchiectasis, and emphysema (summary by Graul-Neumann et al., 2008). Loose, inelastic skin is a clinical feature of many disorders, e.g., geroderma osteodysplasticum (GO; 231070) and Costello syndrome (218040). For a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100). ### Genetic Heterogeneity of Autosomal Dominant Cutis Laxa Also see ADCL2 (614434), caused by mutation in the FBLN5 gene (604580) on chromosome 14q32, and ADCL3 (616603), caused by mutation in the ALDH18A1 (138250) gene on chromosome 10q24. Clinical Features Sestak (1962) reported a father and daughter with cutis laxa. Goltz (1966) studied a family with affected persons in successive generations. Balboni (1963) described a child with typical cutis laxa and multiple vascular anomalies including coarctation of the aorta. The father and a paternal uncle were thought to have the same condition. Beighton (1972) described 2 pedigrees with 2 or more generations affected. In each pedigree there was an instance of male-to-male transmission. In each case, however, the relevant males were not examined by the author. In the early report of Kopp (1888), the father had onset of cutis laxa at age 16, and in the son cutis laxa was present at birth. Other 'dominant' pedigrees were reported by Lewis (1948) (mother and daughter), Reidy (1963) (father and daughter), and Schreiber and Tilley (1961) (4 generations). (Another of the families reported by Schreiber and Tilley (1961), viz., no. 1, had the acromegaloid syndrome (102100).) Damkier et al. (1991) described cutis laxa in 6 members of 5 generations. All were female except for the proband, a 17-year-old man in the most recent generation. The onset of skin manifestations occurred between puberty and early adulthood. In the man's mother and maternal grandmother, numerous gastrointestinal diverticula were demonstrated, and both had been operated on for abdominal hernia and genital prolapse. There were no cardiopulmonary symptoms. Marchase et al. (1980) described a mother and son with cutis laxa and concluded that there were abnormalities in both elastic tissue and collagen. The son had Klippel-Trenaunay-Weber syndrome (149000). An acquired form of cutis laxa, called generalized elastolysis, has been described in at least 17 cases (Harris et al., 1978). In this disorder elastic fibers rather abruptly become fragmented, disorganized and scarce with resultant emphysema, aortic aneurysm and bowel diverticula, in addition to cutis laxa. An erythematous rash suggesting penicillin reaction occurred at the onset of elastolysis in some patients. Hiatal and other hernias and rupture of patellar tendons were also noted. It is well to remember that cutis laxa can be acquired as an autoimmune process (Tsuji et al., 1987). Other phenocopies of genetic disorders on the basis of autoimmune mechanisms are represented by acquired von Willebrand disease (see 193400) and congenital heart block (234700) occurring in the offspring of mothers with systemic lupus erythematosus. Corbett et al. (1994) described a 51-year-old mother and her 23-year-old daughter with congenital cutis laxa and early-onset emphysema. Both mother and daughter had been smokers and were heterozygous (MZ) for alpha-1-antitrypsin deficiency (613490). Urban et al. (2005) provided follow-up on the family described by Corbett et al. (1994): the mother's pulmonary disease progressed to end-stage respiratory failure requiring double lung transplant, and she died at age 61 of renal failure secondary to immunosuppressant treatment. The maternal grandmother, originally reported by Beighton (1972), had congenital cutis laxa and later developed an inguinal hernia, uterine prolapse, dyspnea, and bronchiectasis. The maternal great-grandmother, an uncle, and a cousin were also reportedly affected by cutis laxa, but were unavailable for examination. Tassabehji et al. (1998) reported a 37-year-old Caucasian woman with cutis laxa who underwent her first facial cosmetic surgery at 4 years of age, with 6 subsequent operations. Bilateral herniorraphies were performed at 7 years of age. A cardiac murmur was noted at 4 years of age, and when she presented with reduced exercise tolerance at 19 years, right ventricular hypertrophy was noted. Right ventricular angiography showed hypertrophy of the infundibulum with angiographic narrowing. There were multiple peripheral pulmonary stenoses, including stenoses in very small vessels. The father, described by Reidy (1963), had loose skin on his chest, forearms, and abdomen in addition to facial drooping, and had 2 cosmetic operations in his teenage years. He had required an inguinal herniorraphy, but apart from venous thrombosis at the age of 50 years, had remained in good health. The proband had suffered from Raynaud phenomenon since late adolescence. Zhang et al. (1999) provided clinical information on a patient with cutis laxa in whom Zhang et al. (1997) had identified heterozygosity for a 2012G deletion in the ELN gene (130160.0008). Loose skin, stridor, and feeding difficulties were apparent from birth. Additional clinical findings ascertained during infancy included moderate subglottic stenosis with floppy airway structures, redundant mitral and tricuspid valves, mild dilatation of the proximal aorta and great vessels, and umbilical and inguinal hernias. He underwent inguinal herniorrhaphies at ages 7 months, 3 years, and 14 years. At age 17 years, his height and weight were at the 75th percentile. Physical examination showed an aged appearance, with smooth, loose skin lacking elastic recoil; tortuous, pulsatile external carotid arteries; and a hoarse voice. He complained of fatigue, dyspnea on exertion, and shortness of breath. Aortic root dilatation was described as minimal. Pulmonary function testing showed reduced expiratory flow, suggestive of fixed or collapsible upper airway obstruction. Histologically, dermal collagen fibers appeared normal, but elastic fibers appeared fragmented with a paucity of amorphous elastin in the matrix. Tropoelastin production in cultured fibroblasts from this patient was the lowest of 6 cutis laxa patients studied (Sephel et al., 1989), and an apparent nonspecific increase in type VI collagen (120220) production was noted. Szabo et al. (2006) reported a 3-generation family of Japanese and German ancestry and an unrelated Singaporean girl of Chinese descent with cutis laxa and aortic aneurysmal disease. The proband in the Japanese-German family was an 11-year-old girl who, along with her paternal grandmother, had a mildly dilated aortic root, mild aortic insufficiency, and obvious cutis laxa. Her 38-year-old father had a large aneurysm of the sinuses of Valsalva and ascending aorta, requiring grafting and valve replacement; he had barely noticeable skin laxity. His brother, the proband's uncle, died at age 26 of aortic dissection with no other apparent systemic involvement or skin laxity. Histologic examination of aneurysmal tissue from this patient revealed medial degeneration characterized by a dramatic loss of the elastic lamellae and smooth muscle cells and a lack of atherosclerotic and inflammatory lesions. The daughter of the deceased brother, the proband's cousin, had cutis laxa and mild aortic dilation. The proband and her father and grandmother all had inguinal hernias repaired surgically. The unrelated Singaporean girl, who had no family history of cutis laxa, was noted at birth to have marked laxity of the skin. An echocardiogram at age 5 showed significant dilation of the aortic root at the level of the sinuses of Valsalva. Szabo et al. (2006) concluded that severe aortic disease may be present in patients with cutis laxa and that regular cardiac monitoring is necessary to avert fatal aortic rupture. Graul-Neumann et al. (2008) described a boy with autosomal dominant severe cutis laxa, severe congenital pulmonary disease, which had not previously been reported in ADCL, and supravalvular pulmonary artery stenosis. He was the first child born to unrelated parents. Physical examination at birth revealed generalized loose skin, inguinal and umbilical hernias, and hypotonia. Immediately after birth, he developed respiratory distress syndrome characterized by repeated pneumothoraces and emphysema. At 7 months of age, he developed infantile spasms (308350). At 15 months, he was able to vocalize but could only sit with support. His father had a grade 1 aortic valvular insufficiency but did not show any signs of cutis laxa with normal elasticity and recoil of the skin. Electron microscopy of the proband's skin demonstrated only mild rarefication of elastic fibers (in contrast to most recessive cutis laxa types). No mutations were found in the FBLN4 (604633) or FBLN5 genes. A novel heterozygous splice site mutation in the ELN gene (130160.0019) was detected in the proband and his clinically healthy father. Graul-Neumann et al. (2008) concluded that the variable processing of an identically mutated gene (dominant-negative in the child and haploinsufficiency in the father) caused the highly variable clinical appearance of ADCL in this family. Molecular Genetics Zhang et al. (1997, 1999) and Tassabehji et al. (1998) independently described patients with autosomal dominant cutis laxa and mutations in the elastin gene (see 130160.0008-130160.0010). In the mother and daughter with cutis laxa and severe pulmonary disease described by Beighton (1972) and Corbett et al. (1994), Urban et al. (2005) identified no mutations in the elastin gene by direct sequencing, but detected an abnormal protein in cultured dermal fibroblasts using metabolic labeling and immunoprecipitation. Mutation and gene expression analyses established the presence of a complex tandem duplication in the elastin gene (130160.0016). Immunoprecipitation showed that the mutant tropoelastin was partially secreted and partially retained intracellularly; a polyclonal antibody raised against a unique peptide in the mutant molecule showed both intracellular and matrix staining. Urban et al. (2005) concluded that mutations in the elastin gene can cause cutis laxa associated with a severe pulmonary phenotype. In affected members of a 3-generation family of Japanese and German ancestry and an unrelated Singaporean girl of Chinese descent with cutis laxa and aortic aneurysmal disease, Szabo et al. (2006) identified heterozygosity for a 25-bp deletion (130160.0017) and a 1-bp deletion (130160.0018) in the ELN gene, respectively. History Wiener (1925) reported dominant inheritance of cutis laxa, but Beighton (1972) concluded that the family reported by Wiener (1925) had the Ehlers-Danlos syndrome. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Premature aged appearance CARDIOVASCULAR Heart \- Mitral valve regurgitation \- Aortic valve regurgitation RESPIRATORY Lung \- Emphysema GENITOURINARY External Genitalia (Male) \- Inguinal hernia SKIN, NAILS, & HAIR Skin \- Cutis laxa \- Loose redundant skin \- Skin lacks elastic recoil \- Excessive skin folds \- No skin hyperelasticity \- Normal wound healing Skin Histology \- Sparse, fragmented elastic fibers MISCELLANEOUS \- Genetic heterogeneity \- Onset of skin manifestations from birth to puberty MOLECULAR BASIS \- Caused by mutation in the elastin gene (ELN, 130160.0008 ) \- Caused by mutation in the fibulin 5 gene (FBLN5, 604580.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CUTIS LAXA, AUTOSOMAL DOMINANT 1	c0268350	28,604	omim	https://www.omim.org/entry/123700	2019-09-22T16:42:37	{"doid": ["0070130"], "mesh": ["C562627"], "omim": ["123700"], "orphanet": ["90348"]}
A very rare autosomal recessive, slowly progressive neurodegenerative disorder characterized by the triad of cerebellar ataxia (that generally manifests at adolescence or early adulthood), chorioretinal dystrophy, which may have a later onset (up to the fifth-sixth decade) leading to variable degrees of visual impairment, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). Ataxia-hypogonadism-choroidal dystrophy syndrome belongs to a clinical continuum of neurodegenerative disorders along with the clinically overlapping cerebellar ataxia-hypogonadism 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 [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ataxia-hypogonadism-choroidal dystrophy syndrome	c1859093	28,605	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1180	2021-01-23T18:40:41	{"gard": ["944"], "mesh": ["C565850"], "omim": ["215470"], "umls": ["C1859093"], "icd-10": ["G11.8"], "synonyms": ["Boucher-Neuhäuser syndrome"]}
Lichen scrofulosorum Other namesTuberculosis cutis lichenoides SpecialtyInfectious disease Lichen scrofulosorum is a rare tuberculid that presents as a lichenoid eruption of minute papules in children and adolescents with tuberculosis. The lesions are usually asymptomatic, closely grouped, skin-colored to reddish-brown papules, often perifollicular and are mainly found on the abdomen, chest, back, and proximal parts of the limbs. The eruption is usually associated with a strongly positive tuberculin reaction.[1] Of the three tuberculids, the incidence of lichen scrofulosorum was found to be the lowest (2%) in a large study conducted in Hong Kong. This highlights its rarity and significance as an important marker of undetected tuberculosis.[2] ## See also[edit] * Tuberculid * List of cutaneous conditions ## References[edit] 1. ^ In: Burns T, Breatnach S, Cox N, Griffiths C, editors. (2004). Rook's textbook of dermatology. 7th ed. Oxford: Blackwell Science. pp. 28.1–28.39.CS1 maint: multiple names: authors list (link) 2. ^ Cutaneous tuberculosis in Hongkong: A ten year retrospective study. Int J Dermatol. 1995. pp. 34:26–9. ## External links[edit] Classification D * ICD-10: A18.4 (ILDS A18.484) * DiseasesDB: 34594 * v * t * e Gram-positive bacterial infection: Actinobacteria Actinomycineae Actinomycetaceae * Actinomyces israelii * Actinomycosis * Cutaneous actinomycosis * Tropheryma whipplei * Whipple's disease * Arcanobacterium haemolyticum * Arcanobacterium haemolyticum infection * Actinomyces gerencseriae Propionibacteriaceae * Propionibacterium acnes Corynebacterineae Mycobacteriaceae M. tuberculosis/ M. bovis * Tuberculosis: Ghon focus/Ghon's complex * Pott disease * brain * Meningitis * Rich focus * Tuberculous lymphadenitis * Tuberculous cervical lymphadenitis * cutaneous * Scrofuloderma * Erythema induratum * Lupus vulgaris * Prosector's wart * Tuberculosis cutis orificialis * Tuberculous cellulitis * Tuberculous gumma * Lichen scrofulosorum * Tuberculid * Papulonecrotic tuberculid * Primary inoculation tuberculosis * Miliary * Tuberculous pericarditis * Urogenital tuberculosis * Multi-drug-resistant tuberculosis * Extensively drug-resistant tuberculosis M. leprae * Leprosy: Tuberculoid leprosy * Borderline tuberculoid leprosy * Borderline leprosy * Borderline lepromatous leprosy * Lepromatous leprosy * Histoid leprosy Nontuberculous R1: * M. kansasii * M. marinum * Aquarium granuloma R2: * M. gordonae R3: * M. avium complex/Mycobacterium avium/Mycobacterium intracellulare/MAP * MAI infection * M. ulcerans * Buruli ulcer * M. haemophilum R4/RG: * M. fortuitum * M. chelonae * M. abscessus Nocardiaceae * Nocardia asteroides/Nocardia brasiliensis/Nocardia farcinica * Nocardiosis * Rhodococcus equi Corynebacteriaceae * Corynebacterium diphtheriae * Diphtheria * Corynebacterium minutissimum * Erythrasma * Corynebacterium jeikeium * Group JK corynebacterium sepsis Bifidobacteriaceae * Gardnerella vaginalis This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Lichen scrofulosorum	c0275935	28,606	wikipedia	https://en.wikipedia.org/wiki/Lichen_scrofulosorum	2021-01-18T18:33:43	{"umls": ["C0275935"], "icd-10": ["A18.4"], "wikidata": ["Q6543213"]}
A number sign (#) is used with this entry because of evidence that congenital disorder of glycosylation type Ix (CDG1X) is caused by homozygous mutation in the STT3B gene (608605) on chromosome 3p23. One such patient has been reported. Clinical Features Shrimal et al. (2013) reported a boy, born of consanguineous Iraqi parents, with a congenital disorder of glycosylation. He had severe developmental delay and congenital anomalies, including microcephaly, failure to thrive, lack of visual tracking and optic nerve hypoplasia, cerebellar atrophy, seizures, hypotonia, liver involvement, thrombocytopenia, micropenis, hypoplastic scrotum, and undescended testes. He died at age 4 years. Serum transferrin showed only a slightly abnormal glycosylation pattern, suggesting that this method may not be reliable for determination of the phenotype. Inheritance The transmission pattern of CDG1X in the family reported by Shrimal et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In a boy, born of consanguineous Iraqi parents, with congenital disorder of glycosylation type Ix, Shrimal et al. (2013) identified a homozygous mutation in the STT3B gene (608605.0001). The mutation was found by homozygosity mapping and candidate gene sequencing. Patient cells showed no STT3B mRNA and severely reduced protein expression. Patient cells showed incomplete N-glycosylation that was complemented by wildtype STT3B, as well as lower glycosylation of the STT3B substrates SHBG (182205) and beta-glucuronidase (GUSB; 611499) compared to control cells. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation \- Failure to thrive HEAD & NECK Head \- Microcephaly Eyes \- Optic nerve atrophy \- No visual tracking RESPIRATORY \- Respiratory difficulties ABDOMEN Liver \- Liver dysfunction Gastrointestinal \- Feeding problems GENITOURINARY External Genitalia (Male) \- Micropenis \- Hypoplastic scrotum Internal Genitalia (Male) \- Cryptorchidism NEUROLOGIC Central Nervous System \- Delayed psychomotor development, severe \- Mental retardation \- Seizures \- Hypotonia \- Cerebellar atrophy HEMATOLOGY \- Thrombocytopenia LABORATORY ABNORMALITIES \- Mildly abnormal glycosylation of serum transferrin, type 1 pattern \- Incomplete N-glycosylation of cellular proteins MISCELLANEOUS \- One patient has been reported (last curated January 2014) \- Onset at birth \- Death in childhood MOLECULAR BASIS \- Caused by mutation in the STT3, subunit of the oligosaccharyltransferase complex, S. cerevisiae, homolog of, B gene (STT3B, 608605.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ix	c2931007	28,607	omim	https://www.omim.org/entry/615597	2019-09-22T15:51:33	{"doid": ["0080573"], "mesh": ["C535751"], "omim": ["615597"], "orphanet": ["370924"], "synonyms": ["Alternative titles", "CDG Ix"]}
A rare, genetic bone disorder characterized by the presence of two non-fused talar bone fragments, with the posterior fragment located at the level of the posterior talar process. Patients may present with foot and/or ankle pain (exercise-induced or not), repetitive ankle sprains, chronic ankle ligamentous laxity, restricted ankle motion (i.e. plantar flexion, eversion, and inversion), and mild swelling. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Bipartite talus	c4706298	28,608	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=364198	2021-01-23T18:50:33	{"icd-10": ["Q66.8"]}
Laurence and Cavanagh (1968) described a possibly unique autosomal recessive entity, progressive degeneration of the cerebral cortex in infancy. Atrophy was largely confined to the gray matter of the cerebral cortex and evidence of leukodystrophy or lipidosis was lacking. Two girls in one family, 2 boys in a second, and 1 male in a third were described. In the last case a first cousin once removed may have been affected. Manifestations dated from birth or the first months of life, with complete arrest of development and progression to decerebrate rigidity. The brains showed severe ulegyria with uniformly severe destruction of neurons in the cerebral cortex, astrocyte replacement, and microglial invasion. The authors called attention to a similar disorder in calves in which deficiency of vitamin B1 has been demonstrated (Davies et al., 1965) and reproduced experimentally in calves (Pill, 1967). It is entirely plausible that a genetic predisposition to thiamine deficiency might in the developing organism produce lesions limited to the cerebral cortex, unlike the picture of Wernicke encephalopathy of adults (see 277730). Neuro \- Cerebral cortex atrophy \- Developmental arrest \- Decerebrate rigidity \- Ulegyria Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CEREBROCORTICAL DEGENERATION OF INFANCY	c1859257	28,609	omim	https://www.omim.org/entry/213950	2019-09-22T16:29:49	{"mesh": ["C565863"], "omim": ["213950"]}
Post-vaccination follicular eruption SpecialtyDermatology Post-vaccination follicular eruption is a cutaneous condition that occurs 9 to 11 days following vaccination, and is characterized in multiple follicular, erythematous papules.[1]:393 ## See also[edit] * Skin lesion ## 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. This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Post-vaccination follicular eruption	None	28,610	wikipedia	https://en.wikipedia.org/wiki/Post-vaccination_follicular_eruption	2021-01-18T18:48:30	{"wikidata": ["Q7233596"]}
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. (November 2013) A deceased dear displaying the fibroma in Finland Cutaneous fibromas (also known as deer warts[1]) are common neoplasms occurring in wild and domestic deer of many species and are caused by host-specific viral infections.[2][3][4] The fibromas occur most frequently in animals under 2 years of age, with cases in older deer reported occasionally/rarely.[2] Deer fibromas appear on the skin as hard and round tumors that can be as big as 1 cm in diameter. The tumors are blackish or brown and have a rough textured surface. They do not cause the animal harm unless clumps of fibromas interfere with breathing, eating, or walking. Fibromas have been reported in white-tailed deer (Odocoileus virginianus), mule deer (Odocoileus hemionus), black-tailed deer (Odocoileus hemionus), fallow deer (Cervus dama), red deer (Cervus elaphus), roe deer (Capreolus capreolus), Sika deer (Cervus nippon), moose (Alces alces) and caribou (Rangifer caribou)."[5] They occur across the entirety of the white-tail deer's range.[1] ## Contents * 1 Clinical signs and symptoms * 2 Transmission * 3 Occurrence * 4 Treatment and control * 5 Prognosis * 6 Significance * 7 See also * 8 References * 9 Further reading ## Clinical signs and symptoms[edit] The only visible sign of cutaneous fibroma in white-tailed deer are fleshy wart-like growths on the skin, which are likely caused by biting insects. These growths can vary from individual growths to clusters of warts. These warts can also vary in size from small to very large. Because these growths are only attached to the skin, not to the underlying muscle and bone, they actually have no physical effects on the deer itself. These tumors or warts may however impair the ability to see, eat, or run if they are large enough to inhibit normal behavior. Deer with these growths can still be in perfect health and will show no symptoms of ill health.[6] ## Transmission[edit] The fibromas are most often caused by host-specific papillomaviruses. They may also be due to host-specific poxviruses.[1][4] The transmission of cutaneous fibromas in the white-tailed deer is caused by a virus that is thought to be transmitted through a variety of insect bites or by a deer coming in contact with any contaminated object that scratches or penetrates the skin of the deer or contaminates wounded/damaged skin.[6][4] Deer tend to frequent particular trails during their movements, and may thus potentially become infected by contact with objects on the path previously contaminated by other deer.[2] As fibromas occur more commonly in bucks, the virus is probably often transmitted during sparring.[4] This disease appears temporary, manifesting after about 7 weeks after inoculation and lasting only about two months.[6] Cutaneous fibromas are not transmittable to other livestock or humans if the deer is consumed.[7] ## Occurrence[edit] Fibromas occur most frequently in animals under two years of age. The tumor has been diagnosed in 2.1% of males and 0.4% of females. More bucks are shot (either by law or hunter preference), which influences the sampling.[5] ## Treatment and control[edit] Treatment is not a feasible option for most wild populations. The disease has not been a problem in captive herds. The growths could be removed surgically if it became important, but that would rarely be an issue. Because exposure to the virus leads to immunity, it should be possible to develop a vaccine if prevention becomes necessary. To date, this disease has been too rare to justify such actions.[citation needed] ## Prognosis[edit] Large, ulcerated fibromas are infrequent.[2] In most deer, the fibromas develop to only a few mm in diameter. Tumors then regress; this has been observed both in naturally occurring and experimentally induced cases. Only in an occasional deer do they develop into conspicuous skin tumors. Results of a New York survey indicated that wild deer are exposed and develop an immunity to the fibroma virus early in life.[8][2] ## Significance[edit] Fibromatosis is not an important cause of deer mortality. The disease is not known to infect humans. Although they do not harm the meat, fibromas are repulsive to most people and therefore discourage them from consuming the deer.[7] Some domesticated animals (cattle, dogs, etc.) are subject to "warts" common to their species. There is no reason to believe that fibromatosis of deer is infectious to non-deer domestic animals.[citation needed] ## See also[edit] * Shope papilloma virus ## References[edit] 1. ^ a b c "Cutaneous Fibromas \| Outdoor Alabama". www.outdooralabama.com. Retrieved 2019-08-06. 2. ^ a b c d e Sundberg, J. P.; Nielsen, S. W. (December 1981). "Deer Fibroma: A Review". The Canadian Veterinary Journal. 22 (12): 385–388. ISSN 0008-5286. PMC 1790024. PMID 7039810. 3. ^ Shope, Richard E.; Mangold, Robert; MacNamara, Lester G.; Dumbell, Keith R. (1 December 1958). "An infectious cutaneous fibroma of the Virginia whitetailed deer (Odocoileus virginianus)". The Journal of Experimental Medicine. 108 (6): 797–802. doi:10.1084/jem.108.6.797. PMC 2136923. PMID 13598813. 4. ^ a b c d "Fibromas". Pennsylvania Game Commission. Retrieved 2019-08-06. 5. ^ a b Wadsworth, JR (March 1954). "Fibrosarcomas in a deer". Journal of the American Veterinary Medical Association. 124 (924): 194. PMID 13142953. 6. ^ a b c "Cutaneous Fibromas: A Closer Look (Warts & All)". Mississippi Department of Wildlife, Fisheries, and Parks. 7. ^ a b "Deer Fibroma". Michigan Department of Natural Resources. 8. ^ Sundberg, JP; Nielsen, SW (December 1981). "Deer fibroma: a review". The Canadian Veterinary Journal. 22 (12): 385–8. PMC 1790024. PMID 7039810. ## Further reading[edit] * Lancaster, Wayne D.; Sundberg, John P. (November 1982). "Characterization of papillomaviruses isolated from cutaneous fibromas of white-tailed deer and mule deer". Virology. 123 (1): 212–216. doi:10.1016/0042-6822(82)90307-5. PMID 6293191. * Sundberg, JP; Chiodini, RJ; Nielsen, SW (May 1985). "Transmission of the white-tailed deer cutaneous fibroma". American Journal of Veterinary Research. 46 (5): 1150–4. PMID 2988381. * Sundberg, JP; Hill, DL; Williams, ES; Nielsen, SW (October 1985). "Light and electron microscopic comparisons of cutaneous fibromas in white-tailed and mule deer". American Journal of Veterinary Research. 46 (10): 2200–6. PMID 4062029. * van Rooyen, C. E. (April 1938). "Specific Complement-Fixation with Shope's Fibroma Virus and its Relationship to Virus-Neutralizing Properties of Immune Sera". British Journal of Experimental Pathology. 19 (2): 156–163. PMC 2065285. * King, JM; Woolf, A; Shively, JN (October 1972). "Naturally occurring squirrel fibroma with involvement of internal organs". Journal of Wildlife Diseases. 8 (4): 321–4. doi:10.7589/0090-3558-8.4.321. PMID 4634524. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Deer cutaneous fibroma	None	28,611	wikipedia	https://en.wikipedia.org/wiki/Deer_cutaneous_fibroma	2021-01-18T18:30:44	{"wikidata": ["Q11862684"]}
For a general discussion of hereditary prostate cancer, see 176807. Mapping Berthon et al. (1998) performed a linkage study using a set of European families (French and German) with 3 or more prostate cancer patients per family. They concluded that there is a prostate cancer susceptibility locus on 1q42.2-q43, significantly distant from HPC1 (601518) on 1q24-q25 (Smith et al., 1996). The primary localization was confirmed with several markers by use of 3 different genetic models. They obtained a maximum 2-point lod score of 2.7 with marker D1S2785. Multipoint parametric and nonparametric linkage (NPL) analysis yielded maximum hlod and NPL scores of 2.2 and 3.1, respectively, with an associated P value of 0.001. Homogeneity analysis with multipoint lod scores gave an estimate of the proportion of families with linkage to the 1q42.2-q43 locus of 50%, with a likelihood ratio of 157/1 in favor of heterogeneity. Furthermore, 9 of the 47 families with early-onset prostate cancer (at an age less than 60 years) gave multipoint lod and NPL scores of 3.31 and 3.32, respectively, with P = 0.001. Gibbs et al. (1999) analyzed 152 families with prostate cancer for linkage to markers spanning a 20-cM region of 1q42.2-q43. No significant evidence for linkage was found, by use of both parametric and nonparametric tests, in the total data set, which included 522 genotyped affected men. Rejection of linkage may reflect locus heterogeneity or the confounding effects of sporadic disease in older-onset cases; therefore, the pedigrees were stratified into more homogeneous subsets based on mean age at diagnosis of prostate cancer and number of affected men. Analyses of these subsets also detected no significant evidence for linkage, although lod scores were positive at higher recombination fractions, which is consistent with the presence of a small proportion of families with linkage. The most suggestive evidence of linkage was in families with at least 5 affected men. If heterogeneity is assumed, an estimated 4 to 9% of these 152 families may show linkage in this region. Cancel-Tassin et al. (2001) examined evidence for linkage to the PCAP locus in 64 (37 previously reported French, 24 newly identified French, 2 Spanish and 1 Italian) families with an average number of affected individuals of 3.75 and an average age at diagnosis of 66.4 years. Using both parametric and nonparametric linkage methods, results in favor of linkage were observed with a maximum multipoint NPL score of 2.86 at D1S2785 and a maximum hlod score of 2.65 between markers D1S321 and D1S2842. Homogeneity analysis indicated that up to 50% of the families were linked to this locus. A subset of 25 families with mean age at diagnosis under 66 years of age contributed significantly to the evidence of linkage with a maximum multipoint NPL score of 2.03 at D1S2842. These results suggested that PCAP is the most frequent known locus predisposing to hereditary prostate cancer in southern and western Europe. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	PROSTATE CANCER, HEREDITARY, 8	c2931456	28,612	omim	https://www.omim.org/entry/602759	2019-09-22T16:13:23	{"doid": ["10283"], "mesh": ["C537243"], "omim": ["602759"], "orphanet": ["1331"], "synonyms": ["Alternative titles", "PREDISPOSING FOR PROSTATE CANCER"]}
A number sign (#) is used with this entry because autosomal dominant centronuclear myopathy-1 (CNM1) is caused by heterozygous mutation in the gene encoding dynamin-2 (DNM2; 602378) on chromosome 19p13. Description Autosomal dominant centronuclear myopathy is a congenital myopathy characterized by slowly progressive muscular weakness and wasting. The disorder involves mainly limb girdle, trunk, and neck muscles but may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life, and some affected individuals become wheelchair-bound in their fifties. Ptosis and limitation of eye movements occur frequently. The most prominent histopathologic features include high frequency of centrally located nuclei in a large number of extrafusal muscle fibers (which is the basis of the name of the disorder), radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers (summary by Bitoun et al., 2005). ### Genetic Heterogeneity of Centronuclear Myopathy Centronuclear myopathy is a genetically heterogeneous disorder. See also X-linked CNM (CNMX; 310400), caused by mutation in the MTM1 gene (300415) on chromosome Xq28; CNM2 (255200), caused by mutation in the BIN1 gene (601248) on chromosome 2q14; CNM4 (614807), caused by mutation in the CCDC78 gene (614666) on chromosome 16p13; CNM5 (615959), caused by mutation in the SPEG gene (615950) on chromosome 2q35; and CNM6 (617760), caused by mutation in the ZAK gene (609479) on chromosome 2q31. The mutation in the MYF6 gene that was reported to cause a form of CNM, formerly designated CNM3, has been reclassified as a variant of unknown significance; see 159991.0001. Some patients with mutation in the RYR1 gene (180901) have findings of centronuclear myopathy on skeletal muscle biopsy (see 255320). Clinical Features Spiro et al. (1966) reported an isolated case of what the authors referred to as 'myotubular myopathy.' There was slowly progressive muscle weakness; muscle biopsy showed centrally located nuclei. In the development of skeletal muscle a 'myotubular' stage with centrally located nuclei occurs in utero at about 10 weeks of age. Spiro et al. (1966) thought this disease may represent persistence of fetal muscle. McLeod et al. (1972) reported a family that displayed autosomal dominant inheritance. Slowly progressive muscle weakness began between the first and third decades. It was primarily proximal in distribution but sometimes involved the facial musculature. External ophthalmoplegia and pharyngeal weakness were not features. Sixteen members of the family were affected. Karpati et al. (1970) reported affected mother and daughter. Skeletal muscle pathology showed atrophy predominantly of type 1 muscle fibers, with central nuclei and pale central zones with variably staining granules. These changes were indistinguishable from those in the other genetic varieties of centronuclear myopathy. Mortier et al. (1975) described centronuclear myopathy in teenaged brother and sister whose father may have been affected. Symptoms began in the children at 4 or 5 years of age with a 'sleepy facial expression,' clumsy gait, and easy fatigability. The disease progressed in a few years to generalized muscle weakness and atrophy, ptosis, ophthalmoplegia externa, and areflexia. Distal muscles in the lower limbs were severely affected. The father of the children had ptosis from at least age 20 years and generalized muscle atrophy had been noted at age 25. Wallgren-Pettersson et al. (1995) reviewed the differential diagnosis of the X-linked, autosomal dominant, and autosomal recessive forms of myotubular myopathy. They were aware of 13 reported pedigrees of which only 2 included histologically verified male-to-male transmission of MTM. Of 26 histologically verified cases, onset of symptoms was in the first decade in 9, in the second decade in 4, and later in 12. The clinical features are generalized muscle weakness, often predominantly proximal, but some patients show a definite additional distal involvement. A few patients have calf hypertrophy. The facial muscles may also be involved and some patients have ptosis or ophthalmoplegia. Of the 26 patients, 24 were alive at the time of writing of the reports, at ages ranging from 11 months to 68 years (mean 37 years). One patient had died at the age of 57 years of cardiorespiratory failure and another at 5 years. The autosomal dominant form for the most part has a later onset and milder course than the X-linked form but the clinical features do not seem to be qualitatively different. Bitoun et al. (2007) reported 5 unrelated patients with sporadic MTM due to heterozygous mutations in the DNM2 gene (see, e.g., 602378.0010; 602378.0011). Three had a more severe form of the disorder, with onset at birth necessitating ventilation and nasogastric feeding, and delayed development. The other 2 patients had normal motor development but developed a restrictive respiratory syndrome at ages 10 and 7 years, respectively. All patients had generalized muscle weakness most prominent in the distal lower limbs, and EMG showed myopathic changes. Other variable features included open mouth, arched palate, ptosis, pes cavus, scoliosis, contractures, and hyperlaxity. Skeletal muscle biopsies showed hypotrophy of type 1 fibers and centralized nuclei. The 2 older patients, who were also the least affected, developed loss of deep tendon reflexes at age 8 and 7 years, respectively. Bitoun et al. (2007) noted that the phenotype in these sporadic patients showed earlier onset and greater severity in general compared to other patients with DNM2-related MTM. Bitoun et al. (2009) reported a 34-year-old woman from central Africa with MTM confirmed by muscle biopsy and genetic analysis. Onset of symptoms occurred at age 7 years, with difficulty walking and running. She later developed facial weakness, ptosis, and weakness in the paraspinal, upper, and lower limb muscles. Motor nerve conduction velocities were normal. In her teenage years, she had rapid progression, with onset of ophthalmoparesis, dysphagia, and frequent falls. By age 30, she required a wheelchair and showed a progressive restrictive respiratory syndrome. Molecular Genetics In affected members of 11 families with centronuclear myopathy, Bitoun et al. (2005) identified recurrent and de novo heterozygous missense mutations in the DNM2 gene (see, e.g., 602378.0004-602378.0007), which encodes a protein involved in endocytosis and membrane trafficking, actin assembly, and centrosome cohesion. ### Genetic Modifiers Tosch et al. (2006) provided evidence that mutations in the MTMR14 gene (611089) on chromosome 3p25 may act as modifiers of the centronuclear myopathy phenotype. The authors reported patients with sporadic myotubular myopathy in which each proband carried a heterozygous missense mutation in the MTMR14 gene. The first proband and his unaffected father carried an R336Q substitution (611089.0001). A second mutation was not identified. The other proband carried a Y462C substitution in MTMR14 (611089.0002) and an additional missense mutation in DYN2 (E368K; 602378.0007). The Y462C mutation was found in a control individual. Both variants impaired enzymatic function, the R336Q mutation strongly, and the Y462C mutation to a lesser extent. Tosch et al. (2006) remarked that myotubular myopathy patients with other characterized mutations in DYN2 usually have an age of onset in childhood or adulthood, whereas the age of onset in their patient was neonatal. The report raised the possibility of MTMR14 being a modifier of the phenotype in some cases of centronuclear myopathy. Genotype/Phenotype Correlations Bohm et al. (2012) reported 60 families with genetically confirmed CNM1, including 36 families with mutations in the MID domain of the DNM2 gene, 22 with mutations in the PH domain, and 2 with mutations in the PH-GED linker domain. Combined with previous reports, the most common mutation in CNM1 in the MID domain is R465W (602378.0006), followed by E368K (602378.0007), R369W (602378.0005), and R369Q (602378.0004). The most common mutations in the PH domain are R522H and S619L (602378.0010). Mutations in the PH-GED domain are rare. The phenotype displayed marked inter- and intrafamilial variability, but in general, there were 3 major classes, ranging from the most severe with onset of symptoms in infancy to the least severe with onset in adulthood. At a minimum, all patients had areflexia or hyporeflexia, muscle weakness, and hypotrophic fibers with centralized nuclei on muscle biopsy. S619L was associated with a severe neonatal phenotype with hypotonia and delayed motor milestones, E368K with early onset and severe muscle weakness at birth with partial improvement over time, and R552H with a mild phenotype. Functional studies of the variants were not performed. Pathogenesis Although the myofibers in centronuclear myopathy do not share all the histologic features of embryonic myotubes, the centrally placed nuclei have suggested to many investigators that the primary pathology in this disorder is an arrest of muscle fiber maturation at the myotube stage (Banker, 1986). Mora et al. (1994) suggested that there is only a partial arrest of fiber maturation because they found an intracytoplasmic distribution of dystrophin and beta-spectrin (see 182790), an immature pattern, but no evidence of fetal myosin overexpression as is found in immature myotubes. None of these specimens originated from patients with X-linked centronuclear myopathy, although several may have had the autosomal recessive form. The DNM2 gene is mutant in some cases of autosomal dominant centronuclear myopathy. To investigate the ability of DNM2 mutant proteins to localize to the centrosome, Bitoun et al. (2005) prepared green fluorescent protein (GFP) chimeras using wildtype and mutant DNM2 constructs. Transfected mutants showed reduced labeling in the centrosomes of human fibroblasts, suggesting that DNM2 mutations might cause centronuclear myopathy by interfering with centrosome function. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Facial muscle weakness Eyes \- Ptosis \- Ophthalmoparesis SKELETAL \- Contractures MUSCLE, SOFT TISSUES \- Muscle weakness, primarily proximal \- Distal muscle weakness may occur \- Delayed motor development \- Muscle hypertrophy may occur \- Muscle biopsy shows centralized nuclei \- Atrophy of type 1 fibers \- Type 1 fiber predominance NEUROLOGIC Central Nervous System \- Walking difficulties Peripheral Nervous System \- Areflexia MISCELLANEOUS \- Variable age of onset (range early childhood to adult) \- Slowly progressive MOLECULAR BASIS \- Caused by mutation in the dynamin-2 gene (DNM2, 602378.0004 ). ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MYOPATHY, CENTRONUCLEAR, 1	c1834558	28,613	omim	https://www.omim.org/entry/160150	2019-09-22T16:37:43	{"doid": ["0111223"], "mesh": ["D020914"], "omim": ["160150"], "orphanet": ["169189"], "synonyms": ["Alternative titles", "MYOPATHY, CENTRONUCLEAR, AUTOSOMAL DOMINANT", "MYOTUBULAR MYOPATHY, AUTOSOMAL DOMINANT"]}
To find susceptibility genes for type 1 diabetes (see 222100), Morahan et al. (2001) tested for human homologs of loci implicated in diabetes-prone NOD (nonobese diabetic) mice, together with application of biologically relevant stratification methods. They reported a new susceptibility locus, IDDM18, located near the interleukin-12 p40 gene, IL12B (161561). Significant bias in transmission of IL12B alleles was observed in affected sib pairs and was confirmed in an independent cohort of simplex families. A single base change in the 3-prime untranslated region (UTR) of IL12B showed strong linkage disequilibrium with the IDDM susceptibility locus. Morahan et al. (2001) suggested that variation in IL12B production may influence T-cell responses crucial for either mediating or protecting against IDDM and other autoimmune diseases (Adorini, 2001). Because of the close linkage to IL12B, which maps to 5q31.1-q33.1, IDDM18 presumably is located in the same region. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	DIABETES MELLITUS, INSULIN-DEPENDENT, 18	c1854125	28,614	omim	https://www.omim.org/entry/605598	2019-09-22T16:11:09	{"mesh": ["C565315"], "omim": ["605598"], "synonyms": ["Alternative titles", "INSULIN-DEPENDENT DIABETES MELLITUS 18"]}
The co-epidemic of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major global health challenges in the present time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected.[1] Tuberculosis is the most common contagious infection in HIV-Immunocompromised patients leading to death.[2] These diseases act in combination as HIV drives a decline in immunity while tuberculosis progresses due to defective immune status. This condition becomes more severe in case of multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality (see Multi-drug-resistant tuberculosis). Tuberculosis can occur at any stage of HIV infection. The risk and severity of tuberculosis increases soon after infection with HIV. A study on gold miners of South Africa revealed that the risk of TB was doubled during the first year after HIV seroconversion.[3] Although tuberculosis can be a relatively early manifestation of HIV infection, it is important to note that the risk of tuberculosis progresses as the CD4 cell count decreases along with the progression of HIV infection.[4] The risk of TB generally remains high in HIV-infected patients, remaining above the background risk of the general population even with effective immune reconstitution and high CD4 cell counts with antiretroviral therapy.[5] ## Contents * 1 Tuberculosis and HIV infection * 2 Pathogenesis of co-infection of HIV and tuberculosis * 3 Prevention * 4 Treatment * 5 Research at molecular level * 6 References ## Tuberculosis and HIV infection[edit] Mycobacterium tuberculosis is the most common cause of Tuberculosis disease (TB). Airborne transmission typically causes TB infection in both immunocompetent and immunocompromised hosts. Tuberculosis, is categorized into two types of infection: latent infection or active TB disease. After penetration into the respiratory tract, the Mycobacterium bacilli infect macrophages. T-lymphocytes start producing many cytokines (interferon gamma, interleukin-2, tumour necrosis factor alpha, and macrophage colony-stimulating factor) to activate macrophages and cytotoxic cells to inhibit their intracellular growth. * Latent TB infection occurs when the immune system is successful in controlling the infection. Latent infection is usually asymptomatic and non contagious. * Active TB disease appears when immune response is not sufficient in limiting the growth of infection. TB disease is symptomatic and contagious. In those infected, there is a 5–10% chance that latent TB infection will progress into active tuberculosis disease. If proper treatment is not given in case of active disease, then death rate is about 50%.[6] HIV infection is a lifelong illness with three stages of disease. Medicine to treat HIV can slow or prevent progression from one stage to the next. Treatment can also reduce the chance of transmitting HIV to someone else. * Stage 1 occurs in the first 2 to 4 weeks after infection. When people have acute HIV infection, they have a large amount of virus in their blood and are very contagious. People with acute infection experience a flu-like illness and are often unaware that they're infected. * Stage 2 is sometimes called asymptomatic HIV infection or chronic HIV infection. In this stage, HIV is still active but reproduces at very low levels. This stage varies between individuals but can last a decade or longer. By taking medicine to treat HIV (ART) the right way, this stage can last for several decades. HIV transmission can still occur in this stage. If not on medication, a person's viral load starts to go up and the CD4 cell count begins to go down. * Stage 3 of HIV infection is AIDS. Patients with AIDS have severely damaged immune systems increasing number of severe illnesses they contract (called opportunistic illnesses). Without treatment, people with AIDS typically survive about 3 years. People with AIDS can have a high viral load and be very infectious.[7] ## Pathogenesis of co-infection of HIV and tuberculosis[edit] HIV/TB infection is a bi-directional interaction of the two pathogens. TB disease appears when the immune response is unable to stop the growth of mycobacteria. The cytokine IFN-γ plays a pivotal role in signaling of the immune system during infection. Reduced production of IFN-γ or its cellular receptors lead to severe and fatal TB. During HIV infection, IFN-γ production is decreased dramatically which leads to an increased risk of developing reactivation or reinfection by M. tuberculosis in these HIV/TB patients.[8] TB may also influence HIV evolution. Proinflammatory cytokine production by tuberculous granulomas (in particular TNFα) has been associated with increased HIV viraemia, which might accelerate the course of disease.[9] The risk of death in HIV/TB infected patients is twice that of HIV-infected patients without TB, with most deaths caused by progressive HIV infection, rather than TB.[10] ## Prevention[edit] When HIV-negative children take isoniazid after they have been exposed to tuberculosis, their risk to contract tuberculosis is reduced.[11] A Cochrane review[12] investigated whether giving isoniazid to HIV-positive children can help to prevent this vulnerable group from getting tuberculosis. They included three trials conducted in South Africa and Botswana and found that isoniazid given to all children diagnosed with HIV may reduce the risk of active tuberculosis and death in children who are not on antiretroviral treatment. For children taking antiretroviral medication, no clear benefit was detected. ## Treatment[edit] It is currently recommended that HIV-infected individuals with TB receive combined treatment for both diseases, irrespective of CD4+ cell count. ART (Anti Retroviral Therapy) along with ATT (Anti Tuberculosis Treatment) is the only available treatment in present time.[13] Though the timing of starting ART is the debatable question due to the risk of immune reconstitution inflammatory syndrome (IRIS). The advantages of early ART include reduction in early mortality, reduction in relapses, preventing drug resistance to ATT and reduction in occurrence of HIV-associated infections other than TB.[14] The disadvantages include cumulative toxicity of ART and ATT, drug interactions leading to inflammatory reactions are the limiting factors for choosing the combination of ATT and ART.[15] A systematic review investigated the optimal timing of starting antiretroviral therapy in adults with newly diagnosed pulmonary tuberculosis.[16] The review authors included eight trials, that were generally well-conducted, with over 4500 patients in total. The early provision of antiretroviral therapy in HIV-infected adults with newly diagnosed tuberculosis improved survival in patients who had a low CD4 count (less than 0.050 x 109 cells/L). However, such therapy doubled the risk for IRIS. Regarding patients with higher CD4 counts (more than 0.050 x 109 cells/L), the evidence is not sufficient to make a conclusion about benefits or risks of early antiretroviral therapy. ## Research at molecular level[edit] A study conducted on 452 patients revealed that the genotype responsible for higher IL-10 expression makes HIV infected people more susceptible to tuberculosis infection.[17] Another study on HIV-TB co-infected patients also concluded that higher level of IL-10 and IL-22 makes TB patient more susceptible to Immune reconstitution inflammatory syndrome (IRIS).[18] It is also seen that HIV co-infection with tuberculosis also reduces concentration of immunopathogenic matrix metalloproteinase (MMPs) leading to reduced inflammatory immunopathology.[19] ## References[edit] 1. ^ World Health Organization (2012). Global Tuberculosis Report 2012 (PDF). ISBN 978-92-4-156450-2. 2. ^ World Health Organization (1999). "Tuberculosis infection control in the era of expanding HIV care and treatment" (PDF). Cite journal requires `\|journal=` (help) 3. ^ "Tuberculosis and HIV". January 2013. Cite journal requires `\|journal=` (help) 4. ^ Tuberculosis (TB). AIDS InfoNet. February 4, 2014. 5. ^ Worodria, W.; Massinga-Loembe, M.; Mazakpwe, D.; Luzinda, K.; Menten, J.; Van Leth, F.; Mayanja-Kizza, H.; Kestens, L.; Mugerwa, R. D.; Reiss, P.; Colebunders, R.; TB-IRIS Study Group (2011). "Incidence and Predictors of Mortality and the Effect of Tuberculosis Immune Reconstitution Inflammatory Syndrome in a Cohort of TB/HIV Patients Commencing Antiretroviral Therapy". Journal of Acquired Immune Deficiency Syndromes. 58 (1): 32–37. doi:10.1097/QAI.0b013e3182255dc2. PMID 21654499. Archived from the original on June 24, 2012. 6. ^ L, Aaron; D, Saadoun; I, Calatroni; O, Launay; N, Mémain; V, Vincent; G, Marchal; B, Dupont; O, Bouchaud; D, Valeyre; O, Lortholary (May 2004). "Tuberculosis in HIV-infected patients: a comprehensive review". Clinical Microbiology and Infection. 10 (5): 388–398. doi:10.1111/j.1469-0691.2004.00758.x. PMID 15113314. 7. ^ U.S. Department of Health & Human Services. "STAGES OF HIV INFECTION". AIDS.gov. Retrieved 7 December 2015. 8. ^ Ottenhoff, Tom H.M; Kumararatne, Dinakantha; Casanova, Jean-Laurent (November 1998). "Novel human immunodeficiencies reveal the essential role of type-1 cytokines in immunity to intracellular bacteria". Immunology Today. 19 (11): 491–494. doi:10.1016/S0167-5699(98)01321-8. PMID 9818540. 9. ^ Garrait, V; Cadranel, J; Esvant, H; Herry, I; Morinet, P; Mayaud, C; IsraelBiet, D (September 1997). "Tuberculosis generates a microenvironment enhancing the productive infection of local lymphocytes by HIV". Journal of Immunology. 159 (6): 2824–2830. PMID 9300705. Retrieved 7 December 2015. 10. ^ WHALEN, C; HORSBURGH, CR; HOM, D; LAHART, C; SIMBERKOFF, M; ELLNER, J (January 1995). "Accelerated course of human immunodeficiency virus infection after tuberculosis". American Journal of Respiratory and Critical Care Medicine. 151 (1): 129–135. doi:10.1164/ajrccm.151.1.7812542. PMID 7812542. Retrieved 7 December 2015. 11. ^ Smieja, M. J.; Marchettu, C. A.; Cook, D. J.; Smaill, F. M. (1999). "Isoniazid for preventing tuberculosis in non-HIV infected persons". Cochrane Database of Systematic Reviews (2): CD001363. doi:10.1002/14651858.CD001363. PMC 6532737. PMID 10796642. 12. ^ Zunza, M.; Gray, D. M.; Young, T.; Cotton, M.; Zar, H. J. (2017). "Isoniazid for preventing tuberculosis in HIV-infected children". Cochrane Database of Systematic Reviews. 8 (8): CD006418. doi:10.1002/14651858.CD006418.pub3. PMC 5618450. PMID 28850172. 13. ^ Clinical trial number NCT00933790 for "Comparing Daily vs Intermittent Regimen of ATT in HIV With Pulmonary Tuberculosis" at ClinicalTrials.gov 14. ^ Lawn, Stephen D; Harries, Anthony D; Anglaret, Xavier; Myer, Landon; Wood, Robin (October 2008). "Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa" (PDF). AIDS. 22 (15): 1897–1908. doi:10.1097/qad.0b013e32830007cd. ISSN 0269-9370. PMC 3816249. PMID 18784453. 15. ^ Kapoor, Gauri; Singh, Neha (2018). "Role of apoptotic markers in paediatric acute lymphoblastic leukaemia". Indian Journal of Medical Research. 147 (3): 225–227. doi:10.4103/ijmr.ijmr_906_17. ISSN 0971-5916. PMC 6022391. PMID 29923509. 16. ^ Uthman, Olalekan A.; Okwundu, Charles; Gbenga, Kayode; Volmink, Jimmy; Dowdy, David; Zumla, Alimuddin; Nachega, Jean B. (7 July 2015). "Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed Pulmonary Tuberculosis". Annals of Internal Medicine. 163 (1): 32–9. doi:10.7326/M14-2979. PMID 26148280. 17. ^ Ramaseri Sunder, S.; Hanumanth, S. R.; Nagaraju, R. T.; Venkata, S. K.; Suryadevara, N. C.; Pydi, S. S.; Gaddam, S.; Jonnalagada, S.; Valluri, V. L. (2012). "IL-10 high producing genotype predisposes HIV infected individuals to TB infection". Human Immunology. 73 (6): 605–611. doi:10.1016/j.humimm.2012.03.012. PMID 22507621. 18. ^ Tadokera, Rebecca; Wilkinson, Katalin A.; Meintjes, Graeme A.; Skolimowska, Keira H.; Matthews, Kerryn; Seldon, Ronnett; Rangaka, Molebogeng X.; Maartens, Gary; Wilkinson, Robert J. (April 2013). "Role of the Interleukin 10 Family of Cytokines in Patients With Immune Reconstitution Inflammatory Syndrome Associated With HIV Infection and Tuberculosis". The Journal of Infectious Diseases. 207 (7): 1148–1156. doi:10.1093/infdis/jit002. ISSN 0022-1899. PMC 3583273. PMID 23303806. 19. ^ Walker, N. F.; Clark, S. O.; Oni, T.; Andreu, N.; Tezera, L.; Singh, S.; Saraiva, L. S.; Pedersen, B.; Kelly, D. L.; Tree, J. A.; d'Armiento, J. M.; Meintjes, G.; Mauri, F. A.; Williams, A.; Wilkinson, R. J.; Friedland, J. S.; Elkington, P. T. (2012). "Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases". American Journal of Respiratory and Critical Care Medicine. 185 (9): 989–997. doi:10.1164/rccm.201110-1769OC. PMC 3359940. PMID 22345579. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Tuberculosis in relation to HIV	None	28,615	wikipedia	https://en.wikipedia.org/wiki/Tuberculosis_in_relation_to_HIV	2021-01-18T18:40:11	{"wikidata": ["Q17014545"]}
Devriendt et al. (1996) proposed autosomal recessive inheritance for the disorder observed in 2 brothers but granted that X-linked recessive inheritance could not be excluded with certainty. Two brothers, born of healthy, nonconsanguineous Caucasian parents, had total alopecia at birth, with absent scalp hair, eyelashes, and eyebrows. During adolescence, hair progressively appeared on the scalp, but remained sparse and woolly. Tonic-clonic convulsions started during the first month of life and disappeared after age 4 in both. Electroencephalogram during childhood was normal. When seen at ages 30 and 23, there was alopecia of the scalp with normal eyebrows. Teeth and nails were normal. Both were mildly retarded. Testicular volume was 8 ml bilaterally with a small penis. Serum FSH (118850) levels were elevated, consistent with hypergonadotropic hypogonadism. Scanning electron microscopy showed an abnormal appearance of the hair shaft with damaged or absent cuticula and exposure of the underlying hair cell layers. This was described as central trichoptilosis ('hair plus feathers'), a condition of splitting of the shaft giving it a feathery appearance. Devriendt et al. (1996) noted that, since it is difficult to assess hypergonadotropic hypogonadism before adolescence, it is possible that this may have been the same disorder as that in the children reported by Pridmore et al. (1992), Richieri-Costa and Frota-Pessoa (1979), and Wessel et al. (1987). Several other alopecia-mental retardation syndromes are discussed elsewhere; see 203600, 203650, and 230740. GU \- Small testes \- Small penis Neuro \- Tonic-clonic convulsions \- Mild mental retardation Inheritance \- Autosomal recessive vs. X-linked recessive Endocrine \- Hypergonadotropic hypogonadism Misc \- Seizure onset at one month, ceasing by age 4 years Lab \- Normal childhood EEG \- Elevated serum FSH \- Damaged or absent hair shaft cuticula by EM (central trichoptilosis) Hair \- Congenital total alopecia \- Absent scalp hair, eyelashes, and eyebrows \- Sparse and woolly scalp hair at adolescence ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ALOPECIA-MENTAL RETARDATION SYNDROME WITH CONVULSIONS AND HYPERGONADOTROPIC HYPOGONADISM	c1832593	28,616	omim	https://www.omim.org/entry/601217	2019-09-22T16:15:13	{"mesh": ["C563370"], "omim": ["601217"], "orphanet": ["1014"]}
## Summary ### Clinical characteristics. SGCE myoclonus-dystonia (SGCE-M-D) is a movement disorder characterized by a combination of rapid, brief muscle contractions (myoclonus) and/or sustained twisting and repetitive movements that result in abnormal postures (dystonia). The myoclonic jerks typical of SGCE-M-D most often affect the neck, trunk, and upper limbs with less common involvement of the legs. Approximately 50% of affected individuals have additional focal or segmental dystonia, presenting as cervical dystonia and/or writer's cramp. Non-motor features may include alcohol abuse, obsessive-compulsive disorder (OCD), and anxiety disorders. Symptom onset is usually in the first decade of life and almost always by age 20 years, but ranges from age six months to 80 years. Most affected adults report a dramatic reduction in myoclonus in response to alcohol ingestion. SGCE-M-D is compatible with an active life of normal span. ### Diagnosis/testing. The diagnosis of SGCE-M-D is established in a proband with characteristic clinical features by identification of a heterozygous pathogenic variant in SGCE. ### Management. Treatment of manifestations: Class 1 evidence supports the improvement of myoclonus and dystonia with zonisamide. Benzodiazepines (particularly clonazepam) and antiepileptics used to treat myoclonus (especially valproate and levitiracetam) also improve myoclonus in individuals with myoclonus-dystonia. The response to other antiepileptics (e.g., topiramate) is more variable. Anticholinergic medication may improve dystonia. Botulinum toxin injection may be especially helpful for cervical dystonia. Improvement with L-5-hydroxytryptophan, L-dopa, and the salt of sodium oxybate has been reported. Deep brain stimulation has improved both myoclonus and dystonia, with most targeting the globus pallidus interna (GPi); however, success with ventral intermediate nucleus of the thalamus (VIM) target has also been reported. Other: Symptoms of SGCE-M-D often improve short term with ingestion of alcohol, but the risk of addiction recommends against its long-term use. ### Genetic counseling. SGCE-M-D is inherited in an autosomal dominant manner with penetrance determined by the parental origin of the altered SGCE allele: an SGCE pathogenic variant on the paternally derived (expressed) SGCE allele generally results in disease; a pathogenic variant on the maternally derived (silenced) SGCE allele typically does not result in disease. Most individuals with SGCE-M-D inherited the disorder from a heterozygous parent who may or may not have clinical signs of M-D (as phenotypic expression in the parent would depend on the gender of the transmitting grandparent). Each child of an individual with SGCE-M-D has a 50% chance of inheriting the pathogenic variant. Almost all children who inherit an SGCE pathogenic variant from their father develop symptoms, whereas only ~5% of children who inherit an SGCE pathogenic variant from their mother develop symptoms. Once the SGCE pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic diagnosis are possible. ## Diagnosis ### Suggestive Findings SGCE myoclonus-dystonia (SGCE-M-D) should be suspected in individuals with myoclonus alone or with dystonia that begins in the first or second decade of life. It less frequently presents with isolated dystonia. Recently suggested criteria for the diagnosis of M-D require four major criteria and no exclusionary criteria OR three major criteria, two minor criteria, and no exclusionary criteria [Roze et al 2018]. Major criteria * Myoclonus isolated or predominating over dystonia * Prominence of the motor manifestations in the upper body * Absence of truncal dystonia * Positive family history * Onset before age 18 years Minor criteria * Obsessive-compulsive disorder, anxiety-related disorder, or alcohol dependence * Spontaneous remission of limb dystonia during childhood or adolescence * Alcohol responsiveness Exclusionary criteria * Other neurologic manifestation in addition to myoclonus and/or dystonia (except seizures, which may be present in some individuals with SGCE-M-D) * Abnormal brain MRI examination * Neurophysiologic findings that do not support the diagnosis (defined as muscle contractions shorter than 300 ms that can occur in body parts not affected by dystonia) ### Establishing the Diagnosis The diagnosis of SGCE-M-D is established in a proband with myoclonus and/or dystonia by identification of a heterozygous pathogenic variant in SGCE on molecular genetic testing (see Table 1). Note: (1) SGCE is maternally imprinted and, therefore, expressed only from the paternal allele. While rare cases of maternal inheritance have been reported (see Penetrance and Molecular Genetics), affected individuals typically have a pathogenic variant on the paternal allele. (2) A small number of individuals have been identified with either microdeletions of SGCE or maternal uniparental disomy resulting in methylation of both SGCE alleles (see Genetically Related Disorders). Molecular genetic testing approaches can include single-gene testing and a multigene panel. However, for this disorder, a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1): * Single-gene testing. Sequence analysis of SGCE detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. Single-gene testing is most appropriate in individuals from families with a previously identified SGCE pathogenic variant. * A dystonia multigene panel that includes SGCE and other genes of interest (see Differential Diagnosis) 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. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder, a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. ### Table 1. Molecular Genetic Testing Used in SGCE Myoclonus-Dystonia View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method SGCESequence analysis 3~75% 4 Gene-targeted deletion/duplication analysis 5~25% 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\. Tezenas du Montcel et al [2006], Raymond et al [2008], Roze et al [2008] 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\. DeBerardinis et al [2003], Asmus et al [2005], Asmus et al [2007], Han et al [2007], Grünewald et al [2008], Ritz et al [2009], Peall et al [2014] ## Clinical Characteristics ### Clinical Description SGCE myoclonus-dystonia (SGCE-M-D) is a movement disorder characterized by a combination of rapid, brief muscle contractions (myoclonus), and/or sustained twisting and repetitive movements that result in abnormal postures (dystonia). Onset is most often in the first decade of life or in adolescence. While most affected adults report a dramatic response of myoclonus to ingestion of alcohol [Quinn 1996], the alleviation of findings following alcohol ingestion varies within and between families. Alcohol dependence may be a comorbidity in those who do respond. The myoclonic jerks typical of SGCE-M-D are brief, lightning-like movements most often affecting the neck, trunk, and upper limbs, with legs less prominently affected. In children, leg and trunk myoclonus may in rare cases lead to falls [Luciano et al 2009]. Myoclonus is usually the presenting manifestation of SGCE-M-D. Approximately half of affected individuals (54%) have focal or segmental dystonia that manifests as cervical dystonia and/or writer's cramp [Asmus et al 2002, Klein et al 2002]. In contrast to primary torsion dystonia [Bressman et al 2000], dystonia in the lower limbs is rare, although it has been reported in individuals with infantile onset [Kyllerman et al 1990]. In addition, the dystonia does not tend to worsen or generalize in the course of the disease. Infrequently, dystonia is the only disease manifestation. The involuntary movements are frequently precipitated or worsened by active movements of the affected body parts. Other factors eliciting or enhancing the movements include stress [Kyllerman et al 1990], sudden noise [Asmus et al 2001, Trottenberg et al 2001], caffeine [Nygaard et al 1999], and tactile stimuli [Nygaard et al 1999]. Tremor (postural or other) may be a feature in a subset of individuals [Vidailhet et al 2001]. Psychiatric comorbidities have been reported. One systematic analysis of 307 participants with pathogenic variants in SGCE and M-D found that 65% had one or more psychiatric diagnoses, the most common of which were specific (33%) and social phobias (31%), followed by alcohol dependence (24%) and obsessive-compulsive disorder (OCD) (21%) [Peall et al 2015]. A further comparison of symptomatic and asymptomatic individuals with an SGCE pathogenic variant reported in this study found that OCD and social phobia were ten and 12 times more likely, respectively, in symptomatic individuals. It is unclear if psychiatric features seen in people with SGCE-M-D are a result of the SGCE pathogenic variant or a consequence of living with the disease. One argument against a purely reactive explanation, however, is that OCD is generally not considered a reactive condition. Other neurologic signs and symptoms including dementia and ataxia are rare in SGCE-M-D [Gasser 1998]. Seizures are also rare, but have been reported in at least three families and are no longer considered exclusionary for diagnosis. However, the significance of this finding remains unclear [Foncke et al 2003, O'Riordan et al 2004, Haugarvoll et al 2014]. SGCE-M-D is compatible with an active life of normal span [Nygaard et al 1999]. Although spontaneous remission of SGCE-M-D has been reported [Roze et al 2008], SGCE-M-D may also be gradually progressive [Trottenberg et al 2001], leading to considerable functional disability and sometimes to early retirement [Hjermind et al 2003, Maréchal et al 2003]. Multiple studies support a different disease mechanism for SGCE-M-D than for isolated dystonia. Currently, the leading hypotheses suggest dysfunction of the cerebello-thalamo-cortical or striato-pallido-thalmo-cortical pathways [Popa et al 2014, Roze et al 2015]. ### Genotype-Phenotype Correlations No genotype-phenotype correlations have been identified. ### Penetrance Reduced penetrance on maternal transmission of the disease allele has been observed, suggesting that maternal genomic imprinting of SGCE suppresses expression of the maternally inherited SGCE allele [Zimprich et al 2001]. * Consistent with this hypothesis, two studies demonstrated both paternal transmission of an SGCE pathogenic variant in affected individuals and DNA methylation differences consistent with maternal imprinting [Müller et al 2002, Grabowski et al 2003]. * Because about 5% of affected individuals inherit the SGCE pathogenic variant from their mothers [Zimprich et al 2001, Grabowski et al 2003], the apparent suppression of the M-D phenotype on maternal transmission of the SGCE allele is incomplete. In these instances, the phenotype may be milder. The reasons for loss of the maternal imprint are unknown. ### Nomenclature "Myoclonus-dystonia" is the term used for individuals with an SGCE-like phenotype [Roze et al 2018]. It is distinguished from "myoclonic dystonia," a condition having a primarily dystonic phenotype with longer duration jerks co-occurring in the dystonic body regions. Additional terms used in the past for SGCE-M-D include "inherited myoclonus-dystonia syndrome," "alcohol-responsive myoclonic dystonia," and "hereditary essential myoclonus" [Quinn et al 1988, Quinn 1996, Lang 1997]. ### Prevalence Little is known about the prevalence of SGCE-M-D. The disease has been described in families of many nationalities including mixed European, German, Irish, Turkish, Brazilian, and Canadian. ## Differential Diagnosis Myoclonic dystonia 26 (OMIM 616398), associated with heterozygous pathogenic variants in KCTD17, is closest in phenotype to SGCE myoclonus-dystonia (SGCE-M-D). For further information about myoclonic dystonia 26 and other disorders to consider in the differential diagnosis of SGCE-M-D, see Table 2. ### Table 2. Other Genes of Interest in the Differential Diagnosis of SGCE Myoclonus-Dystonia View in own window Gene(s)DisorderMOIKey Clinical Features of Differential Diagnosis Disorder Overlapping w/SGCE-M-DDistinguishing from SGCE-M-D ADCY5ADCY5-related dyskinesiaAD * Possible cause of isolated M-D 1 * Often childhood onset 2 Typically assoc w/additional features (e.g., chorea, early motor delay, alternating hemiplegia of childhood) ATMVariant ataxia-telangiectasia 3ARDystonia only or dystonia w/myoclonus may be present. * Observed in Mennonite families of Russian origin * High cancer frequency & adverse responses to chemotherapeutic agents assoc w/a common ATM haplotype & homozygosity for c.6200C>A ATN1DRPLAADMyoclonus, epilepsyIn children: * Ataxia * Progressive intellectual deterioration In adults: * Ataxia * Choreoathetosis * Dementia or character changes ATP7BWilson diseaseARDystonia * Biochemical findings: ↓ serum copper & ceruloplasmin concentrations; ↑ urinary copper excretion * Kayser-Fleischer corneal ring ATXN3Spinocerebellar ataxia type 3ADDystonia in 1 individualCerebellar ataxia, pyramidal signs, pontocerebellar atrophy CSTBUnverricht-Lundborg diseaseARMyoclonus, seizures * Ataxia, incoordination, intentional tremor, & dysarthria * Emotional lability, depression, & mild ↓ in intellectual performance over time EPM2A NHLRC1Progressive myoclonus epilepsy, Lafora typeARMyoclonus, seizures * ↑ frequency & intractability of seizures * Cognitive decline apparent at or soon after onset of seizures * Dysarthria & ataxia appear early; spasticity appears late. GCH1GTP cyclohydrolase 1-deficient dopa-responsive dystoniaADM-D in 1 individual 4 * Dramatic & sustained response to levodopa * Typically presents w/gait disturbance, later development of parkinsonism, & diurnal fluctuation of symptoms GNB1GNB1 encephalopathyADM-D in 1 individual w/comorbid OCD & mild DD, 5 neurodevelopmental delay, & other features incl dystonia in 46 others 6One individual w/M-D: * Mild ID * Limited upgaze, hypotonia, & OCD In others w/dystonia: * Notable DD & growth delay, seizures, hypotonia, abnormal MRI * Other symptoms may incl genitourinary & gastrointestinal abnormality, vision, hearing, cardiac, & hematologic abnormalities. KCTD17Myoclonic dystonia 26 (OMIM 616398)ADEarly-onset myoclonic jerks; development of dystonia later in life (in 4 individuals)Early motor delay, severe lingual dystonia, & mild cognitive delay in 2 families w/splice variants 7 mtDNAMERRFMatMyoclonus; seizuresAtaxia & ragged red fibers on muscle biopsy NKX2-1 8Benign hereditary chorea (OMIM 118700)ADMyoclonusDoes not demonstrate aggravation of jerks w/complex motor tasks (in contrast to action-induced myoclonus of M-D). PRKCGSpinocerebellar ataxia type 14ADM-D in 1 individual 9Slowly progressive cerebellar ataxia, dysarthria, & nystagmus RELNRELN myoclonus-dystonia 7AD * Seemingly typical adult-onset M-D reported in 3 families & 2 simplex cases * Alcohol responsiveness & psychiatric comorbidities (5 individuals) 10 * Mean onset: age 22 yrs * Latest onset: age 53 yrs TOR1ADYT1 early-onset isolated dystoniaADUnusual presentation of alcohol-responsive M-D in 1 individual 11Cervical dystonia is uncommon in DYT1 dystonia. TTPAAtaxia with vitamin E deficiencyARDystonia * 1st symptoms incl progressive ataxia, clumsiness of hands, loss of proprioception, & areflexia. * Cerebellar atrophy TUBB2BTUBB2B tubulinopathy (mild form) 12 (see Tubulinopathies Overview)ADM-D in 1 individual * Mild cognitive impairment & skeletal anomalies * Asymmetric pachygyria & dysmorphic basal ganglia on neuroimaging 12 AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; ID = intellectual disability; Mat = maternal inheritance; M-D = myoclonus-dystonia; MOI = mode of inheritance; OCD = obsessive-compulsive disorder 1\. Douglas et al [2017] 2\. Chen et al [2015] 3\. Saunders-Pullman et al [2012], Levy & Lang [2018] 4\. Leuzzi et al [2002] 5\. Jones et al [2019] 6\. Petrovski et al [2016], Steinrücke et al [2016], Lohmann et al [2017], Hemati et al [2018] 7\. Mencacci et al [2015], Graziola et al [2019], Marcé-Grau et al [2019] 8\. Because of the association of hypothyroidism with pathogenic variants in NKX2-1, thyroid hormone screening should be considered in affected individuals. See OMIM 118700, 610978, 600635. 9\. Foncke et al [2010] 10\. Groen et al [2015] 11\. A male with alcohol-responsive M-D who had the typical three-base pair deletion in TOR1A and no pathogenic variant in SGCE was reported [Tezenas du Montcel et al 2006]. His mother was Ashkenazi Jewish and had only writer's cramp. 12\. Geiger et al [2017] Myoclonic dystonia 15 (OMIM 607488). A clinically similar M-D phenotype in a large Canadian family without an identifiable SGCE pathogenic variant showed significant evidence for linkage to markers on chromosome 18p (locus DYT15) [Grimes et al 2002, Han et al 2007]. The M-D phenotype of two other families may also be linked to this chromosome region [Schüle et al 2004]. The overall contribution of this locus to M-D cannot be determined until the gene is identified. For a review of various genetic and secondary forms of dystonia, see Hereditary Dystonia Overview. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with SGCE myoclonus-dystonia (SGCE-M-D) the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended: * Clinical examination to evaluate the location, severity, and progression of dystonia and the severity and progression of myoclonus. This is best done by a neurologic specialist in movement disorders. * Consultation with a clinical geneticist and/or genetic counselor. ### Treatment of Manifestations Medications may improve myoclonus and/or dystonia: * While multiple antiepileptic medications have been reported in case series or individual reports, zonisamide is the first to demonstrate class I evidence of improvement of both myoclonus and dystonia in a double-blind study [Hainque et al 2016]. Valproate and levetiracetam may also be used. Topiramate and carbamazepine have been reported to improve myoclonus [Nygaard et al 1999, Sanjari Moghaddam et al 2018]. * Benzodiazepines, particularly clonazepam, improve mostly myoclonus and tremor [Goetz & Horn 2001]. * Anticholinergic medication may improve dystonia [Goetz & Horn 2001] and botulinum toxin injection may be especially helpful for cervical dystonia [Berardelli & Curra 2002]. * Improvement of dystonia with L-5-hydroxytryptophan has been reported [Scheidtmann et al 2000]. * Improvement with both L-dopa [Luciano et al 2009] and the dopamine-depleting medication tetrabenazine has been reported [Luciano et al 2014]. * One individual with SGCE-M-D who represented a simplex case (i.e., a single occurrence of M-D in the family) showed a robust response to zolpidem [Park et al 2009]. * Gamma-hydroxybutyrate [Priori et al 2000] and sodium oxybate may improve myoclonus [Frucht et al 2005]. Note: Although the symptoms of SGCE-M-D usually resolve with ingestion of alcohol, the risk of long-term addiction to alcohol renders it an unacceptable treatment option. Deep brain stimulation (DBS). Studies of globus pallidus interna (Gpi) and/or ventral intermediate nucleus of the thalamus (VIM) DBS in individuals with M-D determined that both were effective long-term treatments, although GPi is now the more frequently chosen target. Marked improvement in both myoclonus and dystonia as well as good quality of life and social adjustment were seen in a cohort of nine individuals with SGCE-M-D who had GPi DBS for at least five years [Kosutzka et al 2019]. In individuals with a predominant myoclonus phenotype undergoing VIM DBS (3 individuals with SGCE M-D; 2 individuals without an SGCE pathogenic variant), sustained improvement of both myoclonus and dystonia was found over 50 months [Zhang et al 2019]. Stereotactic thalamotomy can improve myoclonus, but caused dysarthria in one individual and mild hemiparesis in another [Gasser et al 1996]. In two others, myoclonus improved, but without significant gain in function [Suchowersky et al 2000]. ### Prevention of Secondary Complications As self-treatment with alcohol is common, proper treatment and counseling regarding alcohol abuse may decrease alcohol-related toxicities, particularly in adolescents. ### Surveillance ### Table 3. Recommended Surveillance for Individuals with Myoclonus-Dystonia View in own window System/ConcernEvaluationFrequency NeurologicNeurologic exam to assess burden of myoclonus & dystonia & review therapy & side effectsAnnually PsychiatricEval for psychiatric featuresAnnually ### Agents/Circumstances to Avoid Use of alcohol to ameliorate symptoms should be avoided due to the risk of alcohol dependence. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management There is concern about teratogenicity with certain antiepileptic medications that are sometimes used in the treatment of myoclonus-dystonia. These should be avoided in women considering pregnancy or who are known to be pregnant. Discussion of the risks and benefits of using a given antiepileptic drug during pregnancy should ideally take place prior to conception. Women with M-D should be counseled about abstaining from alcohol during pregnancy, particularly during the first trimester, as alcohol negatively affects fetal development. See MotherToBaby for further information on medication use during pregnancy. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	SGCE Myoclonus-Dystonia	None	28,617	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1414/	2021-01-18T20:58:53	{"synonyms": ["Dystonia 11 (DYT11)", "DYT-SGCE"]}
A number sign (#) is used with this entry because of evidence that susceptibility to nonmedullary thyroid cancer-5 (NMTC5) is conferred by heterozygous mutation in the HABP2 gene (603924) on chromosome 10q25. One such family has been reported. Description Nonmedullary thyroid cancer (NMTC) comprises cancer of follicular cell origin and accounts for more than 95% of all cases of thyroid cancer. Familial NMTC accounts for 3 to 9% of all cases of thyroid cancer and has an autosomal dominant mode of inheritance. Most cases of familial NMTC are papillary thyroid cancer (PTC), which is the most common type of thyroid cancer (summary by Gara et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of NMTC, see NMTC1 (188550). Clinical Features Gara et al. (2015) reported a large multiplex family with familial NMTC. The pattern of inheritance was autosomal dominant. The proband was the youngest of 7 children, with 1 affected brother. Three members of this family were affected at the time of the initial evaluation. On ultrasound screening, 4 other family members were found to have thyroid neoplasms; PTC was diagnosed in 3 of the 4, and follicular adenoma was diagnosed in 1. Of 8 family members in the fourth generation (age range 7-24 years) who were screened, 2 had small thyroid nodules. None of the family members had a history of other primary cancers. Molecular Genetics In a large multiplex family with familial NMTC, Gara et al. (2015) found a heterozygous missense mutation in the HABP2 gene (G534E; 603924.0002), which segregated with disease in the family. Inheritance of the mutation was autosomal dominant. Overexpression of the mutant protein caused increased colony formation and cellular migration compared to wildtype. Analysis of the Cancer Genome Atlas (TCGA) data in 423 patients with papillary thyroid cancer showed that 4.7% carried the HABP2 G534E variant, as compared with 0.7% of individuals with unknown disease status in multiethnic population databases (p less than 0.001). This suggests that the HABP2 G534E germline variant may be a susceptibility gene for additional cases of familial nonmedullary thyroid cancer. Zhou et al. (2015), Sponziello et al. (2015), and Tomsic et al. (2015) stated that the allele frequency of the G534E variant exceeds the filtering criterion used by Gara et al. (2015); Gara and Kebebew (2015) replied. See 603924.0001. INHERITANCE \- Autosomal dominant NEOPLASIA \- Nonmedullary thyroid carcinoma (papillary and follicular) MISCELLANEOUS \- One family has been reported (last curated September 2015) MOLECULAR BASIS \- Susceptibility conferred by mutation in the hyaluronan-binding protein 2 gene (HABP2, 603924.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	THYROID CANCER, NONMEDULLARY, 5	c4225292	28,618	omim	https://www.omim.org/entry/616535	2019-09-22T15:48:36	{"omim": ["616535"], "orphanet": ["319487"], "synonyms": ["FNMTC", "Familial pure nonmedullary thyroid carcinoma"]}
Turner syndrome is a chromosomal disorder associated with the complete or partial absence of an X chromosome. ## Epidemiology Its prevalence has been estimated at 1 in 5,000 live births (1 in 2,500 female births). ## Clinical description Clinical features are heterogeneous and typical physical anomalies are often mild or absent. Short stature is present in all cases. Ovarian failure, with variable onset depending on the chromosomal anomalies, is frequent. Other visceral manifestations (bone anomalies, lymphoedema, deafness, and cardiovascular, thyroid and gastrointestinal involvement) are less common but should be screened for at diagnosis, then monitored during adolescence and adulthood. ## Etiology X-chromosome monosomy is responsible for less than half of the cases of Turner syndrome and a large majority of cases are caused by the presence of a mosaicism (45,X) and/or an abnormal X or Y chromosome (deletion, isochromosome X, dicentric chromosome). ## Antenatal diagnosis During gestation, typical forms with associated malformations can be diagnosed by ultrasound examination, but mild forms are discovered incidentally following amniocentesis performed for another indication (for example, advanced maternal age). Prenatal counseling after diagnosis of the mild forms is particularly problematic. ## Management and treatment Management should include growth hormone therapy, which leads to a significant increase in final height. ## Prognosis Quality of life and social integration are better when puberty is not induced too late, and in the absence of cardiac disease or deafness. Deafness can lead to learning difficulties and, during adulthood, sterility can have a negative effect on quality of life. The prognosis depends on the presence of heart disease, obesity, arterial hypertension and osteoporosis. Therefore, long-term follow-up is necessary. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Turner syndrome	c0041408	28,619	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=881	2021-01-23T19:09:19	{"gard": ["7831"], "mesh": ["D014424"], "umls": ["C0041408", "C0242526"], "icd-10": ["Q96.0", "Q96.1", "Q96.2", "Q96.3", "Q96.4", "Q96.8", "Q96.9"], "synonyms": ["45,X syndrome", "45,X/46,XX syndrome"]}
A rare inborn error of metabolism characterized by the presence of large amounts of trimethylamine in urine, sweat, and breath, resulting in a fishy body odor in affected individuals. While there are no additional signs and symptoms, the condition can have profound psychosocial consequences. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Severe primary trimethylaminuria	c0342739	28,620	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=468726	2021-01-23T17:32:11	{"mesh": ["C536561"], "omim": ["602079"], "icd-10": ["E88.8"], "synonyms": ["TMAU"]}
Santos et al. (1988) described a brother and sister, offspring of first-cousin parents, with a syndrome of Hirschsprung disease, polydactyly, unilateral renal agenesis, hypertelorism, and congenital deafness. Santos et al. (1988) thought this was different from the disorder in 2 male infants with Hirschsprung disease, polydactyly, and ventricular septal defect (235750). HEENT \- Hypertelorism \- Congenital deafness Limbs \- Polydactyly GU \- Unilateral renal agenesis GI \- Hirschsprung megacolon Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	HIRSCHSPRUNG DISEASE WITH POLYDACTYLY, RENAL AGENESIS, AND DEAFNESS	c2931452	28,621	omim	https://www.omim.org/entry/235740	2019-09-22T16:27:08	{"mesh": ["C537235"], "omim": ["235740"], "orphanet": ["2155"]}
Acral lentiginous melanoma SpecialtyOncology, dermatology SymptomsAreas of dark pigmentation [1] CausesMalignant melanocytes[2][3] Diagnostic methodBiopsy[4] TreatmentBiologic immunotherapy agents[5] Melanoma is a group of serious skin cancers that arise from pigment cells (melanocytes); acral lentiginous melanoma is a kind of lentiginous[6] skin melanoma.[7][8] Although acral lentiginous melanoma is rare in people with lighter skin types, it is the most common subtype in people with darker skins. Acral lentiginous melanoma is observed on the palms, soles, under the nails and in the oral mucosa. It occurs on non-hair-bearing surfaces of the body, which have not necessarily been exposed to sunlight. It is also found on mucous membranes.[9] It is the most common form of melanoma diagnosed amongst Asian and sub-Saharan African ethnic groups.[10] The average age at diagnosis is between sixty and seventy years.[11] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Histology * 4 Treatment * 5 Prognosis * 6 Society * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] Typical signs of acral lentiginous melanoma include the following [1] * Longitudinal tan, black, or brown streak on a nail * Pigmentation of proximal nail fold * Areas of dark pigmentation (palms of hands) Warning signs are new areas of pigmentation, or existing pigmentation that shows change. If caught early, acral lentiginous melanoma has a similar cure rate as the other types of superficial spreading melanoma.[12] ## Causes[edit] Acral lentiginous melanoma is a result of malignant melanocytes at the membrane of the skin (outer layers).[2][3] The pathogenesis of acral lentiginous melanoma remains unknown at this time.[13] ## Diagnosis[edit] Although the ideal method of diagnosis of melanoma is complete excisional biopsy,[14] alternatives may be required according to the location of the melanoma. Dermatoscopy of acral pigmented lesions is very difficult but can be accomplished with diligent focus. Initial confirmation of the suspicion can be done with a small wedge biopsy or small punch biopsy.[4] Thin deep wedge biopsies can heal very well on acral skin, and small punch biopsies can give enough clue to the malignant nature of the lesion. Once this confirmatory biopsy is done, a second complete excisional skin biopsy can be performed with a narrow surgical margin (1 mm). This second biopsy will determine the depth and invasiveness of the melanoma,[15] and will help to define what the final treatment will be. If the melanoma involves the nail fold and the nail bed, complete excision of the nail unit might be required. Final treatment might require wider excision (margins of 0.5 cm or more), digital amputation, lymphangiogram with lymph node dissection, or chemotherapy.[16] ### Histology[edit] Acral lentiginous melanoma (ALM) The main characteristic of acral lentiginous melanoma is continuous proliferation of atypical melanocytes at the dermoepidermal junction.[17] Other histological signs of acral lentiginous melanoma include dermal invasion and desmoplasia.[18] According to Scolyer et al.,[19] ALM "is usually characterized in its earliest recognisable form as single atypical melanocytes scattered along the junctional epidermal layer". ## Treatment[edit] Therapies for metastatic melanoma include the biologic immunotherapy agents ipilimumab, pembrolizumab, and nivolumab; BRAF inhibitors, such as vemurafenib and dabrafenib; and a MEK inhibitor trametinib.[5] ## Prognosis[edit] It has been demonstrated that acral lentiginous melanoma has a poorer prognosis compared to that of cutaneous malignant melanoma (CMM).[20] ## Society[edit] Jamaican musician Bob Marley died of the condition in 1981, aged 36.[21] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ a b Goodheart, Herbert P. (2010-10-25). Goodheart's Same-site Differential Diagnosis: A Rapid Method of Diagnosing and Treating Common Skin Disorders. Lippincott Williams & Wilkins. ISBN 9781605477466. 2. ^ a b Brown, Kimberly M.; Chao, Celia (2014). Melanoma. Elsevier Health Sciences. ISBN 9780323326834. 3. ^ a b Piliang, Melissa Peck (June 2011). "Acral Lentiginous Melanoma". Clinics in Laboratory Medicine. 31 (2): 281–288. doi:10.1016/j.cll.2011.03.005. PMID 21549241. – via ScienceDirect (Subscription may be required or content may be available in libraries.)</ 4. ^ a b ChB, David E. Elder MB; PhD, Sook Jung Yun MD (2014-11-10). Superficial Melanocytic Pathology. Demos Medical Publishing. ISBN 9781620700235. 5. ^ a b Maverakis E, Cornelius LA, Bowen GM, Phan T, Patel FB, Fitzmaurice S, He Y, Burrall B, Duong C, Kloxin AM, Sultani H, Wilken R, Martinez SR, Patel F (2015). "Metastatic melanoma - a review of current and future treatment options". Acta Derm Venereol. 95 (5): 516–524. doi:10.2340/00015555-2035. PMID 25520039. 6. ^ Phan, A.; Touzet, S.; Dalle, S.; Ronger‐Savlé, S.; Balme, B.; Thomas, L. (2007). "Acral lentiginous melanoma: histopathological prognostic features of 121 cases". British Journal of Dermatology. 157 (2): 311–318. doi:10.1111/j.1365-2133.2007.08031.x. ISSN 1365-2133. PMID 17596173. 7. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 8. ^ "acral-lentiginous melanoma". Retrieved 2015-05-23. 9. ^ LeBoit, Philip E. (2006). Pathology and Genetics of Skin Tumours. IARC. ISBN 9789283224143. 10. ^ Farage, Miranda A. (2010-01-22). Textbook of Aging Skin. Springer Science & Business Media. ISBN 9783540896555. 11. ^ Swartz, Mark H. (2014-01-07). Textbook of Physical Diagnosis: History and Examination. Elsevier Health Sciences. ISBN 9780323225076. 12. ^ Hearing, Vincent J.; Leong, Stanley P. L. (2007-11-05). From Melanocytes to Melanoma: The Progression to Malignancy. Springer Science & Business Media. ISBN 9781592599943. 13. ^ ChB, David E. Elder, MB; PhD, Sook Jung Yun, MD (2014-11-10). Superficial Melanocytic Pathology. Demos Medical Publishing. p. 119. ISBN 9781617051869. Retrieved 11 October 2016. 14. ^ Shea, Christopher R.; Reed, Jon A.; Prieto, Victor G. (2014-11-03). Pathology of Challenging Melanocytic Neoplasms: Diagnosis and Management. Springer. ISBN 9781493914449. 15. ^ Barnhill, Raymond L.; Piepkorn, Michael; Busam, Klaus J. (2014-02-18). Pathology of Melanocytic Nevi and Melanoma. Springer Science & Business Media. ISBN 9783642383854. 16. ^ Clarke, Loren E.; Clarke, Jennie T.; Helm, Klaus F. (2014-03-01). Color Atlas of Differential Diagnosis in Dermatopathology. JP Medical Ltd. ISBN 9789350908457. 17. ^ Piliang, Melissa Peck (2009). "Acral Lentiginous Melanoma". Surgical Pathology Clinics. 2 (3): 535–541. doi:10.1016/j.path.2009.08.005. ISSN 1875-9181. PMID 26838538. 18. ^ Mooi, Walter; Krausz, Thomas (2007-09-28). Pathology of Melanocytic Disorders 2ed. CRC Press. ISBN 9781444113808. 19. ^ "FEBS Press". doi:10.1002/(ISSN)1878-0261. 20. ^ Bradford, Porcia T.; Goldstein, Alisa M.; McMaster, Mary L.; Tucker, Margaret A. (2009). "Acral Lentiginous Melanoma: Incidence and Survival Patterns in the United States, 1986-2005". Archives of Dermatology. 145 (4): 427–434. doi:10.1001/archdermatol.2008.609. ISSN 0003-987X. PMC 2735055. PMID 19380664. 21. ^ "Bob Marley Shouldn't Have Died from Melanoma". Skin Cancer Foundation. 2016-02-06. Retrieved 2016-10-11. ## Further reading[edit] * Durbec, F.; Martin, L.; Derancourt, C.; Grange, F. (Apr 2012). "Melanoma of the hand and foot: epidemiological, prognostic and genetic features. A systematic review". The British Journal of Dermatology. 166 (4): 727–739. doi:10.1111/j.1365-2133.2011.10772.x. ISSN 1365-2133. PMID 22175696. ## External links[edit] Classification D * ICD-10: C43 (ILDS C43.L60) * ICD-9-CM: 172.0-173.9 * ICD-O: M8744/3 Scholia has a topic profile for Acral lentiginous melanoma. * v * t * e Skin cancer of nevi and melanomas Melanoma * Mucosal melanoma * Superficial spreading melanoma * Nodular melanoma * lentigo * Lentigo maligna/Lentigo maligna melanoma * Acral lentiginous melanoma * Amelanotic melanoma * Desmoplastic melanoma * Melanoma with features of a Spitz nevus * Melanoma with small nevus-like cells * Polypoid melanoma * Nevoid melanoma * Melanocytic tumors of uncertain malignant potential Nevus/ melanocytic nevus * Nevus of Ito/Nevus of Ota * Spitz nevus * Pigmented spindle cell nevus * Halo nevus * Pseudomelanoma * Blue nevus * of Jadassohn–Tièche * Cellular * Epithelioid * Deep penetrating * Amelanotic * Malignant * Congenital melanocytic nevus (Giant * Medium-sized * Small-sized) * Balloon cell nevus * Dysplastic nevus/Dysplastic nevus syndrome * Acral nevus * Becker's nevus * Benign melanocytic nevus * Nevus spilus * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Acral lentiginous melanoma	c0346037	28,622	wikipedia	https://en.wikipedia.org/wiki/Acral_lentiginous_melanoma	2021-01-18T18:43:28	{"gard": ["9570"], "umls": ["C0346037"], "icd-9": ["173.9", "172.0"], "icd-10": ["C43"], "wikidata": ["Q4675038"]}
Bacterial infection characterized by muscle spasms This article is about the disease. For the physiological use of the term, see Tetanic contraction. Tetanus Other namesLockjaw Muscle spasms (specifically opisthotonos) in a person with tetanus. Painting by Sir Charles Bell, 1809. SpecialtyInfectious disease SymptomsMuscle spasms, fever, headache[1] Usual onset3–21 days following exposure[1] DurationMonths[1] CausesClostridium tetani[1] Risk factorsBreak in the skin[2] Diagnostic methodBased on symptoms[1] PreventionTetanus vaccine[1] TreatmentTetanus immune globulin, muscle relaxants, mechanical ventilation[1][3] Prognosis10% risk of death[1] Frequency209,000 (2015)[4] Deaths56,700 (2015)[5] Tetanus, also known as lockjaw, is a bacterial infection characterized by muscle spasms.[1] In the most common type, the spasms begin in the jaw and then progress to the rest of the body.[1] Each spasm usually lasts a few minutes.[1] Spasms occur frequently for three to four weeks.[1] Some spasms may be severe enough to fracture bones.[6] Other symptoms of tetanus may include fever, sweating, headache, trouble swallowing, high blood pressure, and a fast heart rate.[1][6] Onset of symptoms is typically three to twenty-one days following infection.[1] Recovery may take months.[1] About ten percent of cases prove fatal.[1] Tetanus is caused by an infection with the bacterium Clostridium tetani,[1] which is commonly found in soil, saliva, dust, and manure.[2] The bacteria generally enter through a break in the skin such as a cut or puncture wound by a contaminated object.[2] They produce toxins that interfere with normal muscle contractions.[3] Diagnosis is based on the presenting signs and symptoms.[1] The disease does not spread between people.[1] Tetanus can be prevented by immunization with the tetanus vaccine.[1] In those who have a significant wound and have had fewer than three doses of the vaccine, both vaccination and tetanus immune globulin are recommended.[1] The wound should be cleaned and any dead tissue should be removed.[1] In those who are infected, tetanus immune globulin or, if unavailable, intravenous immunoglobulin (IVIG) is used.[1] Muscle relaxants may be used to control spasms.[3] Mechanical ventilation may be required if a person's breathing is affected.[3] Tetanus occurs in all parts of the world but is most frequent in hot and wet climates where the soil has a high organic content.[1] In 2015 there were about 209,000 infections and about 59,000 deaths globally.[4][5] This is down from 356,000 deaths in 1990.[7] In the US there are about 30 cases per year, almost all of which have not been vaccinated.[8] An early description of the disease was made by Hippocrates in the 5th century BC.[1] The cause of the disease was determined in 1884 by Antonio Carle and Giorgio Rattone at the University of Turin, and a vaccine was developed in 1924.[1] ## Contents * 1 Signs and symptoms * 1.1 Incubation period * 1.2 Generalized tetanus * 1.3 Neonatal tetanus * 1.4 Local tetanus * 1.5 Cephalic tetanus * 2 Cause * 3 Pathophysiology * 3.1 Neurospecific binding * 3.2 Internalization * 3.3 Membrane translocation * 3.4 Enzymatic target cleavage * 4 Diagnosis * 5 Prevention * 5.1 Post-exposure prophylaxis * 6 Treatment * 6.1 Mild tetanus * 6.2 Severe tetanus * 7 Epidemiology * 8 History * 8.1 Etymology * 9 Research * 10 See also * 11 References * 12 External links ## Signs and symptoms[edit] Tetanus often begins with mild spasms in the jaw muscles—also known as lockjaw or trismus. The spasms can also affect the facial muscles resulting in an appearance called risus sardonicus. Chest, neck, back, abdominal muscles, and buttocks may be affected. Back muscle spasms often cause arching, called opisthotonos. Sometimes the spasms affect muscles that help with breathing, which can lead to breathing problems.[9] Prolonged muscular action causes sudden, powerful, and painful contractions of muscle groups, which is called "tetany". These episodes can cause fractures and muscle tears. Other symptoms include fever, headache, restlessness, irritability, feeding difficulties, breathing problems, burning sensation during urination, urinary retention and loss of stool control.[10] Even with treatment, about 10% of people who contract tetanus die.[1] The mortality rate is higher in unvaccinated people and people over 60 years of age.[1] ### Incubation period[edit] The incubation period of tetanus may be up to several months, but is usually about ten days.[11][12] In general, the farther the injury site is from the central nervous system, the longer the incubation period. The shorter the incubation period, the more severe the symptoms.[13] In neonatal tetanus (trismus nascentium), symptoms usually appear from 4 to 14 days after birth, averaging about 7 days. On the basis of clinical findings, four different forms of tetanus have been described.[1] ### Generalized tetanus[edit] Generalized tetanus is the most common type of tetanus, representing about 80% of cases. The generalized form usually presents with a descending pattern. The first sign is trismus, or lockjaw, and the facial spasms called risus sardonicus, followed by stiffness of the neck, difficulty in swallowing, and rigidity of pectoral and calf muscles. Other symptoms include elevated temperature, sweating, elevated blood pressure, and episodic rapid heart rate. Spasms may occur frequently and last for several minutes with the body shaped into a characteristic form called opisthotonos. Spasms continue for up to four weeks, and complete recovery may take months.[1] ### Neonatal tetanus[edit] Main article: Neonatal tetanus Neonatal tetanus (trismus nascentium) is a form of generalized tetanus that occurs in newborns, usually those born to mothers who themselves have not been vaccinated. If the mother has been vaccinated against tetanus, the infants acquire passive immunity and are thus protected.[14] It usually occurs through infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile instrument. As of 1998 neonatal tetanus was common in many developing countries and was responsible for about 14% (215,000) of all neonatal deaths.[15] In 2010 the worldwide death toll was 58,000 newborns. As the result of a public health campaign, the death toll from neonatal tetanus was reduced by 90% between 1990 and 2010, and by 2013 the disease had been largely eliminated from all but 25 countries.[16] Neonatal tetanus is rare in developed countries. ### Local tetanus[edit] Local tetanus is an uncommon form of the disease, in which people have persistent contraction of muscles in the same anatomic area as the injury. The contractions may persist for many weeks before gradually subsiding. Local tetanus is generally milder; only about 1% of cases are fatal, but it may precede the onset of generalized tetanus.[1] ### Cephalic tetanus[edit] Cephalic tetanus is the rarest form of the disease (0.9–3% of cases)[17] and is limited to muscles and nerves in the head.[18] It usually occurs after trauma to the head area, including skull fracture,[19] laceration,[19] eye injury,[18] dental extraction,[20] and otitis media,[21] but it has been observed from injuries to other parts of the body.[22] Paralysis of the facial nerve is most frequently implicated, which may cause lockjaw, facial palsy, or ptosis, but other cranial nerves can also be affected.[20][23] Cephalic tetanus may progress to a more generalized form of the disease.[17][23] Due to its rarity, clinicians may be unfamiliar with the clinical presentation and may not suspect tetanus as the illness.[18] Treatment can be complicated as symptoms may be concurrent with the initial injury that caused the infection.[19] Cephalic tetanus is more likely than other forms of tetanus to be fatal, with the progression to generalized tetanus carrying a 15–30% case fatality rate.[17][19][23] ## Cause[edit] Clostridium tetani is durable due to its endospores. Pictured is the bacterium alone, with a spore being produced, and the spore alone. Tetanus is caused by the tetanus bacterium Clostridium tetani.[1] Tetanus is an international health problem, as C. tetani endospores are ubiquitous. Endospores can be introduced into the body through a puncture wound (penetrating trauma). Due to C. tetani being an anaerobic bacterium, it and its endospores thrive in environments that lack oxygen, such as a puncture wound. The disease occurs almost exclusively in persons inadequately immunized.[24] It is more common in hot, damp climates with soil rich in organic matter. Manure-treated soils may contain spores, as they are widely distributed in the intestines and feces of many animals such as horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens.[1] In agricultural areas, a significant number of human adults may harbor the organism. The spores can also be found on skin surfaces and in contaminated heroin.[1] Heroin users, particularly those who inject the drug subcutaneously, appear to be at high risk of contracting tetanus.[1] Rarely, tetanus can be contracted through surgical procedures, intramuscular injections, compound fractures, and dental infections.[1] Animal bites can transmit tetanus.[1] Tetanus is often associated with rust, especially rusty nails. Although rust itself does not cause tetanus, objects that accumulate rust are often found outdoors or in places that harbor anaerobic bacteria. Additionally, the rough surface of rusty metal provides crevices for dirt containing C. tetani, while a nail affords a means to puncture skin and deliver endospores deep within the body at the site of the wound.[25] An endospore is a non-metabolizing survival structure that begins to metabolize and cause infection once in an adequate environment. Hence, stepping on a nail (rusty or not) may result in a tetanus infection, as the low-oxygen (anaerobic) environment may exist under the skin, and the puncturing object can deliver endospores to a suitable environment for growth.[26] It is a common misconception that rust itself is the cause and that a puncture from a rust-free nail is not a risk.[27][28] ## Pathophysiology[edit] A neurotransmitter-filled vesicle before and after exposure to the tetanus toxin. The cleavage of the VAMP protein by the toxin inhibits vesicle fusion and neurotransmitter release into the synapse. Tetanus neurotoxin (TeNT) binds to the presynaptic membrane of the neuromuscular junction, is internalized and is transported back through the axon until it reaches the central nervous system.[29] Here, it selectively binds to and is transported into inhibitory neurons via endocytosis.[30] It then leaves the vesicle for the neuron cytosol where it cleaves vesicle associated membrane protein (VAMP) synaptobrevin, which is necessary for membrane fusion of small synaptic vesicles (SSV's).[29] SSV's carry neurotransmitter to the membrane for release, so inhibition of this process blocks neurotransmitter release. Tetanus toxin specifically blocks the release of the neurotransmitters GABA and glycine from inhibitory neurons. These neurotransmitters keep overactive motor neurons from firing and also play a role in the relaxation of muscles after contraction. When inhibitory neurons are unable to release their neurotransmitters, motor neurons fire out of control and muscles have difficulty relaxing. This causes the muscle spasms and spastic paralysis seen in tetanus infection.[29] The tetanus toxin, tetanospasmin, is made up of a heavy chain and a light chain. There are three domains, each of which contributes to the pathophysiology of the toxin.[31] The heavy chain has two of the domains. The N-terminal side of the heavy chain helps with membrane translocation, and the C-terminal side helps the toxin locate the specific receptor site on the correct neuron. The light chain domain cleaves the VAMP protein once it arrives in the inhibitory neuron cytosol.[31] There are four main steps tetanus's mechanism of action: binding to the neuron, internalization of the toxin, membrane translocation, and cleavage of the target VAMP. ### Neurospecific binding[edit] The toxin travels from the wound site to the neuromuscular junction through the bloodstream where it binds to the presynaptic membrane of a motor neuron. The heavy chain C-terminal domain aids in the binding to the correct site, recognizing and binding to the correct glycoproteins and glycolipids in the presynaptic membrane. The toxin binds to a site that will be taken into the neuron as an endocytic vesicle that will travel all the way down the axon, past the cell body, and down the dendrites to the dendritic terminal at the spine and central nervous system. Here it will be released into the synaptic cleft and allowed to bind with the presynaptic membrane of inhibitory neurons in a similar manner seen with the binding to the motor neuron.[30] ### Internalization[edit] Tetanus toxin is then internalized again via endocytosis, this time in an acidic vesicle.[31] In a mechanism not well understood, depolarization caused by the firing of the inhibitory neuron causes the toxin to be pulled into the neuron inside vesicles. ### Membrane translocation[edit] The toxin then needs a way to get out of the vesicle and into the neuron cytosol in order for it to act on its target. The low pH of the vesicle lumen causes a conformational change in the toxin, shifting it from a water-soluble form to a hydrophobic form.[30] With the hydrophobic patches exposed, the toxin is able to slide into the vesicle membrane. The toxin forms an ion channel in the membrane that is nonspecific for Na+, K+, Ca2+, and Cl- ions.[29] There is a consensus among experts that this new channel is involved in the translocation of the toxin's light chain from the inside of the vesicle to the neuron cytosol, but the mechanism is not well understood or agreed upon. It has been proposed that the channel could allow the light chain (unfolded from the low pH environment) to leave through the toxin pore,[32] or that the pore could alter the electrochemical gradient enough, by letting in or out ions, to cause osmotic lysis of the vesicle, spilling the vesicle's contents.[33] ### Enzymatic target cleavage[edit] The light chain of the tetanus toxin is a zinc-dependent protease. It shares a common zinc protease motif (His-Glu-Xaa-Xaa-His) that researchers hypothesized was essential for target cleavage until this was more recently confirmed by experiment: when all zinc was removed from the neuron with heavy metal chelators, the toxin was inhibited, only to be reactivated when the zinc was added back in.[29] The light chain binds to VAMP and cleaves it between Gln76 and Phe77. Without VAMP, vesicles holding the neurotransmitters needed for motor neuron regulation (GABA and Glycine) cannot be released, causing the above-mentioned deregulation of motor neurons and muscle tension.[34] ## Diagnosis[edit] There are currently no blood tests for diagnosing tetanus. The diagnosis is based on the presentation of tetanus symptoms and does not depend upon isolation of the bacterium, which is recovered from the wound in only 30% of cases and can be isolated from people without tetanus. Laboratory identification of C. tetani can be demonstrated only by production of tetanospasmin in mice.[1] Having recently experienced head trauma may indicate cephalic tetanus if no other diagnosis has been made. The "spatula test" is a clinical test for tetanus that involves touching the posterior pharyngeal wall with a soft-tipped instrument and observing the effect. A positive test result is the involuntary contraction of the jaw (biting down on the "spatula") and a negative test result would normally be a gag reflex attempting to expel the foreign object. A short report in The American Journal of Tropical Medicine and Hygiene states that, in an affected subject research study, the spatula test had a high specificity (zero false-positive test results) and a high sensitivity (94% of infected people produced a positive test).[35] ## Prevention[edit] Unlike many infectious diseases, recovery from naturally acquired tetanus does not usually result in immunity to tetanus. This is due to the extreme potency of the tetanospasmin toxin. Tetanospasmin will likely be lethal before it will provoke an immune response. Tetanus can be prevented by vaccination with tetanus toxoid.[36] The CDC recommends that adults receive a booster vaccine every ten years,[1] and standard care practice in many places is to give the booster to any person with a puncture wound who is uncertain of when he or she was last vaccinated, or if he or she has had fewer than three lifetime doses of the vaccine. The booster may not prevent a potentially fatal case of tetanus from the current wound, however, as it can take up to two weeks for tetanus antibodies to form.[37] In children under the age of seven, the tetanus vaccine is often administered as a combined vaccine, DPT/DTaP vaccine, which also includes vaccines against diphtheria and pertussis. For adults and children over seven, the Td vaccine (tetanus and diphtheria) or Tdap (tetanus, diphtheria, and acellular pertussis) is commonly used.[36] The World Health Organization certifies countries as having eliminated maternal or neonatal tetanus. Certification requires at least two years of rates of less than 1 case per 1000 live births. 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.[38] ### Post-exposure prophylaxis[edit] Tetanus toxoid can be given in case of a suspected exposure to tetanus. In such cases, it can be given with or without tetanus immunoglobulin (also called tetanus antibodies or tetanus antitoxin[39]). It can be given as intravenous therapy or by intramuscular injection. The guidelines for such events in the United States for non-pregnant people 11 years and older are as follows:[1] Vaccination status Clean, minor wounds All other wounds Unknown or less than 3 doses of tetanus toxoid containing vaccine Tdap and recommend catch-up vaccination Tdap and recommend catch-up vaccination Tetanus immunoglobulin 3 or more doses of tetanus toxoid containing vaccine AND less than 5 years since last dose No indication No indication 3 or more doses of tetanus toxoid containing vaccine AND 5–10 years since last dose No indication Tdap preferred (if not yet received) or Td 3 or more doses of tetanus toxoid containing vaccine AND more than 10 years since last dose Tdap preferred (if not yet received) or Td Tdap preferred (if not yet received) or Td ## Treatment[edit] Tetanus deaths per million persons in 2012 0–1 1–2 2–3 4–8 9–13 14–28 29–151 ### Mild tetanus[edit] Mild cases of tetanus can be treated with:[40] * Tetanus immunoglobulin (TIG),[1] also called tetanus antibodies or tetanus antitoxin.[39] It can be given as intravenous therapy or by intramuscular injection. * Antibiotic therapy to reduce toxin production. Metronidazole IV is a preferred treatment.[40] * Benzodiazepines can be used to control muscle spasms. Options include diazepam and lorazepam, oral or IV.[40] ### Severe tetanus[edit] Severe cases will require admission to intensive care. In addition to the measures listed above for mild tetanus:[40] * Human tetanus immunoglobulin injected intrathecally (increases clinical improvement from 4% to 35%) * Tracheotomy and mechanical ventilation for 3 to 4 weeks. Tracheotomy is recommended for securing the airway because the presence of an endotracheal tube is a stimulus for spasm * Magnesium sulfate, as an intravenous (IV) infusion, to control spasm and autonomic dysfunction * Diazepam as a continuous IV infusion * The autonomic effects of tetanus can be difficult to manage (alternating hyper- and hypotension hyperpyrexia/hypothermia) and may require IV labetalol, magnesium, clonidine, or nifedipine Drugs such as diazepam or other muscle relaxants can be given to control the muscle spasms. In extreme cases it may be necessary to paralyze the person with curare-like drugs and use a mechanical ventilator. In order to survive a tetanus infection, the maintenance of an airway and proper nutrition are required. An intake of 3,500 to 4,000 calories and at least 150 g of protein per day is often given in liquid form through a tube directly into the stomach (percutaneous endoscopic gastrostomy), or through a drip into a vein (parenteral nutrition). This high-caloric diet maintenance is required because of the increased metabolic strain brought on by the increased muscle activity. Full recovery takes 4 to 6 weeks because the body must regenerate destroyed nerve axon terminals. The antibiotic of choice is metronidazole. It can be given as intravenously, by mouth, or by rectum.[41][40] Of likewise efficiency is penicillin, but some raise the concern of provoking spasms because it inhibits GABA receptor, which is already affected by tetanospasmin.[42] ## Epidemiology[edit] Disability-adjusted life year for tetanus per 100,000 inhabitants in 2004. no data ≤10 10-25 25-50 50-75 75-100 100-125 125-150 150-200 200-250 250-500 500-750 ≥750 In 2013 it caused about 59,000 deaths – down from 356,000 in 1990.[7] Tetanus – in particular, the neonatal form – remains a significant public health problem in non-industrialized countries with 59,000 newborns worldwide dying in 2008 as a result of neonatal tetanus.[43][44] In the United States, from 2000 through 2007 an average of 31 cases were reported per year.[1] Nearly all of the cases in the United States occur in unimmunized individuals or individuals who have allowed their inoculations to lapse.[1] * Tetanus cases reported worldwide (1990-2004). Ranging from some (in dark red) to very few (in light yellow) (grey, no data). * Tetanus deaths between 1990 and 2017 by age group[45] ## History[edit] Tetanus was well known to ancient people who recognized the relationship between wounds and fatal muscle spasms.[46] In 1884, Arthur Nicolaier isolated the strychnine-like toxin of tetanus from free-living, anaerobic soil bacteria. The etiology of the disease was further elucidated in 1884 by Antonio Carle and Giorgio Rattone, two pathologists of the University of Turin, who demonstrated the transmissibility of tetanus for the first time. They produced tetanus in rabbits by injecting pus from a person with fatal tetanus into their sciatic nerves.[1] In 1891, C. tetani was isolated from a human victim by Kitasato Shibasaburō, who later showed that the organism could produce disease when injected into animals, and that the toxin could be neutralized by specific antibodies. In 1897, Edmond Nocard showed that tetanus antitoxin induced passive immunity in humans, and could be used for prophylaxis and treatment. Tetanus toxoid vaccine was developed by P. Descombey in 1924, and was widely used to prevent tetanus induced by battle wounds during World War II.[1] ### Etymology[edit] The word tetanus comes from the Ancient Greek: τέτανος, romanized: tetanos, lit. 'taut', which is further from the Ancient Greek: τείνειν, romanized: teinein, lit. 'to stretch'.[47] ## Research[edit] There is insufficient evidence to recommending treating or preventing tetanus with vitamin C.[48] ## See also[edit] * Renshaw cell * Tetanized state * Tetanospasmin ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as Atkinson, William (May 2012). Tetanus Epidemiology and Prevention of Vaccine-Preventable Diseases (12 ed.). Public Health Foundation. pp. 291–300. ISBN 9780983263135. Archived from the original on February 13, 2015. Retrieved 12 February 2015. This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention. 2. ^ a b c "Tetanus Causes and Transmission". www.cdc.gov. January 9, 2013. Archived from the original on 12 February 2015. Retrieved 12 February 2015. 3. ^ a b c d "Tetanus For Clinicians". cdc.gov. January 9, 2013. Archived from the original on 12 February 2015. Retrieved 12 February 2015. 4. ^ a b Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, et al. (GBD 2015 Disease and Injury Incidence and Prevalence Collaborators) (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282. 5. ^ a b Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, et al. (GBD 2015 Mortality and Causes of Death Collaborators) (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/S0140-6736(16)31012-1. PMC 5388903. PMID 27733281. 6. ^ a b "Tetanus Symptoms and Complications". cdc.gov. January 9, 2013. Archived from the original on 12 February 2015. Retrieved 12 February 2015. 7. ^ a b Naghavi M, Wang H, Lozano R, Davis A, Liang X, Zhou M, et al. (GBD 2013 Mortality and Causes of Death Collaborators) (January 2015). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 385 (9963): 117–71. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442. 8. ^ "About Tetanus". Centers for Disease Control and Prevention. United States Government. Retrieved 4 August 2019. 9. ^ "Tetanus - Epidemiology of Vaccine Preventable Diseases". CDC. 2020-05-10. Archived from the original on 2020-05-10. Retrieved 2020-05-18. "Laryngospasm (spasm of the vocal cords) and/or spasm of the muscles of respiration leads to interference with breathing." 10. ^ Schleiss, Mark R. (2020). "Chapter 238: Tetanus". In Kliegman, Robert (ed.). Nelson Textbook of Pediatrics. Elsevier. p. 6253. ISBN 978-0-323-52950-1. 11. ^ Vandelaer J, Birmingham M, Gasse F, Kurian M, Shaw C, Garnier S (July 2003). "Tetanus in developing countries: an update on the Maternal and Neonatal Tetanus Elimination Initiative". Vaccine. 21 (24): 3442–5. doi:10.1016/S0264-410X(03)00347-5. PMID 12850356. 12. ^ Brauner JS, Vieira SR, Bleck TP (July 2002). "Changes in severe accidental tetanus mortality in the ICU during two decades in Brazil". Intensive Care Med. 28 (7): 930–5. doi:10.1007/s00134-002-1332-4. PMID 12122532. S2CID 21772357. 13. ^ Farrar JJ, Yen LM, Cook T, Fairweather N, Binh N, Parry J, Parry CM (September 2000). "Tetanus". J. Neurol. Neurosurg. Psychiatry. 69 (3): 292–301. doi:10.1136/jnnp.69.3.292. PMC 1737078. PMID 10945801. 14. ^ "Tetanus and neonatal tetanus (NT)". WHO Western Pacific Region. Archived from the original on 2014-05-03. 15. ^ "Maternal and Neonatal Tetanus Elimination by 2005" (PDF). UNICEF. November 2000. Archived (PDF) from the original on 2007-01-11. Retrieved 2007-01-26. 16. ^ "Elimination of Maternal and Neonatal Tetanus". UNICEF. Archived from the original on 21 February 2014. Retrieved 17 February 2014. 17. ^ a b c Doshi A, Warrell C, Dahdaleh D, Kullmann D (February 2014). "Just a graze? Cephalic tetanus presenting as a stroke mimic". Pract Neurol. 14 (1): 39–41. doi:10.1136/practneurol-2013-000541. PMID 24052566. S2CID 32389452. 18. ^ a b c Del Pilar Morales E, Bertrán Pasarell J, Cardona Rodriguez Z, Almodovar Mercado JC, Figueroa Navarro A (2014). "Cephalic tetanus following penetrating eye trauma: a case report". Bol Asoc Med P R. 106 (2): 25–9. PMID 25065047. 19. ^ a b c d Adeleye AO, Azeez AL (October 2012). "Fatal tetanus complicating an untreated mild open head injury: a case-illustrated review of cephalic tetanus". Surgical Infections. 13 (5): 317–20. doi:10.1089/sur.2011.023. PMID 23039234. 20. ^ a b Ajayi E, Obimakinde O (July 2011). "Cephalic tetanus following tooth extraction in a Nigerian woman". J Neurosci Rural Pract. 2 (2): 201–2. doi:10.4103/0976-3147.83597. PMC 3159367. PMID 21897694. 21. ^ Ugwu GI, Okolugbo NE (2012). "Otogenic tetanus: case series". West Afr J Med. 31 (4): 277–9. PMID 23468033. 22. ^ Kwon JC, Park Y, Han ZA, Song JE, Park HS (January 2013). "Trismus in cephalic tetanus from a foot injury". Korean J. Intern. Med. 28 (1): 121. doi:10.3904/kjim.2013.28.1.121. PMC 3543954. PMID 23346010. 23. ^ a b c Seo DH, Cho DK, Kwon HC, Kim TU (February 2012). "A case of cephalic tetanus with unilateral ptosis and facial palsy". Ann Rehabil Med. 36 (1): 167–70. doi:10.5535/arm.2012.36.1.167. PMC 3309317. PMID 22506253. 24. ^ Wells CL, Wilkins TD (1996). "Clostridia: Sporeforming Anaerobic Bacilli". In Baron S (ed.). Baron's Medical Microbiology. Univ of Texas Medical Branch. ISBN 978-0-9631172-1-2. Archived from the original on 2009-02-06. 25. ^ Edmonds, Molly (2009-07-29). "Causes of Tetanus". HowStuffWorks. Archived from the original on 22 November 2015. Retrieved 9 November 2015. 26. ^ Todar, Kenneth. "Tetanus". Lectures in Microbiology. University of Wisconsin, Madison - Dept. of Bacteriology. Archived from the original on 2013-03-11. 27. ^ O'Connor, Anahad (February 22, 2005), "The Claim: Stepping on a Rusty Nail Can Cause Tetanus", The New York Times 28. ^ Jennings K (2013-10-08). Because I Said So!: The Truth Behind the Myths, Tales, and Warnings Every Generation Passes Down to Its Kids. Simon and Schuster. pp. 13–. ISBN 978-1-4767-0696-2. 29. ^ a b c d e Pellizzari R, Rossetto O, Schiavo G, Montecucco C (February 1999). Clementi F, Fesce R, Meldolesi J, Valtorta F (eds.). "Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 354 (1381): 259–68. doi:10.1098/rstb.1999.0377. PMC 1692495. PMID 10212474. 30. ^ a b c Montecucco C, Schiavo G (July 1994). "Mechanism of action of tetanus and botulinum neurotoxins". Molecular Microbiology. 13 (1): 1–8. doi:10.1111/j.1365-2958.1994.tb00396.x. PMID 7527117. S2CID 45069991. 31. ^ a b c Masuyer G, Conrad J, Stenmark P (August 2017). "The structure of the tetanus toxin reveals pH-mediated domain dynamics". EMBO Reports. 18 (8): 1306–1317. doi:10.15252/embr.201744198. PMC 5538627. PMID 28645943. 32. ^ Beise J, Hahnen J, Andersen-Beckh B, Dreyer F (January 1994). "Pore formation by tetanus toxin, its chain and fragments in neuronal membranes and evaluation of the underlying motifs in the structure of the toxin molecule". Naunyn-Schmiedeberg's Archives of Pharmacology. 349 (1): 66–73. doi:10.1007/BF00178208. PMID 8139702. S2CID 9398335. 33. ^ Cabiaux V, Lorge P, Vandenbranden M, Falmagne P, Ruysschaert JM (April 1985). "Tetanus toxin induces fusion and aggregation of lipid vesicles containing phosphatidylinositol at low pH". Biochemical and Biophysical Research Communications. 128 (2): 840–9. doi:10.1016/0006-291X(85)90123-8. PMID 3994725. 34. ^ Foran P, Shone CC, Dolly JO (December 1994). "Differences in the protease activities of tetanus and botulinum B toxins revealed by the cleavage of vesicle-associated membrane protein and various sized fragments". Biochemistry. 33 (51): 15365–74. doi:10.1021/bi00255a017. PMID 7803399. 35. ^ Apte NM, Karnad DR (October 1995). "Short Report: The Spatula Test: A Simple Bedside Test to Diagnose Tetanus". American Journal of Tropical Medicine and Hygiene. 53 (4): 386–7. doi:10.4269/ajtmh.1995.53.386. PMID 7485691. 36. ^ a b "Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures. Recommendations of the Immunization Practices Advisory committee (ACIP)". MMWR. Recommendations and Reports. 40 (RR-10): 1–28. August 1991. PMID 1865873. 37. ^ Porter JD, Perkin MA, Corbel MJ, Farrington CP, Watkins JT, Begg NT (1992). "Lack of early antitoxin response to tetanus booster". Vaccine. 10 (5): 334–6. doi:10.1016/0264-410X(92)90373-R. PMID 1574917. 38. ^ "Uganda announces elimination of Maternal and Neonatal Tetanus". Archived from the original on 2015-02-11. Retrieved 2011-07-14. 39. ^ a b tetanus in Encyclopædia Britannica. Last Updated 7-17-2013 40. ^ a b c d e World Health Organization. "Current recommendations for treatment of tetanus during humanitarian emergencies". Disease Control in Humanitarian Emergencies (English). WHO. Archived from the original on 13 March 2014. Retrieved 12 June 2013. 41. ^ Thwaites, C. Louise; Yen, Lam Minh (13 August 2018). "Tetanus". In J. Larry Jameson (ed.). Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2). Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, Dan L. Longo, Joseph Loscalzo. McGraw-Hill Education. p. 2884. ISBN 978-1-259-64403-0. 42. ^ Rodrigo, Chaturaka; Fernando, Deepika; Rajapakse, Senaka (2014). "Pharmacological management of tetanus: an evidence-based review". Critical Care. Springer Science and Business Media LLC. 18 (2): 217. doi:10.1186/cc13797. ISSN 1364-8535. PMC 4057067. PMID 25029486. 43. ^ "Maternal and Neonatal Tetanus Elimination Initiative" (PDF). Pampers UNICEF 2010 Campaign: 2. Archived (PDF) from the original on 2014-02-01. 44. ^ Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, et al. (June 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. 45. ^ "Deaths from tetanus, by age". Our World in Data. Retrieved 13 January 2020. 46. ^ Pearce JM (1996). "Notes on tetanus (lockjaw)". Journal of Neurology, Neurosurgery, and Psychiatry. 60 (3): 332. doi:10.1136/jnnp.60.3.332. PMC 1073859. PMID 8609513. 47. ^ tetanus Archived 2012-06-26 at the Wayback Machine. CollinsDictionary.com. Collins English Dictionary - Complete & Unabridged 11th Edition. Retrieved October 01, 2012 48. ^ Hemilä, Harri; Koivula, Teija (2013-11-13). "Vitamin C for preventing and treating tetanus". The Cochrane Database of Systematic Reviews (11): CD006665. doi:10.1002/14651858.CD006665.pub3. hdl:10138/225863. ISSN 1469-493X. PMID 24226506. ## External links[edit] Wikipedia's health care articles can be viewed offline with the Medical Wikipedia app. Wikimedia Commons has media related to Tetanus. * Tetanus Information from Medline Plus * Tetanus Surveillance -- United States, 1998-2000 (Data and Analysis) * "Tetanus". MedlinePlus. U.S. National Library of Medicine. Classification D * ICD-10: A33-A35 * ICD-9-CM: 037, 771.3 * MeSH: D013742 * DiseasesDB: 2829 External resources * MedlinePlus: 000615 * eMedicine: emerg/574 * v * t * e * Firmicutes (low-G+C) Infectious diseases * Bacterial diseases: G+ Bacilli Lactobacillales (Cat-) Streptococcus α optochin susceptible * S. pneumoniae * Pneumococcal infection optochin resistant * Viridans streptococci: S. mitis * S. mutans * S. oralis * S. sanguinis * S. sobrinus * S. anginosus group β A * bacitracin susceptible: S. pyogenes * Group A streptococcal infection * Streptococcal pharyngitis * Scarlet fever * Erysipelas * Rheumatic fever B * bacitracin resistant, CAMP test+: S. agalactiae * Group B streptococcal infection ungrouped * Streptococcus iniae * Cutaneous Streptococcus iniae infection γ * D * BEA+: Streptococcus bovis Enterococcus * BEA+: Enterococcus faecalis * Urinary tract infection * Enterococcus faecium Bacillales (Cat+) Staphylococcus Cg+ * S. aureus * Staphylococcal scalded skin syndrome * Toxic shock syndrome * MRSA Cg- * novobiocin susceptible * S. epidermidis * novobiocin resistant * S. saprophyticus Bacillus * Bacillus anthracis * Anthrax * Bacillus cereus * Food poisoning Listeria * Listeria monocytogenes * Listeriosis Clostridia Clostridium (spore-forming) motile: * Clostridium difficile * Pseudomembranous colitis * Clostridium botulinum * Botulism * Clostridium tetani * Tetanus nonmotile: * Clostridium perfringens * Gas gangrene * Clostridial necrotizing enteritis Finegoldia (non-spore forming) * Finegoldia magna Mollicutes Mycoplasmataceae * Ureaplasma urealyticum * Ureaplasma infection * Mycoplasma genitalium * Mycoplasma pneumoniae * Mycoplasma pneumonia Anaeroplasmatales * Erysipelothrix rhusiopathiae * Erysipeloid Authority control * BNE: XX534412 * BNF: cb119374217 (data) * GND: 4190325-0 * LCCN: sh85134166 * NDL: 00563005 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Tetanus	c0039614	28,623	wikipedia	https://en.wikipedia.org/wiki/Tetanus	2021-01-18T18:45:47	{"gard": ["5144"], "mesh": ["D013742"], "umls": ["C0039614"], "orphanet": ["3299"], "wikidata": ["Q47790"]}
Gestational thrombocytopenia SpecialtyObstetrics Hematology Gestational (incidental) thrombocytopenia is a condition that commonly affects pregnant women. Thrombocytopenia is defined as the drop in platelet count from the normal range of 150,000 –400,000 / μL to a count lower than 150,000 / μL.[1] There is still ongoing research to determine the reason for the lowering of platelet count in women with a normal pregnancy. Some researchers speculate the cause to be dependent on dilution, decreased production of platelets, or an increased turnover event.[2] Although women with normal pregnancy experience a low platelet count, women experiencing a continuous drop in platelet will be diagnosed with thrombocytopenia and women with levels greater than 70,000 / μL will be diagnosed with gestational thrombocytopenia.[2] Thrombocytopenia affects approximately 7-10% of pregnant women and of the 7-10%, within that population; approximately 70-80% have gestational thrombocytopenia [3] Gestational Thrombocytopenia is a disorder similar to immune thrombocytopenia (ITP) and is difficult to differentiate between the two disorders.[2] Therefore, a medical history is conducted to because a diagnostic test is unavailable.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Mechanism * 4 Diagnosis * 4.1 Blood Test * 4.2 Ultrasound * 4.3 Bone Marrow Aspiration and/or Biopsy * 5 Prevention * 6 Treatment * 7 Prognosis * 8 Research * 9 History * 10 References * 11 External links ## Signs and symptoms[edit] Although there are no alarming symptoms related to gestational thrombocytopenia, an individual with thrombocytopenia might show the following symptoms[4] – * Nose bleeds * Gums bleeding * Blood in urine/stool * Easily bruised * Enlarged spleen * Jaundice * Continuous bleeding due to cuts * Heavy menstrual flow * Rash-like spots (petechiae), mainly on the lower legs ## Causes[edit] It is evident that there is a decrease in platelet count during pregnancy; however, the cause of the decrease is unknown.[2] However researchers theorize that the decrease in platelet count is due to the decreased production of platelets and/or increased destruction of platelets.[4] ## Mechanism[edit] Generally, there is a decrease in platelet count in pregnant women and it will be due to many reasons.[1] The two main causes of thrombocytopenia are a decrease in the production of platelets in the bone marrow and an increase in the destruction of the platelets.[4] Platelets, along with other components of the blood, are produced in the spongy tissue found in the bone, known as bone marrow.[5] Low platelet count maybe due to the decreased production of platelets in the bone marrow.[5] A decreased production would be due to vitamin B12 deficiency, iron deficiency, aplastic anemia, viral infections, chemotherapy, alcohol consumption, leukemia, myelodysplasia, and cirrhosis.[5] During pregnancy, the fetus’ waste products diffuse into the mother’s sinuses (blood stream), and cause the mother's spleen to become overactive and enlarged.[6] Normally, the spleen filters and removes the waste products and with the overload of unwanted substances in the bloodstream, the spleen will remove blood cells too quickly [6] or store the platelets.[4] In both cases, the overactive spleen would cause a decrease in the circulation of the platelets.[4] ## Diagnosis[edit] Gestational thrombocytopenia will become evident during the mid-second trimester through the third trimester of pregnancy and it is diagnosed based on exclusion.[2] For example, women with a history of immune thrombocytopenia or thrombocytopenia, prior to pregnancy, will not be diagnosed with gestational thrombocytopenia.[2] Patients with low platelet counts, lower than 70,000 / μL, will be difficult to diagnose. The reason is because low platelet counts maybe due to gestational thrombocytopenia or immune thrombocytopenia.[7] In such cases, a treatment of immune thrombocytopenia therapy (corticosteroids, or intravenous immunoglobulin) will be instructed.[7] If there is an improvement in the platelet levels, the patient will be diagnosed with immune thrombocytopenia, and if not the patient will be diagnosed with severe gestational thrombocytopenia[2] In order for the physician to determine the underlying cause of the gestational thrombocytopenia, the following tests are conducted - ### Blood Test[edit] During routine prenatal checkups, the physician will conduct a complete blood count test to determine the components of blood.[8] The complete blood count will provide further information about platelet levels along.[8] The physician may conduct a blood test for platelet antibodies, which maybe produced as a result of a certain drug, such as quinine.[8] The physician may also conduct blood clot test by adding chemicals to blood to determine how long it takes for the blood to clot.[8] ### Ultrasound[edit] The physician may conduct an ultrasound around the spleen to determine if the spleen is enlarged due to an overactive spleen.[8] The ultrasound will provide an image of the spleen and the doctor will compare it to a normal sized spleen.[8] ### Bone Marrow Aspiration and/or Biopsy[edit] The physician may conduct a bone marrow aspiration and/or bone marrow biopsy, if they suspect there is a decreased production of platelets in the bone marrow.[8] A bone marrow aspiration and bone marrow biopsy may be conducted at the same time.[8] ## Prevention[edit] There is no known information regarding the prevention of this disorder. There is no known information regarding the group of women who are likely to be diagnosed with this disorder. ## Treatment[edit] Women, diagnosed with gestational thrombocytopenia, will have their complete blood test conducted during each pre-natal visit and monitored by the doctor.[7] Having diagnosed gestational thrombocytopenia, women should continue their normal activities because the diagnosis does not change the management of pregnancy.[7] Also, the diagnosis of gestational thrombocytopenia poses no harm or risk to the mother or the fetus.[9] There are no diagnostic tests available for gestational thrombocytopenia; rather it is diagnosed based on exclusion.[7] Women who have a history of immune thrombocytopenia or thrombocytopenia prior to becoming pregnant would not be diagnosed with gestational thrombocytopenia[7] Women who have platelet levels lower than 70,000 / μL, during pregnancy, maybe experiencing severe gestational thrombocytopenia or immune thrombocytopenia.[7] In such cases, if the treatment of immune thrombocytopenia therapy (corticosteroids, or intravenous immunoglobulin)[2] does not improve the platelet count, the patient will be diagnosed with severe gestational thrombocytopenia.[2] Severe gestational thrombocytopenia may pose a risk for complications with the use of epidural or general anesthesia during delivery.[7] ## Prognosis[edit] Those who have no previous history of thrombocytopenia, besides the occurrence in previous pregnancies (gestational thrombocytopenia), the platelet levels will go back to a normal range 1–2 months after the delivery.[7] Post delivery, approximately 1–3 months later, women with gestational thrombocytopenia should have a complete blood test conducted.[7] Lastly, gestational thrombocytopenia is a disorder that may reoccur in future pregnancies [3] ## Research[edit] Roberto Stasi, a researcher in the department of Haematology at the St. Georges Hospital in London, UK brings up an excellent point of being able to know the precise diagnosis of the disorder during the stages of pregnancy.[10] This would help physicians treat the patient and help the patient with the management of the pregnancy.[10] ## History[edit] A history of this disorder has not yet been established. ## References[edit] 1. ^ a b Perepu U, Rosenstein L. Maternal thrombocytopenia in pregnancy. Proc Obstet Gynecol. 2013;3(1): Article 6 [15 p.]. Available from: http://ir.uiowa.edu/pog/. Free full text article 2. ^ a b c d e f g h i j Mccrae, Keith R. "Thrombocytopenia in Pregnancy." Platelets (2013): 909-28. Web 3. ^ a b 2013 Clinical. Practice Guide on. Thrombocytopenia in Pregnancy. Presented by the American. Society of Hematology. Anita Rajasekhar, MD, MS 4. ^ a b c d e "Thrombocytopenia (low platelet count) Symptoms - Mayo Clinic". www.mayoclinic.org. Retrieved 2015-11-30. 5. ^ a b c "Low Platelet Count (Thrombocytopenia)". Healthline. Retrieved 2015-12-01. 6. ^ a b "Hypersplenism: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-12-01. 7. ^ a b c d e f g h i j Gernsheimer, T., A. H. James, and R. Stasi. "How I Treat Thrombocytopenia in Pregnancy." Blood 121.1 (2012): 38-47. Web. 8. ^ a b c d e f g h "Low Platelet Count (Thrombocytopenia)". Healthline. Retrieved 2015-12-02. 9. ^ Myers, Bethan, and Edward Truelove. "Diagnosis And Management Of Thrombocytopenia In Pregnancy." Fetal and Maternal Medicine Review Fet. Matern. Med. Rev. 22.02 (2011): 144-67. Web. 10. ^ a b Stasi, Roberto (2012). "How to approach Thrombocytopenia". Hematology. ## External links[edit] Classification D * ICD-10: O99.1 * ICD-9-CM: 649.3 * v * t * e Pathology of pregnancy, childbirth and the puerperium Pregnancy Pregnancy with abortive outcome * Abortion * Ectopic pregnancy * Abdominal * Cervical * Interstitial * Ovarian * Heterotopic * Embryo loss * Fetal resorption * Molar pregnancy * Miscarriage * Stillbirth Oedema, proteinuria and hypertensive disorders * Gestational hypertension * Pre-eclampsia * HELLP syndrome * Eclampsia Other, predominantly related to pregnancy Digestive system * Acute fatty liver of pregnancy * Gestational diabetes * Hepatitis E * Hyperemesis gravidarum * Intrahepatic cholestasis of pregnancy Integumentary system / dermatoses of pregnancy * Gestational pemphigoid * Impetigo herpetiformis * Intrahepatic cholestasis of pregnancy * Linea nigra * Prurigo gestationis * Pruritic folliculitis of pregnancy * Pruritic urticarial papules and plaques of pregnancy (PUPPP) * Striae gravidarum Nervous system * Chorea gravidarum Blood * Gestational thrombocytopenia * Pregnancy-induced hypercoagulability Maternal care related to the fetus and amniotic cavity * amniotic fluid * Oligohydramnios * Polyhydramnios * Braxton Hicks contractions * chorion / amnion * Amniotic band syndrome * Chorioamnionitis * Chorionic hematoma * Monoamniotic twins * Premature rupture of membranes * Obstetrical bleeding * Antepartum * placenta * Circumvallate placenta * Monochorionic twins * Placenta accreta * Placenta praevia * Placental abruption * Twin-to-twin transfusion syndrome Labor * Amniotic fluid embolism * Cephalopelvic disproportion * Dystocia * Shoulder dystocia * Fetal distress * Locked twins * Nuchal cord * Obstetrical bleeding * Postpartum * Pain management during childbirth * placenta * Placenta accreta * Preterm birth * Postmature birth * Umbilical cord prolapse * Uterine inversion * Uterine rupture * Vasa praevia Puerperal * Breastfeeding difficulties * Low milk supply * Cracked nipples * Breast engorgement * Childbirth-related posttraumatic stress disorder * Diastasis symphysis pubis * Postpartum bleeding * Peripartum cardiomyopathy * Postpartum depression * Postpartum psychosis * Postpartum thyroiditis * Puerperal fever * Puerperal mastitis Other * Concomitant conditions * Diabetes mellitus * Systemic lupus erythematosus * Thyroid disorders * Maternal death * Sexual activity during pregnancy * Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Gestational thrombocytopenia	c0563311	28,624	wikipedia	https://en.wikipedia.org/wiki/Gestational_thrombocytopenia	2021-01-18T19:05:03	{"icd-9": ["649.3"], "icd-10": ["O99.1"], "wikidata": ["Q2253109"]}
Extrapulmonary tuberculosis that is located in lymph node Mycobacterial cervical lymphadenitis Other namesScrofula, scrophula, struma, the King's evil Scrofula of the neck SpecialtyInfectious disease Look up scrofula in Wiktionary, the free dictionary. The disease mycobacterial cervical lymphadenitis, also known as scrofula and historically as king's evil, involves a lymphadenitis of the cervical lymph nodes associated with tuberculosis as well as nontuberculous (atypical) mycobacteria. ## Contents * 1 Disease * 1.1 Signs and symptoms * 2 Diagnosis * 2.1 Pathology * 3 Treatment * 3.1 17th century * 3.2 20th century to present * 4 Prognosis * 5 History * 6 Case studies * 7 See also * 8 References * 9 External links ## Disease[edit] Scrofula is the term used for lymphadenopathy of the neck, usually as a result of an infection in the lymph nodes, known as lymphadenitis. It can be caused by tuberculous or nontuberculous mycobacteria. About 95% of the scrofula cases in adults are caused by Mycobacterium tuberculosis, most often in immunocompromised patients (about 50% of cervical tuberculous lymphadenopathy). In immunocompetent children, scrofula is often caused by atypical mycobacteria (Mycobacterium scrofulaceum) and other nontuberculous mycobacteria (NTM). Unlike the adult cases, only 8% of cases in children are tuberculous. With the stark decrease of tuberculosis in the second half of the 20th century, scrofula became a less common disease in adults, but remained common in children. With the appearance of AIDS, however, it has shown a resurgence, and presently affects about 5% of severely immunocompromised patients.[citation needed] ### Signs and symptoms[edit] The most usual signs and symptoms are the appearance of a chronic, painless mass in the neck, which is persistent and usually grows with time. The mass is referred to as a "cold abscess", because there is no accompanying local color or warmth and the overlying skin acquires a violaceous (bluish-purple) color. NTM infections do not show other notable constitutional symptoms, but scrofula caused by tuberculosis is usually accompanied by other symptoms of the disease, such as fever, chills, malaise and weight loss in about 43% of the patients. As the lesion progresses, skin becomes adhered to the mass and may rupture, forming a sinus and an open wound. King’s Evil was known as a frequent disorder in the 17th century that was caused by bad blood that coagulated in spongy organs such as the thyroid and the lymph nodes. A Hippocratic treatise stated that King’s Evil was caused by an accumulation of phlegm that resulted in an imbalance or disease of the body humors which are blood, bile, lymph, and phlegm. The fatal outcome some patients experienced was due to a cheese-like presentation of the lungs and the King’s Evil lesions. It was also associated with pulmonary tuberculosis.[1] Cervical lymphadenitis is commonly caused by an infection of mycobacterial to the head region. This disease is very inconsistent; cases can have different laboratory findings. Sometimes the disease can occur due to tuberculosis disease. However it is urgent that on a case by case basis that you determine if it is caused by tuberculous or nontuberculous mycobacterial. This is due to the fact that treatment often differs between the two.[2] ## Diagnosis[edit] Diagnosis is usually performed by needle aspiration biopsy or excisional biopsy of the mass and the histological demonstration of stainable acid-fast bacteria in the case of infection by M. tuberculosis (Ziehl-Neelsen stain), or the culture of NTM using specific growth and staining techniques. ### Pathology[edit] The classical histologic pattern of scrofula features caseating granulomas with central acellular necrosis (caseous necrosis) surrounded by granulomatous inflammation with multinucleated giant cells. Although tuberculous and non tuberculosis lymphadenitis are morphologically identical, the pattern is somewhat distinct from other causes of bacterial lymphadenitis.[3] ## Treatment[edit] ### 17th century[edit] The treatment for mycobacterial cervical lymphadenitis consisted primarily of small incisions to remove the surrounding soft tissue and/or the abnormal mass. Until the 18th century, doctors thought the only way to cure the disease was to be touched by a member of a royal family. In both France and England, the kings who were thought to have an inherited miraculous power to cure the illness, touched crowds of infected people. The "touchings" began in France with the reign of Phillip I (1060–1108) and in England with the reign of Henry I (1100–1135). This act of public healing by powerful kings and royal family members encouraged the nickname "King's Evil".[4] After the touching, the sovereign presented the afflicted with an angel on a gold-plated coin that was to be hung around the infected person by a ribbon. This was used as a way of warding off the disease. This coin could have weighed as much as 5 grams and was considered a touch piece of great value.[5] The royal touch and surgical removal were not the only methods of healing employed: Scrophularia nodosa (common name: Figwort) , which has nodular roots that resemble the swollen lymph nodes of the afflicted, was thought to be useful in treating the disease, according to the Doctrine of signatures \- the plant being hung around the neck of the afflicted - and indeed Figwort does, in fact, contain chemicals that can help decrease inflammation, irritation and discomfort.[6] ### 20th century to present[edit] Treatments are highly dependent on the kind of infection. Surgical excision of the scrofula does not work well for M. tuberculosis infections, and has a high rate of recurrence and formation of fistulae.[citation needed] Furthermore, surgery may spread the disease to other organs. The best approach is to use conventional treatment of tuberculosis with antibiotics. The cocktail-drug treatment of tuberculosis (and inactive meningitis) includes rifampicin along with pyrazinamide, isoniazid, ethambutol, and streptomycin ("PIERS"). Scrofula caused by NTM, however, responds well to surgery, but is usually resistant to antibiotics.[citation needed] The affected nodes can be removed either by repeated aspiration, curettage or total excision (with the risk in the latter procedure, however, often causing unsightly scarring, damage to the facial nerve, or both).[citation needed] Many different therapeutic options exist, particularly regarding non tuberculosis mycobacterial infections, such as incision and drainage, aspiration biopsy and chemotherapy. All of these methods have proved to result in a cure of the disease. However different treatments can cause different side effects along the way to recovery. Some of these side effects include facial nerve injury and scarring. it is important to cater your course of treatment to each patient and take into account their history as well as their severity of infection.[7] ## Prognosis[edit] With adequate treatment, clinical remission is practically 100%. In NTM infections, with adequate surgical treatment, clinical remission is greater than 95%. It is recommended that persons in close contact with the diseased person, such as family members, be tested for tuberculosis. ## History[edit] The word comes from the medieval Latin scrofula, diminutive of scrofa, meaning brood sow. In the beginning of the Modern Age Western Europeans believed that royal touch, the touch of the sovereign of England or France, could cure diseases owing to the divine right of sovereigns. Henry VI of England is alleged to have cured a girl with it. Scrofula was therefore also known as the King's evil. From 1633, the Book of Common Prayer of the Anglican Church contained a ceremony for this, and it was traditional for the monarch (king or queen) to present to the touched person a coin—usually an angel, a gold coin the value of which varied from about 6 shillings to about 10 shillings. In England this practice continued until the early 18th century, and was continued by the Jacobite pretenders until the extinction of the House of Stuart with the death of the pretender Henry IX. King Henry IV of France is reported as often touching and healing as many as 1,500 individuals at a time. Queen Anne touched the infant Samuel Johnson in 1712,[8] but King George I put an end to the practice as being "too Catholic".[citation needed] The kings of France continued the custom until Louis XV stopped it in the 18th century, though it was briefly revived by Charles X in 1825. Physicians, healers, and patent medicine sellers offered a wide range of cures for scrofula or the King's Evil. Since ancient times, mercury, referred to as cinnabar, quicksilver or calomel, was administered as an ointment or pill or inhaled as a vapor to treat skin diseases. Mercury taken internally induced vomiting and sweating, reactions believed to cure the disease. In 1830 the New-York Medical and Physical Journal continued to recommend mercury as the best cure for scrofula, stating it caused an irritation that would counteract the disease and increased the working of the glands.[9] Alternative treatments were also offered. Many rejected the harsh side effects of mercury, claiming their cures were made of "natural" or "vegetable" ingredients. Patent medicines labeled as sarsaparilla were recommended for scrofula.[10] Examples of treatments recommended between the 17th and 19th century include the following: * Herbalist Nicholas Culpepper (1616–1654) claimed to have treated his daughter for scrofula with lesser celandine, and cured her within a week.[11] * In the 18th century, Elizabeth Pearson, an Irish herbalist, proposed a treatment for scrofula involving herbs and a poultice and extract of vegetable, and in 1815, Sir Gerard Noel presented a petition to the House of Commons advocating her treatment.[12] * In 1768 the Englishman John Morley produced a handbook entitled Essay on the Nature and Cure of Scrophulous Disorders, Commonly Called the King's Evil. The book starts by listing the typical symptoms and indications of how far the disease had progressed. It then goes into detail with a number of case studies, describing the specific case of the patient, the various treatments used and their effectiveness. The forty-second edition was printed in 1824. * Richard Carter, a frontier healer in Kentucky, recommended several treatments for the King's Evil, or scrofula, in his 1815 home medical guide Valuable Vegetable Medical Prescriptions for the cure of all Nervous and Putrid Disorders.[13] * In the 19th century in the United States, the patent medicine Swaim's Panacea was advertised to cure scrofula. Swaim's Panacea contained mercury.[14] In 1924, French historian Marc Bloch wrote a book on the history of the royal touch: The Royal Touch: Sacred Monarchy and Scrofula in England and France (original in French).[15] ## Case studies[edit] A three-year-old healthy young female presented with a bilateral cervical lymph node enlarged. The patient was admitted to the hospital after tuberculosis skin test became positive and further examination showed several other enlarged lymph nodes near her neck. At the hospital, she underwent an exploration surgery where they excised part of her presented lymph node and drained her retropharynx. The drained retropharynx grew methicillin-resistant Staphylococcus epidermidis and Streptococcus mitis. After these findings, the patient received oral linezolid for ten days and had antimicrobial drug therapy for 14 days. Once the patient returned for a follow up appointment, the lymph node was not gone and had only slightly decreased in size. Due to this, it had to be completely removed from her neck. After she recovered and went home, there were no repeat signs that the infection was back for over a year.[16] ## See also[edit] * Scrofuloderma * Tuberculosis diagnosis * Tuberculosis treatment * Touch pieces ## References[edit] 1. ^ Duarte G, Ignacio; Chuaqui F, Claudia (April 2016). "History of scrofula: from humoral dyscrasia to consumption". Revista Medica De Chile. 144 (4): 503–507. doi:10.4067/S0034-98872016000400012. ISSN 0717-6163. PMID 27401383. 2. ^ Bayazit, YA; Bayazit, N; Namiduru, M. (2004). "Mycobacterial cervical lymphadenitis". ORL J Otorhinolaryngol Relat Spec. 66 (5): 275–80. doi:10.1159/000081125. PMID 15583442. 3. ^ Rosado FG, Stratton CW, Mosse CA (November 2011). "Clinicopathologic correlation of epidemiologic and histopathologic features of pediatric bacterial lymphadenitis". Arch Pathol Lab Med. 135(11):1490–93. doi:10.5858/arpa.2010-0581-OA. PMID 22032579. 4. ^ Sturdy, David J. (1992). "The Royal Touch in England". European Monarchy: Its Evolution and Practice from Roman Antiquity to Modern Times. Franz Steiner Verlag. p. 190. ISBN 3515062335. 5. ^ "Gold coin used in the ceremony of touching for the king's evil". BL.uk. The British Library. Retrieved 2020-12-15. 6. ^ Lane Furdell, Elizabeth (2001). The Royal Doctors, 1485–1714: Medical Personnel at the Tudor and Stuart Courts. University Rochester Press. p. 190. ISBN 1580460518. 7. ^ Mandell, DL; Wald, ER; Michaels, MG; Dohar, JE (2003). "Management of Nontuberculous Mycobacterial Cervical Lymphadenitis". Arch Otolaryngol Head Neck Surg. 129 (3): 341–44. doi:10.1001/archotol.129.3.341. 8. ^ Henry Hitchings (2005). Dr Johnson's Dictionary: The Extraordinary Story of the Book that Defined the World. John Murray. p. 11. 9. ^ https://books.google.com/books?id=ksJXAAAAMAAJ&pg=PA328&lpg=PA328&dq=scrofula+and+mercury#v=twopage&q=scrofula%20and%20mercury&f=false 10. ^ Resor, Cynthia (March 18, 2020). "What is scrofula? Can it be cured?". 11. ^ Reader's Digest Field Guide to the Wild Flowers of Britain. Reader's Digest. 1981. p. 26. ISBN 9780276002175. 12. ^ "Petition of Mrs. Pearson Respecting Her Discovery For the Cure of Scrofula, or King's Evil". Hansard. 31: 1086–87. 3 July 1815. 13. ^ iarchive:2545048R.nlm.nih.gov/page/n141/mode/2up/search/scrofula 14. ^ Young, James Harvey. The Toadstool Millionaires, ch. 5 (1961) 15. ^ Bloch, M. (Anderson, J. E., trans), The Royal Touch: Sacred Monarchy and Scrofula in England and France (Les Rois Thaumaturges), Routledge & Kegan Paul, (London), 1973. 16. ^ Syed, S. S., Aderinboye, O., Hanson, K. E., & Spitzer, E. D. (2010). Acute Cervical Lymphadenitis Caused by Mycobacterium florentinum. Emerging Infectious Diseases, 16(9), 1486-1487. https://dx.doi.org/10.3201/eid1609.100433. ## External links[edit] Wikimedia Commons has media related to Tuberculous cervical lymphadenitis. * Werrett, Simon. "Healing the Nation’s Wounds: Royal Ritual and Experimental Philosophy in Restoration England". History of Science 38 (2000): 377–399. * Scrofula at MedPix Images Classification D * ICD-10: A18.4 * ICD-9-CM: 017.2 * MeSH: D014388 * DiseasesDB: 31259 External resources * MedlinePlus: 001354 * eMedicine: ent/524 * v * t * e Gram-positive bacterial infection: Actinobacteria Actinomycineae Actinomycetaceae * Actinomyces israelii * Actinomycosis * Cutaneous actinomycosis * Tropheryma whipplei * Whipple's disease * Arcanobacterium haemolyticum * Arcanobacterium haemolyticum infection * Actinomyces gerencseriae Propionibacteriaceae * Propionibacterium acnes Corynebacterineae Mycobacteriaceae M. tuberculosis/ M. bovis * Tuberculosis: Ghon focus/Ghon's complex * Pott disease * brain * Meningitis * Rich focus * Tuberculous lymphadenitis * Tuberculous cervical lymphadenitis * cutaneous * Scrofuloderma * Erythema induratum * Lupus vulgaris * Prosector's wart * Tuberculosis cutis orificialis * Tuberculous cellulitis * Tuberculous gumma * Lichen scrofulosorum * Tuberculid * Papulonecrotic tuberculid * Primary inoculation tuberculosis * Miliary * Tuberculous pericarditis * Urogenital tuberculosis * Multi-drug-resistant tuberculosis * Extensively drug-resistant tuberculosis M. leprae * Leprosy: Tuberculoid leprosy * Borderline tuberculoid leprosy * Borderline leprosy * Borderline lepromatous leprosy * Lepromatous leprosy * Histoid leprosy Nontuberculous R1: * M. kansasii * M. marinum * Aquarium granuloma R2: * M. gordonae R3: * M. avium complex/Mycobacterium avium/Mycobacterium intracellulare/MAP * MAI infection * M. ulcerans * Buruli ulcer * M. haemophilum R4/RG: * M. fortuitum * M. chelonae * M. abscessus Nocardiaceae * Nocardia asteroides/Nocardia brasiliensis/Nocardia farcinica * Nocardiosis * Rhodococcus equi Corynebacteriaceae * Corynebacterium diphtheriae * Diphtheria * Corynebacterium minutissimum * Erythrasma * Corynebacterium jeikeium * Group JK corynebacterium sepsis Bifidobacteriaceae * Gardnerella vaginalis * v * t * e Lymphatic disease: organ and vessel diseases Thymus * Abscess * Hyperplasia * Hypoplasia * DiGeorge syndrome * Ectopic thymus * Thymoma * Thymic carcinoma Spleen * Asplenia * Asplenia with cardiovascular anomalies * Accessory spleen * Polysplenia * Wandering spleen * Splenomegaly * Banti's syndrome * Splenic infarction * Splenic tumor Lymph node * Lymphadenopathy * Generalized lymphadenopathy * Castleman's disease * Intranodal palisaded myofibroblastoma * Kikuchi disease * Tonsils * see Template:Respiratory pathology Lymphatic vessels * Lymphangitis * Lymphangiectasia * Lymphedema * Primary lymphedema * Congenital lymphedema * Lymphedema praecox * Lymphedema tarda * Lymphedema–distichiasis syndrome * Milroy's disease * Secondary lymphedema * Bullous lymphedema * Factitial lymphedema * Postinflammatory lymphedema * Postmastectomy lymphangiosarcoma * Waldmann disease Authority control * GND: 4531817-7 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Mycobacterial cervical lymphadenitis	c0041316	28,625	wikipedia	https://en.wikipedia.org/wiki/Mycobacterial_cervical_lymphadenitis	2021-01-18T18:31:57	{"mesh": ["D014388"], "umls": ["C0242830", "C0041316"], "icd-9": ["017.2"], "wikidata": ["Q4678337"]}
Bee disease This article's lead section may be too short to adequately summarize its key points. Please consider expanding the lead to provide an accessible overview of all important aspects of the article. (June 2015) Field test for American foulbrood American foulbrood (AFB, Histolysis infectiosa perniciosa larvae apium, Pestis americana larvae apium), caused by the spore-forming bacteria Paenibacillus larvae ssp. larvae (formerly classified as Bacillus larvae[1]), is a highly infectious bee disease. It is the most widespread and destructive of the bee brood diseases. ## Contents * 1 Characteristics * 2 History * 3 Diagnosis * 4 Disease spread * 5 Treatment * 6 References * 7 External links ## Characteristics[edit] Paenibacillus larvae is a rod-shaped bacterium, which is visible only under a high power microscope. Larvae up to 3 days old become infected by ingesting spores that are present in their food. Young larvae less than 24 hours old are most susceptible to infection. Spores germinate in the gut of the larva and the vegetative form of the bacteria begins to grow, taking its nourishment from the larva. Spores will not germinate in larvae over 3 days old. Infected larvae normally die after their cell is sealed. The vegetative form of the bacterium will die but not before it produces many millions of spores. Each dead larva may contain as many as 100 million spores. This disease only affects the bee larvae but is highly infectious and deadly to bee brood. Infected larvae darken and die.[2][3] ## History[edit] Until 1906 American foulbrood was not differentiated from European foulbrood, and the condition was simply referred to as foulbrood. Thereafter, the terms European and American were used to distinguish the diseases.[4] However the designations do not refer to the geographical distributions but to the areas where they were first investigated scientifically.[5] In 1907, it was demonstrated conclusively that the bacterium Bacillus larvae was the cause of American foulbrood disease by fulfilling Koch's postulates.[6] The geographical origin of AFB is unknown, but it is found almost worldwide.[7][8] ## Diagnosis[edit] Lab testing is necessary for definitive diagnosis, but a good field test is to touch a dead larva with a toothpick or twig. It will be sticky and "ropey" (drawn out). Foulbrood also has a characteristic odor, and experienced beekeepers with a good sense of smell can often detect the disease upon opening a hive.[9] However, this odour may not be noticeable until the disease is in an advanced stage. Since response and treatment is required as early as possible to protect other colonies, absence of odour cannot be relied on as indicating absence of foulbrood. Only regular and thorough inspection of the brood can identify the disease in its early stages. The most reliable disease diagnosis is done by sending in some possibly affected brood comb to a laboratory specialized in identifying honey bee diseases.[10] ## Disease spread[edit] When cleaning infected cells, bees distribute spores throughout the colony. Disease spreads rapidly throughout the hive as the bees, trying to remove the spore-laden dead larvae, contaminate brood food. Nectar stored in contaminated cells will contain spores and soon the brood chamber becomes filled with contaminated honey. As this honey is moved up into the supers, the entire hive becomes contaminated with spores. When the colony becomes weak from AFB infection, robber bees may enter and take contaminated honey back to their hives, thereby spreading the disease to other colonies and apiaries.[11] Beekeepers also may spread disease by moving equipment (frames or supers) from contaminated hives to healthy ones. American foulbrood spores are extremely resistant to desiccation and can remain viable for more than 40 years in honey and beekeeping equipment. Therefore, honey from an unknown source should never be used as bee feed, and used beekeeping equipment should be assumed to be contaminated unless known to be otherwise.[12] Beehives with American foul brood should be burned due to spores that remain viable for up to 40 years. ## Treatment[edit] European Union law requires all infected hives and equipment to be destroyed.[13] In the US, many State Apiary Inspectors require an AFB diseased hive to be burned completely. The spores can survive up to 40 years and are difficult to destroy. A less radical method of containing the spread of disease is burning only the frames and comb and thoroughly flame scorching the interior of the hive body, bottom board and covers. Dipping the hive parts in hot paraffin wax or a 3% sodium hypochlorite solution (bleach) also renders the AFB spores innocuous.[14] It is also possible to sterilize an infected hive without damaging either the structure of the hive or the stores of honey and pollen it contains by sufficiently lengthy exposure to an atmosphere of ethylene oxide gas, as in a closed chamber, as hospitals do to sterilize equipment that cannot withstand steam sterilization.[15] Antibiotics, in non-resistant strains of the pathogen, can prevent the vegetative state of the bacterium forming. Drug treatment to prevent the American foulbrood spores from successfully germinating and proliferating is possible using oxytetracycline hydrochloride (Terramycin).[16] Another drug treatment, tylosin tartrate, was approved by the US Food and Drug Administration (FDA) in 2005.[17] Chemical treatment is sometimes used prophylactically, but this is a source of considerable controversy because certain strains of the bacterium seem to be rapidly developing resistance.[18] In addition, hives that are contaminated with millions of American foulbrood spores have to be prophylactically treated indefinitely. Once the treatment is suspended, the American foulbrood spores germinate successfully again leading to a disease outbreak. Thomas Brady at Brigham Young University and Heather Hendrickson at Massey University are currently studying phage therapy to treat American foulbrood.[19][20] Lactic acid-producing bacteria inhibit the growth of the spore and vegetative cells of Paenibacillus larvae under laboratory conditions. However, the bacteria made no difference to infected honey bee colonies.[21] ## References[edit] 1. ^ Marian JELINSKI, http://www.apidologie.org/articles/apido/abs/1985/01/Apidologie_0044-8435_1985_16_1_ART0007/Apidologie_0044-8435_1985_16_1_ART0007.html Archived 2015-09-23 at the Wayback Machine 2. ^ Foul brood disease of honey bees:recognition and control Archived March 18, 2009, at the Wayback Machine Central Science Laboratory National Bee Unit, Department for Environment, Food and Rural Affairs (DEFRA); United Kingdom (excellent publication with many pictures) 3. ^ "Bees Disease: One Step Closer To A Cure." Archived 2019-10-09 at the Wayback Machine ScienceDaily 4 May 2008 4. ^ Phillips (1906) 5. ^ Shimanuki, Hachiro; Knox, David A. Diagnosis of Honey Bee Diseases Archived 2006-12-09 at the Wayback Machine USDA 6. ^ White 1907 7. ^ Matheson, 1993,1996 8. ^ American Foulbrood disease Archived 2011-07-18 at the Wayback Machine A.M. Alippi Laboratorio de Fitopatologia, Facultad de Ciencias Agrarias y Forestales Universidad Nacional deL a Plata, Calle 60 y 118, C.C. 31, 1900 La Plata, Argentina 9. ^ "American Foulbrood (AFB)". Bear Country Bees. Archived from the original on 2016-08-09. 10. ^ USDA Agricultural Research Service Submission of Samples for Diagnosis Archived 2011-02-04 at the Wayback Machine (2007) 11. ^ von Büren, R.S.; et al. (2019). "High-resolution maps of Swiss apiaries and their applicability to study spatial distribution of brood diseases". PeerJ. 7: e6393. doi:10.7717/peerj.6393. PMC 6360077. PMID 30723636. 12. ^ American Foul Brood-Prevention and Control Archived 2008-06-26 at the Wayback Machine Pennsylvania Department of Agriculture 13. ^ Bee disease confirmed in Perthshire. Scottish Government. Published: 28 May 2020. https://www.gov.scot/news/bee-disease-confirmed-in-perthshire-1/ 14. ^ Dobbelaere W, de Graaf DC, Reybroeck W, Desmedt E, Peeters JE, Jacobs FJ Disinfection of wooden structures contaminated with Paenibacillus larvae subsp. larvae spores Journal of Applied Microbology (Aug 2, 2001) 15. ^ Robinson (1972). "Gas Sterilization of Beekeeping Equipment Contaminated by the American Foulbrood Organism, Bacillus larvae". The Florida Entomologist. 55 (1): 43–51. doi:10.2307/3493642. JSTOR 3493642. 16. ^ Calderone, Nicholas Management of Honey Bee Brood Diseases Archived July 27, 2011, at the Wayback Machine (January 2001) Cornell University 17. ^ USDA Agricultural Research Service New Antibiotic Approved for Treating Bacterial Honey Bee Disease Archived 2010-10-08 at the Wayback Machine 18. ^ Powell, Gordon Cleaning up American Foulbrood Archived 2006-03-15 at the Wayback Machine Iowa Honey Producers Association, The Buzz Newsletter (Jan 2006) 19. ^ Brady, T. Scott; Merrill, Bryan D.; Hilton, Jared A.; Payne, Ashley M.; Stephenson, Michael B.; Hope, Sandra (2017). "Bacteriophages as an alternative to conventional antibiotic use for the prevention or treatment of Paenibacillus larvae in honeybee hives". Journal of Invertebrate Pathology. 150: 94–100. doi:10.1016/j.jip.2017.09.010. ISSN 1096-0805. PMID 28917651. 20. ^ Morton, Jamie (2018-01-14). "Virus vs disease: New bid to help our honeybees". NZ Herald. ISSN 1170-0777. Archived from the original on 2018-02-19. Retrieved 2020-03-12. 21. ^ Sepideh, Lamei (2018-05-03). "The effect of honeybee-specific lactic acid bacteria on american foulbrood disease of honeybees". pub.epsilon.slu.se. Archived from the original on 2018-06-12. Retrieved 2018-06-12. Wikimedia Commons has media related to American foulbrood. ## External links[edit] * Learn to identify American foulbrood in 90 seconds YouTube video showing the 'Ropiness test' and scales. * v * t * e Honey bee types and characteristics Bee castes * Queen bee * Worker bee * Laying worker bee * Drone Lifecycle * Bee colony * Honey bee life cycle * Brood * Bee learning and communication * Swarming Subspecies and breeds * Africanized bee * Buckfast bee * Carniolan honey bee * European dark bee * Italian bee * Russian honey bee * Maltese honey bee * Western honey bee * Apis mellifera scutellata * Honey bee race Cultivation * Beekeeping * Apiology * Beeswax * Honey * Honey extraction * Propolis * Royal jelly Equipment * Apiary * Beehive * Langstroth hive * Hive frame * Honey super * Wax foundation * Horizontal top-bar hive * Hive tool * Queen clip * Bee smoker * Honey extractor * Queen excluder * Jenter kit Parasites and diseases * Varroa destructor * Varroa sensitive hygiene * Small hive beetle * Waxworm * American foulbrood * Deformed wing virus * Colony collapse disorder Lists * Topics in beekeeping * Diseases of the honey bee Beekeeping by countries * Australia * Hungary * India * Ireland * Nepal * New Zealand * Ukraine * United Kingdom * United States [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	American foulbrood	None	28,626	wikipedia	https://en.wikipedia.org/wiki/American_foulbrood	2021-01-18T19:00:29	{"wikidata": ["Q18002779"]}
Bladder cancer is a disease in which certain cells in the bladder become abnormal and multiply uncontrollably to form a tumor. The bladder is a muscular organ in the lower abdomen that stores urine until it can be removed (excreted) from the body. Bladder cancer may cause blood in the urine, pain during urination, frequent urination, the feeling of needing to urinate without being able to, or lower back pain. Many of these signs and symptoms are nonspecific, which means they may occur in multiple disorders. People who have one or more of these nonspecific health problems often do not have bladder cancer, but have another condition such as an infection. Bladder cancer develops when tumors form in the tissue that lines the bladder. There are several types of bladder cancer, categorized by the type of cell in the tissue that becomes cancerous. The most common type is transitional cell carcinoma (also known as urothelial carcinoma); others include squamous cell carcinoma and adenocarcinoma. If the tumor spreads (metastasizes) beyond the lining of the bladder into nearby tissues or organs, it is known as invasive bladder cancer. ## Frequency In the United States, bladder cancer is the fourth most common type of cancer in men. Bladder cancer occurs four times more often in men than in women, with about 60,000 men and 18,000 women diagnosed with the condition each year. ## Causes Cancers occur when genetic mutations build up in critical genes, specifically those that control cell growth and division (proliferation) or the repair of damaged DNA. These changes allow cells to grow and divide uncontrollably to form a tumor. In nearly all cases of bladder cancer, these genetic changes are acquired during a person's lifetime and are present only in certain cells in the bladder. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in bladder cancer cells. It is unclear whether genetic changes that are inherited and present in all of the body's cells (germline mutations) play a significant role in causing bladder cancer. Somatic mutations in the FGFR3, PIK3CA, KDM6A, and TP53 genes are common in bladder cancers. Each of these genes plays a critical role in regulating gene activity and cell growth, ensuring cells do not grow and divide too rapidly or uncontrollably. It is likely that mutations in these genes disrupt normal gene regulation, contributing to the uncontrolled cell growth that can lead to tumor formation in bladder cancer. Mutations in many other genes have been found to be associated with bladder cancer; each of these additional genes is associated with a small percentage of cases. Most of these genes are also involved in regulating the normal activity of genes and the growth of cells. Additionally, deletions of part or all of chromosome 9 are commonly found in bladder cancer. Research shows that several genes that control cell growth and division are located on chromosome 9. It is likely that a loss of one or more of these genes plays a role in the early development and progression of bladder cancer. Researchers have identified many lifestyle and environmental factors that expose individuals to cancer-causing compounds (carcinogens), which increase the rate at which somatic mutations occur, contributing to a person's risk of developing bladder cancer. The greatest risk factor is long-term tobacco smoking. It is estimated that half of people with bladder cancer have a history of tobacco smoking. Other environmental risk factors include chronic bladder inflammation, exposure to certain industrial chemicals, certain herbal medicines common in Asia, a parasitic infection called schistosomiasis, and long-term use of urinary catheters. ### Learn more about the genes and chromosome associated with Bladder cancer * ARID1A * ATM * CDKN2A * CREBBP * EP300 * FGFR3 * HRAS * KDM6A * KMT2D * PIK3CA * PTEN * RAF1 * RB1 * TP53 * chromosome 9 Additional Information from NCBI Gene: * CCNE1 * CDKN1A * ELF3 * ERBB2 * FAT1 * KMT2A * KMT2B * KMT2C * MDM2 * RAC1 * RHOB * SPTAN1 * STAG2 ## Inheritance Pattern Bladder cancer is typically not inherited. It is usually associated with somatic mutations that occur in certain cells in the bladder during a person's lifetime. In rare families, the risk of bladder cancer is inherited. In these cases, the cancer risk follows an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing the disease. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop bladder cancer. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Bladder cancer	c0005684	28,627	medlineplus	https://medlineplus.gov/genetics/condition/bladder-cancer/	2021-01-27T08:25:34	{"gard": ["12210"], "mesh": ["D001749"], "omim": ["109800"], "synonyms": []}
A rare embryonic tumor of the neuroepithelial tissue characterized clinically by increased intracranial pressure and cerebellar dysfunction, with the most common presenting symptoms being headache, vomiting, and ataxia. The disease can be classified according to histological (classic, anaplastic, large-cell, or desmoplatic medulloblastoma, or medulloblastoma with extensive nodularity) and molecular criteria (WNT-activated, sonic-hedgehoc-activated, group 3, group 4). ## Epidemiology Medulloblastoma (MB) is the most common malignant brain tumor in childhood. Annual incidence varies according to age a group, and is estimated in the USA at 0.47/100,000 in children (0-14 years of age), 0.11/100,000 in adolescents and young adults, 0.02/100,000 in adults (over 40 years of age). Males are more affected than females. ## Clinical description Age of disease onset is variable and can occur in patients ranging in age from the newborn period to adulthood (peak age at presentation is children 3-6 years, with only 25% of patients being between 15 and 44 years). The most common presenting symptoms are headache, vomiting, and ataxia. Additional features that may be observed include lethargy, motor or cranial nerve impairment, gaze palsy, visual impairment due to hydrocephalia, vertigo/hearing loss, behavioral changes/irritability, and extracranial pain (e.g. back pain in those with spinal metastases). Around 30% of pediatric cases present with metastases at diagnosis. Most metastases occur within the central nervous system by seeding via the cerebrospinal fluid (cranial or spinal), while spread to extracranial organs (e.g. bone marrow, liver, lungs) is very rare at diagnosis. In a minority of patients, MB is associated with Gorlin syndrome, familial adenomatous polyposis (FAP; the association of FAP and MB is referred to as the Turcot syndrome with polyposis) or with Li-Fraumeni Syndrome. Increased susceptibility to certain tumors (neuroblastoma), hematological malignancies (acute lymphoblastic leukemia, acute myeloid leukemia) or disorders caused by mutations in genes encoding components of the RAS signaling pathway (Noonan syndrome or neurofibromatosis-Noonan syndrome) have been reported in MB. ## Etiology To date, the exact etiology of MB is still unknown but genomic data has identified multiple candidate genes that contribute to the pathogenesis of different subgroups of MB. This includes inhibitors of the sonic hedgehog pathway SUFU (10q24.32), Ptch1 (9q22.32), the RNA helicase DDX3X (Xp11.3-p11.23), chromatin regulators KDM6A (Xp11.2) and N-CoR complex genes BCOR (Xp11.4), and the Parkinson's disease genes KMT2D (12q13.12), SMARCA4 (19p13.3), c-myc (8q24.21), MYCN (2p24.3), and TP53 (17p13.1). ## Diagnostic methods MB occurs in the vermis and 20% occurs in the hemispheres of the cerebellum. WNT-activated MB may arise from the dorsal brainstem. Histologically, MB is characterized by small, round cells that stain blue with haematoxylin spectrum and appearance ranges from tumors with extensive nodularity to those with large cell/anaplastic features. Apart from classical MB, four histological variants of MB are recognized: anaplastic MB, large cell MB, MB with extensive nodularity, and desmoplastic/nodular MB. Four different molecular subgroups (WNT-activated, sonic-hedgehoc-activated, group 3, group 4) have been identified. ## Differential diagnosis Differential diagnosis includes other brain tumors (ependymoma, glial tumor, atypical teratoid rhabdoid tumor) and other causes of cerebellar alterations (infectious or cystic lesions, hemorrhages). ## Genetic counseling Genetic counseling is indicated in specific constellations, e.g. in sonic hedgehoc-activated MB (Gorlin-syndrome, Li-Fraumeni-Syndrome, BRCA2), CTNNB1-negative WNT-activated MB (Turcot-syndrome). ## Management and treatment Initially, patients need to be checked for increased intracranial pressure, which if present, needs to be controlled either by medication (e.g. steroids) or by neurosurgical drainage (e.g. external drainage). The postoperative treatment depends on age, histological and molecular subgroup, and result of staging assessments (cranial and spinal MRI, assessment of lumbar cerebrospinal fluid if lumbar puncture is not contraindicated). In children older than 3-5 years, combinations of chemotherapy and craniospinal irradiation are applied. In younger children, brain sparing therapies avoiding irradiation can be administered in very specific constellations. ## Prognosis The overall survival rates are now 80% in standard risk patients, and 30-60 % in high-risk patients. Relapse occurs in nearly 75% of pediatric cases within 2 years. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Medulloblastoma	c0025149	28,628	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=616	2021-01-23T17:48:43	{"gard": ["7005"], "mesh": ["D008527"], "omim": ["155255"], "umls": ["C0025149"], "icd-10": ["C71.6"]}
A number sign (#) is used with this entry because of evidence that primary ciliary dyskinesia-34 (CILD34) is caused by homozygous mutation in the DNAJB13 gene (610263) on chromosome 11q13. Description Primary ciliary dyskinesia-34 (CILD34) is an autosomal recessive disorder characterized by childhood onset of recurrent sinopulmonary infections due to impaired ciliary function. Affected males are infertile due to impaired sperm function and viability. Laterality defects have not been observed in this type of CILD (summary by El Khouri et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400). Clinical Features El Khouri et al. (2016) reported an adult brother and sister, born of consanguineous parents, with primary ciliary dyskinesia diagnosed in their fifties. Both had recurrent respiratory infections, including bronchiectasis, rhinosinusitis, and otitis, that began in childhood. Nasal nitric oxide was very low. Transmission electron microscopy of nasal biopsy respiratory cilia showed multiple cilia lacking central microtubules, including mainly cilia with a '9+0' pattern. Videomicroscopy showed decreased ciliary beating frequency compared to controls, and the beating pattern was abnormal. The man was infertile due to severe oligo-astheno-terato-zoospermia and necrozoospermia. Total sperm count and viability were severely decreased. An unrelated 14-year-old girl with CILD had a similar disorder: she had low nasal nitric oxide, but studies of nasal and bronchial biopsies were inconclusive because of the very low number of cilia. None of the patients had laterality defects. Inheritance The transmission pattern of CILD34 in the families reported by El Khouri et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In 3 patients from 2 unrelated families with CILD34, El Khouri et al. (2016) identified 2 different homozygous loss-of-function mutations in the DNAJB13 gene (610263.0001 and 610263.0002). The mutations were found by exome sequencing. One mutation resulted in a truncated protein, whereas the other was a missense mutation that resulted in undetectable DNAJB13 levels in patient samples, consistent with a loss of function. Transmission electron microscopy analysis of patient respiratory cilia showed an abnormal percentage of cilia lacking central microtubules, indicating that DNAJB13 is critical for upholding the integrity of the central complex in motile cilia and flagella. INHERITANCE \- Autosomal recessive RESPIRATORY \- Recurrent sinopulmonary infections due to impaired ciliary function GENITOURINARY External Genitalia (Male) \- Infertility due to impaired sperm motility \- Decreased sperm count \- Decreased sperm viability LABORATORY ABNORMALITIES \- Decreased nasal nitric oxide \- Decreased ciliary beating frequency \- Abnormal ciliary beating pattern \- Increased percentage of cilia lacking central microtubules (9 + 0 pattern) MISCELLANEOUS \- Onset in childhood \- No laterality defects \- Three patients from 2 unrelated families have been reported (last curated August 2016) MOLECULAR BASIS \- Caused by mutation in the DNAJ/HSP40 homolog, subfamily B, member 13 gene (DNAJB13, 610263.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CILIARY DYSKINESIA, PRIMARY, 34	c4310722	28,629	omim	https://www.omim.org/entry/617091	2019-09-22T15:46:56	{"doid": ["0110610"], "omim": ["617091", "244400"], "orphanet": ["244"], "synonyms": ["Alternative titles", "PCD", "CILIARY DYSKINESIA, PRIMARY, 34, WITHOUT SITUS INVERSUS"]}
Penile agenesis is a rare urogenital tract malformation characterized by complete congenital absence of the phallus. It is usually accompanied by a well-developed scrotum and presence of a skin tag at the anal verge (with or without a urethral meatal opening within it). Often, other genitourinary (e.g. cryptorchidism, renal agenesis and dysplasia, urinary reflux, prostate agenesis) as well as non-genitourinary abnormalities (including skeletal and neural disorders, anal stenosis, imperforate anus, cardiac defects) are associated. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Penile agenesis	c1387005	28,630	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=49	2021-01-23T17:25:33	{"gard": ["4272"], "mesh": ["C536649"], "umls": ["C1387005"], "icd-10": ["Q55.5"], "synonyms": ["Aphallia", "Penis agenesis"]}
A rare acquired immunodeficiency disease characterized by adult-onset absolute neutrophil counts less than 1.5 x 10^9/L on at least 3 occasions in a 3 month period that cannot be attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause. Recurrent aphtous stomatitis and a history of mild bacterial infections are typically associated. A benign outcome with a low rate of severe infections and no secondary malignancies is observed. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Adult idiopathic neutropenia	c1842930	28,631	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2688	2021-01-23T18:16:56	{"mesh": ["C564320"], "omim": ["607847"], "umls": ["C1842930"], "icd-10": ["D70"], "synonyms": ["Adult chronic idiopathic neutropenia"]}
Blue toe syndrome SpecialtyCardiology Blue toe syndrome is a situation that may reflect atherothrombotic microembolism, causing transient focal ischaemia, occasionally with minor apparent tissue loss, but without diffuse forefoot ischemia.[1] The development of blue or violaceous toes can also occur with trauma, cold-induced injury, disorders producing generalized cyanosis, decreased arterial flow, impaired venous outflow, and abnormal circulating blood.[2][3][4][5][6][7][8][9] The terms "blue toe syndrome", "grey toe syndrome" and "purple toe syndrome" are sometimes used interchangeably.[10] Studies may include echocardiography, thoracic and abdominal CT or MRI,[11][12][13][14][15][16][17][18][excessive citations] peripheral arterial run off imaging studies,[19] hypercoagulopathy labs,[20] and interrogation of syndromes that lead to peripheral vascular pathology.[21] ## See also[edit] * Warfarin#Purple toe syndrome * Cholesterol embolism ## References[edit] 1. ^ 'Standards for vascular reporting' 2. ^ Matchett WJ, McFarland DR, Eidt JF, Moursi MM (2000). "Blue toe syndrome: treatment with intra-arterial stents and review of therapies". J Vasc Interv Radiol. 11 (5): 585–92. doi:10.1016/s1051-0443(07)61610-8. PMID 10834489. 3. ^ Applebaum RM, Kronzon I (1996). "Evaluation and management of cholesterol embolization and the blue toe syndrome". Curr Opin Cardiol. 11 (5): 533–42. doi:10.1097/00001573-199609000-00013. PMID 8889381. 4. ^ Ishihara T, Ohkubo T, Nakano T, Ohsawa N (1996). "[Cholesterol (cholestelin) embolization syndrome--blue toe syndrome]". Ryoikibetsu Shokogun Shirizu (14): 469–72. PMID 9047906. 5. ^ Rosenberg GD, Killewich LA (1995). "Blue toe syndrome from a "coral reef" aorta". Ann Vasc Surg. 9 (6): 561–4. doi:10.1007/BF02018830. PMID 8746834. S2CID 45124442. 6. ^ Sottiurai VS, Omlie W (1994). "Femoral artery hypoplasia and persistent sciatic artery with blue toe syndrome: a case report, histologic analysis and review of the literature". Int Angiol. 13 (2): 154–9. PMID 7963875. 7. ^ O'Keeffe ST, Woods BO, Breslin DJ, Tsapatsaris NP (1992). "Blue toe syndrome. Causes and management". Arch Intern Med. 152 (11): 2197–202. doi:10.1001/archinte.1992.00400230023004. PMID 1444678. 8. ^ Choi KH, Yoo J, Huh JW, Jeong YI, Kim MS, Jue MS, Park HJ (2016). "Blue Toe Syndrome as an Early Sign of Disseminated Intravascular Coagulation". Ann Dermatol. 28 (3): 400–1. doi:10.5021/ad.2016.28.3.400. PMC 4884725. PMID 27274647. 9. ^ Hirschmann JV, Raugi GJ (January 2009). "Blue (or purple) toe syndrome". J. Am. Acad. Dermatol. 60 (1): 1–20, quiz 21–2. doi:10.1016/j.jaad.2008.09.038. PMID 19103358. 10. ^ Hirschmann JV, Raugi GJ (January 2009). "Blue (or purple) toe syndrome". J. Am. Acad. Dermatol. 60 (1): 1–20, quiz 21–2. doi:10.1016/j.jaad.2008.09.038. PMID 19103358. 11. ^ Blackshear JL, Oldenburg WA, Cohen MD (Dec 1994). "Making the diagnosis when the patient has 'blue toes'". Geriatrics. 49 (12): 37–9, 43–5. PMID 7982584. 12. ^ Kopani K, Liao S, Shaffer K (2009). "The Coral Reef Aorta: Diagnosis and Treatment Following CT". Radiol. Case Rep. 4 (1): 209. doi:10.2484/rcr.v4i1.209. PMC 5106526. PMID 27843516. 13. ^ Belczak SQ, Sincos IR, Aun R, Costa KV, Araujo EA (Apr 2014). "Coral reef aorta, emergency surgical: case report and literature review". Einstein (Sao Paulo). 12 (2): 237–41. doi:10.1590/s1679-45082014rc2772. PMID 25003933. 14. ^ Schulte KM, Reiher L, Grabitz L, Sandmann W (Nov 2000). "Coral reef aorta: a long-term study of 21 patients". Ann Vasc Surg. 14 (6): 626–33. doi:10.1007/s100169910091. PMID 11128458. S2CID 25265011. 15. ^ "Diagnosis and Treatment Following CT". Radiol. Case Rep. 4 (1): 209. Oct 2016. 16. ^ Policha A, Moudgill N, Eisenberg J, Rao A, DiMuzio P (2013). "Coral reef aorta: case report and review of the literature". Vascular. 21 (4): 251–9. doi:10.1177/1708538113478764. PMID 23518854. S2CID 63550. 17. ^ Qvarfordt PG, Reilly LM, Sedwitz MM, Ehrenfeld WK, Stoney RJ (1984). ""Coral reef" atherosclerosis of the suprarenal aorta: a unique clinical entity". J Vasc Surg. 1 (6): 903–9. doi:10.1067/mva.1984.avs0010903. PMID 6492313. 18. ^ Grotemeyer D, Pourhassan S, Rehbein H, Voiculescu A, Reinecke P, Sandmann W (2007). "The coral reef aorta - a single centre experience in 70 patients". Int J Angiol. 16 (3): 98–105. doi:10.1055/s-0031-1278258. PMC 2733021. PMID 22477301. 19. ^ Blackshear JL, Oldenburg WA, Cohen MD (Dec 1994). "Making the diagnosis when the patient has 'blue toes'". Geriatrics. 49 (12): 37–9, 43–5. PMID 7982584. 20. ^ Blackshear JL, Oldenburg WA, Cohen MD (Dec 1994). "Making the diagnosis when the patient has 'blue toes'". Geriatrics. 49 (12): 37–9, 43–5. PMID 7982584. 21. ^ Blackshear JL, Oldenburg WA, Cohen MD (Dec 1994). "Making the diagnosis when the patient has 'blue toes'". Geriatrics. 49 (12): 37–9, 43–5. PMID 7982584. ## External links[edit] * Pictures are available on this link. 'Blue toe syndrome' * Nijhof IS, Majoie IM, Dijkhorst-Oei LT, Bousema MT (2007). "[Blue toe syndrome; a sign of end-arterial occlusion]". Ned Tijdschr Geneeskd. 151 (23): 1261–7. PMID 17624153. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Blue toe syndrome	c0242645	28,632	wikipedia	https://en.wikipedia.org/wiki/Blue_toe_syndrome	2021-01-18T18:36:50	{"mesh": ["D018438"], "umls": ["C0242645"], "wikidata": ["Q4930176"]}
"Anorexia" and "Anorexic" redirect here. For lack of appetite, see Anorexia (symptom). For the medication, see Anorectic. For other uses, see Anorexia (disambiguation). Type of eating disorder Anorexia nervosa Other namesAnorexia "Miss A—" depicted in 1866 and in 1870 after treatment. She was one of the earliest case studies of anorexia. From the published medical papers of Sir William Gull. SpecialtyPsychiatry, Clinical psychology SymptomsLow weight, fear of gaining weight, strong desire to be thin, food restrictions[1] ComplicationsOsteoporosis, infertility, heart damage, suicide[1] Usual onsetTeen years to young adulthood[1] CausesUnknown[2] Risk factorsFamily history, high-level athletics, modelling, dancing[2][3][4] Differential diagnosisBody dysmorphic disorder, bulimia nervosa, substance use disorder, hyperthyroidism, inflammatory bowel disease, dysphagia, cancer[5][6] TreatmentCognitive behavioral therapy, hospitalisation to restore weight[1][7] Prognosis5% risk of death over 10 years[3][8] Frequency2.9 million (2015)[9] Deaths600 (2015)[10] Anorexia nervosa, often referred to simply as anorexia,[11] is an eating disorder, characterized by low weight, food restriction, fear of gaining weight and a strong desire to be thin.[1] Many people with anorexia see themselves as overweight even though they are, in fact, underweight.[1][2] They often deny that they have a problem with low weight.[3] They weigh themselves frequently, eat small amounts and only eat certain foods.[1] Some exercise excessively, force themselves to vomit, or use laxatives to lose weight.[1] Complications may include osteoporosis, infertility and heart damage, among others.[1] Women will often stop having menstrual periods.[3] In extreme cases, people with anorexia who continually refuse significant dietary intake and weight restoration interventions, and are declared incompetent to make decisions by a psychiatrist, may be fed by force under restraint via nasogastric tube[12] after asking their parents or proxies[13] to make the decision for them.[14] The cause is currently unknown.[2] There appear to be some genetic components with identical twins more often affected than fraternal twins.[2] Cultural factors also appear to play a role, with societies that value thinness having higher rates of disease.[3] Additionally, it occurs more commonly among those involved in activities that value thinness, such as high-level athletics, modeling and dancing.[3][4] Anorexia often begins following a major life-change or stress-inducing event.[3] The diagnosis requires a significantly low weight.[3] The severity of disease is based on body mass index (BMI) in adults with mild disease having a BMI of greater than 17, moderate a BMI of 16 to 17, severe a BMI of 15 to 16, and extreme a BMI less than 15.[3] In children a BMI for age percentile of less than the 5th percentile is often used.[3] Treatment of anorexia involves restoring a healthy weight, treating the underlying psychological problems and addressing behaviors that promote the problem.[1] While medications do not help with weight gain, they may be used to help with associated anxiety or depression.[1] Different therapy methods may be useful, such as cognitive behavioral therapy or an approach where parents assume responsibility for feeding their child known as Maudsley family therapy.[1][15] Sometimes people require admission to a hospital to restore weight.[7] Evidence for benefit from nasogastric tube feeding, however is unclear;[16] such an intervention may be highly distressing for both anorexia patients and healthcare staff when administered against the patient's will under restraint.[12] Some people with anorexia will just have a single episode and recover while others may have recurring episodes over years.[7] Many complications improve or resolve with regaining of weight.[7] Globally, anorexia is estimated to affect 2.9 million people as of 2015[update].[9] It is estimated to occur in 0.9% to 4.3% of women and 0.2% to 0.3% of men in Western countries at some point in their life.[17] About 0.4% of young women are affected in a given year and it is estimated to occur ten times more commonly among women than men.[3][17] Rates in most of the developing world are unclear.[3] Often it begins during the teen years or young adulthood.[1] While anorexia became more commonly diagnosed during the 20th century it is unclear if this was due to an increase in its frequency or simply better diagnosis.[2] In 2013 it directly resulted in about 600 deaths globally, up from 400 deaths in 1990.[18] Eating disorders also increase a person's risk of death from a wide range of other causes, including suicide.[1][17] About 5% of people with anorexia die from complications over a ten-year period, a nearly six times increased risk.[3][8] The term "anorexia nervosa" was first used in 1873 by William Gull to describe this condition.[19] ## Contents * 1 Signs and symptoms * 1.1 Interoceptive * 1.2 Associated problems * 2 Causes * 2.1 Genetic * 2.2 Environmental * 2.3 Psychological * 2.4 Sociological * 2.5 Media effects * 3 Mechanisms * 4 Diagnosis * 4.1 DSM-5 * 4.1.1 Subtypes * 4.1.2 Levels of severity * 4.2 Investigations * 4.3 Differential diagnoses * 5 Treatment * 5.1 Diet * 5.2 Therapy * 5.3 Medication * 5.4 Admission to hospital * 5.5 Nutrition * 6 Prognosis * 6.1 Complications * 6.1.1 Cardiac complications * 6.2 Relapse * 7 Epidemiology * 7.1 Underrepresentation * 8 History * 9 Etymology * 10 See also * 11 References * 12 Further reading * 13 External links ## Signs and symptoms[edit] The back of a person with anorexia Anorexia nervosa is an eating disorder characterized by attempts to lose weight, to the point of starvation. A person with anorexia nervosa may exhibit a number of signs and symptoms, the type and severity of which may vary and may be present but not readily apparent.[20] Anorexia nervosa, and the associated malnutrition that results from self-imposed starvation, can cause complications in every major organ system in the body.[21] Hypokalaemia, a drop in the level of potassium in the blood, is a sign of anorexia nervosa.[22][23] A significant drop in potassium can cause abnormal heart rhythms, constipation, fatigue, muscle damage and paralysis.[24] Symptoms may include: * A low body mass index for one's age and height. * Amenorrhea, a symptom that occurs after prolonged weight loss; causing menstruation to stop, hair to become brittle, and skin to become yellow and unhealthy. * Fear of even the slightest weight gain; taking all precautionary measures to avoid weight gain or becoming "overweight".[25] * Rapid, continuous weight loss.[26] * Lanugo: soft, fine hair growing over the face and body.[23] * An obsession with counting calories and monitoring fat contents of food. * Preoccupation with food, recipes, or cooking; may cook elaborate dinners for others, but not eat the food themselves or consume a very small portion. * Food restrictions despite being underweight or at a healthy weight. * Food rituals, such as cutting food into tiny pieces, refusing to eat around others and hiding or discarding of food. * Purging: May use laxatives, diet pills, ipecac syrup, or water pills to flush food out of their system after eating or may engage in self-induced vomiting though this is a more common symptom of bulimia. * Excessive exercise[27] including micro-exercising, for example making small persistent movements of fingers or toes.[28] * Perception of self as overweight, in contradiction to an underweight reality. * Intolerance to cold and frequent complaints of being cold; body temperature may lower (hypothermia) in an effort to conserve energy due to malnutrition.[29] * Hypotension or orthostatic hypotension. * Bradycardia or tachycardia. * Depression, anxiety disorders and insomnia. * Solitude: may avoid friends and family and become more withdrawn and secretive. * Abdominal distension. * Halitosis (from vomiting or starvation-induced ketosis). * Dry hair and skin, as well as hair thinning. * Chronic fatigue.[25] * Rapid mood swings. * Having feet discoloration causing an orange appearance. * Having severe muscle tension, aches and pains. * Evidence/habits of self harming or self-loathing. * Admiration of thinner people. * Infertility. ### Interoceptive[edit] Interoception involves the conscious and unconscious sense of the internal state of the body, and it has an important role in homeostasis and regulation of emotions.[30] Aside from noticeable physiological dysfunction, interoceptive deficits also prompt individuals with anorexia to concentrate on distorted perceptions of multiple elements of their body image.[31] This exists in both people with anorexia and in healthy individuals due to impairment in interoceptive sensitivity and interoceptive awareness.[31] Aside from weight gain and outer appearance, people with anorexia also report abnormal bodily functions such as indistinct feelings of fullness.[32] This provides an example of miscommunication between internal signals of the body and the brain. Due to impaired interoceptive sensitivity, powerful cues of fullness may be detected prematurely in highly sensitive individuals, which can result in decreased calorie consumption and generate anxiety surrounding food intake in anorexia patients.[33] People with anorexia also report difficulty identifying and describing their emotional feelings and the inability to distinguish emotions from bodily sensations in general, called alexithymia.[32] Interoceptive awareness and emotion are deeply intertwined, and could mutually impact each other in abnormalities.[33] Anorexia patients also exhibit emotional regulation difficulties that ignite emotionally-cued eating behaviors, such as restricting food or excessive exercising.[33] Impaired interoceptive sensitivity and interoceptive awareness can lead anorexia patients to adapt distorted interpretations of weight gain that are cued by physical sensations related to digestion (e.g., fullness).[33] Combined, these interoceptive and emotional elements could together trigger maladaptive and negatively reinforced behavioral responses that assist in the maintenance of anorexia.[33] In addition to metacognition, people with anorexia also have difficulty with social cognition including interpreting others’ emotions, and demonstrating empathy.[34] Abnormal interoceptive awareness and interoceptive sensitivity shown through all of these examples have been observed so frequently in anorexia that they have become key characteristics of the illness.[32] ### Associated problems[edit] Other psychological issues may factor into anorexia nervosa; some fulfill the criteria for a separate Axis I diagnosis or a personality disorder which is coded Axis II and thus are considered comorbid to the diagnosed eating disorder. Some people have a previous disorder which may increase their vulnerability to developing an eating disorder and some develop them afterwards.[35] The presence of Axis I or Axis II psychiatric comorbidity has been shown to affect the severity and type of anorexia nervosa symptoms in both adolescents and adults.[36] Obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder (OCPD) are highly comorbid with AN, particularly the restrictive subtype.[37] OCPD is linked with more severe symptomatology and worse prognosis.[38] The causality between personality disorders and eating disorders has yet to be fully established.[39] Other comorbid conditions include depression,[40] alcoholism,[41] borderline and other personality disorders,[42][43] anxiety disorders,[44] attention deficit hyperactivity disorder,[45] and body dysmorphic disorder (BDD).[46] Depression and anxiety are the most common comorbidities,[47] and depression is associated with a worse outcome.[47] Autism spectrum disorders occur more commonly among people with eating disorders than in the general population.[48] Zucker et al. (2007) proposed that conditions on the autism spectrum make up the cognitive endophenotype underlying anorexia nervosa and appealed for increased interdisciplinary collaboration.[49] ## Causes[edit] Dysregulation of the serotonin pathways has been implicated in the cause and mechanism of anorexia.[50] There is evidence for biological, psychological, developmental, and sociocultural risk factors, but the exact cause of eating disorders is unknown.[50] ### Genetic[edit] Genetic correlations of anorexia with psychiatric and metabolic traits. Anorexia nervosa is highly heritable.[50] Twin studies have shown a heritability rate of between 28 and 58%.[51] First-degree relatives of those with anorexia have roughly 12 times the risk of developing anorexia.[52] Association studies have been performed, studying 128 different polymorphisms related to 43 genes including genes involved in regulation of eating behavior, motivation and reward mechanics, personality traits and emotion. Consistent associations have been identified for polymorphisms associated with agouti-related peptide, brain derived neurotrophic factor, catechol-o-methyl transferase, SK3 and opioid receptor delta-1.[53] Epigenetic modifications, such as DNA methylation, may contribute to the development or maintenance of anorexia nervosa, though clinical research in this area is in its infancy.[54][55] A 2019 study found a genetic relationship with mental disorders, such as schizophrenia, obsessive–compulsive disorder, anxiety disorder and depression; and metabolic functioning with a negative correlation with fat mass, type 2 diabetes and leptin.[56] ### Environmental[edit] Obstetric complications: prenatal and perinatal complications may factor into the development of anorexia nervosa, such as preterm birth,[57] maternal anemia, diabetes mellitus, preeclampsia, placental infarction, and neonatal heart abnormalities.[58] Neonatal complications may also have an influence on harm avoidance, one of the personality traits associated with the development of AN.[medical citation needed] Neuroendocrine dysregulation: altered signalling of peptides that facilitate communication between the gut, brain and adipose tissue, such as ghrelin, leptin, neuropeptide Y and orexin, may contribute to the pathogenesis of anorexia nervosa by disrupting regulation of hunger and satiety.[59][60] Gastrointestinal diseases: people with gastrointestinal disorders may be more at risk of developing disorders of eating practices than the general population, principally restrictive eating disturbances.[61] An association of anorexia nervosa with celiac disease has been found.[62] The role that gastrointestinal symptoms play in the development of eating disorders seems rather complex. Some authors report that unresolved symptoms prior to gastrointestinal disease diagnosis may create a food aversion in these persons, causing alterations to their eating patterns. Other authors report that greater symptoms throughout their diagnosis led to greater risk. It has been documented that some people with celiac disease, irritable bowel syndrome or inflammatory bowel disease who are not conscious about the importance of strictly following their diet, choose to consume their trigger foods to promote weight loss. On the other hand, individuals with good dietary management may develop anxiety, food aversion and eating disorders because of concerns around cross contamination of their foods.[61] Some authors suggest that medical professionals should evaluate the presence of an unrecognized celiac disease in all people with eating disorder, especially if they present any gastrointestinal symptom (such as decreased appetite, abdominal pain, bloating, distension, vomiting, diarrhea or constipation), weight loss, or growth failure; and also routinely ask celiac patients about weight or body shape concerns, dieting or vomiting for weight control, to evaluate the possible presence of eating disorders,[62] especially in women.[63] Studies have hypothesized the continuance of disordered eating patterns may be epiphenomena of starvation. The results of the Minnesota Starvation Experiment showed normal controls exhibit many of the behavioral patterns of AN when subjected to starvation. This may be due to the numerous changes in the neuroendocrine system, which results in a self-perpetuating cycle.[64][65][66] Anorexia nervosa is more likely to occur in a person's pubertal years. Some explanatory hypotheses for the rising prevalence of eating disorders in adolescence are "increase of adipose tissue in girls, hormonal changes of puberty, societal expectations of increased independence and autonomy that are particularly difficult for anorexic adolescents to meet; [and] increased influence of the peer group and its values."[67] ### Psychological[edit] Early theories of the cause of anorexia linked it to childhood sexual abuse or dysfunctional families;[68][69] evidence is conflicting, and well-designed research is needed.[50] The fear of food is known as sitiophobia,[70] cibophobia,[71] and is part of the differential diagnosis.[72][73] Other psychological causes of anorexia include low self-esteem, feeling like there is lack of control, depression, anxiety, and loneliness.[74] Some anorexic people might be perfectionists or have an obsessive compulsive personality which makes them stick to a restricted diet.[75] ### Sociological[edit] Anorexia nervosa has been increasingly diagnosed since 1950;[76] the increase has been linked to vulnerability and internalization of body ideals.[67] People in professions where there is a particular social pressure to be thin (such as models and dancers) were more likely to develop anorexia,[77] and those with anorexia have much higher contact with cultural sources that promote weight loss.[78] This trend can also be observed for people who partake in certain sports, such as jockeys and wrestlers.[79] There is a higher incidence and prevalence of anorexia nervosa in sports with an emphasis on aesthetics, where low body fat is advantageous, and sports in which one has to make weight for competition.[80] Family group dynamics can play a role in the cause of anorexia including negative expressed emotion in overprotective families where blame is frequently experienced among its members.[81][82][83] When there is a constant pressure from people to be thin, teasing and bullying can cause low self-esteem and other psychological symptoms.[74] ### Media effects[edit] Persistent exposure to media that presents body ideals may constitute a risk factor for body dissatisfaction and anorexia nervosa. The cultural ideal for body shape for men versus women continues to favor slender women and athletic, V-shaped muscular men. A 2002 review found that, of the magazines most popular among people aged 18 to 24 years, those read by men, unlike those read by women, were more likely to feature ads and articles on shape than on diet.[84] Body dissatisfaction and internalization of body ideals are risk factors for anorexia nervosa that threaten the health of both male and female populations.[85] Websites that stress the importance of attainment of body ideals extol and promote anorexia nervosa through the use of religious metaphors, lifestyle descriptions, "thinspiration" or "fitspiration" (inspirational photo galleries and quotes that aim to serve as motivators for attainment of body ideals).[86] Pro-anorexia websites reinforce internalization of body ideals and the importance of their attainment.[86] The media portray a false view of what people truly look like. In magazines and movies and even on billboards most of the actors/models are digitally altered in multiple ways. People then strive to look like these "perfect" role models when in reality they are not near perfection themselves.[87] ## Mechanisms[edit] Evidence from physiological, pharmacological and neuroimaging studies suggest serotonin (also called 5-HT) may play a role in anorexia. While acutely ill, metabolic changes may produce a number of biological findings in people with anorexia that are not necessarily causative of the anorexic behavior. For example, abnormal hormonal responses to challenges with serotonergic agents have been observed during acute illness, but not recovery. Nevertheless, increased cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid (a metabolite of serotonin), and changes in anorectic behavior in response to acute tryptophan depletion (tryptophan is a metabolic precursor to serotonin) support a role in anorexia. The activity of the 5-HT2A receptors has been reported to be lower in patients with anorexia in a number of cortical regions, evidenced by lower binding potential of this receptor as measured by PET or SPECT, independent of the state of illness. While these findings may be confounded by comorbid psychiatric disorders, taken as a whole they indicate serotonin in anorexia.[88][89] These alterations in serotonin have been linked to traits characteristic of anorexia such as obsessiveness, anxiety, and appetite dysregulation.[66] Neuroimaging studies investigating the functional connectivity between brain regions have observed a number of alterations in networks related to cognitive control, introspection, and sensory function. Alterations in networks related to the dorsal anterior cingulate cortex may be related to excessive cognitive control of eating related behaviors. Similarly, altered somatosensory integration and introspection may relate to abnormal body image.[90] A review of functional neuroimaging studies reported reduced activations in "bottom up" limbic region and increased activations in "top down" cortical regions which may play a role in restrictive eating.[91] Compared to controls, recovered anorexics show reduced activation in the reward system in response to food, and reduced correlation between self reported liking of a sugary drink and activity in the striatum and anterior cingulate cortex. Increased binding potential of 11C radiolabelled raclopride in the striatum, interpreted as reflecting decreased endogenous dopamine due to competitive displacement, has also been observed.[92] Structural neuroimaging studies have found global reductions in both gray matter and white matter, as well as increased cerebrospinal fluid volumes. Regional decreases in the left hypothalamus, left inferior parietal lobe, right lentiform nucleus and right caudate have also been reported[93] in acutely ill patients. However, these alterations seem to be associated with acute malnutrition and largely reversible with weight restoration, at least in nonchronic cases in younger people.[94] In contrast, some studies have reported increased orbitofrontal cortex volume in currently ill and in recovered patients, although findings are inconsistent. Reduced white matter integrity in the fornix has also been reported.[95] ## Diagnosis[edit] A diagnostic assessment includes the person's current circumstances, biographical history, current symptoms, and family history. The assessment also includes a mental state examination, which is an assessment of the person's current mood and thought content, focusing on views on weight and patterns of eating. ### DSM-5[edit] Anorexia nervosa is classified under the Feeding and Eating Disorders in the latest revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM 5). There is no specific BMI cutoff that defines low weight required for the diagnosis of anorexia nervosa.[96][3] The diagnostic criteria for anorexia nervosa (all of which needing to be met for diagnosis) include:[7] * Restriction of energy intake relative to requirements leading to a low body weight. * Intense fear of gaining weight or persistent behaviors that interfere with gaining weight. * Disturbance in the way a person's weight or body shape is experienced or a lack of recognition about the risks of the low body weight. Relative to the previous version of the DSM (DSM-IV-TR), the 2013 revision (DSM5) reflects changes in the criteria for anorexia nervosa, most notably that of the amenorrhea criterion being removed.[7][97] Amenorrhea was removed for several reasons: it does not apply to males, it is not applicable for females before or after the age of menstruation or taking birth control pills, and some women who meet the other criteria for AN still report some menstrual activity.[7] #### Subtypes[edit] There are two subtypes of AN:[21][98] * Binge-eating/purging type: the individual utilizes binge eating or displays purging behavior as a means for losing weight.[98] It is different from bulimia nervosa in terms of the individual's weight. An individual with binge-eating/purging type anorexia can maintain a healthy or normal weight, but is usually significantly underweight. People with bulimia nervosa on the other hand can sometimes be overweight.[25] * Restricting type: the individual uses restricting food intake, fasting, diet pills, or exercise as a means for losing weight;[21] they may exercise excessively to keep off weight or prevent weight gain, and some individuals eat only enough to stay alive.[21][25] In the restrictive type, there are no recurrent episodes of binge-eating or purging present.[96] #### Levels of severity[edit] Body mass index (BMI) is used by the DSM-5 as an indicator of the level of severity of anorexia nervosa. The DSM-5 states these as follows:[99] * Mild: BMI of greater than 17 * Moderate: BMI of 16–16.99 * Severe: BMI of 15–15.99 * Extreme: BMI of less than 15 ### Investigations[edit] Medical tests to check for signs of physical deterioration in anorexia nervosa may be performed by a general physician or psychiatrist, including: * Complete Blood Count (CBC): a test of the white blood cells, red blood cells and platelets used to assess the presence of various disorders such as leukocytosis, leukopenia, thrombocytosis and anemia which may result from malnutrition.[100] * Urinalysis: a variety of tests performed on the urine used in the diagnosis of medical disorders, to test for substance abuse, and as an indicator of overall health[101] * Chem-20: Chem-20 also known as SMA-20 a group of twenty separate chemical tests performed on blood serum. Tests include cholesterol, protein and electrolytes such as potassium, chlorine and sodium and tests specific to liver and kidney function.[102] * Glucose tolerance test: Oral glucose tolerance test (OGTT) used to assess the body's ability to metabolize glucose. Can be useful in detecting various disorders such as diabetes, an insulinoma, Cushing's Syndrome, hypoglycemia and polycystic ovary syndrome.[103] * Serum cholinesterase test: a test of liver enzymes (acetylcholinesterase and pseudocholinesterase) useful as a test of liver function and to assess the effects of malnutrition.[104] * Liver Function Test: A series of tests used to assess liver function some of the tests are also used in the assessment of malnutrition, protein deficiency, kidney function, bleeding disorders, and Crohn's Disease.[105] * Luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH): Tests the pituitary glands' response to GnRh, a hormone produced in the hypothalamus. Hypogonadism is often seen in anorexia nervosa cases.[22] * Creatine kinase (CK) test: measures the circulating blood levels of creatine kinase an enzyme found in the heart (CK-MB), brain (CK-BB) and skeletal muscle (CK-MM).[106] * Blood urea nitrogen (BUN) test: urea nitrogen is the byproduct of protein metabolism first formed in the liver then removed from the body by the kidneys. The BUN test is primarily used to test kidney function. A low BUN level may indicate the effects of malnutrition.[107] * BUN-to-creatinine ratio: A BUN to creatinine ratio is used to predict various conditions. A high BUN/creatinine ratio can occur in severe hydration, acute kidney failure, congestive heart failure, and intestinal bleeding. A low BUN/creatinine ratio can indicate a low protein diet, celiac disease, rhabdomyolysis, or cirrhosis of the liver.[108][109] * Electrocardiogram (EKG or ECG): measures electrical activity of the heart. It can be used to detect various disorders such as hyperkalemia.[110] * Electroencephalogram (EEG): measures the electrical activity of the brain. It can be used to detect abnormalities such as those associated with pituitary tumors.[111] * Thyroid screen: test used to assess thyroid functioning by checking levels of thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3).[112] ### Differential diagnoses[edit] Main article: Anorexia nervosa (differential diagnoses) A variety of medical and psychological conditions have been misdiagnosed as anorexia nervosa; in some cases the correct diagnosis was not made for more than ten years. The distinction between the diagnosis of anorexia nervosa, bulimia nervosa and eating disorder not otherwise specified (EDNOS) is often difficult to make as there is considerable overlap between people diagnosed with these conditions. Seemingly minor changes in people's overall behavior or attitude can change a diagnosis from anorexia: binge-eating type to bulimia nervosa. A main factor differentiating binge-purge anorexia from bulimia is the gap in physical weight. Someone with bulimia nervosa is ordinarily at a healthy weight, or slightly overweight. Someone with binge-purge anorexia is commonly underweight.[113] People with the binge-purging subtype of AN may be significantly underweight and typically do not binge-eat large amounts of food, yet they purge the small amount of food they eat.[113] In contrast, those with bulimia nervosa tend to be at normal weight or overweight and binge large amounts of food.[113] It is not unusual for a person with an eating disorder to "move through" various diagnoses as their behavior and beliefs change over time.[49] ## Treatment[edit] There is no conclusive evidence that any particular treatment for anorexia nervosa works better than others; however, there is enough evidence to suggest that early intervention and treatment are more effective.[114] Treatment for anorexia nervosa tries to address three main areas. * Restoring the person to a healthy weight; * Treating the psychological disorders related to the illness; * Reducing or eliminating behaviours or thoughts that originally led to the disordered eating.[115] Although restoring the person's weight is the primary task at hand, optimal treatment also includes and monitors behavioral change in the individual as well.[116] There is some evidence that hospitalisation might adversely affect long term outcome.[117] Psychotherapy for individuals with AN is challenging as they may value being thin and may seek to maintain control and resist change.[118] Some studies demonstrate that family based therapy in adolescents with AN is superior to individual therapy.[119] Due to the nature of the condition, treatment of people with AN can be difficult because they are afraid of gaining weight. Initially developing a desire to change is important.[120] ### Diet[edit] Diet is the most essential factor to work on in people with anorexia nervosa, and must be tailored to each person's needs. Food variety is important when establishing meal plans as well as foods that are higher in energy density.[121] People must consume adequate calories, starting slowly, and increasing at a measured pace.[27] Evidence of a role for zinc supplementation during refeeding is unclear.[16] ### Therapy[edit] Family-based treatment (FBT) has been shown to be more successful than individual therapy for adolescents with AN.[8][122] Various forms of family-based treatment have been proven to work in the treatment of adolescent AN including conjoint family therapy (CFT), in which the parents and child are seen together by the same therapist, and separated family therapy (SFT) in which the parents and child attend therapy separately with different therapists.[8] Proponents of family therapy for adolescents with AN assert that it is important to include parents in the adolescent's treatment.[8] A four- to five-year follow up study of the Maudsley family therapy, an evidence-based manualized model, showed full recovery at rates up to 90%.[123] Although this model is recommended by the NIMH,[124] critics claim that it has the potential to create power struggles in an intimate relationship and may disrupt equal partnerships.[medical citation needed] There is tentative evidence that family therapy is as effective as treatment as usual and it is unclear if family therapy is more effective than educational interventions.[125] Cognitive behavioral therapy (CBT) is useful in adolescents and adults with anorexia nervosa;[126] acceptance and commitment therapy is a type of CBT, which has shown promise in the treatment of AN.[127] Cognitive remediation therapy (CRT) is used in treating anorexia nervosa.[128] ### Medication[edit] Pharmaceuticals have limited benefit for anorexia itself.[129][96] There is a lack of good information from which to make recommendations concerning the effectiveness of antidepressants in treating anorexia.[130] ### Admission to hospital[edit] AN has a high mortality[131] and patients admitted in a severely ill state to medical units are at particularly high risk. Diagnosis can be challenging, risk assessment may not be performed accurately, consent and the need for compulsion may not be assessed appropriately, refeeding syndrome may be missed or poorly treated and the behavioural and family problems in AN may be missed or poorly managed.[132] The MARSIPAN guidelines recommend that medical and psychiatric experts work together in managing severely ill people with AN.[133] ### Nutrition[edit] The rate of refeeding can be difficult to establish, because the fear of refeeding syndrome (RFS) can lead to underfeeding. It is thought that RFS, with falling phosphate and potassium levels, is more likely to occur when BMI is very low, and when medical comorbidities such as infection or cardiac failure, are present. In those circumstances, it is recommended to start refeeding slowly but to build up rapidly as long as RFS does not occur. Recommendations on energy requirements vary, from 5–10 kcal/kg/day in the most medically compromised patients, who appear to have the highest risk of RFS, to 1900 kcal/day.[134][135] ## Prognosis[edit] Deaths due to eating disorders per million persons in 2012 0-1 1-2 2-3 3-4 4-25 AN has the highest mortality rate of any psychological disorder.[8] The mortality rate is 11 to 12 times greater than in the general population, and the suicide risk is 56 times higher.[22] Half of women with AN achieve a full recovery, while an additional 20–30% may partially recover.[8][22] Not all people with anorexia recover completely: about 20% develop anorexia nervosa as a chronic disorder.[114] If anorexia nervosa is not treated, serious complications such as heart conditions[20] and kidney failure can arise and eventually lead to death.[136] The average number of years from onset to remission of AN is seven for women and three for men. After ten to fifteen years, 70% of people no longer meet the diagnostic criteria, but many still continue to have eating-related problems.[137] Alexithymia influences treatment outcome.[129] Recovery is also viewed on a spectrum rather than black and white. According to the Morgan-Russell criteria, individuals can have a good, intermediate, or poor outcome. Even when a person is classified as having a "good" outcome, weight only has to be within 15% of average, and normal menstruation must be present in females. The good outcome also excludes psychological health. Recovery for people with anorexia nervosa is undeniably positive, but recovery does not mean a return to normal.[medical citation needed] ### Complications[edit] Anorexia nervosa can have serious implications if its duration and severity are significant and if onset occurs before the completion of growth, pubertal maturation, or the attainment of peak bone mass.[138][medical citation needed] Complications specific to adolescents and children with anorexia nervosa can include the following: Growth retardation may occur, as height gain may slow and can stop completely with severe weight loss or chronic malnutrition. In such cases, provided that growth potential is preserved, height increase can resume and reach full potential after normal intake is resumed.[medical citation needed] Height potential is normally preserved if the duration and severity of illness are not significant or if the illness is accompanied by delayed bone age (especially prior to a bone age of approximately 15 years), as hypogonadism may partially counteract the effects of undernutrition on height by allowing for a longer duration of growth compared to controls.[medical citation needed] Appropriate early treatment can preserve height potential, and may even help to increase it in some post-anorexic subjects, due to factors such as long-term reduced estrogen-producing adipose tissue levels compared to premorbid levels.[medical citation needed] In some cases, especially where onset is before puberty, complications such as stunted growth and pubertal delay are usually reversible.[139] Anorexia nervosa causes alterations in the female reproductive system; significant weight loss, as well as psychological stress and intense exercise, typically results in a cessation of menstruation in women who are past puberty. In patients with anorexia nervosa, there is a reduction of the secretion of gonadotropin releasing hormone in the central nervous system, preventing ovulation.[140] Anorexia nervosa can also result in pubertal delay or arrest. Both height gain and pubertal development are dependent on the release of growth hormone and gonadotropins (LH and FSH) from the pituitary gland. Suppression of gonadotropins in people with anorexia nervosa has been documented.[141] Typically, growth hormone (GH) levels are high, but levels of IGF-1, the downstream hormone that should be released in response to GH are low; this indicates a state of “resistance” to GH due to chronic starvation.[142] IGF-1 is necessary for bone formation, and decreased levels in anorexia nervosa contribute to a loss of bone density and potentially contribute to osteopenia or osteoporosis.[142] Anorexia nervosa can also result in reduction of peak bone mass. Buildup of bone is greatest during adolescence, and if onset of anorexia nervosa occurs during this time and stalls puberty, low bone mass may be permanent.[143] Hepatic steatosis, or fatty infiltration of the liver, can also occur, and is an indicator of malnutrition in children.[144] Neurological disorders that may occur as complications include seizures and tremors. Wernicke encephalopathy, which results from vitamin B1 deficiency, has been reported in patients who are extremely malnourished; symptoms include confusion, problems with the muscles responsible for eye movements and abnormalities in walking gait. The most common gastrointestinal complications of anorexia nervosa are delayed stomach emptying and constipation, but also include elevated liver function tests, diarrhea, acute pancreatitis, heartburn, difficulty swallowing, and, rarely, superior mesenteric artery syndrome.[145] Delayed stomach emptying, or gastroparesis, often develops following food restriction and weight loss; the most common symptom is bloating with gas and abdominal distension, and often occurs after eating. Other symptoms of gastroparesis include early satiety, fullness, nausea, and vomiting. The symptoms may inhibit efforts at eating and recovery, but can be managed by limiting high-fiber foods, using liquid nutritional supplements, or using metoclopramide to increase emptying of food from the stomach.[145] Gastroparesis generally resolves when weight is regained. #### Cardiac complications[edit] Anorexia nervosa increases the risk of sudden cardiac death, though the precise cause is unknown. Cardiac complications include structural and functional changes to the heart.[146] Some of these cardiovascular changes are mild and are reversible with treatment, while others may be life-threatening. Cardiac complications can include arrhythmias, abnormally slow heart beat, low blood pressure, decreased size of the heart muscle, reduced heart volume, mitral valve prolapse, myocardial fibrosis, and pericardial effusion.[146] Abnormalities in conduction and repolarization of the heart that can result from anorexia nervosa include QT prolongation, increased QT dispersion, conduction delays, and junctional escape rhythms.[146] Electrolyte abnormalities, particularly hypokalemia and hypomagnesemia, can cause anomalies in the electrical activity of the heart, and result in life-threatening arrhythmias. Hypokalemia most commonly results in anorexic patients when restricting is accompanied by purging (induced vomiting or laxative use). Hypotension (low blood pressure) is common, and symptoms include fatigue and weakness. Orthostatic hypotension, a marked decrease in blood pressure when standing from a supine position, may also occur. Symptoms include lightheadedness upon standing, weakness, and cognitive impairment, and may result in fainting or near-fainting.[146] Orthostasis in anorexia nervosa indicates worsening cardiac function and may indicate a need for hospitalization.[146] Hypotension and orthostasis generally resolve upon recovery to a normal weight. The weight loss in anorexia nervosa also causes atrophy of cardiac muscle. This leads to decreased ability to pump blood, a reduction in the ability to sustain exercise, a diminished ability to increase blood pressure in response to exercise, and a subjective feeling of fatigue.[147] Some individuals may also have a decrease in cardiac contractility. Cardiac complications can be life-threatening, but the heart muscle generally improves with weight gain, and the heart normalizes in size over weeks to months, with recovery.[147] Atrophy of the heart muscle is a marker of the severity of the disease, and while it is reversible with treatment and refeeding, it is possible that it may cause permanent, microscopic changes to the heart muscle that increase the risk of sudden cardiac death.[146] Individuals with anorexia nervosa may experience chest pain or palpitations; these can be a result of mitral valve prolapse. Mitral valve prolapse occurs because the size of the heart muscle decreases while the tissue of the mitral valve remains the same size. Studies have shown rates of mitral valve prolapse of around 20 percent in those with anorexia nervosa, while the rate in the general population is estimated at 2–4 percent.[148] It has been suggested that there is an association between mitral valve prolapse and sudden cardiac death, but it has not been proven to be causative, either in patients with anorexia nervosa or in the general population.[146] ### Relapse[edit] Rates of relapse after treatment range from 9–52% with many studies reporting a relapse rate of at least 25%.[96] Relapse occurs in approximately a third of people in hospital, and is greatest in the first six to eighteen months after release from an institution.[149] ## Epidemiology[edit] Anorexia is estimated to occur in 0.9% to 4.3% of women and 0.2% to 0.3% of men in Western countries at some point in their life.[17] About 0.4% of young females are affected in a given year and it is estimated to occur three to ten times less commonly in males.[3][17][149] Rates in most of the developing world are unclear.[3] Often it begins during the teen years or young adulthood.[1] The lifetime rate of atypical anorexia nervosa, a form of ED-NOS in which the person loses a significant amount of weight and is at risk for serious medical complications despite having a higher body-mass index, is much higher, at 5–12%.[150] While anorexia became more commonly diagnosed during the 20th century it is unclear if this was due to an increase in its frequency or simply better diagnosis.[2] Most studies show that since at least 1970 the incidence of AN in adult women is fairly constant, while there is some indication that the incidence may have been increasing for girls aged between 14 and 20.[17] According to researcher Ben Radford who wrote in Skeptical Inquirer "I found many examples of flawed, misleading, and sometimes completely wrong information and data being copied and widely disseminated among eating disorder organizations and educators without anyone bothering to consult the original research to verify its accuracy". Radford states that misleading statistics and data have been ignored by organizations like the National Eating Disorder Association who has not released data for "incidence of anorexia from 1984–2017" he states that each agency continues to report incorrect numbers assuming that someone else has checked the accuracy.[151] ### Underrepresentation[edit] Eating disorders are less reported in preindustrial, non-westernized countries than in Western countries. In Africa, not including South Africa, the only data presenting information about eating disorders occurs in case reports and isolated studies, not studies investigating prevalence. Data shows in research that in westernized civilizations, ethnic minorities have very similar rates of eating disorders, contrary to the belief that eating disorders predominantly occur in white people.[medical citation needed] Men (and women) who might otherwise be diagnosed with anorexia may not meet the DSM IV criteria for BMI since they have muscle weight, but have very little fat.[152] Male and female athletes are often overlooked as anorexic.[152] Research emphasizes the importance to take athletes' diet, weight and symptoms into account when diagnosing anorexia, instead of just looking at weight and BMI. For athletes, ritualized activities such as weigh-ins place emphasis on weight, which may promote the development of eating disorders among them.[citation needed] While women use diet pills, which is an indicator of unhealthy behavior and an eating disorder, men use steroids, which contextualizes the beauty ideals for genders.[50] In a Canadian study, 4% of boys in grade nine used anabolic steroids.[50] Anorexic men are sometimes referred to as manorexic.[153] ## History[edit] Main article: History of anorexia nervosa Two images of an anorexic woman published in 1900 in "Nouvelle Iconographie de la Salpêtrière". The case was titled "Un cas d'anorexie hysterique" (A case of hysteric anorexia). The term "anorexia nervosa" was coined in 1873 by Sir William Gull, one of Queen Victoria's personal physicians.[19] The history of anorexia nervosa begins with descriptions of religious fasting dating from the Hellenistic era[154] and continuing into the medieval period. The medieval practice of self-starvation by women, including some young women, in the name of religious piety and purity also concerns anorexia nervosa; it is sometimes referred to as anorexia mirabilis.[155][156] The earliest medical descriptions of anorexic illnesses are generally credited to English physician Richard Morton in 1689.[154] Case descriptions fitting anorexic illnesses continued throughout the 17th, 18th and 19th centuries.[157] In the late 19th century anorexia nervosa became widely accepted by the medical profession as a recognized condition. In 1873, Sir William Gull, one of Queen Victoria's personal physicians, published a seminal paper which coined the term "anorexia nervosa" and provided a number of detailed case descriptions and treatments.[157] In the same year, French physician Ernest-Charles Lasègue similarly published details of a number of cases in a paper entitled De l'Anorexie hystérique.[158] Awareness of the condition was largely limited to the medical profession until the latter part of the 20th century, when German-American psychoanalyst Hilde Bruch published The Golden Cage: the Enigma of Anorexia Nervosa in 1978. Despite major advances in neuroscience,[159] Bruch's theories tend to dominate popular thinking. A further important event was the death of the popular singer and drummer Karen Carpenter in 1983, which prompted widespread ongoing media coverage of eating disorders.[160] ## Etymology[edit] The term is of Greek origin: an- (ἀν-, prefix denoting negation) and orexis (ὄρεξις, "appetite"), translating literally to a nervous loss of appetite.[161] ## See also[edit] * Eating recovery * Idée fixe * Inedia * List of people with anorexia nervosa * National Association of Anorexia Nervosa and Associated Disorders * Orthorexia nervosa * Pro-ana ## References[edit] 1. ^ a b c d e f g h i j k l m n o "What are Eating Disorders?". NIMH. Archived from the original on 23 May 2015. Retrieved 24 May 2015. 2. ^ a b c d e f g Attia E (2010). "Anorexia nervosa: current status and future directions". Annual Review of Medicine. 61 (1): 425–35. doi:10.1146/annurev.med.050208.200745. PMID 19719398. 3. ^ a b c d e f g h i j k l m n o p Diagnostic and statistical manual of mental disorders : DSM-5 (5 ed.). Washington: American Psychiatric Publishing. 2013. pp. 338–345. ISBN 978-0-89042-555-8. 4. ^ a b Arcelus J, Witcomb GL, Mitchell A (March 2014). "Prevalence of eating disorders amongst dancers: a systemic review and meta-analysis". European Eating Disorders Review. 22 (2): 92–101. doi:10.1002/erv.2271. PMID 24277724. 5. ^ Parker R, Sharma A (2008). General Medicine. Elsevier Health Sciences. p. 56. ISBN 978-0723434610. 6. ^ M.D, Michael B. First (19 November 2013). DSM-5 Handbook of Differential Diagnosis. American Psychiatric Pub. ISBN 9781585624621 – via Google Books. 7. ^ a b c d e f g "Feeding and eating disorders" (PDF). American Psychiatric Publishing. 2013. Archived from the original (PDF) on 1 May 2015. Retrieved 9 April 2015. 8. ^ a b c d e f g Espie J, Eisler I (2015). "Focus on anorexia nervosa: modern psychological treatment and guidelines for the adolescent patient". Adolescent Health, Medicine and Therapeutics. 6: 9–16. doi:10.2147/AHMT.S70300. PMC 4316908. PMID 25678834. 9. ^ a b Vos, Theo; Allen, Christine; Arora, Megha; Barber, Ryan M.; Bhutta, Zulfiqar A.; Brown, Alexandria; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Z.; Coggeshall, Megan; Cornaby, Leslie; Dandona, Lalit; Dicker, Daniel J.; Dilegge, Tina; Erskine, Holly E.; Ferrari, Alize J.; Fitzmaurice, Christina; Fleming, Tom; Forouzanfar, Mohammad H.; Fullman, Nancy; Gething, Peter W.; Goldberg, Ellen M.; Graetz, Nicholas; Haagsma, Juanita A.; Hay, Simon I.; Johnson, Catherine O.; Kassebaum, Nicholas J.; Kawashima, Toana; et al. (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282. 10. ^ Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, et al. (GBD 2015 Mortality and Causes of Death Collaborators) (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/S0140-6736(16)31012-1. PMC 5388903. PMID 27733281. 11. ^ Sari Fine Shepphird (2009). 100 Questions & Answers About Anorexia Nervosa. Jones & Bartlett Learning. p. xvi. ISBN 978-1-4496-3079-9. Archived from the original on 8 September 2017. 12. ^ a b Kodua, Michael; Mackenzie, Jay-Marie; Smyth, Nina (2020). "Nursing assistants' experiences of administering manual restraint for compulsory nasogastric feeding of young persons with anorexia nervosa". International Journal of Mental Health Nursing. n/a (n/a). doi:10.1111/inm.12758. ISSN 1447-0349. PMID 32578949. 13. ^ "Proxy definition and meaning \| Collins English Dictionary". www.collinsdictionary.com. Retrieved 2 October 2020. 14. ^ "Force-Feeding of Anorexic Patients and the Right to Die" (PDF). 15. ^ Hay P (July 2013). "A systematic review of evidence for psychological treatments in eating disorders: 2005-2012". The International Journal of Eating Disorders. 46 (5): 462–9. doi:10.1002/eat.22103. PMID 23658093. 16. ^ a b "Eating Disorders: Core Interventions in the Treatment and Management of Anorexia Nervosa, Bulimia Nervosa and Related Eating Disorders" (PDF). 2004. p. 103. PMID 23346610. 17. ^ a b c d e f Smink FR, van Hoeken D, Hoek HW (August 2012). "Epidemiology of eating disorders: incidence, prevalence and mortality rates". Current Psychiatry Reports. 14 (4): 406–14. doi:10.1007/s11920-012-0282-y. PMC 3409365. PMID 22644309. 18. ^ Naghavi M, Wang H, Lozano R, Davis A, Liang X, Zhou M, et al. (January 2015). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 385 (9963): 117–71. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442. 19. ^ a b Gull WW (September 1997). "Anorexia nervosa (apepsia hysterica, anorexia hysterica). 1868". Obesity Research. 5 (5): 498–502. doi:10.1002/j.1550-8528.1997.tb00677.x. PMID 9385628. 20. ^ a b Surgenor LJ, Maguire S (2013). "Assessment of anorexia nervosa: an overview of universal issues and contextual challenges". Journal of Eating Disorders. 1 (1): 29. doi:10.1186/2050-2974-1-29. PMC 4081667. PMID 24999408. 21. ^ a b c d Strumia R (September 2009). "Skin signs in anorexia nervosa". Dermato-Endocrinology. 1 (5): 268–70. doi:10.4161/derm.1.5.10193. PMC 2836432. PMID 20808514. 22. ^ a b c d Miller KK (September 2013). "Endocrine effects of anorexia nervosa". Endocrinology and Metabolism Clinics of North America. 42 (3): 515–28. doi:10.1016/j.ecl.2013.05.007. PMC 3769686. PMID 24011884. 23. ^ a b Walsh JM, Wheat ME, Freund K (August 2000). "Detection, evaluation, and treatment of eating disorders the role of the primary care physician". Journal of General Internal Medicine. 15 (8): 577–90. doi:10.1046/j.1525-1497.2000.02439.x. PMC 1495575. PMID 10940151. 24. ^ Stargrove MB, Treasure J, McKee DL (2008). Herb, Nutrient, and Drug Interactions: Clinical Implications and Therapeutic Strategies. Elsevier Health Sciences. ISBN 978-0-323-02964-3. Retrieved 9 April 2015. 25. ^ a b c d Nolen-Hoeksema S (2013). Abnormal Psychology. New York: McGraw Hill. pp. 339–41. ISBN 978-0-07-803538-8. 26. ^ "Anorexia Nervosa". National Association of Anorexia Nervosa and Associated Disorders. Archived from the original on 13 April 2014. Retrieved 15 April 2014. 27. ^ a b Marzola E, Nasser JA, Hashim SA, Shih PA, Kaye WH (November 2013). "Nutritional rehabilitation in anorexia nervosa: review of the literature and implications for treatment". BMC Psychiatry. 13 (1): 290. doi:10.1186/1471-244X-13-290. PMC 3829207. PMID 24200367. 28. ^ Robinson, Paul H. (2006). Community treatment of eating disorders. Chichester: John Wiley & Sons. p. 66. ISBN 978-0-470-01676-3. 29. ^ Haller E (December 1992). "Eating disorders. A review and update". The Western Journal of Medicine. 157 (6): 658–62. PMC 1022101. PMID 1475950. 30. ^ Khalsa SS, Adolphs R, Cameron OG, Critchley HD, Davenport PW, Feinstein JS, et al. (June 2018). "Interoception and Mental Health: A Roadmap". Biological Psychiatry. Cognitive Neuroscience and Neuroimaging. 3 (6): 501–513. doi:10.1016/j.bpsc.2017.12.004. PMC 6054486. PMID 29884281. 31. ^ a b Badoud D, Tsakiris M (June 2017). "From the body's viscera to the body's image: Is there a link between interoception and body image concerns?". Neuroscience and Biobehavioral Reviews. 77: 237–246. doi:10.1016/j.neubiorev.2017.03.017. PMID 28377099. S2CID 768206. 32. ^ a b c Khalsa SS, Lapidus RC (2016). "Can Interoception Improve the Pragmatic Search for Biomarkers in Psychiatry?". Frontiers in Psychiatry. 7: 121. doi:10.3389/fpsyt.2016.00121. PMC 4958623. PMID 27504098. 33. ^ a b c d e Boswell JF, Anderson LM, Anderson DA (June 2015). "Integration of Interoceptive Exposure in Eating Disorder Treatment". Clinical Psychology: Science and Practice. 22 (2): 194–210. doi:10.1111/cpsp.12103. 34. ^ Kasperek-Zimowska BJ, Zimowski JG, Biernacka K, Kucharska-Pietura K, Rybakowski F (2014). "Impaired social cognition processes in Asperger syndrome and anorexia nervosa. In search for endophenotypes of social cognition". Psychiatria Polska. 50 (3): 533–42. doi:10.12740/PP/OnlineFirst/33485. PMID 27556112. 35. ^ Strober, Michael; Freeman, Roberta; Lampert, Carlyn; Diamond, Jane (2007). "The association of anxiety disorders and obsessive compulsive personality disorder with anorexia nervosa: Evidence from a family study with discussion of nosological and neurodevelopmental implications". International Journal of Eating Disorders. 40 (S3): S46–S51. doi:10.1002/eat.20429. ISSN 1098-108X. PMID 17610248. 36. ^ Brand-Gothelf, Ayelet; Leor, Shani; Apter, Alan; Fennig, Silvana (2014). "The Impact of Comorbid Depressive and Anxiety Disorders on Severity of Anorexia Nervosa in Adolescent Girls". The Journal of Nervous and Mental Disease. 202 (10): 759–762. doi:10.1097/NMD.0000000000000194. ISSN 0022-3018. PMID 25265267. S2CID 6023688. 37. ^ Godier LR, Park RJ (2014). "Compulsivity in anorexia nervosa: a transdiagnostic concept". Frontiers in Psychology. 5: 778. doi:10.3389/fpsyg.2014.00778. PMC 4101893. PMID 25101036. 38. ^ Crane AM, Roberts ME, Treasure J (November 2007). "Are obsessive-compulsive personality traits associated with a poor outcome in anorexia nervosa? A systematic review of randomized controlled trials and naturalistic outcome studies". The International Journal of Eating Disorders. 40 (7): 581–8. doi:10.1002/eat.20419. PMID 17607713. 39. ^ Gárriz, Miguel; Andrés-Perpiñá, Susana; Plana, Maria Teresa; Flamarique, Itziar; Romero, Sonia; Julià, Laia; Castro-Fornieles, Josefina (30 April 2020). "Personality disorder traits, obsessive ideation and perfectionism 20 years after adolescent-onset anorexia nervosa: a recovered study". Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. doi:10.1007/s40519-020-00906-7. ISSN 1590-1262. PMID 32350776. S2CID 216649851. "However, prospective studies are still scarce and the results from current literature regarding causal connections between AN and personality are unavailable." 40. ^ Casper RC (1998). "Depression and eating disorders". Depression and Anxiety. 8 Suppl 1 (Suppl 1): 96–104. doi:10.1002/(SICI)1520-6394(1998)8:1+<96::AID-DA15>3.0.CO;2-4. PMID 9809221. 41. ^ Zernig G, Saria A, Kurz M, O'Malley S (24 March 2000). Handbook of Alcoholism. CRC Press. p. 293. ISBN 978-1-4200-3696-1. 42. ^ Sansone RA, Levitt JL (21 August 2013). Personality Disorders and Eating Disorders: Exploring the Frontier. Routledge. p. 28. ISBN 978-1-135-44280-4. 43. ^ Halmi KA (November 2013). "Perplexities of treatment resistance in eating disorders". BMC Psychiatry. 13: 292. doi:10.1186/1471-244X-13-292. PMC 3829659. PMID 24199597. 44. ^ Swinbourne JM, Touyz SW (July 2007). "The co-morbidity of eating disorders and anxiety disorders: a review". European Eating Disorders Review. 15 (4): 253–74. doi:10.1002/erv.784. PMID 17676696. 45. ^ Cortese S, Bernardina BD, Mouren MC (September 2007). "Attention-deficit/hyperactivity disorder (ADHD) and binge eating". Nutrition Reviews. 65 (9): 404–11. doi:10.1111/j.1753-4887.2007.tb00318.x. PMID 17958207. 46. ^ Wilhelm S, Phillips KA, Steketee G (18 December 2012). Cognitive-Behavioral Therapy for Body Dysmorphic Disorder: A Treatment Manual. Guilford Press. p. 270. ISBN 978-1-4625-0790-0. 47. ^ a b Berkman ND, Bulik CM, Brownley KA, Lohr KN, Sedway JA, Rooks A, Gartlehner G (April 2006). "Management of eating disorders" (PDF). Evidence Report/Technology Assessment (135): 1–166. PMC 4780981. PMID 17628126. Archived (PDF) from the original on 22 December 2014. 48. ^ Huke V, Turk J, Saeidi S, Kent A, Morgan JF (September 2013). "Autism spectrum disorders in eating disorder populations: a systematic review". European Eating Disorders Review. 21 (5): 345–51. doi:10.1002/erv.2244. PMID 23900859. 49. ^ a b Zucker NL, Losh M, Bulik CM, LaBar KS, Piven J, Pelphrey KA (November 2007). "Anorexia nervosa and autism spectrum disorders: guided investigation of social cognitive endophenotypes" (PDF). Psychological Bulletin. 133 (6): 976–1006. doi:10.1037/0033-2909.133.6.976. PMID 17967091. Archived (PDF) from the original on 20 April 2010. 50. ^ a b c d e f Rikani AA, Choudhry Z, Choudhry AM, Ikram H, Asghar MW, Kajal D, et al. (October 2013). "A critique of the literature on etiology of eating disorders". Annals of Neurosciences. 20 (4): 157–61. doi:10.5214/ans.0972.7531.200409. PMC 4117136. PMID 25206042. 51. ^ Thornton LM, Mazzeo SE, Bulik CM (2011). "The heritability of eating disorders: methods and current findings". Behavioral Neurobiology of Eating Disorders. Current Topics in Behavioral Neurosciences. 6. pp. 141–56. doi:10.1007/7854_2010_91. ISBN 978-3-642-15130-9. PMC 3599773. PMID 21243474. 52. ^ Hildebrandt T, Downey A (4 July 2013). "The Neurobiology of Eating Disorders". In Charney D, Sklar P, Buxbaum J, Nestler E (eds.). Neurobiology of Mental Illness (4th ed.). Oxford University Press. ISBN 9780199934959. 53. ^ Rask-Andersen M, Olszewski PK, Levine AS, Schiöth HB (March 2010). "Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake". Brain Research Reviews. 62 (2): 147–64. doi:10.1016/j.brainresrev.2009.10.007. PMID 19931559. S2CID 37635456. 54. ^ Pjetri E, Schmidt U, Kas MJ, Campbell IC (July 2012). "Epigenetics and eating disorders". Current Opinion in Clinical Nutrition and Metabolic Care. 15 (4): 330–5. doi:10.1097/MCO.0b013e3283546fd3. PMID 22617563. S2CID 27183934. 55. ^ Hübel, Christopher; Marzi, Sarah J.; Breen, Gerome; Bulik, Cynthia M. (2019). "Epigenetics in eating disorders: a systematic review". Molecular Psychiatry. 24 (6): 901–915. doi:10.1038/s41380-018-0254-7. ISSN 1476-5578. PMC 6544542. PMID 30353170. 56. ^ Watson HJ, Yilmaz Z, Thornton LM, Hübel C, Coleman JR, Gaspar HA, et al. (August 2019). "Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa". Nature Genetics. 51 (8): 1207–1214. doi:10.1038/s41588-019-0439-2. PMC 6779477. PMID 31308545. 57. ^ Larsen, Janne Tidselbak; Bulik, Cynthia M.; Thornton, Laura M.; Koch, Susanne Vinkel; Petersen, Liselotte (2020). "Prenatal and perinatal factors and risk of eating disorders". Psychological Medicine: 1–11. doi:10.1017/S0033291719003945. ISSN 0033-2917. PMID 31910913. 58. ^ Jones, Candace; Pearce, Brad; Barrera, Ingrid; Mummert, Amanda (7 September 2017). "Fetal programming and eating disorder risk". Journal of Theoretical Biology. 428: 26–33. doi:10.1016/j.jtbi.2017.05.028. ISSN 0022-5193. PMID 28571669. 59. ^ Davis JF, Choi DL, Benoit SC (2011). "24. Orexigenic Hypothalamic Peptides Behavior and Feeding – 24.5 Orexin". In Preedy VR, Watson RR, Martin CR (eds.). Handbook of Behavior, Food and Nutrition. Springer. pp. 361–2. ISBN 978-0-387-92271-3. 60. ^ Smitka K, Papezova H, Vondra K, Hill M, Hainer V, Nedvidkova J (2013). "The role of "mixed" orexigenic and anorexigenic signals and autoantibodies reacting with appetite-regulating neuropeptides and peptides of the adipose tissue-gut-brain axis: relevance to food intake and nutritional status in patients with anorexia nervosa and bulimia nervosa". International Journal of Endocrinology. 2013: 483145. doi:10.1155/2013/483145. PMC 3782835. PMID 24106499. 61. ^ a b Satherley R, Howard R, Higgs S (January 2015). "Disordered eating practices in gastrointestinal disorders" (PDF). Appetite (Review). 84: 240–50. doi:10.1016/j.appet.2014.10.006. PMID 25312748. S2CID 25805182. Archived from the original (PDF) on 24 September 2019. Retrieved 4 July 2019. 62. ^ a b Bern EM, O'Brien RF (August 2013). "Is it an eating disorder, gastrointestinal disorder, or both?". Current Opinion in Pediatrics (Review). 25 (4): 463–70. doi:10.1097/MOP.0b013e328362d1ad. PMID 23838835. S2CID 5417088. "Several case reports brought attention to the association of anorexia nervosa and celiac disease.(...) Some patients present with the eating disorder prior to diagnosis of celiac disease and others developed anorexia nervosa after the diagnosis of celiac disease. Healthcare professionals should screen for celiac disease with eating disorder symptoms especially with gastrointestinal symptoms, weight loss, or growth failure.(...) Celiac disease patients may present with gastrointestinal symptoms such as diarrhea, steatorrhea, weight loss, vomiting, abdominal pain, anorexia, constipation, bloating, and distension due to malabsorption. Extraintestinal presentations include anemia, osteoporosis, dermatitis herpetiformis, short stature, delayed puberty, fatigue, aphthous stomatitis, elevated transaminases, neurologic problems, or dental enamel hypoplasia.(...) it has become clear that symptomatic and diagnosed celiac disease is the tip of the iceberg; the remaining 90% or more of children are asymptomatic and undiagnosed." 63. ^ Quick VM, Byrd-Bredbenner C, Neumark-Sztainer D (May 2013). "Chronic illness and disordered eating: a discussion of the literature". Advances in Nutrition (Review). 4 (3): 277–86. doi:10.3945/an.112.003608. PMC 3650496. PMID 23674793. 64. ^ Zandian M, Ioakimidis I, Bergh C, Södersten P (September 2007). "Cause and treatment of anorexia nervosa". Physiology & Behavior. 92 (1–2): 283–90. doi:10.1016/j.physbeh.2007.05.052. PMID 17585973. S2CID 43620773. 65. ^ Thambirajah MS (2007). Case Studies in Child and Adolescent Mental Health. Radcliffe Publishing. p. 145. ISBN 978-1-85775-698-2. OCLC 84150452. 66. ^ a b Kaye W (April 2008). "Neurobiology of anorexia and bulimia nervosa". Physiology & Behavior. 94 (1): 121–35. doi:10.1016/j.physbeh.2007.11.037. PMC 2601682. PMID 18164737. 67. ^ a b Herpertz-Dahlmann B, Bühren K, Remschmidt H (June 2013). "Growing up is hard: mental disorders in adolescence". Deutsches Ärzteblatt International. 110 (25): 432–9, quiz 440. doi:10.3238/arztebl.2013.0432. PMC 3705204. PMID 23840288. 68. ^ Wonderlich SA, Brewerton TD, Jocic Z, Dansky BS, Abbott DW (August 1997). "Relationship of childhood sexual abuse and eating disorders". Journal of the American Academy of Child and Adolescent Psychiatry. 36 (8): 1107–15. doi:10.1097/00004583-199708000-00018. PMID 9256590. 69. ^ Connors ME, Morse W (January 1993). "Sexual abuse and eating disorders: a review". The International Journal of Eating Disorders. 13 (1): 1–11. doi:10.1002/1098-108x(199301)13:1<1::aid-eat2260130102>3.0.co;2-p. PMID 8477269. 70. ^ Worthen, Dennis (2001). P & G Pharmacy Handbook. p. 65. 71. ^ Ensminger, Audrey (1983). Foods & nutrition encyclopedia. p. 423. 72. ^ Colman, Andrew (2015). A Dictionary of Psychology. OUP Oxford. p. 851. ISBN 978-0-19-105784-7. 73. ^ Textbook of Clinical Gastroenterology and Hepatology (2 ed.). John Wiley & Sons. 2012. p. 69. ISBN 978-1-118-32142-3. 74. ^ a b "Factors That May Contribute to Eating Disorders \| National Eating Disorders Association". www.nationaleatingdisorders.org. Archived from the original on 3 March 2016. Retrieved 1 March 2016. 75. ^ "Anorexia Nervosa". 76. ^ "Eating disorders and culture". The Harvard Mental Health Letter. 20 (9): 7. March 2004. PMID 15044128. 77. ^ Francisco, Rita (2018), Cuzzolaro, Massimo; Fassino, Secondo (eds.), "Studies on Body Image, Eating, and Weight in Models, Dancers, and Aesthetic Athletes", Body Image, Eating, and Weight: A Guide to Assessment, Treatment, and Prevention, Springer International Publishing, pp. 401–411, doi:10.1007/978-3-319-90817-5_29, ISBN 978-3-319-90817-5 78. ^ Becker, Anne E. (2018). "Sociocultural influences on body image and eating disturbance". In Brownell, Kelly D.; Walsh, B. Timothy (eds.). Eating Disorders and Obesity, Third Edition: A Comprehensive Handbook. Guilford Publications. pp. 127–133. ISBN 978-1-4625-3609-2. 79. ^ Anderson-Fye, Eileen P. and Becker, Anne E. (2004) "Sociocultural Aspects of Eating Disorders" pp. 565–89 in Handbook of Eating Disorders and Obesity, J. Kevin (ed.). Thompson. Hoboken, NJ: John Wiley & Sons. 80. ^ Baum A (2006). "Eating disorders in the male athlete" (PDF). Sports Medicine. 36 (1): 1–6. doi:10.2165/00007256-200636010-00001. PMID 16445307. S2CID 15296296. Archived (PDF) from the original on 4 June 2015. 81. ^ Kyriacou O, Treasure J, Schmidt U (2008) Expressed emotion in eating disordersassessed via self-report: An examination offactors associated with expressed emo-tion in carers of people with anorexia nervosa in comparison to control families.Int J Eat Disord.41:37–46. 82. ^ Yager J. Managing Patients with Severe and Enduring Anorexia Nervosa: When Is Enough, Enough?. J. Nerv. Ment. Dis.. 2020;208(4):277-282. doi:10.1097/NMD.0000000000001124 83. ^ "Eating Disorders Anorexia Causes \| Eating Disorders". Psychiatric Disorders and Mental Health Issues. Archived from the original on 7 March 2016. Retrieved 1 March 2016. 84. ^ Labre MP (April 2002). "Adolescent boys and the muscular male body ideal". The Journal of Adolescent Health. 30 (4): 233–42. doi:10.1016/S1054-139X(01)00413-X. PMID 11927235. 85. ^ Izydorczyk, Bernadetta; Sitnik-Warchulska, Katarzyna (29 March 2018). "Sociocultural Appearance Standards and Risk Factors for Eating Disorders in Adolescents and Women of Various Ages". Frontiers in Psychology. 9: 429. doi:10.3389/fpsyg.2018.00429. ISSN 1664-1078. PMC 5885084. PMID 29651268. 86. ^ a b Norris ML, Boydell KM, Pinhas L, Katzman DK (September 2006). "Ana and the Internet: a review of pro-anorexia websites". The International Journal of Eating Disorders. 39 (6): 443–7. doi:10.1002/eat.20305. PMID 16721839. 87. ^ Harrison, Kristen (2001). "Ourselves, Our Bodies: Thin-Ideal Media, Self-Discrepancies, and Eating Disorder Symptomatology in Adolescents". Journal of Social and Clinical Psychology. 20 (3): 289–323. doi:10.1521/jscp.20.3.289.22303. 88. ^ Kaye WH, Frank GK, Bailer UF, Henry SE, Meltzer CC, Price JC, et al. (May 2005). "Serotonin alterations in anorexia and bulimia nervosa: new insights from imaging studies". Physiology & Behavior. 85 (1): 73–81. doi:10.1016/j.physbeh.2005.04.013. PMID 15869768. S2CID 25676759. 89. ^ Kaye WH, Bailer UF, Frank GK, Wagner A, Henry SE (September 2005). "Brain imaging of serotonin after recovery from anorexia and bulimia nervosa". Physiology & Behavior. 86 (1–2): 15–7. doi:10.1016/j.physbeh.2005.06.019. PMID 16102788. S2CID 17250708. 90. ^ Gaudio S, Wiemerslage L, Brooks SJ, Schiöth HB (December 2016). "A systematic review of resting-state functional-MRI studies in anorexia nervosa: Evidence for functional connectivity impairment in cognitive control and visuospatial and body-signal integration". Neuroscience and Biobehavioral Reviews. 71: 578–589. doi:10.1016/j.neubiorev.2016.09.032. PMID 27725172. 91. ^ Fuglset TS, Landrø NI, Reas DL, Rø Ø (2016). "Functional brain alterations in anorexia nervosa: a scoping review". Journal of Eating Disorders. 4: 32. doi:10.1186/s40337-016-0118-y. PMC 5125031. PMID 27933159. 92. ^ Adan R, Kaye W. "Neurocircuitry of Eating Disorders". Behavioral Neurobiology of Eating Disorders: 6 (Current Topics in Behavioral Neurosciences). Springer Berlin Heidelberg. 93. ^ Titova OE, Hjorth OC, Schiöth HB, Brooks SJ (April 2013). "Anorexia nervosa is linked to reduced brain structure in reward and somatosensory regions: a meta-analysis of VBM studies". BMC Psychiatry. 13: 110. doi:10.1186/1471-244X-13-110. PMC 3664070. PMID 23570420. 94. ^ King JA, Frank GK, Thompson PM, Ehrlich S (February 2018). "Structural Neuroimaging of Anorexia Nervosa: Future Directions in the Quest for Mechanisms Underlying Dynamic Alterations". Biological Psychiatry. 83 (3): 224–234. doi:10.1016/j.biopsych.2017.08.011. PMC 6053269. PMID 28967386. 95. ^ Frank GK (August 2015). "Advances from neuroimaging studies in eating disorders". CNS Spectrums. 20 (4): 391–400. doi:10.1017/S1092852915000012. PMC 4989857. PMID 25902917. 96. ^ a b c d Mitchell JE, Peterson CB (April 2020). "Anorexia Nervosa". The New England Journal of Medicine. 382 (14): 1343–1351. doi:10.1056/NEJMcp1803175. PMID 32242359. 97. ^ Estour B, Galusca B, Germain N (2014). "Constitutional thinness and anorexia nervosa: a possible misdiagnosis?". Frontiers in Endocrinology. 5: 175. doi:10.3389/fendo.2014.00175. PMC 4202249. PMID 25368605. 98. ^ a b Peat C, Mitchell JE, Hoek HW, Wonderlich SA (November 2009). "Validity and utility of subtyping anorexia nervosa". The International Journal of Eating Disorders. 42 (7): 590–4. doi:10.1002/eat.20717. PMC 2844095. PMID 19598270. 99. ^ Singleton, Joanne K. (12 November 2014). Primary Care, Second Edition: An Interprofessional Perspective. Springer Publishing Company. ISBN 978-0-8261-7147-4. Retrieved 9 April 2015. 100. ^ "CBC". MedlinePlus : U.S. National Library of Medicine. Archived from the original on 25 May 2013. Retrieved 31 May 2013. 101. ^ Urinalysis at Medline Archived 4 April 2010 at the Wayback Machine. Nlm.nih.gov (26 January 2012). Retrieved on 4 February 2012. 102. ^ Chem-20 at Medline Archived 5 April 2015 at the Wayback Machine. Nlm.nih.gov. Retrieved on 4 February 2012. 103. ^ Lee H, Oh JY, Sung YA, Chung H, Cho WY (October 2009). "The prevalence and risk factors for glucose intolerance in young Korean women with polycystic ovary syndrome". Endocrine. 36 (2): 326–32. doi:10.1007/s12020-009-9226-7. PMID 19688613. S2CID 207361456. 104. ^ Montagnese C, Scalfi L, Signorini A, De Filippo E, Pasanisi F, Contaldo F (December 2007). "Cholinesterase and other serum liver enzymes in underweight outpatients with eating disorders". The International Journal of Eating Disorders. 40 (8): 746–50. doi:10.1002/eat.20432. PMID 17610252. 105. ^ Narayanan V, Gaudiani JL, Harris RH, Mehler PS (May 2010). "Liver function test abnormalities in anorexia nervosa--cause or effect". The International Journal of Eating Disorders. 43 (4): 378–81. doi:10.1002/eat.20690. PMID 19424979. 106. ^ Walder A, Baumann P (December 2008). "Increased creatinine kinase and rhabdomyolysis in anorexia nervosa". The International Journal of Eating Disorders. 41 (8): 766–7. doi:10.1002/eat.20548. PMID 18521917. 107. ^ BUN at Medline Archived 9 April 2010 at the Wayback Machine. Nlm.nih.gov (26 January 2012). Retrieved on 4 February 2012. 108. ^ Sheridan AM, Bonventre JV (July 2000). "Cell biology and molecular mechanisms of injury in ischemic acute renal failure". Current Opinion in Nephrology and Hypertension. 9 (4): 427–34. doi:10.1097/00041552-200007000-00015. PMID 10926180. 109. ^ Nelsen DA (December 2002). "Gluten-sensitive enteropathy (celiac disease): more common than you think". American Family Physician. 66 (12): 2259–66. PMID 12507163. 110. ^ Pepin J, Shields C (February 2012). "Advances in diagnosis and management of hypokalemic and hyperkalemic emergencies". Emergency Medicine Practice. 14 (2): 1–17, quiz 17–8. PMID 22413702. 111. ^ "Electroencephalogram". Medline Plus. 26 January 2012. Archived from the original on 27 January 2012. Retrieved 4 February 2012. 112. ^ Misra M, Klibanski A (2011). "The neuroendocrine basis of anorexia nervosa and its impact on bone metabolism". Neuroendocrinology. 93 (2): 65–73. doi:10.1159/000323771. PMC 3214929. PMID 21228564. 113. ^ a b c Nolen-Hoeksema S (2014). "Eating disorders". Abnormal Psychology (Sixth ed.). New York: McGraw-Hill Education. p. 341. ISBN 978-0-07-803538-8. 114. ^ a b Lock JD, Fitzpatrick KK (March 2009). "Anorexia nervosa". BMJ Clinical Evidence. 2009. PMC 2907776. PMID 19445758. 115. ^ National Institute of Mental Health. "Eating disorders". Archived from the original on 23 March 2015. Retrieved 23 March 2015. 116. ^ National Collaborating Centre for Mental Health (2004). Eating Disorders: Core interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders. London, The British Psychological Society and The Royal College of Psychiatrists. 117. ^ Gowers SG, Weetman J, Shore A, Hossain F, Elvins R (February 2000). "Impact of hospitalisation on the outcome of adolescent anorexia nervosa". The British Journal of Psychiatry. 176 (2): 138–41. doi:10.1192/bjp.176.2.138. PMID 10755050. 118. ^ Nolen-Hoeksema, S (2014). Abnormal Psychology (Sixth ed.). McGraw-Hill Education. p. 357. ISBN 978-1-259-06072-4. 119. ^ Blessitt E, Voulgari S, Eisler I (November 2015). "Family therapy for adolescent anorexia nervosa". Current Opinion in Psychiatry. 28 (6): 455–60. doi:10.1097/yco.0000000000000193. PMID 26382158. S2CID 33438815. 120. ^ Garner DM, Garfinkel PE (1 January 1997). Handbook of Treatment for Eating Disorders. Guilford Press. ISBN 978-1-57230-186-3. 121. ^ Whitnet E, Rolfes SR (2011). Understanding Nutrition. United States: Wadsworth Cengage Learning. p. 255. ISBN 978-1-133-58752-1. Archived from the original on 24 November 2015. 122. ^ Russell GF, Szmukler GI, Dare C, Eisler I (December 1987). "An evaluation of family therapy in anorexia nervosa and bulimia nervosa". Archives of General Psychiatry. 44 (12): 1047–56. doi:10.1001/archpsyc.1987.01800240021004. PMID 3318754. 123. ^ le Grange D, Eisler I (January 2009). "Family interventions in adolescent anorexia nervosa". Child and Adolescent Psychiatric Clinics of North America. 18 (1): 159–73. doi:10.1016/j.chc.2008.07.004. PMID 19014864. 124. ^ "Eating Disorders". National Institute of Mental Health (NIMH). 2011. Archived from the original on 1 October 2013. Retrieved 29 September 2013. 125. ^ Fisher CA, Skocic S, Rutherford KA, Hetrick SE (May 2019). "Family therapy approaches for anorexia nervosa". The Cochrane Database of Systematic Reviews. 5: CD004780. doi:10.1002/14651858.CD004780.pub4. PMC 6497182. PMID 31041816. 126. ^ Whitfield G, Davidson A (2007). Cognitive Behavioural Therapy Explained. Radcliffe Publishing. ISBN 978-1-85775-603-6. Retrieved 9 April 2015. 127. ^ Keltner NL, Steele D (6 August 2014). Psychiatric Nursing. Elsevier Health Sciences. ISBN 978-0-323-29352-5. Retrieved 9 April 2015. 128. ^ Tchanturia K, Lounes N, Holttum S (November 2014). "Cognitive remediation in anorexia nervosa and related conditions: a systematic review". European Eating Disorders Review. 22 (6): 454–62. doi:10.1002/erv.2326. PMID 25277720. 129. ^ a b Pinna F, Sanna L, Carpiniello B (2015). "Alexithymia in eating disorders: therapeutic implications". Psychology Research and Behavior Management. 8: 1–15. doi:10.2147/PRBM.S52656. PMC 4278740. PMID 25565909. 130. ^ Claudino AM, Hay P, Lima MS, Bacaltchuk J, Schmidt U, Treasure J (January 2006). "Antidepressants for anorexia nervosa". The Cochrane Database of Systematic Reviews (1): CD004365. doi:10.1002/14651858.CD004365.pub2. PMID 16437485. 131. ^ Arcelus J, Mitchell AJ, Wales J, Nielsen S (July 2011). "Mortality rates in patients with anorexia nervosa and other eating disorders. A meta-analysis of 36 studies". Archives of General Psychiatry. 68 (7): 724–31. doi:10.1001/archgenpsychiatry.2011.74. PMID 21727255. 132. ^ Robinson P (2012). "Avoiding deaths in hospital from anorexia nervosa: the MARSIPAN project". Psychiatrist. 36 (3): 109–13. doi:10.1192/pb.bp.111.036699. 133. ^ Royal_College_of_Psychiatrists (2014). MARSIPAN Archived 21 April 2016 at the Wayback Machine: Management of Really Sick Patients with Anorexia Nervosa. Second edition. Page 6 134. ^ O'Connor G, Nicholls D (June 2013). "Refeeding hypophosphatemia in adolescents with anorexia nervosa: a systematic review". Nutrition in Clinical Practice. 28 (3): 358–64. doi:10.1177/0884533613476892. PMC 4108292. PMID 23459608. 135. ^ http://%5Bhttps[permanent dead link]://www.nice.org.uk/guidance/cg32/chapter/1-Guidance#what-to-give-in-hospital-and-the-community%20NICE%20guideline%20on%20Nutrition%20support%5D Archived 4 August 2017 at the Wayback Machine 136. ^ Bouquegneau A, Dubois BE, Krzesinski JM, Delanaye P (August 2012). "Anorexia nervosa and the kidney". American Journal of Kidney Diseases. 60 (2): 299–307. doi:10.1053/j.ajkd.2012.03.019. PMID 22609034. 137. ^ Nolen-Hoeksema S (2014). "Eating Disorders". Abnormal Psychology (Sixth ed.). New York: McGraw Hill Education. p. 342. ISBN 978-0-07-803538-8. 138. ^ Donaldson AA, Gordon CM (10 May 2020). "Skeletal Complications of Eating Disorders". Metabolism. Metabolism: Clinical and Experimental. 64 (9): 943–951. doi:10.1016/j.metabol.2015.06.007. PMC 4546560. PMID 26166318. 139. ^ "Core interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders" (PDF). National Collaborating Centre for Mental Health. 2004. Archived (PDF) from the original on 27 March 2014. 140. ^ Vyver E, Steinegger C, Katzman DK (2008). "Eating disorders and menstrual dysfunction in adolescents". Annals of the New York Academy of Sciences. 1135 (1): 253–64. Bibcode:2008NYASA1135..253V. doi:10.1196/annals.1429.013. PMID 18574232. 141. ^ Devlin MJ, Walsh BT, Katz JL, Roose SP, Linkie DM, Wright L, et al. (April 1989). "Hypothalamic-pituitary-gonadal function in anorexia nervosa and bulimia". Psychiatry Research. 28 (1): 11–24. doi:10.1016/0165-1781(89)90193-5. PMID 2500676. S2CID 39940665. 142. ^ a b Støving RK, Chen JW, Glintborg D, Brixen K, Flyvbjerg A, Hørder K, Frystyk J (June 2007). "Bioactive insulin-like growth factor (IGF) I and IGF-binding protein-1 in anorexia nervosa". The Journal of Clinical Endocrinology and Metabolism. 92 (6): 2323–9. doi:10.1210/jc.2006-1926. PMID 17389700. 143. ^ Misra M, Klibanski A (June 2014). "Anorexia nervosa and bone". The Journal of Endocrinology. 221 (3): R163-76. doi:10.1530/JOE-14-0039. PMC 4047520. PMID 24898127. 144. ^ Kleinman R (1 April 2008). Walker's Pediatric Gastrointestinal Disease. PMPH-USA. ISBN 978-1-55009-364-3. Retrieved 9 April 2015. 145. ^ a b Norris ML, Harrison ME, Isserlin L, Robinson A, Feder S, Sampson M (March 2016). "Gastrointestinal complications associated with anorexia nervosa: A systematic review". The International Journal of Eating Disorders. 49 (3): 216–37. doi:10.1002/eat.22462. PMID 26407541. 146. ^ a b c d e f g Sachs KV, Harnke B, Mehler PS, Krantz MJ (March 2016). "Cardiovascular complications of anorexia nervosa: A systematic review". The International Journal of Eating Disorders. 49 (3): 238–48. doi:10.1002/eat.22481. PMID 26710932. 147. ^ a b Goldberg SJ, Comerci GD, Feldman L (January 1988). "Cardiac output and regional myocardial contraction in anorexia nervosa". Journal of Adolescent Health Care. 9 (1): 15–21. doi:10.1016/0197-0070(88)90013-7. PMID 3335466. 148. ^ Johnson GL, Humphries LL, Shirley PB, Mazzoleni A, Noonan JA (August 1986). "Mitral valve prolapse in patients with anorexia nervosa and bulimia". Archives of Internal Medicine. 146 (8): 1525–9. doi:10.1001/archinte.1986.00360200083014. PMID 3460535. 149. ^ a b Hasan TF, Hasan H (2011). "Anorexia nervosa: a unified neurological perspective". International Journal of Medical Sciences. 8 (8): 679–703. doi:10.7150/ijms.8.679. PMC 3204438. PMID 22135615. 150. ^ Zanetti T (2013). "Epidemiology of Eating Disorders". Eating Disorders and the Skin. pp. 9–15. doi:10.1007/978-3-642-29136-4_2. ISBN 978-3-642-29135-7. 151. ^ Radford, Ben (2018). "Medical Misinformation in the Media: Is Anorexia on the Rise?" (PDF). Skeptical Inquirer. Committee for Skeptical Inquirer. 42 (1): 46–49. 152. ^ a b Bonci CM, Bonci LJ, Granger LR, Johnson CL, Malina RM, Milne LW, et al. (2008). "National athletic trainers' association position statement: preventing, detecting, and managing disordered eating in athletes". Journal of Athletic Training. 43 (1): 80–108. doi:10.4085/1062-6050-43.1.80. PMC 2231403. PMID 18335017. 153. ^ Crilly L (2 April 2012). Hope with Eating Disorders. Hay House, Inc. ISBN 978-1-84850-906-1. Retrieved 9 April 2015. 154. ^ a b Pearce JM (2004). "Richard Morton: origins of anorexia nervosa". European Neurology. 52 (4): 191–2. doi:10.1159/000082033. PMID 15539770. S2CID 30482453. 155. ^ Espi Forcen F (April 2013). "Anorexia mirabilis: the practice of fasting by Saint Catherine of Siena in the late Middle Ages". The American Journal of Psychiatry. 170 (4): 370–1. doi:10.1176/appi.ajp.2012.12111457. PMID 23545792. 156. ^ Harris JC (November 2014). "Anorexia nervosa and anorexia mirabilis: Miss K. R--and St Catherine Of Siena". JAMA Psychiatry. 71 (11): 1212–3. doi:10.1001/jamapsychiatry.2013.2765. PMID 25372187. 157. ^ a b Gull, Sir William Withey (1894). T D Acland (ed.). Medical Papers. p. 309. 158. ^ Lasègue E (6 September 1873). "On Hysterical Anorexia". Medical Times and Gazette. See also Laségue (September 1997). "On hysterical anorexia (a). 1873". Obesity Research. 5 (5): 492–7. doi:10.1002/j.1550-8528.1997.tb00676.x. PMID 9385627. 159. ^ Arnold C (2012). Decoding Anorexia: How Breakthroughs in Science Offer Hope for Eating Disorders. Routledge Press. ISBN 978-0-415-89867-6. 160. ^ Arnold C (29 March 2016). "Anorexia: you don't just grow out of it". The Guardian. Archived from the original on 29 March 2016. Retrieved 29 March 2016. 161. ^ Klein DA, Walsh BT (April 2004). "Eating disorders: clinical features and pathophysiology". Physiology & Behavior. 81 (2): 359–74. doi:10.1016/j.physbeh.2004.02.009. PMID 15159176. S2CID 29361114. ## Further reading[edit] * Bailey AP, Parker AG, Colautti LA, Hart LM, Liu P, Hetrick SE (2014). "Mapping the evidence for the prevention and treatment of eating disorders in young people". Journal of Eating Disorders. 2 (1): 5. doi:10.1186/2050-2974-2-5. PMC 4081733. PMID 24999427. * Coelho GM, Gomes AI, Ribeiro BG, Soares E (2014). "Prevention of eating disorders in female athletes". Open Access Journal of Sports Medicine. 5: 105–13. doi:10.2147/OAJSM.S36528. PMC 4026548. PMID 24891817. * Luca A, Luca M, Calandra C (February 2015). "Eating Disorders in Late-life". Aging and Disease. 6 (1): 48–55. doi:10.14336/AD.2014.0124. PMC 4306473. PMID 25657852. ## External links[edit] Wikimedia Commons has media related to Anorexia nervosa. Wikiquote has quotations related to: Anorexia nervosa * National Association of Anorexia Nervosa and Associated Disorders * Society of Clinical Psychology—Anorexia Classification D * ICD-10: F50.0-F50.1 * ICD-9-CM: 307.1 * OMIM: 606788 * MeSH: D000856 * DiseasesDB: 749 External resources * MedlinePlus: 000362 * eMedicine: emerg/34 med/144 * Patient UK: Anorexia nervosa * v * t * e Psychiatry Subspecialties * Addiction psychiatry * Biological psychiatry * Child and adolescent psychiatry * Cognitive neuropsychiatry * Cross-cultural psychiatry * Developmental disability * Descriptive psychiatry * Eating disorder * Emergency psychiatry * Forensic psychiatry * Geriatric psychiatry * Immuno-psychiatry * Liaison psychiatry * Military psychiatry * Narcology * Neuropsychiatry * Palliative medicine * Pain medicine * Psychotherapy * Sleep medicine Organizations * American Academy of Child and Adolescent Psychiatry * American Board of Psychiatry and Neurology * American Neuropsychiatric Association * American Psychiatric Association * Campaign Against Psychiatric Abuse * Chinese Society of Psychiatry * Democratic Psychiatry * European Psychiatric Association * Global Initiative on Psychiatry * Hong Kong College of Psychiatrists * Independent Psychiatric Association of Russia * Indian Psychiatric Society * National Institute of Mental Health * Philadelphia Association * Royal Australian and New Zealand College of Psychiatrists * Royal College of Psychiatrists * Working Commission to Investigate the Use of Psychiatry for Political Purposes * World Psychiatric Association * Taiwanese Society of Child and Adolescent Psychiatry Related topics * Anti-psychiatry * Behavioral medicine * Clinical neuroscience * Imaging genetics * Neuroimaging * Neurophysiology * Philosophy of psychiatry * Political abuse of psychiatry * Insulin shock therapy * Electroconvulsive therapy * Pentylenetetrazol * Biopsychiatry controversy * Controversies about psychiatry * Psychiatrist * Psychiatric epidemiology * Psychiatric genetics * Psychiatric hospital * Psychiatric survivors movement * Psychosomatic medicine * Psycho-oncology * Psychopharmacology * Psychosurgery * Psychoanalysis Lists * Outline of the psychiatric survivors movement * Psychiatrists * Neurological conditions and disorders * Counseling topics * Psychotherapies * Psychiatric medications * by condition treated * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Anorexia nervosa	c0003125	28,633	wikipedia	https://en.wikipedia.org/wiki/Anorexia_nervosa	2021-01-18T18:37:53	{"mesh": ["D000856"], "umls": ["C0003125"], "wikidata": ["Q131749"]}
Refsum disease Other namesAdult Refsum disease, heredopathia atactica polyneuritiformis, phytanic acid oxidase deficiency and phytanic acid storage disease,[1][2][3][4] Phytanic acid SpecialtyNeurology Refsum disease is an autosomal recessive[5] neurological disease that results in the over-accumulation of phytanic acid in cells and tissues. It is one of several disorders named after Norwegian neurologist Sigvald Bernhard Refsum (1907–1991).[6][7] Refsum disease typically is adolescent onset and is diagnosed by above average levels of phytanic acid. Humans obtain the necessary phytanic acid primarily through diet. It is still unclear what function phytanic acid plays physiologically in humans, but has been found to regulate fatty acid metabolism in the liver of mice.[8] ## Contents * 1 Presentation * 2 Cause * 3 Diagnosis * 3.1 Classification * 4 Treatment * 5 Biological sources of phytanic acid * 6 See also * 7 References * 8 External links ## Presentation[edit] Individuals with Refsum disease present with neurologic damage, cerebellar degeneration, and peripheral neuropathy. Onset is most commonly in childhood/adolescence with a progressive course, although periods of stagnation or remission occur. Symptoms also include ataxia, scaly skin (ichthyosis), difficulty hearing, and eye problems including retinitis pigmentosa, cataracts, and night blindness.[9] In 80% of patients diagnosed with Refsum disease, sensorineural hearing loss has been reported.[8] This is hearing loss as the result of damage to the inner ear or the nerve connectIng ear to the brain.[citation needed] ## Cause[edit] Refsum disease is a peroxisomal disorder caused by the impaired alpha-oxidation of branched chain fatty acids resulting in buildup of phytanic acid and its derivatives in the plasma and tissues. This may be due to deficiencies of phytanoyl-CoA hydroxylase or peroxin-7 activity. In general, Refsum disease is caused by PHYH mutations.[1][10] PEX7 gene mutations can interrupt the peroxisomal transport of proteins as this gene codes for the peroxin 7 protein receptor. These mutations in the PEX7 gene generally lead to rhizomelic chondrodysplasia punctata type 1- which impairs development of many parts of the body.[11] Refsum disease is inherited in an autosomal recessive pattern, meaning that it requires both copies of the mutation to inherit the disease.[citation needed] ## Diagnosis[edit] Histopathologic examination of the skin from a suspected patient commonly shows hyperkeratosis, hyper-granulosis and acanthosis. The presence of cells in the basal and suprabasal layers of the epidermis containing variably sized vacuoles with accumulated lipids is pathognomonic for the disease.[12] ### Classification[edit] Adult Refsum disease may be divided into the adult Refsum disease 1 and adult Refsum disease 2 subtypes. The former stems from mutations in the phytanoyl-CoA hydroxylase (PAHX aka PHYH) gene, on the PHYH locus at 10p13 on chromosome 6q22-24.[11] It was initially believed this was the sole mutation; however 55% of cases are now attributed to mutations in other genes.[13] Refsum disease 2 stems from mutations in the peroxin 7 (PEX7) gene.[1][10] This mutation on the PEX7 gene is also on chromosome 6q22-24, and was found in patients presenting with accumulation of phytanic acid with no PHYH mutation.[11] Adult Refsum disease should not be confused with infantile Refsum disease, a peroxisome biogenesis disorder resulting from deficiencies in the catabolism of very long chain fatty acids and branched chain fatty acids (such as phytanic acid) and plasmalogen biosynthesis.[1][10] ## Treatment[edit] Since phytanic acid is not endogenously produced in the human body, individuals with Refsum disease are commonly placed on a phytanic acid-restricted diet and avoid the consumption of fats from ruminant animals and certain fish, such as tuna, cod, and haddock.[9][14] Grass feeding animals and their milk are also avoided.[13] Recent research has shown that CYP4 isoform enzymes could help reduce the over-accumulation of phytanic acid in vivo.[15] Plasmapheresis is another medical intervention used to treat patients. This involves the filtering of blood to ensure there is no accumulation of phytanic acid.[13] ## Biological sources of phytanic acid[edit] In ruminant animals, the gut fermentation of consumed plant materials liberates phytol, a constituent of chlorophyll, which is then converted to phytanic acid and stored in fats.[16] Although humans cannot derive significant amounts of phytanic acid from the consumption of chlorophyll present in plant materials, it has been proposed that the great apes (bonobos, chimpanzees, gorillas and orangutans) can derive significant amounts of phytanic acid from the hindgut fermentation of plant materials.[17] ## See also[edit] * Global DARE Foundation (Patient Advocacy Group for Refsum Disease) * The Myelin Project * List of cutaneous conditions ## References[edit] 1. ^ a b c d Online Mendelian Inheritance in Man (OMIM): 266500 2. ^ Freedberg; et al. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. p. 499. ISBN 978-0-07-138076-8. 3. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. p. 564. ISBN 978-0-7216-2921-6. 4. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 5. ^ Jayaram, H.; Downes, S. M. (March 2008). "Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report". Journal of Medical Case Reports (Free full text). 2: 80. doi:10.1186/1752-1947-2-80. PMC 2275283. PMID 18336720. 6. ^ Refsum S (1945). "Heredoataxia hemeralopica polyneuritiformis - et tidligere ikke beskrevet familiært syndrom? En foreløbig meddelelse". Nordisk Medicin (in Norwegian). 28: 2682–6. 7. ^ Refsum S (1946). "Heredopathia atactica polyneuritiformis. A familial syndrome not hitherto described. A contribution to the clinical study of hereditary diseases of the nervous system". Acta Psych. Neur. (Suppl.38): 1–303. 8. ^ a b Nogueira, C.; Meehan, T. & O’Donoghue, G. (2014). "Refsum's Disease and Cochlear Implantation". Annals of Otology, Rhinology, and Laryngology. 123 (6): 425–427. doi:10.1177/0003489414526846. PMID 24690989. S2CID 39345035. 9. ^ a b National Institutes of Health. "Synonym(s): Phytanic Acid Storage Disease, Heredopathia Atactica Polyneuritiformis <Internet>". Retrieved 8 July 2007. 10. ^ a b c Online Mendelian Inheritance in Man (OMIM): 266510 11. ^ a b c Lambert-Hamill, M.; Mitchell, J.; Wierzbicki, A. S.; Haasjes, J.; Brites, P.; Waterham, H. R.; et al. (2003). "Identification of PEX7 as the Second gene involved in Refsum disease". The American Journal of Human Genetics. 72 (2): 471–477. doi:10.1086/346093. PMC 379239. PMID 12522768. 12. ^ Davies, M. G.; Marks, R.; Dykes, P.J.; Reynolds, D. (1977). "Epidermal abnormali-ties in Refsum's disease". Br J Dermatol. 97 (4): 401–406. doi:10.1111/j.1365-2133.1977.tb14248.x. PMID 73380. S2CID 12698297. 13. ^ a b c Metoyer, K. "Adult Refsum Disease. In C. Noggle". The Encyclopedia of Neuropsychological Disorders. 14. ^ Baldwin, R. J.; et al. (2010). "The effectiveness of long-term dietary therapy in the treatment of adult Refsum disease" (PDF). J Neurol Neurosurg Psychiatry. 81 (9): 954–957. doi:10.1136/jnnp.2008.161059. PMID 20547622. S2CID 207002195. 15. ^ Xu F, Ng VY, Kroetz DL, de Montellano PR (2006). "CYP4 isoform specificity in the omega-hydroxylation of phytanic acid, a potential route to elimination of the causative agent of Refsum's disease". J. Pharmacol. Exp. Ther. 318 (2): 835–9. doi:10.1124/jpet.106.104976. PMID 16707724. S2CID 23068060. 16. ^ Verhoeven, N. M.; Wanders, R. J.; Poll-The, B. T.; Saudubray, J. M.; Jakobs, C. (1998). "The metabolism of phytanic acid and pristanic acid in man: a review". Journal of Inherited Metabolic Disease. 21 (7): 697–728. doi:10.1023/A:1005476631419. PMID 9819701. S2CID 10325980. 17. ^ Watkins, P. A.; Moser, A. B.; Toomer, C. B.; Steinberg, S. J.; Moser, H. W.; Karaman, M. W.; Ramaswamy, K.; Siegmund, K. D.; Lee, D. R.; Ely, J. J.; Ryder, O. A.; Hacia, J. G. (2010). "Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions". BMC Physiology. 10: 19. doi:10.1186/1472-6793-10-19. PMC 2964658. PMID 20932325. ## External links[edit] * GeneReview/NCBI/NIH/UW entry on Refsum Disease Classification D * ICD-10: G60.1 * ICD-9-CM: 356.3 * OMIM: 266500 * MeSH: D012035 * DiseasesDB: 11213 External resources * eMedicine: derm/705 * Patient UK: Refsum disease * v * t * e Diseases relating to the peripheral nervous system Mononeuropathy Arm median nerve * Carpal tunnel syndrome * Ape hand deformity ulnar nerve * Ulnar nerve entrapment * Froment's sign * Ulnar tunnel syndrome * Ulnar claw radial nerve * Radial neuropathy * Wrist drop * Cheiralgia paresthetica long thoracic nerve * Winged scapula * Backpack palsy Leg lateral cutaneous nerve of thigh * Meralgia paraesthetica tibial nerve * Tarsal tunnel syndrome plantar nerve * Morton's neuroma superior gluteal nerve * Trendelenburg's sign sciatic nerve * Piriformis syndrome Cranial nerves * See Template:Cranial nerve disease Polyneuropathy and Polyradiculoneuropathy HMSN * Charcot–Marie–Tooth disease * Dejerine–Sottas disease * Refsum's disease * Hereditary spastic paraplegia * Hereditary neuropathy with liability to pressure palsy * Familial amyloid neuropathy Autoimmune and demyelinating disease * Guillain–Barré syndrome * Chronic inflammatory demyelinating polyneuropathy Radiculopathy and plexopathy * Brachial plexus injury * Thoracic outlet syndrome * Phantom limb Other * Alcoholic polyneuropathy Other General * Complex regional pain syndrome * Mononeuritis multiplex * Peripheral neuropathy * Neuralgia * Nerve compression syndrome * v * t * e Genetic disorder, organelle: Peroxisomal disorders and lysosomal structural disorders Peroxisome biogenesis disorder * Zellweger syndrome * Neonatal adrenoleukodystrophy * Infantile Refsum disease * Adult Refsum disease-2 * RCP 1 Enzyme-related * Acatalasia * RCP 2&3 * Mevalonate kinase deficiency * D-bifunctional protein deficiency * Adult Refsum disease-1 Transporter-related * X-linked adrenoleukodystrophy Lysosomal * Danon disease See also: proteins, intermediates [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Refsum disease	c2749345	28,634	wikipedia	https://en.wikipedia.org/wiki/Refsum_disease	2021-01-18T18:55:09	{"gard": ["5691"], "mesh": ["D012035", "C567602"], "umls": ["C2749345"], "orphanet": ["773"], "wikidata": ["Q177809"]}
Autoimmune retinopathy SpecialtyImmunology Ophthalmology Autoimmune retinopathy (AIR) is a rare disease in which the patient's immune system attacks proteins in the retina, leading to loss of eyesight. The disease is poorly understood, but may be the result of cancer or cancer chemotherapy.[1] The disease is an autoimmune condition characterized by vision loss, blind spots, and visual field abnormalities. It can be divided into cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR).[2] The condition is associated with retinal degeneration caused by autoimmune antibodies recognizing retinal proteins as antigens and targeting them.[3] AIR's prevalence is extremely rare, with CAR being more common than MAR.[2] It is more commonly diagnosed in females (approximately 60% of diagnosed patients are females) in the age range of 50-60.[2] ## Contents * 1 Types * 1.1 Cancer-associated retinopathy * 1.2 Melanoma-associated retinopathy * 2 Signs and symptoms * 3 Diagnosis * 4 Treatment * 4.1 Immunoglobulin * 4.2 Plasmapheresis * 4.3 Corticosteroids * 5 References ## Types[edit] ### Cancer-associated retinopathy[edit] A division of AIR, cancer-associated retinopathy is a paraneoplastic syndrome, which is a disorder caused by an immune system response to an abnormality. Autoimmune antibodies target proteins in retinal photoreceptor cells. The proteins targeted as antigenic are recoverin, α‐enolase and transducin.[4] This autoimmune response leads to photoreceptor cell death.[4] It causes progressive vision loss that can lead to blindness.[5] CAR is typically associated with the anti-recoverin antibody.[2] ### Melanoma-associated retinopathy[edit] Retinal bipolar cells (cells in retina that transmit signals) react with the antibodies, leading to cell death. Although it is less prevalent than CAR, diagnosed cases of MAR continue to increase while CAR numbers decrease.[2] ## Signs and symptoms[edit] Both CAR and MAR share the same symptoms. This is because they are both paraneoplastic syndromes. AIR symptoms are numerous and shared by many other diseases.[2] Symptoms Painless Vision Loss Blind Spots in Vision Photopsia Nyctalopia Scotomas Dislike/avoidance of light Loss of contrast sensitivity Incomplete colour blindness Decreased night vision [2][6][7] ## Diagnosis[edit] Diagnosis of AIR can be difficult due to the overlap of symptoms with other disorders.[2] Examination of the fundus (inner surface of eye) can show no results or it can show narrowing of the blood vessels, abnormal colouration of the optic disc, and retinal atrophy.[2][5] Fundus examination results are not indicative of autoimmune retinopathy but they are used to initiate the diagnostic process. An electroretinogram (eye test used to see abnormalities in the retina) is used to detect AIR. An abnormal electroretinogram (ERG) with respect to light and dark adaptations indicates AIR.[2] The ERG also allows differentiation between cancer-associated retinopathy and melanoma-associated retinopathy.[2] If the ERG shows cone responses, CAR can be prematurely diagnosed.[2] If the ERG shows a significant decrease in b-wave amplitude, MAR can be prematurely diagnosed.[2][8] To confirm, analysis for anti-retinal antibodies through Western blotting of serum collected from the patient is done.[2][5] ## Treatment[edit] Due to the difficulty of diagnosis, managing this disease is a challenge. For this reason, there is no established treatment for AIR. Clinicians try to reduce and control the autoimmune system attack to prevent any irreversible retinal damage.[5] Methods of treatment include intravenous immunoglobulin (IVIG), plasmapheresis, and corticosteroids.[5] ### Immunoglobulin[edit] Immunoglobulin samples are obtained from a large pool of healthy, matched donors (10000 - 20000).[9] The immunoglobulin mixture is then administered through IV at a rate of 0.4g/kg/day for 5 days.[5] Antibodies in the IVIG mixture interact with binding sites of the disease-associated antibodies (such as anti-recoverin antibodies).[9] This prevents binding to proteins targeted as antigenic and reduces disease activity.[9] Responses to this treatment can vary and are impacted if the patient is diagnosed with any type of cancer.[10] Patients who respond positively show improvement in the clarity of their vision and their visual field.[9] ### Plasmapheresis[edit] Plasmapheresis involves separating blood into two parts - blood cells and plasma.[11] The blood plasma components, such as the antibodies, are treated outside of the body. After removal of the disease-associated antibodies, the blood cells and plasma are transfused back into the body.[11] Response to this treatment depends on how much retinal damage has been done. Patients who respond positively show significant visual gains.[5] ### Corticosteroids[edit] Corticosteroids are administered through IV or orally. They cause lymphocytopenia, a condition where white blood cell levels are abnormally low.[12] Corticosteroids cause white blood cell death, lowering their numbers throughout the body.[12] They also cause white blood cells to recirculate away from the area of damage (the retina).[12] This minimizes damage caused by the antibodies produced by the white blood cells. Often, this is treatment is combined with plasmapheresis.[5] Instead of treating the plasma and blood cells, they are replaced with a healthy donor mixture. Patients who respond positively show improved visual fields and an almost complete disappearance of anti-retinal antibodies.[13] ## References[edit] 1. ^ Grange, Landon; Dalal, Monica; Nussenblatt, Robert B.; Sen, H. Nida (February 2014). "Autoimmune Retinopathy". American Journal of Ophthalmology. 157 (2): 266–272.e1. doi:10.1016/j.ajo.2013.09.019. PMC 3946999. PMID 24315290. 2. ^ a b c d e f g h i j k l m n Grange, Landon; Dalal, Monica; Nussenblatt, Robert B.; Sen, H. Nida (2016-10-31). "Autoimmune Retinopathy". American Journal of Ophthalmology. 157 (2): 266–272.e1. doi:10.1016/j.ajo.2013.09.019. ISSN 0002-9394. PMC 3946999. PMID 24315290. 3. ^ Adamus, Grazyna; Ren, Gaoying; Weleber, Richard G (2004-06-04). "Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy". BMC Ophthalmology. 4: 5. doi:10.1186/1471-2415-4-5. ISSN 1471-2415. PMC 446200. PMID 15180904. 4. ^ a b Weixler, Benjamin; Oertli, Daniel; Nebiker, Christian Andreas (2015-12-20). "Cancer‐associated retinopathy as the leading symptom in colon cancer". Clinical Case Reports. 4 (2): 171–176. doi:10.1002/ccr3.463. ISSN 2050-0904. PMC 4736525. PMID 26862417. 5. ^ a b c d e f g h Braithwaite, T.; Vugler, A.; Tufail, A. (2012-01-01). "Autoimmune retinopathy". Ophthalmologica. 228 (3): 131–142. doi:10.1159/000338240. ISSN 1423-0267. PMID 22846442. S2CID 19694235. 6. ^ Larson, T. A.; Gottlieb, C. C.; Zein, W. M.; Nussenblatt, R. B.; Sen, H. N. (2010-04-17). "Autoimmune Retinopathy: Prognosis and Treatment". Investigative Ophthalmology & Visual Science. 51 (13): 6375. ISSN 1552-5783. 7. ^ Abazari, Azin; Allam, Souha S.; Adamus, Grazyna; Ghazi, Nicola G. (2016-11-21). "Optical Coherence Tomography Findings in Autoimmune Retinopathy". American Journal of Ophthalmology. 153 (4): 750–756.e1. doi:10.1016/j.ajo.2011.09.012. ISSN 0002-9394. PMC 3495560. PMID 22245461. 8. ^ "The Absent-Minded Professor: An Unusual Complication of Melanoma". www.cancernetwork.com. 2008-12-01. Retrieved 2016-11-21. 9. ^ a b c d Pyne, D.; Ehrenstein, M.; Morris, V. (2002-04-01). "The therapeutic uses of intravenous immunoglobulins in autoimmune rheumatic diseases". Rheumatology. 41 (4): 367–374. doi:10.1093/rheumatology/41.4.367. ISSN 1462-0324. PMID 11961165. 10. ^ Adamus, Grazyna; Ren, Gaoying; Weleber, Richard G. (2004-01-01). "Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy". BMC Ophthalmology. 4: 5. doi:10.1186/1471-2415-4-5. ISSN 1471-2415. PMC 446200. PMID 15180904. 11. ^ a b Lobo, David R; García-Berrocal, Jose Ramon; Ramírez-Camacho, Rafael (2014-06-26). "New prospects in the diagnosis and treatment of immune-mediated inner ear disease". World Journal of Methodology. 4 (2): 91–98. doi:10.5662/wjm.v4.i2.91. ISSN 2222-0682. PMC 4202484. PMID 25332908. 12. ^ a b c Hall, Bruce M. (1999). "Corticosteroids in autoimmune diseases". Australian Prescriber. 22: 9–11. doi:10.18773/austprescr.1999.008. 13. ^ Bursztyn, Lulu L. C. D.; Belrose, Jillian C.; Coupland, Stuart G.; Fraser, J. Alexander; Proulx, Alain A. (2015). "Remission of Nonparaneoplastic Autoimmune Retinopathy After Minimal Steroid Treatment". Retinal Cases & Brief Reports. 9 (2): 173–176. doi:10.1097/ICB.0000000000000131. PMID 25764315. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autoimmune retinopathy	c3203657	28,635	wikipedia	https://en.wikipedia.org/wiki/Autoimmune_retinopathy	2021-01-18T18:29:22	{"gard": ["12034"], "umls": ["C3203657"], "wikidata": ["Q19595988"]}
A rare acute myeloid leukemia (AML) characterized by the presence of acute leukemia with at least 20% peripheral blood or bone marrow blasts with morphological features of myelodysplasia, or occurrence in patients with a prior history of a myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm, with MDS-related cytogenetic abnormalities, in the absence of specific genetic abnormalities characteristic of AML with recurrent genetic abnormalities. Prior cytotoxic or radiation therapy for an unrelated disease must be excluded. The condition occurs mainly in elderly patients and is rare in children. Patients often present with severe pancytopenia. Prognosis is generally poor. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Acute myeloid leukaemia with myelodysplasia-related features	c1292773	28,636	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=86845	2021-01-23T18:36:31	{"gard": ["12761"], "omim": ["601626"], "umls": ["C1292773"], "icd-10": ["C92.8"], "synonyms": ["AML with multilineage dysplasia", "AML with myelodysplasia-related features", "Acute myeloid leukemia with multilineage dysplasia"]}
SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities. All people with this condition have extremely short stature with particularly short arms and legs. Other features include unusual bowing of the leg bones; a small chest with short ribs and curved collar bones; short, broad fingers; and folds of extra skin on the arms and legs. Structural abnormalities of the brain cause seizures, profound developmental delay, and intellectual disability. Several affected individuals also have had episodes in which their breathing slows or stops for short periods (apnea). Acanthosis nigricans, a progressive skin disorder characterized by thick, dark, velvety skin, is another characteristic feature of SADDAN that develops in infancy or early childhood. ## Frequency This disorder is very rare; it has been described in only a small number of individuals worldwide. ## Causes Mutations in the FGFR3 gene cause SADDAN. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. A mutation in this gene may cause the FGFR3 protein to be overly active, which leads to the disturbances in bone growth that are characteristic of this disorder. Researchers have not determined how the mutation disrupts brain development or causes acanthosis nigricans. ### Learn more about the gene associated with SADDAN * FGFR3 ## Inheritance Pattern SADDAN is considered an autosomal dominant disorder because one mutated copy of the FGFR3 gene in each cell is sufficient to cause the condition. The few described cases of SADDAN have been caused by new mutations in the FGFR3 gene and occurred in people with no history of the disorder in their family. No individuals with this disorder are known to have had children; therefore, the disorder has not been passed to the next generation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	SADDAN	c2674173	28,637	medlineplus	https://medlineplus.gov/genetics/condition/saddan/	2021-01-27T08:24:47	{"gard": ["9443"], "mesh": ["D000130"], "omim": ["616482"], "synonyms": []}
The term hemangioendothelioma describes several types of vascular neosplasms and includes both non-cancerous (benign) and cancerous (malignant) growths. The term has also been applied to those that show "borderline" behavior, intermediate between entirely benign hemangiomas and highly malignant angiosarcomas. Hemangioendotheliomas are caused by abnormal growth of blood vessel cells, although the exact underlying cause for the abnormal growth is unknown. They can also develop in an organ, such as the liver or lung. They usually grow slowly and can sometimes spread to other tissues in the body (metastasize). Examples of types of hemangioendotheliomas include spindle cell hemangioma; papillary intralymphatic (Dabska tumor); retiform; kaposiform; epithelioid; pseudomyogenic (epithelioid sarcoma-like hemangioendothelioma); and composite. Treatment depends on the type of hemangioendothelioma present but typically includes surgical excision (removal). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hemangioendothelioma	c0018915	28,638	gard	https://rarediseases.info.nih.gov/diseases/6557/hemangioendothelioma	2021-01-18T18:00:08	{"mesh": ["D006390"], "umls": ["C0018915"], "synonyms": []}
Congenital neutropenia-myelofibrosis-nephromegaly syndrome is rare, genetic, primary immunodeficiency disorder characterized by severe congenital neutropenia, bone marrow fibrosis and neutrophil dysfunction which is refractory to granulocyte colony-stimulating factor, manifesting with life-threatening infections and/or deep-seated abscesses, hepato-/splenomegaly, thrombocytopenia, hypergammaglobulinemia, anemia with reticulocytosis and nephromegaly. Other reported features include osteosclerosis and neurological abnormalities (e.g. developmental delay, cortical blindness, hearing loss, thin corpus callosum or dysrhythima on EEG). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Congenital neutropenia-myelofibrosis-nephromegaly syndrome	c3809031	28,639	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=369852	2021-01-23T17:02:41	{"omim": ["615285"], "icd-10": ["D70"], "synonyms": ["Congenital neutropenia-bone marrow fibrosis-nephromegaly syndrome", "VPS45 deficiency"]}
"Health effects of smoking" and "Dangers of smoking" redirect here. For cannabis, see Effects of cannabis. For smoking crack cocaine, see Crack cocaine § Health issues. Smoking can damage many parts of the body. Tobacco use has predominantly negative effects on human health and concern about health effects of tobacco has a long history. Research has focused primarily on cigarette tobacco smoking.[1][2] Tobacco smoke contains more than 70 chemicals that cause cancer.[3] Tobacco also contains nicotine, which is a highly addictive psychoactive drug. When tobacco is smoked, nicotine causes physical and psychological dependency. Cigarettes sold in underdeveloped countries tend to have higher tar content, and are less likely to be filtered, potentially increasing vulnerability to tobacco smoking related disease in these regions.[4] Tobacco use is the single greatest cause of preventable death globally.[5] As many as half of people who use tobacco die from complications of tobacco use.[3] The World Health Organization (WHO) estimates that each year tobacco causes about 6 million deaths (about 10% of all deaths) with 600,000 of these occurring in non-smokers due to second hand smoke.[3][6] In the 20th century tobacco is estimated to have caused 100 million deaths.[3] Similarly, the United States Centers for Disease Control and Prevention describes tobacco use as "the single most important preventable risk to human health in developed countries and an important cause of premature death worldwide."[7] Currently, the number of premature deaths in the U.S. from tobacco use per year outnumber the number of workers employed in the tobacco industry by 4 to 1.[8] According to a 2014 review in the New England Journal of Medicine, tobacco will, if current smoking patterns persist, kill about 1 billion people in the 21st century, half of them before the age of 70.[9] Tobacco use leads most commonly to diseases affecting the heart, liver and lungs. Smoking is a major risk factor for infections like pneumonia, heart attacks, strokes, chronic obstructive pulmonary disease (COPD) (including emphysema and chronic bronchitis), and several cancers (particularly lung cancer, cancers of the larynx and mouth, bladder cancer, and pancreatic cancer). It also causes peripheral arterial disease and high blood pressure. The effects depend on the number of years that a person smokes and on how much the person smokes. Starting smoking earlier in life and smoking cigarettes higher in tar increases the risk of these diseases. Also, environmental tobacco smoke, or secondhand smoke, has been shown to cause adverse health effects in people of all ages.[10] Tobacco use is a significant factor in miscarriages among pregnant smokers, and it contributes to a number of other health problems of the fetus such as premature birth, low birth weight, and increases by 1.4 to 3 times the chance of sudden infant death syndrome (SIDS).[11] Incidence of erectile dysfunction is approximately 85 percent higher in male smokers compared to non-smokers.[12][13] Several countries have taken measures to control the consumption of tobacco with usage and sales restrictions as well as warning messages printed on packaging. Additionally, smoke-free laws that ban smoking in public places such as workplaces, theaters, and bars and restaurants reduce exposure to secondhand smoke and help some people who smoke to quit, without negative economic effects on restaurants or bars.[3] Tobacco taxes that increase the price are also effective, especially in developing countries.[3] The idea that tobacco use caused some diseases, including mouth cancers, was initially, in the late 1700s and the 1800s, widely accepted by the medical community.[14] In the 1880s, automation slashed the cost of cigarettes, and use expanded.[15][16] From the 1890s onwards, associations of tobacco use with cancers and vascular disease were regularly reported; a meta-analysis citing 167 other works was published in 1930, and concluded that tobacco use caused cancer.[17][18] Increasingly solid observational evidence was published throughout the 1930s, and in 1938, Science published a paper showing that tobacco users live substantially shorter lives. Case-control studies were published in Nazi Germany in 1939 and 1943, and one in the Netherlands in 1948, but widespread attention was first drawn by five case-control studies published in 1950 by researchers from the US and UK. These studies were widely criticized as showing correlation, not causality. Follow up prospective cohort studies in the early 1950s clearly found that smokers died faster, and were more likely to die of lung cancer and cardiovascular disease.[14] These results were first widely accepted in the medical community, and publicized among the general public, in the mid-1960s.[14] Part of a series on Tobacco History * History of tobacco Chemistry * Tobacco * Tobacco smoke Biology * Nicotiana (Nicotiana tabacum) * Nicotine * Tobacco diseases * Types of tobacco Personal and social impact * Health effects * Prevalence of consumption * Nicotine marketing * Tobacco and art * Tobacco and other drugs * Tobacco control * Religious views * Tobacco politics * Tobacco smoking * Tobacconist Production * Cultivation of tobacco * Curing of tobacco * Tobacco industry * Tobacco products * v * t * e ## Contents * 1 History * 1.1 Pre-cigarette * 1.2 Early observational studies * 1.3 Causality * 1.4 Public awareness * 2 Health effects of smoking * 2.1 Mortality * 2.2 Cancer * 2.3 Pulmonary * 2.4 Cardiovascular disease * 2.5 Renal * 2.6 Influenza * 2.7 Mouth * 2.8 Infection * 2.9 Impotence * 2.10 Female infertility * 2.11 Psychological * 2.11.1 Immediate effects * 2.11.2 Stress * 2.11.3 Social and behavioral * 2.11.4 Cognitive function * 2.12 Pregnancy * 2.13 Drug interactions * 2.14 Multigenerational effects * 2.15 Other harm * 2.16 Benefits * 3 Mechanism * 3.1 Chemical carcinogens * 3.2 Radioactive carcinogens * 3.3 Oxidation and inflammation * 3.4 Nicotine * 4 Forms of exposure * 4.1 Second-hand smoke * 4.2 Chewing tobacco * 4.3 Cigars * 4.4 Hookahs * 4.5 Dipping tobacco * 5 Prevention * 6 Usage * 7 See also * 8 References * 9 Bibliography * 10 External links ## History[edit] ### Pre-cigarette[edit] Concern about health effects of tobacco has a long history. The coughing, throat irritation, and shortness of breath caused by smoking have always been obvious.[citation needed] During Early Modern times, West African Muslim scholars knew the negative health effects of smoking tobacco. The dangers of tobacco smoking were documented in the Timbuktu manuscripts.[19] Pipe smoking gradually became generally accepted as a cause of mouth cancers following work done in the 1700s. An association between a variety of cancers and tobacco use was repeatedly observed from the late 1800s into the early 1920s. An association between tobacco use and vascular disease was reported from the late 1800s onwards.[citation needed] Gideon Lincecum, an American naturalist and practitioner of botanical medicine, wrote in the early 19th century on tobacco: "This poisonous plant has been used a great deal as a medicine by the old school faculty, and thousands have been slain by it. ... It is a very dangerous article, and use it as you will, it always diminishes the vital energies in exact proportion to the quantity used – it may be slowly, but it is very sure."[20] The 1880s invention of automated cigarette-making machinery in the American South made it possible to mass-produce cigarettes at low cost, and smoking became common. This led to a backlash and a tobacco prohibition movement, which challenged tobacco use as harmful and brought about some bans on tobacco sale and use.[15] In 1912, American Dr. Isaac Adler was the first to strongly suggest that lung cancer is related to smoking.[21] In 1924, economist Irving Fisher wrote an anti-smoking article for Reader's Digest which said "...tobacco lowers the whole tone of the body and decreases its vital power and resistance ... tobacco acts like a narcotic poison, like opium, and like alcohol, though usually in a less degree".[22] Reader's Digest for many years published frequent anti-smoking articles.[citation needed] Prior to World War I, lung cancer was considered to be a rare disease, which most physicians would never see during their career.[23][24] With the postwar rise in popularity of cigarette smoking, however, came an epidemic of lung cancer.[25] ### Early observational studies[edit] From the 1890s onwards, associations of tobacco use with cancers and vascular disease were regularly reported.[14] In 1930, Fritz Lickint of Dresden, Germany, published[18][17] a metaanalysis citing 167 other works to link tobacco use to lung cancer.[17] Lickint showed that lung cancer sufferers were likely to be smokers. He also argued that tobacco use was the best way to explain the fact that lung cancer struck men four or five times more often than women (since women smoked much less),[18] and discussed the causal effect of smoking on cancers of the liver and bladder.[17] It may be suggested that the chief reason that the subject has received so little attention from members of the medical profession is that the majority of them as of the general community practice smoking in one form of another, and do not wish to inquire too closely into a habit in defense of which so much can be said from the hedonistic but so little from the hygienic standpoint Rolleston, J. D. (1932-07-01). "The Cigarette Habit". British Journal of Inebriety (Alcoholism and Drug Addiction). 30 (1): 1–27. doi:10.1111/j.1360-0443.1932.tb04849.x. ISSN 1360-0443. More observational evidence was published throughout the 1930s, and in 1938, Science published a paper showing that tobacco users live substantially shorter lives. It built a survival curve from family history records kept at the Johns Hopkins School of Hygiene and Public Health. This result was ignored or incorrectly explained away.[14] An association between tobacco and heart attacks was first mentioned in the 1930; a large case–control study found a significant association in 1940, but avoided saying anything about cause, on the grounds that such a conclusion would cause controversy and doctors were not yet ready for it.[14] Official hostility to tobacco use was widespread in Nazi Germany where case-control studies were published in 1939 and 1943. Another was published in the Netherlands in 1948. A case-control study on lung cancer and smoking, done in 1939 by Franz Hermann Müller, had serious weaknesses in its methodology, but study design problems were better addressed in subsequent studies.[14] The association of anti-tobacco research and public health measures with the Nazi leadership may have contributed to the lack of attention paid to these studies.[18] They were also published in German and Dutch. These studies were widely ignored.[26] In 1947 the British Medical Council held a conference to discuss the reason for the rise in lung cancer deaths; unaware of the German studies, they planned and started their own.[14] Five case-control studies published in 1950 by researchers from the US and UK did draw widespread attention.[27] The strongest results were found by "Smoking and carcinoma of the lung. Preliminary report", by Richard Doll and Austin Hill,[28][14] and the 1950 Wynder and Graham Study, entitled "Tobacco Smoking as a Possible Etiologic Factor in Bronchiogenic Carcinoma: A Study of Six Hundred and Eighty-Four Proved Cases". These two studies were the largest, and the only ones to carefully exclude ex-smokers from their nonsmokers group. The other three studies also reported that, to quote one, "smoking was powerfully implicated in the causation of lung cancer".[27] The Doll and Hill paper reported that "heavy smokers were fifty times as likely as non-smokers to contract lung cancer".[28][27] ### Causality[edit] The case-control studies clearly showed a close link between smoking and lung cancer, but were criticized for not showing causality. Follow-up large prospective cohort studies in the early 1950s showed clearly that smokers died faster, and were more likely to die of lung cancer, cardiovascular disease, and a list of other diseases which lengthened as the studies continued[14] The British Doctors Study, a longitudinal study of some 40,000 doctors, began in 1951.[29] By 1954 it had evidence from three years of doctors' deaths, based on which the government issued advice that smoking and lung cancer rates were related[30][29] (the British Doctors Study last reported in 2001,[29] by which time there were approximately 40 linked diseases).[14] The British Doctors Study demonstrated that about half of the persistent cigarette smokers born in 1900–1909 were eventually killed by their addiction (calculated from the logarithms of the probabilities of surviving from 35–70, 70–80, and 80–90) and about two thirds of the persistent cigarette smokers born in the 1920s would eventually be killed by their addiction.[citation needed] ### Public awareness[edit] In 1953, scientists at the Sloan-Kettering Institute in New York City demonstrated that cigarette tar painted on the skin of mice caused fatal cancers.[26] This work attracted much media attention; the New York Times and Life both covered the issue. The Reader's Digest published an article entitled "Cancer by the Carton".[26]:14 On January 11, 1964, the United States Surgeon General's Report on Smoking and Health was published; this led millions of American smokers to quit, the banning of certain advertising, and the requirement of warning labels on tobacco products.[citation needed] These results were first widely accepted in the medical community, and publicized among the general public, in the mid-1960s.[14] The medical community's resistance to the idea that tobacco caused disease has been attributed to bias from nicotine-dependent doctors, the novelty of the adaptations needed to apply epidemiological techniques and heuristics to non-infectious diseases, and tobacco industry pressure.[14] The health effects of smoking have been significant for the development of the science of epidemiology. As the mechanism of carcinogenicity is radiomimetic or radiological, the effects are stochastic. Definite statements can be made only on the relative increased or decreased probabilities of contracting a given disease. For a particular individual, it is impossible to definitively prove a direct causal link between exposure to a radiomimetic poison such as tobacco smoke and the cancer that follows; such statements can only be made at the aggregate population level. Tobacco companies have capitalized on this philosophical objection and exploited the doubts of clinicians, who consider only individual cases, on the causal link in the stochastic expression of the toxicity as actual disease.[31] There have been multiple court cases against tobacco companies for having researched the health effects of tobacco, but having then suppressed the findings or formatted them to imply lessened or no hazard.[31] After a ban on smoking in all enclosed public places was introduced in Scotland in March 2006, there was a 17 percent reduction[when?] in hospital admissions for acute coronary syndrome. 67% of the decrease occurred in non-smokers.[32] ## Health effects of smoking[edit] Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. Tobacco was ranked 3rd in dependence, 14th in physical harm, and 12th in social harm.[33] Smoking most commonly leads to diseases affecting the heart and lungs and will commonly affect areas such as hands or feet. First signs of smoking related health issues often show up as numbness in the extremities, with smoking being a major risk factor for heart attacks, chronic obstructive pulmonary disease (COPD), emphysema, and cancer, particularly lung cancer, cancers of the larynx and mouth, and pancreatic cancer.[34] Overall life expectancy is also reduced in long term smokers, with estimates ranging from 10[29] to 17.9[35] years fewer than nonsmokers.[36] About one half of long term male smokers will die of illness due to smoking.[37] The association of smoking with lung cancer is strongest, both in the public perception and etiologically. Among male smokers, the lifetime risk of developing lung cancer is 17.2%; among female smokers, the risk is 11.6%. This risk is significantly lower in nonsmokers: 1.3% in men and 1.4% in women.[38] A person's increased risk of contracting disease is related to the length of time that a person continues to smoke as well as the amount smoked. However, even smoking one cigarette a day raises the risk of coronary heart disease by about 50% or more, and for stroke by about 30%. Smoking 20 cigarettes a day entails a higher risk, but not proportionately.[39][40] If someone stops smoking, then these chances gradually decrease as the damage to their body is repaired. A year after quitting, the risk of contracting heart disease is half that of a continuing smoker.[41] The health risks of smoking are not uniform across all smokers. Risks vary according to the amount of tobacco smoked, with those who smoke more at greater risk. Smoking so-called "light" cigarettes does not reduce the risk.[42] ### Mortality[edit] Smoking is the cause of about 5 million deaths per year.[43] This makes it the most common cause of preventable early death.[44] One study found that male and female smokers lose on average of 13.2 and 14.5 years of life, respectively.[45] Another found a loss of life of 6.8 years.[46] Each cigarette that is smoked is estimated to shorten life by an average of 11 minutes.[47][48][49] At least half of all lifelong smokers die earlier as a result of smoking.[29] Smokers are three times as likely to die before the age of 60 or 70 as non-smokers.[29][50][51] In the United States, cigarette smoking and exposure to tobacco smoke accounts for roughly one in five,[52] or at least 443,000 premature deaths annually.[53] To put this into context, ABC's Peter Jennings (who would later die at 67 from complications of lung cancer due to his life-long smoking habit) famously reported that in the US alone, tobacco kills the equivalent of three jumbo jets full of people crashing every day, with no survivors.[54] On a worldwide basis, this equates to a single jumbo jet every hour.[55] A 2015 study found that about 17% of mortality due to cigarette smoking in the United States is due to diseases other than those usually believed to be related.[56] It is estimated that there are between 1 and 1.4 deaths per million cigarettes smoked. In fact, cigarette factories are the most deadly factories in the history of the world.[57][58] See the below chart detailing the highest-producing cigarette factories, and their estimated deaths caused annually due to the health detriments of cigarettes.[57] * Share of deaths from smoking, 2017[59] * The number of deaths attributed to smoking per 100,000 people in 2017[60] ### Cancer[edit] Share of cancer deaths attributed to tobacco in 2016.[61] Play media Effects of smoking include both immediate and long-term lung damage. The primary risks of tobacco usage include many forms of cancer, particularly lung cancer,[62] kidney cancer,[63] cancer of the larynx and head and neck,[64][65] bladder cancer,[66] cancer of the esophagus,[67] cancer of the pancreas[68] and stomach cancer.[69] Studies have established a relationship between tobacco smoke, including secondhand smoke, and cervical cancer in women.[70] There is some evidence suggesting a small increased risk of myeloid leukemia,[71] squamous cell sinonasal cancer, liver cancer, colorectal cancer, cancers of the gallbladder, the adrenal gland, the small intestine, and various childhood cancers.[69] The possible connection between breast cancer and tobacco is still uncertain.[72][medical citation needed] Lung cancer risk is highly affected by smoking, with up to 90% of cases being caused by tobacco smoking.[73] Risk of developing lung cancer increases with number of years smoking and number of cigarettes smoked per day.[74] Smoking can be linked to all subtypes of lung cancer. Small-cell carcinoma (SCLC) is the most closely associated with almost 100% of cases occurring in smokers.[75] This form of cancer has been identified with autocrine growth loops, proto-oncogene activation and inhibition of tumour suppressor genes. SCLC may originate from neuroendocrine cells located in the bronchus called Feyrter cells.[76] The risk of dying from lung cancer before age 85 is 22.1% for a male smoker and 11.9% for a female smoker, in the absence of competing causes of death. The corresponding estimates for lifelong nonsmokers are a 1.1% probability of dying from lung cancer before age 85 for a man of European descent, and a 0.8% probability for a woman.[77] ### Pulmonary[edit] Since establishing causation through experimental trials was not possible due to ethical restrictions, a lengthy study was conducted in order to establish the strong association necessary to allow for legislative action against tobacco consumption.[citation needed] In smoking, long term exposure to compounds found in the smoke (e.g., carbon monoxide and cyanide) are believed to be responsible for pulmonary damage and for loss of elasticity in the alveoli, leading to emphysema and COPD. Chronic obstructive pulmonary disease (COPD) caused by smoking is a permanent, incurable (often terminal) reduction of pulmonary capacity characterised by shortness of breath, wheezing, persistent cough with sputum, and damage to the lungs, including emphysema and chronic bronchitis.[78] The carcinogen acrolein and its derivatives also contribute to the chronic inflammation present in COPD.[79] ### Cardiovascular disease[edit] Smoking can cause atherosclerosis, leading to coronary artery disease and peripheral arterial disease. Tobacco stains on primarily the second and third fingers of a heavy smoker Inhalation of tobacco smoke causes several immediate responses within the heart and blood vessels. Within one minute the heart rate begins to rise, increasing by as much as 30 percent during the first 10 minutes of smoking. Carbon monoxide in tobacco smoke exerts negative effects by reducing the blood's ability to carry oxygen.[80] Smoking also increases the chance of heart disease, stroke, atherosclerosis, and peripheral vascular disease.[81][82] Several ingredients of tobacco lead to the narrowing of blood vessels, increasing the likelihood of a blockage, and thus a heart attack or stroke. According to a study by an international team of researchers, people under 40 are five times more likely to have a heart attack if they smoke.[83][84] Exposure to tobacco smoke is known to increase oxidative stress in the body by various mechanisms, including depletion of plasma antioxidants such as vitamin C.[85] Recent research by American biologists has shown that cigarette smoke also influences the process of cell division in the cardiac muscle and changes the heart's shape.[86] The usage of tobacco has also been linked to Buerger's disease (thromboangiitis obliterans), the acute inflammation and thrombosis (clotting) of arteries and veins of the hands and feet.[87] Although cigarette smoking causes a greater increase in the risk of cancer than cigar smoking, cigar smokers still have an increased risk for many health problems, including cancer, when compared to non-smokers.[88][89] As for second-hand smoke, the NIH study points to the large amount of smoke generated by one cigar, saying "cigars can contribute substantial amounts of tobacco smoke to the indoor environment; and, when large numbers of cigar smokers congregate in a cigar smoking event, the amount of ETS (i.e. second-hand smoke) produced is sufficient to be a health concern for those regularly required to work in those environments."[90] Smoking tends to increase blood cholesterol levels. Furthermore, the ratio of high-density lipoprotein (HDL, also known as the "good" cholesterol) to low-density lipoprotein (LDL, also known as the "bad" cholesterol) tends to be lower in smokers compared to non-smokers. Smoking also raises the levels of fibrinogen and increases platelet production (both involved in blood clotting) which makes the blood thicker and more likely to clot. Carbon monoxide binds to hemoglobin (the oxygen-carrying component in red blood cells), resulting in a much stabler complex than hemoglobin bound with oxygen or carbon dioxide—the result is permanent loss of blood cell functionality. Blood cells are naturally recycled after a certain period of time, allowing for the creation of new, functional red blood cells. However, if carbon monoxide exposure reaches a certain point before they can be recycled, hypoxia (and later death) occurs. All these factors make smokers more at risk of developing various forms of arteriosclerosis (hardening of the arteries). As the arteriosclerosis progresses, blood flows less easily through rigid and narrowed blood vessels, making the blood more likely to form a thrombosis (clot). Sudden blockage of a blood vessel may lead to an infarction (stroke or heart attack). However, it is also worth noting that the effects of smoking on the heart may be more subtle. These conditions may develop gradually given the smoking-healing cycle (the human body heals itself between periods of smoking), and therefore a smoker may develop less significant disorders such as worsening or maintenance of unpleasant dermatological conditions, e.g. eczema, due to reduced blood supply. Smoking also increases blood pressure and weakens blood vessels.[91] ### Renal[edit] In addition to increasing the risk of kidney cancer, smoking can also contribute to additional renal damage. Smokers are at a significantly increased risk for chronic kidney disease than non-smokers.[92] A history of smoking encourages the progression of diabetic nephropathy.[93] ### Influenza[edit] A study of an outbreak of an (H1N1) influenza in an Israeli military unit of 336 healthy young men to determine the relation of cigarette smoking to the incidence of clinically apparent influenza, revealed that, of 168 smokers, 68.5 percent had influenza, as compared with 47.2 percent of nonsmokers. Influenza was also more severe in the smokers; 50.6 percent of them lost work days or required bed rest, or both, as compared with 30.1 percent of the nonsmokers.[94] According to a study of 1,900 male cadets after the 1968 Hong Kong A2 influenza epidemic at a South Carolina military academy, compared with nonsmokers, heavy smokers (more than 20 cigarettes per day) had 21% more illnesses and 20% more bed rest, light smokers (20 cigarettes or fewer per day) had 10% more illnesses and 7% more bed rest.[95] The effect of cigarette smoking upon epidemic influenza was studied prospectively among 1,811 male college students. Clinical influenza incidence among those who daily smoked 21 or more cigarettes was 21% higher than that of non-smokers. Influenza incidence among smokers of 1 to 20 cigarettes daily was intermediate between non-smokers and heavy cigarette smokers.[95] Surveillance of a 1979 influenza outbreak at a military base for women in Israel revealed that influenza symptoms developed in 60.0% of the current smokers vs. 41.6% of the nonsmokers.[96] Smoking seems to cause a higher relative influenza-risk in older populations than in younger populations. In a prospective study of community-dwelling people 60–90 years of age, during 1993, of unimmunized people 23% of smokers had clinical influenza as compared with 6% of non-smokers.[97] Smoking may substantially contribute to the growth of influenza epidemics affecting the entire population.[94] However, the proportion of influenza cases in the general non-smoking population attributable to smokers has not yet been calculated.[citation needed] ### Mouth[edit] Dental radiograph showing bone loss in a 32 year old heavy smoker. Perhaps the most serious oral condition that can arise is that of oral cancer. However, smoking also increases the risk for various other oral diseases, some almost completely exclusive to tobacco users. The National Institutes of Health, through the National Cancer Institute, determined in 1998 that "cigar smoking causes a variety of cancers including cancers of the oral cavity (lip, tongue, mouth, throat), esophagus, larynx, and lung."[90] Pipe smoking involves significant health risks,[98][99] particularly oral cancer.[100] Roughly half of periodontitis or inflammation around the teeth cases are attributed to current or former smoking. Smokeless tobacco causes gingival recession and white mucosal lesions. Up to 90% of periodontitis patients who are not helped by common modes of treatment are smokers. Smokers have significantly greater loss of bone height than nonsmokers, and the trend can be extended to pipe smokers to have more bone loss than nonsmokers.[101] Smoking has been proven to be an important factor in the staining of teeth.[102][103] Halitosis or bad breath is common among tobacco smokers.[104] Tooth loss has been shown to be 2[105] to 3 times[106] higher in smokers than in non-smokers.[107] In addition, complications may further include leukoplakia, the adherent white plaques or patches on the mucous membranes of the oral cavity, including the tongue.[108] ### Infection[edit] Smoking is also linked to susceptibility to infectious diseases, particularly in the lungs (pneumonia). Smoking more than 20 cigarettes a day increases the risk of tuberculosis by two to four times,[109][110] and being a current smoker has been linked to a fourfold increase in the risk of invasive disease caused by the pathogenic bacteria Streptococcus pneumoniae.[111] It is believed that smoking increases the risk of these and other pulmonary and respiratory tract infections both through structural damage and through effects on the immune system. The effects on the immune system include an increase in CD4+ cell production attributable to nicotine, which has tentatively been linked to increased HIV susceptibility.[112] Smoking increases the risk of Kaposi's sarcoma in people without HIV infection.[113] One study found this only with the male population and could not draw any conclusions for the female participants in the study.[114] ### Impotence[edit] The incidence of impotence (difficulty achieving and maintaining penile erection) is approximately 85 percent higher in male smokers compared to non-smokers.[115] Smoking is a key cause of erectile dysfunction (ED).[12][115] It causes impotence because it promotes arterial narrowing and damages cells lining the inside of the arteries, thus leading to reduce penile blood flow.[116] ### Female infertility[edit] See also: Female infertility § Tobacco smoking Smoking is harmful to the ovaries, potentially causing female infertility, and the degree of damage is dependent upon the amount and length of time a woman smokes. Nicotine and other harmful chemicals in cigarettes interfere with the body's ability to create estrogen, a hormone that regulates folliculogenesis and ovulation. Also, cigarette smoking interferes with folliculogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and the uterine myometrium.[117] Some damage is irreversible, but stopping smoking can prevent further damage.[118][119] Smokers are 60% more likely to be infertile than non-smokers.[120] Smoking reduces the chances of in vitro fertilization (IVF) producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%.[120] ### Psychological[edit] American Psychologist stated, "Smokers often report that cigarettes help relieve feelings of stress. However, the stress levels of adult smokers are slightly higher than those of nonsmokers, adolescent smokers report increasing levels of stress as they develop regular patterns of smoking, and smoking cessation leads to reduced stress. Far from acting as an aid for mood control, nicotine dependency seems to exacerbate stress. This is confirmed in the daily mood patterns described by smokers, with normal moods during smoking and worsening moods between cigarettes. Thus, the apparent relaxant effect of smoking only reflects the reversal of the tension and irritability that develop during nicotine depletion. Dependent smokers need nicotine to remain feeling normal."[121] #### Immediate effects[edit] Users report feelings of relaxation, sharpness, calmness, and alertness.[122] Those new to smoking may experience nausea, dizziness, increased blood pressure, narrowed arteries, and rapid heart beat. Generally, the unpleasant symptoms will eventually vanish over time, with repeated use, as the body builds a tolerance to the chemicals in the cigarettes, such as nicotine.[citation needed] #### Stress[edit] Smokers report higher levels of everyday stress.[123] Several studies have monitored feelings of stress over time and found reduced stress after quitting.[124][125] The deleterious mood effects of abstinence explain why smokers suffer more daily stress than non-smokers and become less stressed when they quit smoking. Deprivation reversal also explains much of the arousal data, with deprived smokers being less vigilant and less alert than non-deprived smokers or non-smokers.[123] Recent studies have shown a positive relationship between psychological distress and salivary cotinine levels in smoking and non-smoking adults, indicating that both firsthand and secondhand smoke exposure may lead to higher levels of mental stress.[126] #### Social and behavioral[edit] Medical researchers have found that smoking is a predictor of divorce.[127] Smokers have a 53% greater chance of divorce than nonsmokers.[128] #### Cognitive function[edit] The usage of tobacco can also create cognitive dysfunction. There seems to be an increased risk of Alzheimer's disease (AD), although "case–control and cohort studies produce conflicting results as to the direction of the association between smoking and AD".[129] Smoking has been found to contribute to dementia and cognitive decline,[130] reduced memory and cognitive abilities in adolescents,[131] and brain shrinkage (cerebral atrophy).[132][133] Most notably, some studies have found that patients with Alzheimer's disease are more likely not to have smoked than the general population, which has been interpreted to suggest that smoking offers some protection against Alzheimer's. However, the research in this area is limited and the results are conflicting; some studies show that smoking increases the risk of Alzheimer's disease.[134] A recent review of the available scientific literature concluded that the apparent decrease in Alzheimer's risk may be simply because smokers tend to die before reaching the age at which Alzheimer's normally occurs. "Differential mortality is always likely to be a problem where there is a need to investigate the effects of smoking in a disorder with very low incidence rates before age 75 years, which is the case of Alzheimer's disease," it stated, noting that smokers are only half as likely as non-smokers to survive to the age of 80.[129] Some older analyses have claimed that non-smokers are up to twice as likely as smokers to develop Alzheimer's disease.[135] However, a more current analysis found that most of the studies, which showed a preventing effect, had a close affiliation to the tobacco industry. Researchers without tobacco lobby influence have concluded the complete opposite: Smokers are almost twice as likely as nonsmokers to develop Alzheimer's disease.[136] Former and current smokers have a lower incidence of Parkinson's disease compared to people who have never smoked,[137][138] although the authors stated that it was more likely that the movement disorders which are part of Parkinson's disease prevented people from being able to smoke than that smoking itself was protective. Another study considered a possible role of nicotine in reducing Parkinson's risk: nicotine stimulates the dopaminergic system of the brain, which is damaged in Parkinson's disease, while other compounds in tobacco smoke inhibit MAO-B, an enzyme which produces oxidative radicals by breaking down dopamine.[139] In many respects, nicotine acts on the nervous system in a similar way to caffeine. Some writings have stated that smoking can also increase mental concentration; one study documents a significantly better performance on the normed Advanced Raven Progressive Matrices test after smoking.[140] Most smokers, when denied access to nicotine, exhibit withdrawal symptoms such as irritability, jitteriness, dry mouth, and rapid heart beat.[141] The onset of these symptoms is very fast, nicotine's half-life being only two hours.[142] The psychological dependence may linger for months or even many years. Unlike some recreational drugs, nicotine does not measurably alter a smoker's motor skills, judgement, or language abilities while under the influence of the drug. Tobacco withdrawal has been shown to cause clinically significant distress.[143] A very large percentage of schizophrenics smoke tobacco as a form of self-medication.[144][145][146][147] The high rate of tobacco use by the mentally ill is a major factor in their decreased life expectancy, which is about 25 years shorter than the general population.[148] Following the observation that smoking improves condition of people with schizophrenia, in particular working memory deficit, nicotine patches had been proposed as a way to treat schizophrenia.[149] Some studies suggest that a link exists between smoking and mental illness, citing the high incidence of smoking amongst those suffering from schizophrenia[150] and the possibility that smoking may alleviate some of the symptoms of mental illness,[151] but these have not been conclusive. In 2015, a meta-analysis found that smokers were at greater risk of developing psychotic illness.[152] Recent studies have linked smoking to anxiety disorders, suggesting the correlation (and possibly mechanism) may be related to the broad class of anxiety disorders, and not limited to just depression. Current and ongoing research attempt to explore the addiction-anxiety relationship. Data from multiple studies suggest that anxiety disorders and depression play a role in cigarette smoking.[153] A history of regular smoking was observed more frequently among individuals who had experienced a major depressive disorder at some time in their lives than among individuals who had never experienced major depression or among individuals with no psychiatric diagnosis.[154] People with major depression are also much less likely to quit due to the increased risk of experiencing mild to severe states of depression, including a major depressive episode.[155] Depressed smokers appear to experience more withdrawal symptoms on quitting, are less likely to be successful at quitting, and are more likely to relapse.[156] ### Pregnancy[edit] Main article: Smoking and pregnancy A number of studies have shown that tobacco use is a significant factor in miscarriages among pregnant smokers, and that it contributes to a number of other threats to the health of the fetus. It slightly increases the risk of neural tube defects.[157] Environmental tobacco smoke exposure and maternal smoking during pregnancy have been shown to cause lower infant birth weights.[158] Studies have shown an association between prenatal exposure to environmental tobacco smoke and conduct disorder in children.[medical citation needed] As well, post-natal tobacco smoke exposure may cause similar behavioral problems in children.[medical citation needed] ### Drug interactions[edit] Smoking is known to increase levels of liver enzymes that break down drugs and toxins. That means that drugs cleared by these enzymes are cleared more quickly in smokers, which may result in the drugs not working. Specifically, levels of CYP1A2 and CYP2A6 are induced:[159][160] substrates for 1A2 include caffeine and tricyclic antidepressants such as amitriptyline; substrates for 2A6 include the anticonvulsant valproic acid. ### Multigenerational effects[edit] Main article: Epigenetic effects of smoking ### Other harm[edit] See also: Women and smoking § Unique gender differences and health effects for Females Protein AZGP1 Studies suggest that smoking decreases appetite, but did not conclude that overweight people should smoke or that their health would improve by smoking. This is also a cause of heart diseases.[161] Smoking also decreases weight by overexpressing the gene AZGP1, which stimulates lipolysis.[162] Smoking causes about 10% of the global burden of fire deaths,[163] and smokers are placed at an increased risk of injury-related deaths in general, partly due to also experiencing an increased risk of dying in a motor vehicle crash.[164] Smoking increases the risk of symptoms associated with Crohn's disease (a dose-dependent effect with use of greater than 15 cigarettes per day).[165][166][167][168] There is some evidence for decreased rates of endometriosis in infertile smoking women,[169] although other studies have found that smoking increases the risk in infertile women.[170] There is little or no evidence of a protective effect in fertile women. Some preliminary data from 1996 suggested a reduced incidence of uterine fibroids,[171] but overall the evidence is unconvincing.[172] Current research shows that tobacco smokers who are exposed to residential radon are twice as likely to develop lung cancer as non-smokers.[173] As well, the risk of developing lung cancer from asbestos exposure is twice as likely for smokers than for non-smokers.[174] New research has found that women who smoke are at significantly increased risk of developing an abdominal aortic aneurysm, a condition in which a weak area of the abdominal aorta expands or bulges, and is the most common form of aortic aneurysm.[175] Smoking leads to an increased risk of bone fractures, especially hip fractures.[176] It also leads to slower wound-healing after surgery, and an increased rate of postoperative healing complication.[177] Tobacco smokers are 30-40% more likely to develop type 2 diabetes than non-smokers, and the risk increases with the number of cigarettes smoked. Furthermore, diabetic smokers have worse outcomes than diabetic non-smokers.[178][179] ### Benefits[edit] In addition to the numerous documented negative health effects of smoking, several types of "smoker's paradoxes" (cases where smoking appears to have specific beneficial effects) have been observed.[180] Smoking may prevent Parkinson's disease.[181] ## Mechanism[edit] See also: List of additives in cigarettes ### Chemical carcinogens[edit] See also: List of cigarette smoke carcinogens Benzopyrene diol epoxide, an extremely carcinogenic (cancer-causing) metabolite of benzopyrene, a polycyclic aromatic hydrocarbon produced by burning tobacco Benzopyrene, a major mutagen in tobacco smoke, in an adduct to DNA[182] Smoke, or any partially burnt organic matter, contains carcinogens (cancer-causing agents). The potential effects of smoking, such as lung cancer, can take up to 20 years to manifest themselves. Historically, women began smoking en masse later than men, so an increased death rate caused by smoking amongst women did not appear until later. The male lung cancer death rate decreased in 1975 — roughly 20 years after the initial decline in cigarette consumption in men. A fall in consumption in women also began in 1975[183] but by 1991 had not manifested in a decrease in lung cancer-related mortalities amongst women.[184] Smoke contains several carcinogenic pyrolytic products that bind to DNA and cause genetic mutations. Particularly potent carcinogens are polycyclic aromatic hydrocarbons (PAH), which are toxicated to mutagenic epoxides. The first PAH to be identified as a carcinogen in tobacco smoke was benzopyrene, which has been shown to toxicate into an epoxide that irreversibly attaches to a cell's nuclear DNA, which may either kill the cell or cause a genetic mutation. If the mutation inhibits programmed cell death, the cell can survive to become a cancer cell. Similarly, acrolein, which is abundant in tobacco smoke, also irreversibly binds to DNA, causes mutations and thus also cancer. However, it needs no activation to become carcinogenic.[185] There are over 19 known carcinogens in cigarette smoke.[186] The following are some of the most potent carcinogens: * Polycyclic aromatic hydrocarbons are tar components produced by pyrolysis in smoldering organic matter and emitted into smoke. Several of these PAH's are already toxic in their normal form, however, many of then can become more toxic to the liver. Due to the hydrophobic nature of PAH's they do not dissolve in water and are hard to expel from the body. In order to make the PAH more soluble in water, the liver creates an enzyme called Cytochrome P450 which adds an additional oxygen to the PAH, turning it into a mutagenic epoxides, which is more soluble, but also more reactive.[187] The first PAH to be identified as a carcinogen in tobacco smoke was benzopyrene, which been shown to toxicate into a diol epoxide and then permanently attach to nuclear DNA, which may either kill the cell or cause a genetic mutation. The DNA contains the information on how the cell function; in practice, it contains the recipes for protein synthesis. If the mutation inhibits programmed cell death, the cell can survive to become a cancer, a cell that does not function like a normal cell. The carcinogenicity is radiomimetic, i.e. similar to that produced by ionizing nuclear radiation. Tobacco manufacturers have experimented with combustion less vaporizer technology to allow cigarettes to be consumed without the formation of carcinogenic benzopyrenes.[188] Although such products have become increasingly popular, they still represent a very small fraction of the market, and no conclusive evidence has shown to prove or disprove the positive health claims.[citation needed] * Acrolein is a pyrolysis product that is abundant in cigarette smoke. It gives smoke an acrid smell and an irritating, tear causing effect and is a major contributor to its carcinogenicity. Like PAH metabolites, acrolein is also an electrophilic alkylating agent and permanently binds to the DNA base guanine, by a conjugate addition followed by cyclization into a hemiaminal. The acrolein-guanine adduct induces mutations during DNA copying and thus causes cancers in a manner similar to PAHs. However, acrolein is 1000 times more abundant than PAHs in cigarette smoke and is able to react as is, without metabolic activation. Acrolein has been shown to be a mutagen and carcinogen in human cells. The carcinogenicity of acrolein has been difficult to study by animal experimentation, because it has such a toxicity that it tends to kill the animals before they develop cancer.[185] Generally, compounds able to react by conjugate addition as electrophiles (so-called Michael acceptors after Michael reaction) are toxic and carcinogenic, because they can permanently alkylate DNA, similarly to mustard gas or aflatoxin. Acrolein is only one of them present in cigarette smoke; for example, crotonaldehyde has been found in cigarette smoke.[189] Michael acceptors also contribute to the chronic inflammation present in tobacco disease.[79] * Nitrosamines are a group of carcinogenic compounds found in cigarette smoke but not in uncured tobacco leaves. Nitrosamines form on flue-cured tobacco leaves during the curing process through a chemical reaction between nicotine and other compounds contained in the uncured leaf and various oxides of nitrogen found in all combustion gasses. Switching to Indirect fire curing has been shown to reduce nitrosamine levels to less than 0.1 parts per million.[190][191] Sidestream tobacco smoke, or exhaled mainstream smoke, is particularly harmful. Because exhaled smoke exists at lower temperatures than inhaled smoke, chemical compounds undergo changes which can cause them to become more dangerous. As well, smoke undergoes changes as it ages, which causes the transformation of the compound NO into the more toxic NO2. Further, volatilization causes smoke particles to become smaller, and thus more easily embedded deep into the lung of anyone who later breathes the air.[192] ### Radioactive carcinogens[edit] In addition to chemical, nonradioactive carcinogens, tobacco and tobacco smoke contain small amounts of lead-210 (210Pb) and polonium-210 (210Po), both of which are radioactive carcinogens. The presence of polonium-210 in mainstream cigarette smoke has been experimentally measured at levels of 0.0263–0.036 pCi (0.97–1.33 mBq),[193][194] which is equivalent to about 0.1 pCi per milligram of smoke (4 mBq/mg); or about 0.81 pCi of lead-210 per gram of dry condensed smoke (30 Bq/kg). Research by NCAR radiochemist Ed Martell suggested that radioactive compounds in cigarette smoke are deposited in "hot spots" where bronchial tubes branch, that tar from cigarette smoke is resistant to dissolving in lung fluid and that radioactive compounds have a great deal of time to undergo radioactive decay before being cleared by natural processes. Indoors, these radioactive compounds can linger in secondhand smoke, and greater exposure would occur when these radioactive compounds are inhaled during normal breathing, which is deeper and longer than when inhaling cigarettes. Damage to the protective epithelial tissue from smoking only increases the prolonged retention of insoluble polonium-210 compounds produced from burning tobacco. Martell estimated that a carcinogenic radiation dose of 80–100 rads is delivered to the lung tissue of most smokers who die of lung cancer.[195][196][197] Smoking an average of 1.5 packs per day gives a radiation dose of 60-160 mSv/year,[198][199] compared with living near a nuclear power station (0.0001 mSv/year)[200][201] or the 3.0 mSv/year average dose for Americans.[201][202] Some of the mineral apatite in Florida used to produce phosphate for U.S. tobacco crops contains uranium, radium, lead-210 and polonium-210 and radon.[203][204] The radioactive smoke from tobacco fertilized this way is deposited in lungs and releases radiation even if a smoker quits the habit. The combination of carcinogenic tar and radiation in a sensitive organ such as lungs increases the risk of cancer.[citation needed] In contrast, a 1999 review of tobacco smoke carcinogens published in the Journal of the National Cancer Institute states that "levels of polonium-210 in tobacco smoke are not believed to be great enough to significantly impact lung cancer in smokers."[205] In 2011 Hecht has also stated that the "levels of 210Po in cigarette smoke are probably too low to be involved in lung cancer induction".[206] ### Oxidation and inflammation[edit] Free radicals and pro-oxidants in cigarettes damage blood vessels and oxidize LDL cholesterol.[207] Only oxidized LDL cholesterol is taken-up by macrophages, which become foam cells, leading to atherosclerotic plaques.[207] Cigarette smoke increases proinflammatory cytokines in the bloodstream, causing atherosclerosis.[207] The pro-oxidative state also leads to endothelial dysfunction,[207] which is another important cause of atherosclerosis.[208] ### Nicotine[edit] Main article: Nicotine Nicotine molecule Nicotine, which is contained in cigarettes and other smoked tobacco products, is a stimulant and is one of the main factors leading to continued tobacco smoking. Nicotine is a highly addictive psychoactive chemical. When tobacco is smoked, most of the nicotine is pyrolyzed; a dose sufficient to cause mild somatic dependency and mild to strong psychological dependency remains. The amount of nicotine absorbed by the body from smoking depends on many factors, including the type of tobacco, whether the smoke is inhaled, and whether a filter is used. There is also a formation of harmane (a MAO inhibitor) from the acetaldehyde in cigarette smoke, which seems to play an important role in nicotine addiction[209] probably by facilitating dopamine release in the nucleus accumbens in response to nicotine stimuli. According to studies by Henningfield and Benowitz, nicotine is more addictive than cannabis, caffeine, ethanol, cocaine, and heroin when considering both somatic and psychological dependence. However, due to the stronger withdrawal effects of ethanol, cocaine and heroin, nicotine may have a lower potential for somatic dependence than these substances.[210][211] About half of Canadians who currently smoke have tried to quit.[212] McGill University health professor Jennifer O'Loughlin stated that nicotine addiction can occur as soon as five months after the start of smoking.[213] Ingesting a compound by smoking is one of the most rapid and efficient methods of introducing it into the bloodstream, second only to injection, which allows for the rapid feedback which supports the smokers' ability to titrate their dosage. On average it takes about ten seconds for the substance to reach the brain. As a result of the efficiency of this delivery system, many smokers feel as though they are unable to cease. Of those who attempt cessation and last three months without succumbing to nicotine, most are able to remain smoke-free for the rest of their lives.[214][failed verification] There exists a possibility of depression in some who attempt cessation, as with other psychoactive substances. Depression is also common in teenage smokers; teens who smoke are four times as likely to develop depressive symptoms as their nonsmoking peers.[215] Although nicotine does play a role in acute episodes of some diseases (including stroke, impotence, and heart disease) by its stimulation of adrenaline release, which raises blood pressure,[91] heart and respiration rate, and free fatty acids, the most serious longer term effects are more the result of the products of the smouldering combustion process. This has led to the development of various nicotine delivery systems, such as the nicotine patch or nicotine gum, that can satisfy the addictive craving by delivering nicotine without the harmful combustion by-products. This can help the heavily dependent smoker to quit gradually, while discontinuing further damage to health.[citation needed] Recent evidence has shown that smoking tobacco increases the release of dopamine in the brain, specifically in the mesolimbic pathway, the same neuro-reward circuit activated by drugs of abuse such as heroin and cocaine. This suggests nicotine use has a pleasurable effect that triggers positive reinforcement.[216] One study found that smokers exhibit better reaction-time and memory performance compared to non-smokers, which is consistent with increased activation of dopamine receptors.[217] Neurologically, rodent studies have found that nicotine self-administration causes lowering of reward thresholds—a finding opposite that of most other drugs of abuse (e.g. cocaine and heroin). The carcinogenity of tobacco smoke is not explained by nicotine per se, which is not carcinogenic or mutagenic, although it is a metabolic precursor for several compounds which are.[citation needed] In addition, it inhibits apoptosis, therefore accelerating existing cancers.[218] Also, NNK, a nicotine derivative converted from nicotine, can be carcinogenic. It is worth noting that nicotine, although frequently implicated in producing tobacco addiction, is not significantly addictive when administered alone.[219][non-primary source needed] The addictive potential manifests itself after co-administration of an MAOI, which specifically causes sensitization of the locomotor response in rats, a measure of addictive potential.[220] ## Forms of exposure[edit] ### Second-hand smoke[edit] Main article: Passive smoking Posted sign to avoid passive smoking in York University, Toronto, Ontario, Canada Second-hand smoke is a mixture of smoke from the burning end of a cigarette, pipe or cigar, and the smoke exhaled from the lungs of smokers. It is involuntarily inhaled, lingers in the air hours after cigarettes have been extinguished, and may cause a wide range of adverse health effects, including cancer, respiratory infections and asthma.[221] Non-smokers who are exposed to second-hand smoke at home or work are thought, due to a wide variety of statistical studies, to increase their heart disease risk by 25–30% and their lung cancer risk by 20–30%. Second-hand smoke has been estimated to cause 38,000 deaths per year, of which 3,400 are deaths from lung cancer in non-smokers.[222] The current US Surgeon General's Report concludes that there is no established risk-free level of exposure to second-hand smoke. Short exposures to second-hand smoke are believed to cause blood platelets to become stickier, damage the lining of blood vessels, decrease coronary flow velocity reserves, and reduce heart rate variability, potentially increasing the risk of heart attack.[citation needed] New research indicates that private research conducted by cigarette company Philip Morris in the 1980s showed that second-hand smoke was toxic, yet the company suppressed the finding during the next two decades.[221] ### Chewing tobacco[edit] Chewing tobacco has been known to cause cancer, particularly of the mouth and throat.[223] According to the International Agency for Research on Cancer, "Some health scientists have suggested that smokeless tobacco should be used in smoking cessation programmes and have made implicit or explicit claims that its use would partly reduce the exposure of smokers to carcinogens and the risk for cancer. These claims, however, are not supported by the available evidence."[223] Oral and spit tobacco increase the risk for leukoplakia, a precursor to oral cancer.[224] ### Cigars[edit] Like other forms of smoking, cigar smoking poses a significant health risk depending on dosage: risks are greater for those who inhale more when they smoke, smoke more cigars, or smoke them longer.[89] The risk of dying from any cause is significantly greater for cigar smokers, with the risk particularly higher for smokers less than 65 years old, and with risk for moderate and deep inhalers reaching levels similar to cigarette smokers.[225] The increased risk for those smoking 1–2 cigars per day is too small to be statistically significant,[226] and the health risks of the 3/4 of cigar smokers who smoke less than daily are not known[227] and are hard to measure. Although it has been claimed that people who smoke few cigars have no increased risk, a more accurate statement is that their risks are proportionate to their exposure.[88] Health risks are similar to cigarette smoking in nicotine addiction, periodontal health, tooth loss, and many types of cancer, including cancers of the mouth, throat, and esophagus. Cigar smoking also can cause cancers of the lung and larynx, where the increased risk is less than that of cigarettes. Many of these cancers have extremely low cure rates. Cigar smoking also increases the risk of lung and heart diseases such as chronic obstructive pulmonary disease.[89] ### Hookahs[edit] A common belief among users is that the smoke of a hookah (waterpipe, narghile) is significantly less dangerous than that from cigarettes.[228] The water moisture induced by the hookah makes the smoke less irritating and may give a false sense of security and reduce concerns about true health effects.[229] Doctors at institutions including the Mayo Clinic have stated that use of hookah can be as detrimental to a person's health as smoking cigarettes,[230][231] and a study by the World Health Organization also confirmed these findings.[232] Each hookah session typically lasts more than 40 minutes, and consists of 50 to 200 inhalations that each range from 0.15 to 0.50 liters of smoke.[233][234] In an hour-long smoking session of hookah, users consume about 100 to 200 times the smoke of a single cigarette;[233][235] A study in the Journal of Periodontology found that water pipe smokers were marginally more likely than regular smokers to show signs of gum disease, showing rates 5-fold higher than non-smokers rather than the 3.8-fold risk that regular smokers show.[236] According to USA Today, people who smoked water pipes had five times the risk of lung cancer of non-smokers.[237] A study on hookah smoking and cancer in Pakistan was published in 2008. Its objective was "to find serum CEA levels in ever/exclusive hookah smokers, i.e. those who smoked only hookah (no cigarettes, bidis, etc.), prepared between 1 and 4 times a day with a quantity of up to 120 g of a tobacco-molasses mixture each (i.e. the tobacco weight equivalent of up to 60 cigarettes of 1 g each) and consumed in 1 to 8 sessions". Carcinoembryonic antigen (CEA) is a marker found in several forms of cancer. Levels in exclusive hookah smokers were lower compared to cigarette smokers although the difference was not as statistically significant as that between a hookah smoker and a non-smoker. Also, the study concluded that heavy hookah smoking (2–4 daily preparations; 3–8 sessions a day; >2 hrs to ≤ 6 hours) substantially raises CEA levels.[238] Hookah smokers were nearly 6 times more likely to develop lung cancer as compared to healthy non-smokers in Kashmir (India).[239] ### Dipping tobacco[edit] Dipping tobacco, commonly referred to as snuff, is also put in the mouth, but it is a flavored powder. it is placed between the cheek and gum. Dipping tobacco does not need to be chewed for the nicotine to be absorbed. First-time users of these products often become nauseated and dizzy. Long-term effects include bad breath, yellowed teeth, and an increased risk of oral cancer.[citation needed] Users of dipping tobacco are believed to face less risk of some cancers than are smokers, but are still at greater risk than people who do not use any tobacco products.[240] They also have an equal risk of other health problems directly linked to nicotine, such as increased rate of atherosclerosis.[citation needed] ## Prevention[edit] Education and counselling by physicians of children and adolescents have been found to be effective in decreasing tobacco use.[241] * Average price of a pack of 20 cigarettes, measured in international dollars in 2014.[242] * Taxes as a share of cigarette price, 2014[243] * Types of bans on tobacco advertising, 2014[244] * Support to help quit tobacco use, 2014[245] ## Usage[edit] Percentage of females smoking any tobacco product Percentage of males smoking any tobacco product. Note that there is a difference between the scales used for females and for males.[5] Though tobacco may be consumed by either smoking or other smokeless methods such as chewing, the World Health Organization (WHO) only collects data on smoked tobacco.[1] Smoking has therefore been studied more extensively than any other form of tobacco consumption.[2] In 2000, smoking was practiced by 1.22 billion people, predicted to rise to 1.45 billion people in 2010 and 1.5 to 1.9 billion by 2025. If prevalence had decreased by 2% a year since 2000 this figure would have been 1.3 billion in 2010 and 2025.[246] Despite dropping by 0.4 percent from 2009 to 2010, the United States still reports an average of 17.9 percent usage.[52] As of 2002, about twenty percent of young teens (13–15) smoked worldwide, with 80,000 to 100,000 children taking up the addiction every day, roughly half of whom live in Asia. Half of those who begin smoking in adolescent years are projected to go on to smoke for 15 to 20 years.[247] Teens are more likely to use e-cigarettes than cigarettes. About 31% of teenagers who use e-cigs started smoking within six months, compared to 8% of non-smokers. Manufacturers do not have to report what is in e-cigs, and most teens either say e-cigs contain only flavoring, or that they do not know what they contain.[248][249] The WHO states that "Much of the disease burden and premature mortality attributable to tobacco use disproportionately affect the poor". Of the 1.22 billion smokers, 1 billion live in developing or transitional nations. Rates of smoking have leveled off or declined in the developed world.[250] In the developing world, however, tobacco consumption was rising by 3.4% per year as of 2002.[247] The WHO in 2004 projected 58.8 million deaths to occur globally,[251]:8 from which 5.4 million are tobacco-attributed,[251]:23 and 4.9 million as of 2007.[252] As of 2002, 70% of the deaths are in developing countries.[252] The shift in prevalence of tobacco smoking to a younger demographic, mainly in the developing world, can be attributed to several factors. The tobacco industry spends up to $12.5 billion annually on advertising, which is increasingly geared towards adolescents in the developing world because they are a vulnerable audience for the marketing campaigns. Adolescents have more difficulty understanding the long-term health risks that are associated with smoking and are also more easily influenced by "images of romance, success, sophistication, popularity, and adventure which advertising suggests they could achieve through the consumption of cigarettes". This shift in marketing towards adolescents and even children in the tobacco industry is debilitating to organizations' and countries' efforts to improve child health and mortality in the developing world. It reverses or halts the effects of the work that has been done to improve health care in these countries, and although smoking is deemed as a "voluntary" health risk, the marketing of tobacco towards very impressionable adolescents in the developing world makes it less of a voluntary action and more of an inevitable shift.[4] Many government regulations have been passed to protect citizens from harm caused by public environmental tobacco smoke. The "Pro-Children Act of 2001" prohibits smoking within any facility that provides health care, day care, library services, or elementary and secondary education to children in the US.[253] On May 23, 2011, New York City enforced a smoking ban for all parks, beaches, and pedestrian malls in an attempt to eliminate threats posed to civilians by environmental tobacco smoke.[254] ## See also[edit] * E. Cuyler Hammond * List of cigarette smoke carcinogens * Safety of electronic cigarettes * Adverse effects of electronic cigarettes ## References[edit] 1. ^ a b "Prevalence of current tobacco use among adults aged=15 years (percentage)". World Health Organization. Archived from the original on 2008-12-11. Retrieved 2009-01-02. 2. ^ a b "Mayo report on addressing the worldwide tobacco epidemic through effective, evidence-based treatment". World Health Organization. p. 2. Retrieved 2009-01-02. 3. ^ a b c d e f "Tobacco Fact sheet N°339". May 2014. Retrieved 13 May 2015. 4. ^ a b Nichter M, Cartwright E (1991). "Saving the Children for the Tobacco Industry". Medical Anthropology Quarterly. 5 (3): 236–56. doi:10.1525/maq.1991.5.3.02a00040. JSTOR 648675. 5. ^ a b World Health Organization (2008). WHO Report on the Global Tobacco Epidemic 2008: The MPOWER Package (PDF). Geneva: World Health Organization. p. 8. ISBN 978-92-4-159628-2. 6. ^ "The top 10 causes of death". Retrieved 13 May 2015. 7. ^ "Nicotine: A Powerful Addiction Archived 2009-05-01 at the Wayback Machine." Centers for Disease Control and Prevention. 8. ^ "These Two Industries Kill More People Than They Employ". IFLScience. Retrieved 2019-03-09. 9. ^ Jha P, Peto R (January 2014). "Global effects of smoking, of quitting, and of taxing tobacco". The New England Journal of Medicine. 370 (1): 60–8. doi:10.1056/nejmra1308383. PMID 24382066. S2CID 4299113. 10. ^ Vainio H (June 1987). "Is passive smoking increasing cancer risk?". Scandinavian Journal of Work, Environment & Health. 13 (3): 193–6. doi:10.5271/sjweh.2066. PMID 3303311. 11. ^ "The health consequences of involuntary exposure to tobacco smoke: a report of the Surgeon General" (PDF). Atlanta, U.S., page 93: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2006. Retrieved 2009-02-15.CS1 maint: location (link) 12. ^ a b Peate I (2005). "The effects of smoking on the reproductive health of men". British Journal of Nursing. 14 (7): 362–6. doi:10.12968/bjon.2005.14.7.17939. PMID 15924009. 13. ^ Korenman SG (2004). "Epidemiology of erectile dysfunction". Endocrine. 23 (2–3): 87–91. doi:10.1385/ENDO:23:2-3:087. PMID 15146084. S2CID 29133230. 14. ^ a b c d e f g h i j k l m Doll R (June 1998). "Uncovering the effects of smoking: historical perspective" (PDF). Statistical Methods in Medical Research. 7 (2): 87–117. doi:10.1177/096228029800700202. PMID 9654637. S2CID 154707. Archived from the original (PDF) on 2018-10-01. Retrieved 2018-09-30. 15. ^ a b Alston LJ, Dupré R, Nonnenmacher T (2002). "Social reformers and regulation: the prohibition of cigarettes in the United States and Canada". Explorations in Economic History. 39 (4): 425–445. doi:10.1016/S0014-4983(02)00005-0. 16. ^ James R (2009-06-15). "A Brief History Of Cigarette Advertising". TIME. Retrieved 2012-03-25. 17. ^ a b c d Haustein K (2004). "Fritz Lickint (1898–1960) – Ein Leben als Aufklärer über die Gefahren des Tabaks". Suchtmed (in German). 6 (3): 249–255. Archived from the original on November 5, 2014. 18. ^ a b c d Proctor RN (February 2001). "Commentary: Schairer and Schöniger's forgotten tobacco epidemiology and the Nazi quest for racial purity". International Journal of Epidemiology. 30 (1): 31–4. doi:10.1093/ije/30.1.31. PMID 11171846. 19. ^ Djian, Jean-Michel (24 May 2007). Timbuktu manuscripts: Africa’s written history unveiled Archived 11 November 2009 at the Wayback Machine. Unesco, ID 37896. 20. ^ Lincecum, Gideon. "Nicotiana tabacum". Giden Lincecum Herbarium. University of Texas. Retrieved 9 December 2012. 21. ^ Adler IA (1980). "Classics in oncology. Primary malignant growths of the lung. Isaac A. Adler, A.M., M.D". Ca. 30 (5): 295–301. doi:10.3322/canjclin.30.5.295. PMID 6773624. S2CID 6967224. 22. ^ Irving Fisher (1924). "Does tobacco injure the human body?". Readers Digest. Archived from the original on 2014-04-18. 23. ^ Witschi H (November 2001). "A short history of lung cancer". Toxicological Sciences. 64 (1): 4–6. doi:10.1093/toxsci/64.1.4. PMID 11606795. 24. ^ Adler I (1912). Primary malignant growths of the lungs and bronchi: a pathological and clinical study. New York: Longmans, Green. OCLC 14783544.[page needed], cited in Spiro SG, Silvestri GA (September 2005). "One hundred years of lung cancer". American Journal of Respiratory and Critical Care Medicine. 172 (5): 523–9. doi:10.1164/rccm.200504-531OE. PMID 15961694. S2CID 21653414. 25. ^ National Cancer Institute. "20 Year Lag Time Between Smoking and Lung Cancer". Archived from the original on 17 February 2003. 26. ^ a b c Oreskes N Conway EM (2010). Merchants of Doubt: How a Handful of Scientists Obscured the Truth on Issues from Tobacco Smoke to Global Warming. San Francisco, CA: Bloomsbury Press. p. 15. ISBN 978-1-59691-610-4. 27. ^ a b c Michaels, David (2008). Doubt is their product: how industry's assault on science threatens your health. Oxford [Oxfordshire]: Oxford University Press. pp. 4–5. ISBN 978-0-19-530067-3. 28. ^ a b Doll R, Hill AB (September 1950). "Smoking and carcinoma of the lung; preliminary report". British Medical Journal. 2 (4682): 739–48. doi:10.1136/bmj.2.4682.739. PMC 2038856. PMID 14772469. 29. ^ a b c d e f Doll R, Peto R, Boreham J, Sutherland I (June 2004). "Mortality in relation to smoking: 50 years' observations on male British doctors". BMJ. 328 (7455): 1519. doi:10.1136/bmj.38142.554479.AE. PMC 437139. PMID 15213107. 30. ^ Doll R, Hill AB (June 2004). "The mortality of doctors in relation to their smoking habits: a preliminary report. 1954". BMJ. 328 (7455): 1529–33, discussion 1533. doi:10.1136/bmj.328.7455.1529. PMC 437141. PMID 15217868. 31. ^ a b Brandt AM (2007). The cigarette century: the rise, fall and deadly persistence of the product that defined America. New York: Basic Books, a member of the Perseus Books Group. ISBN 978-0-465-07047-3. 32. ^ Pell JP, Haw S, Cobbe S, Newby DE, Pell AC, Fischbacher C, McConnachie A, Pringle S, Murdoch D, Dunn F, Oldroyd K, Macintyre P, O'Rourke B, Borland W (July 2008). "Smoke-free legislation and hospitalizations for acute coronary syndrome" (PDF). The New England Journal of Medicine. 359 (5): 482–91. doi:10.1056/NEJMsa0706740. hdl:1893/16659. PMID 18669427. 33. ^ Nutt D, King LA, Saulsbury W, Blakemore C (March 2007). "Development of a rational scale to assess the harm of drugs of potential misuse". Lancet. 369 (9566): 1047–53. doi:10.1016/s0140-6736(07)60464-4. PMID 17382831. S2CID 5903121. 34. ^ ASPA. "Health Effects of Tobacco". Archived from the original on 2014-09-20. Retrieved 8 September 2014. 35. ^ "Life Expectancy at Age 30: Nonsmoking Versus Smoking Men". Tobacco Documents Online. Archived from the original on 2012-04-19. Retrieved 2012-05-06. 36. ^ Ferrucci L, Izmirlian G, Leveille S, Phillips CL, Corti MC, Brock DB, Guralnik JM (April 1999). "Smoking, physical activity, and active life expectancy". American Journal of Epidemiology. 149 (7): 645–53. doi:10.1093/oxfordjournals.aje.a009865. PMID 10192312. 37. ^ Doll R, Peto R, Wheatley K, Gray R, Sutherland I (October 1994). "Mortality in relation to smoking: 40 years' observations on male British doctors". BMJ. 309 (6959): 901–11. doi:10.1136/bmj.309.6959.901. PMC 2541142. PMID 7755693. 38. ^ Villeneuve PJ, Mao Y (1994). "Lifetime probability of developing lung cancer, by smoking status, Canada". Canadian Journal of Public Health. 85 (6): 385–8. PMID 7895211. 39. ^ Kenneth Johnson (Jan 24, 2018). "Just one cigarette a day seriously elevates cardiovascular risk". British Medical Journal. 360: k167. doi:10.1136/bmj.k167. PMID 29367307. S2CID 46825572. 40. ^ "Just one cigarette a day can cause serious heart problems". New Scientist. Feb 3, 2020. 41. ^ "Benefits of Quitting – American Lung Association". Stop Smoking. American Lung Association. Retrieved 2012-05-06. 42. ^ "Light Cigarettes and Cancer Risk". National Cancer Institute. 2005-08-18. Retrieved 8 September 2014. 43. ^ Rizzuto D, Fratiglioni L (2014). "Lifestyle factors related to mortality and survival: a mini-review". Gerontology. 60 (4): 327–35. doi:10.1159/000356771. PMID 24557026. 44. ^ Samet JM (May 2013). "Tobacco smoking: the leading cause of preventable disease worldwide". Thoracic Surgery Clinics. 23 (2): 103–12. doi:10.1016/j.thorsurg.2013.01.009. PMID 23566962. 45. ^ Centers for Disease Control and Prevention (CDC) (April 2002). "Annual smoking-attributable mortality, years of potential life lost, and economic costs—United States, 1995–1999". MMWR. Morbidity and Mortality Weekly Report. 51 (14): 300–3. PMID 12002168. 46. ^ Streppel MT, Boshuizen HC, Ocké MC, Kok FJ, Kromhout D (April 2007). "Mortality and life expectancy in relation to long-term cigarette, cigar and pipe smoking: the Zutphen Study". Tobacco Control. 16 (2): 107–13. doi:10.1136/tc.2006.017715. PMC 2598467. PMID 17400948. 47. ^ "Archived copy" (PDF). Archived from the original (PDF) on 2009-12-29. Retrieved 2009-11-13.CS1 maint: archived copy as title (link) 48. ^ "HEALTH \| Cigarettes 'cut life by 11 minutes'". BBC News. 1999-12-31. Retrieved 2012-03-25. 49. ^ Shaw, M. (2000). "Time for a smoke? One cigarette reduces your life by 11 minutes". BMJ. 320 (7226): 53. doi:10.1136/bmj.320.7226.53. PMC 1117323. PMID 10617536. 50. ^ Mamun AA, Peeters A, Barendregt J, Willekens F, Nusselder W, Bonneux L (March 2004). "Smoking decreases the duration of life lived with and without cardiovascular disease: a life course analysis of the Framingham Heart Study". European Heart Journal. 25 (5): 409–15. doi:10.1016/j.ehj.2003.12.015. PMID 15033253. 51. ^ Thun MJ, Day-Lally CA, Calle EE, Flanders WD, Heath CW (September 1995). "Excess mortality among cigarette smokers: changes in a 20-year interval". American Journal of Public Health. 85 (9): 1223–30. doi:10.2105/AJPH.85.9.1223. PMC 1615570. PMID 7661229. 52. ^ a b "America's Health Rankings – 2011" (PDF). United Health Foundation. December 2011. p. 12. 53. ^ Centers for Disease Control and Prevention (CDC) (November 2008). "Smoking-attributable mortality, years of potential life lost, and productivity losses—United States, 2000–2004". MMWR. Morbidity and Mortality Weekly Report. 57 (45): 1226–8. PMID 19008791. 54. ^ Never Say Die, an ABC News special by Peter Jennings 6/27/1996 55. ^ "21st Century Could See a Billion Tobacco Victims" (PDF). Tobacco News Flash. 3 (12): 1. 2007. Archived from the original (PDF) on 2012-04-26. Retrieved 2012-05-06. 56. ^ Carter BD, Abnet CC, Feskanich D, Freedman ND, Hartge P, Lewis CE, Ockene JK, Prentice RL, Speizer FE, Thun MJ, Jacobs EJ (February 2015). "Smoking and mortality—beyond established causes". The New England Journal of Medicine. 372 (7): 631–40. doi:10.1056/NEJMsa1407211. PMID 25671255. S2CID 34821377. 57. ^ a b Proctor, Robert N (2012-02-16). "The history of the discovery of the cigarette–lung cancer link: evidentiary traditions, corporate denial, global toll: Table 1". Tobacco Control. 21 (2): 87–91. doi:10.1136/tobaccocontrol-2011-050338. ISSN 0964-4563. PMID 22345227. 58. ^ Cohen, Bernard L. (September 1991). "Catalog of Risks Extended and Updated". Health Physics. 61 (3): 317–335. doi:10.1097/00004032-199109000-00002. ISSN 0017-9078. PMID 1880022. 59. ^ "Share of deaths from smoking". Our World in Data. Retrieved 5 March 2020. 60. ^ "Death rate from smoking". Our World in Data. Retrieved 5 March 2020. 61. ^ "Share of cancer deaths attributed to tobacco". Our World in Data. Retrieved 5 March 2020. 62. ^ "Lung Cancer and Smoking" (PDF). Fact Sheet. www.LegacyForHealth.org. 2010-11-23. Archived from the original (PDF) on 2013-03-15. Retrieved 2012-05-06. 63. ^ Lipworth L, Tarone RE, McLaughlin JK (December 2006). "The epidemiology of renal cell carcinoma". The Journal of Urology. 176 (6 Pt 1): 2353–8. doi:10.1016/j.juro.2006.07.130. PMID 17085101. 64. ^ "Risks and causes of laryngeal cancer". Cancer Research UK. Retrieved 21 June 2015. 65. ^ "Head and Neck Cancer: Risk Factors and Prevention". ASCO. 2012-06-26. Retrieved 21 June 2015. 66. ^ Boffetta P (September 2008). "Tobacco smoking and risk of bladder cancer". Scandinavian Journal of Urology and Nephrology. Supplementum. 42 (218): 45–54. doi:10.1080/03008880802283664. PMID 18815916. S2CID 39577281. 67. ^ "Esophagus Cancer". American Cancer Society. 2011-08-11. Retrieved 2012-05-06. 68. ^ Iodice S, Gandini S, Maisonneuve P, Lowenfels AB (July 2008). "Tobacco and the risk of pancreatic cancer: a review and meta-analysis". Langenbeck's Archives of Surgery. 393 (4): 535–45. doi:10.1007/s00423-007-0266-2. PMID 18193270. S2CID 23516238. 69. ^ a b Kuper H, Boffetta P, Adami HO (September 2002). "Tobacco use and cancer causation: association by tumour type". Journal of Internal Medicine. 252 (3): 206–24. doi:10.1046/j.1365-2796.2002.01022.x. PMID 12270001. S2CID 6132726. 70. ^ Vineis P, Alavanja M, Buffler P, Fontham E, Franceschi S, Gao YT, Gupta PC, Hackshaw A, Matos E, Samet J, Sitas F, Smith J, Stayner L, Straif K, Thun MJ, Wichmann HE, Wu AH, Zaridze D, Peto R, Doll R (January 2004). "Tobacco and cancer: recent epidemiological evidence". Journal of the National Cancer Institute. 96 (2): 99–106. doi:10.1093/jnci/djh014. PMID 14734699. 71. ^ Sasco AJ, Secretan MB, Straif K (August 2004). "Tobacco smoking and cancer: a brief review of recent epidemiological evidence". Lung Cancer. 45 Suppl 2: S3–9. doi:10.1016/j.lungcan.2004.07.998. PMID 15552776. 72. ^ "What are the risk factors for breast cancer?". American Cancer Society. Retrieved 31 May 2015. 73. ^ Pesch, B., Kendzia, B., Gustavsson, P., Jöckel, K.-H., Johnen, G., Pohlabeln, H., … Brüning, T. (2012). Cigarette smoking and lung cancer – relative risk estimates for the major histological types from a pooled analysis of case-control studies. International Journal of Cancer. Journal International Du Cancer, 131(5), 1210–1219. 74. ^ United States Department of Health & Human Services. Reducing the Health Consequences of Smoking: 25 Years of Progress. A Report of the Surgeon General. From http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/NNBBXS Accessed: Nov 2012 75. ^ Kalemkerian, G. P., Akerley, W., Bogner, P., Borghaei, H., Chow, L. Q., Downey, R. J., … Hughes, M. (2013). Small Cell Lung Cancer: Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN, 11(1), 78–98. 76. ^ Champaneria MC, Modlin IM, Kidd M, Eick GN (2006). "Friedrich Feyrter: a precise intellect in a diffuse system". Neuroendocrinology. 83 (5–6): 394–404. doi:10.1159/000096050. PMID 17028417. S2CID 25627846. 77. ^ Thun MJ, Hannan LM, Adams-Campbell LL, Boffetta P, Buring JE, Feskanich D, Flanders WD, Jee SH, Katanoda K, Kolonel LN, Lee IM, Marugame T, Palmer JR, Riboli E, Sobue T, Avila-Tang E, Wilkens LR, Samet JM (September 2008). "Lung cancer occurrence in never-smokers: an analysis of 13 cohorts and 22 cancer registry studies". PLOS Medicine. 5 (9): e185. doi:10.1371/journal.pmed.0050185. PMC 2531137. PMID 18788891. 78. ^ Devereux G (May 2006). "ABC of chronic obstructive pulmonary disease. Definition, epidemiology, and risk factors". BMJ. 332 (7550): 1142–4. doi:10.1136/bmj.332.7550.1142. PMC 1459603. PMID 16690673. 79. ^ a b Facchinetti F, Amadei F, Geppetti P, Tarantini F, Di Serio C, Dragotto A, Gigli PM, Catinella S, Civelli M, Patacchini R (November 2007). "Alpha,beta-unsaturated aldehydes in cigarette smoke release inflammatory mediators from human macrophages". American Journal of Respiratory Cell and Molecular Biology. 37 (5): 617–23. doi:10.1165/rcmb.2007-0130OC. PMID 17600310. 80. ^ Glantz SA, Parmley WW (April 1995). "Passive smoking and heart disease. Mechanisms and risk". JAMA. 273 (13): 1047–53. CiteSeerX 10.1.1.598.9772. doi:10.1001/jama.1995.03520370089043. PMID 7897790. 81. ^ Shah RS, Cole JW (July 2010). "Smoking and stroke: the more you smoke the more you stroke". Expert Review of Cardiovascular Therapy. 8 (7): 917–32. doi:10.1586/erc.10.56. PMC 2928253. PMID 20602553. 82. ^ "How Does Smoking Affect the Heart and Blood Vessels?". NHLBI. Retrieved 9 September 2015. 83. ^ "Health : Young smokers' heart attack risk". BBC. 2004-08-24. Retrieved 2005-12-18. 84. ^ Mähönen MS, McElduff P, Dobson AJ, Kuulasmaa KA, Evans AE (2004). "Current smoking and the risk of non-fatal myocardial infarction in the WHO MONICA Project populations". Tobacco Control. 13 (3): 244–250. doi:10.1136/tc.2003.003269. PMC 1747894. PMID 15333879. 85. ^ Saha SP, Bhalla DK, Whayne TF, Gairola C (Autumn 2007). "Cigarette smoke and adverse health effects: An overview of research trends and future needs". The International Journal of Angiology. 16 (3): 77–83. doi:10.1055/s-0031-1278254. PMC 2733016. PMID 22477297. 86. ^ "Cigarette Smoke Changes Heart's Shape". InfoNIAC.com. Retrieved 2009-01-10. 87. ^ Joyce JW (May 1990). "Buerger's disease (thromboangiitis obliterans)". Rheumatic Diseases Clinics of North America. 16 (2): 463–70. PMID 2189162. 88. ^ a b Burns DM (1998). "Cigar smoking: overview and current state of the science" (PDF). In Shopland DR, Burns DM, Hoffmann D, Cummings KM, Amacher RH (eds.). Cigars: Health Effects and Trends. Smoking and Tobacco Control Monograph No. 9. National Cancer Institute. pp. 1–20. 89. ^ a b c Symm B, Morgan MV, Blackshear Y, Tinsley S (July 2005). "Cigar smoking: an ignored public health threat". The Journal of Primary Prevention. 26 (4): 363–75. doi:10.1007/s10935-005-5389-z. PMID 15995804. S2CID 23999589. 90. ^ a b National Institutes of Health (1998-04-10). "Background on Cigar Monograph: Cigars: Health Effects and Trends". Archived from the original on 2008-05-13. Retrieved 2008-01-04. 91. ^ a b Narkiewicz K, Kjeldsen SE, Hedner T (2005). "Is smoking a causative factor of hypertension?". Blood Pressure. 14 (2): 69–71. doi:10.1080/08037050510034202. PMID 16036482. S2CID 40476025. 92. ^ Yacoub R, Habib H, Lahdo A, Al Ali R, Varjabedian L, Atalla G, Kassis Akl N, Aldakheel S, Alahdab S, Albitar S (November 2010). "Association between smoking and chronic kidney disease: a case control study". BMC Public Health. 10: 731. doi:10.1186/1471-2458-10-731. PMC 3004836. PMID 21108832. 93. ^ Sawicki PT, Didjurgeit U, Mühlhauser I, Bender R, Heinemann L, Berger M (February 1994). "Smoking is associated with progression of diabetic nephropathy". Diabetes Care. 17 (2): 126–31. doi:10.2337/diacare.17.2.126. PMID 8137682. S2CID 22581830. 94. ^ a b Kark JD, Lebiush M, Rannon L (October 1982). "Cigarette smoking as a risk factor for epidemic a(h1n1) influenza in young men". The New England Journal of Medicine. 307 (17): 1042–6. doi:10.1056/NEJM198210213071702. PMID 7121513. 95. ^ a b Finklea JF, Sandifer SH, Smith DD (November 1969). "Cigarette smoking and epidemic influenza". American Journal of Epidemiology. 90 (5): 390–9. doi:10.1093/oxfordjournals.aje.a121084. PMID 5356947. 96. ^ Kark JD, Lebiush M (May 1981). "Smoking and epidemic influenza-like illness in female military recruits: a brief survey". American Journal of Public Health. 71 (5): 530–2. doi:10.2105/AJPH.71.5.530. PMC 1619723. PMID 7212144. 97. ^ Nicholson KG, Kent J, Hammersley V (August 1999). "Influenza A among community-dwelling elderly persons in Leicestershire during winter 1993-4; cigarette smoking as a risk factor and the efficacy of influenza vaccination". Epidemiology and Infection. 123 (1): 103–8. doi:10.1017/S095026889900271X. PMC 2810733. PMID 10487646. 98. ^ American Cancer Society (2004). "Questions About Smoking, Tobacco, and Health". JNCI Journal of the National Cancer Institute. 96 (11): 853–861. doi:10.1093/jnci/djh144. PMID 15173269. Retrieved 2008-01-04. 99. ^ Henley SJ, Thun MJ, Chao A, Calle EE (June 2004). "Association between exclusive pipe smoking and mortality from cancer and other diseases". Journal of the National Cancer Institute. 96 (11): 853–61. doi:10.1093/jnci/djh144. PMID 15173269. 100. ^ Commission on Life Sciences. Environmental Tobacco Smoke: Measuring Exposures and Assessing Health Effects (1986). Retrieved 2008-01-04. 101. ^ Johnson GK, Slach NA (April 2001). "Impact of tobacco use on periodontal status". Journal of Dental Education. 65 (4): 313–21. doi:10.1002/j.0022-0337.2001.65.4.tb03401.x. PMID 11336116. 102. ^ Reibel J (2003). "Tobacco and oral diseases. Update on the evidence, with recommendations". Medical Principles and Practice. 12 Suppl 1: 22–32. doi:10.1159/000069845. PMID 12707498. 103. ^ Ness L, Rosekrans D, Welford JF (January 1977). "An epidemiologic study of factors affecting extrinsic staining of teeth in an English population". Community Dentistry and Oral Epidemiology. 5 (1): 55–60. doi:10.1111/j.1600-0528.1977.tb01617.x. PMID 264419. 104. ^ "Helping you to Stop Smoking!". Archived from the original on 2008-08-28. Retrieved 2008-01-04. 105. ^ Züllich G, Damm KH, Braun W, Lisboa BP (May 1975). "Studies on biliary excreted metabolites of [G-3H]digitoxin in rats". Archives Internationales de Pharmacodynamie et de Therapie. 215 (1): 160–7. PMID 1156044. 106. ^ Dietrich T, Maserejian NN, Joshipura KJ, Krall EA, Garcia RI (April 2007). "Tobacco use and incidence of tooth loss among US male health professionals". Journal of Dental Research. 86 (4): 373–7. doi:10.1177/154405910708600414. PMC 2582143. PMID 17384035. 107. ^ Al-Bayaty FH, Wahid NA, Bulgiba AM (February 2008). "Tooth mortality in smokers and nonsmokers in a selected population in Sana'a, Yemen". Journal of Periodontal Research. 43 (1): 9–13. doi:10.1111/j.1600-0765.2007.00988.x. PMID 18230101. 108. ^ "Leukoplakia Causes". Mayo Clinic. Retrieved 31 May 2015. 109. ^ Davies PD, Yew WW, Ganguly D, Davidow AL, Reichman LB, Dheda K, Rook GA (April 2006). "Smoking and tuberculosis: the epidemiological association and immunopathogenesis". Transactions of the Royal Society of Tropical Medicine and Hygiene. 100 (4): 291–8. doi:10.1016/j.trstmh.2005.06.034. PMID 16325875. 110. ^ Jha P, Jacob B, Gajalakshmi V, Gupta PC, Dhingra N, Kumar R, Sinha DN, Dikshit RP, Parida DK, Kamadod R, Boreham J, Peto R (March 2008). "A nationally representative case-control study of smoking and death in India". The New England Journal of Medicine. 358 (11): 1137–47. doi:10.1056/NEJMsa0707719. PMID 18272886. S2CID 92980. 111. ^ Nuorti JP, Butler JC, Farley MM, Harrison LH, McGeer A, Kolczak MS, Breiman RF (March 2000). "Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team". The New England Journal of Medicine. 342 (10): 681–9. doi:10.1056/NEJM200003093421002. PMID 10706897. 112. ^ Arcavi L, Benowitz NL (November 2004). "Cigarette smoking and infection". Archives of Internal Medicine. 164 (20): 2206–16. doi:10.1001/archinte.164.20.2206. PMID 15534156. 113. ^ Goedert JJ, Vitale F, Lauria C, Serraino D, Tamburini M, Montella M, Messina A, Brown EE, Rezza G, Gafà L, Romano N (November 2002). "Risk factors for classical Kaposi's sarcoma". Journal of the National Cancer Institute. 94 (22): 1712–8. doi:10.1093/jnci/94.22.1712. PMID 12441327. 114. ^ "MEDLINEplus: Smoking Cuts Risk of Rare Cancer". Retrieved 8 September 2014. 115. ^ a b "The Tobacco Reference Guide". Archived from the original on 2006-07-15. Retrieved 2006-07-15. 116. ^ Kendirci M, Nowfar S, Hellstrom WJ (January 2005). "The impact of vascular risk factors on erectile function". Drugs of Today. 41 (1): 65–74. doi:10.1358/dot.2005.41.1.875779. PMID 15753970. 117. ^ Dechanet C, Anahory T, Mathieu Daude JC, Quantin X, Reyftmann L, Hamamah S, Hedon B, Dechaud H (2011). "Effects of cigarette smoking on reproduction". Human Reproduction Update. 17 (1): 76–95. doi:10.1093/humupd/dmq033. PMID 20685716. 118. ^ FERTILITY FACT > Female Risks Archived 2007-09-22 at the Wayback Machine By the American Society for Reproductive Medicine (ASRM). Retrieved on Jan 4, 2009 119. ^ "protectyourfertility.com" (PDF). Archived from the original (PDF) on 24 September 2015. Retrieved 8 September 2014. 120. ^ a b fertility services: a commissioning aid – June 2009, from the Department of Health UK 121. ^ Parrott AC (October 1999). "Does cigarette smoking cause stress?". The American Psychologist. 54 (10): 817–20. doi:10.1037/0003-066X.54.10.817. PMID 10540594. 122. ^ Lagrue G, Lebargy F, Cormier A (2001). "Des récepteurs nicotiniques à la dépendance tabagique : perspectives thérapeutiques" [From nicotinic receptors to smoking dependence: Therapeutic prospects]. Alcoologie et Addictologie (in French). 23 (2 Suppl): 39S–42S. 123. ^ a b Parrott AC (January 1998). "Nesbitt's Paradox resolved? Stress and arousal modulation during cigarette smoking". Addiction. 93 (1): 27–39. CiteSeerX 10.1.1.465.2496. doi:10.1046/j.1360-0443.1998.931274.x. PMID 9624709. 124. ^ Hughes JR (October 1992). "Tobacco withdrawal in self-quitters". Journal of Consulting and Clinical Psychology. 60 (5): 689–97. doi:10.1037/0022-006X.60.5.689. PMID 1401384. 125. ^ Cohen S, Lichtenstein E (1990). "Perceived stress, quitting smoking, and smoking relapse". Health Psychology. 9 (4): 466–78. doi:10.1037/0278-6133.9.4.466. PMID 2373070. 126. ^ Hamer M, Stamatakis E, Batty GD (August 2010). "Objectively assessed secondhand smoke exposure and mental health in adults: cross-sectional and prospective evidence from the Scottish Health Survey". Archives of General Psychiatry. 67 (8): 850–5. doi:10.1001/archgenpsychiatry.2010.76. PMID 20529994. 127. ^ Bachman JG, Wadsworth KN, O'Malley PM, Johnston LD, Schulenberg JE (1997). Smoking, drinking, and drug use in young adulthood: the impacts of new freedoms and new responsibilities. Hillsdale, N.J: L. Erlbaum Associates. p. 70. ISBN 978-0-8058-2547-3. 128. ^ Doherty EW, Doherty WJ (1998). "Smoke gets in your eyes: Cigarette smoking and divorce in a national sample of American adults". Families, Systems, & Health. 16 (4): 393–400. doi:10.1037/h0089864. 129. ^ a b Almeida OP, Hulse GK, Lawrence D, Flicker L (January 2002). "Smoking as a risk factor for Alzheimer's disease: contrasting evidence from a systematic review of case-control and cohort studies". Addiction. 97 (1): 15–28. doi:10.1046/j.1360-0443.2002.00016.x. PMID 11895267. S2CID 22936675. 130. ^ Anstey KJ, von Sanden C, Salim A, O'Kearney R (August 2007). "Smoking as a risk factor for dementia and cognitive decline: a meta-analysis of prospective studies". American Journal of Epidemiology. 166 (4): 367–78. doi:10.1093/aje/kwm116. PMID 17573335. 131. ^ Jacobsen LK, Krystal JH, Mencl WE, Westerveld M, Frost SJ, Pugh KR (January 2005). "Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers". Biological Psychiatry. 57 (1): 56–66. doi:10.1016/j.biopsych.2004.10.022. PMID 15607301. S2CID 10146493. 132. ^ Brody AL, Mandelkern MA, Jarvik ME, Lee GS, Smith EC, Huang JC, Bota RG, Bartzokis G, London ED (January 2004). "Differences between smokers and nonsmokers in regional gray matter volumes and densities". Biological Psychiatry. 55 (1): 77–84. doi:10.1016/S0006-3223(03)00610-3. PMID 14706428. S2CID 25442824. 133. ^ Akiyama H, Meyer JS, Mortel KF, Terayama Y, Thornby JI, Konno S (November 1997). "Normal human aging: factors contributing to cerebral atrophy". Journal of the Neurological Sciences. 152 (1): 39–49. doi:10.1016/S0022-510X(97)00141-X. PMID 9395125. S2CID 24676760. 134. ^ Cataldo JK, Prochaska JJ, Glantz SA (2010). "Cigarette smoking is a risk factor for Alzheimer's Disease: an analysis controlling for tobacco industry affiliation". Journal of Alzheimer's Disease. 19 (2): 465–80. doi:10.3233/JAD-2010-1240. PMC 2906761. PMID 20110594. 135. ^ Fratiglioni L, Wang HX (August 2000). "Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological studies". Behavioural Brain Research. 113 (1–2): 117–20. doi:10.1016/S0166-4328(00)00206-0. PMID 10942038. S2CID 4045868. 136. ^ Cataldo JK, Prochaska JJ, Glantz SA (Jul 2010). "Cigarette smoking is a risk factor for Alzheimer's Disease: an analysis controlling for tobacco industry affiliation". Journal of Alzheimer's Disease. 19 (2): 465–80. doi:10.3233/JAD-2010-1240. PMC 2906761. PMID 20110594. 137. ^ Allam MF, Campbell MJ, Hofman A, Del Castillo AS, Fernández-Crehuet Navajas R (June 2004). "Smoking and Parkinson's disease: systematic review of prospective studies". Movement Disorders. 19 (6): 614–21. doi:10.1002/mds.20029. PMID 15197698. S2CID 36001133. 138. ^ Allam MF, Campbell MJ, Del Castillo AS, Fernández-Crehuet Navajas R (2004). "Parkinson's disease protects against smoking?". Behavioural Neurology. 15 (3–4): 65–71. doi:10.1155/2004/516302. PMC 5488608. PMID 15706049. 139. ^ Quik M (September 2004). "Smoking, nicotine and Parkinson's disease". Trends in Neurosciences. 27 (9): 561–8. doi:10.1016/j.tins.2004.06.008. PMID 15331239. S2CID 42385863. 140. ^ Stough C, Mangan G, Bates T, Pellett O (November 1994). "Smoking and Raven IQ". Psychopharmacology. 116 (3): 382–4. doi:10.1007/BF02245346. PMID 7892431. S2CID 19155259. 141. ^ Jarvis MJ (January 2004). "Why people smoke". BMJ. 328 (7434): 277–9. doi:10.1136/bmj.328.7434.277. PMC 324461. PMID 14751901. 142. ^ "NICOU - Clinical: Nicotine and Metabolites, Urine". www.mayomedicallaboratories.com. Retrieved 2018-01-03. 143. ^ Hughes JR (April 2006). "Clinical significance of tobacco withdrawal". Nicotine & Tobacco Research. 8 (2): 153–6. doi:10.1080/14622200500494856. PMID 16766409. 144. ^ McNeill A (2001). "Smoking and mental health – a review of the literature" (PDF). SmokeFree London Programme. Retrieved 2008-10-05. Cite journal requires `\|journal=` (help) 145. ^ Meltzer H, Gill B, Petticrew M, Hinds K (1995). OPCS Surveys of Psychiatric Morbidity Report 3: Economic Activity and Social Functioning of Adults With Psychiatric Disorders. London, Her Majesty’s Stationery Office.[page needed] 146. ^ Kelly C, McCreadie RG (November 1999). "Smoking habits, current symptoms, and premorbid characteristics of schizophrenic patients in Nithsdale, Scotland". The American Journal of Psychiatry. 156 (11): 1751–7. doi:10.1176/ajp.156.11.1751 (inactive 2020-12-09). PMID 10553739.CS1 maint: DOI inactive as of December 2020 (link) 147. ^ Hughes JR, Hatsukami DK, Mitchell JE, Dahlgren LA (August 1986). "Prevalence of smoking among psychiatric outpatients". The American Journal of Psychiatry. 143 (8): 993–7. CiteSeerX 10.1.1.470.8010. doi:10.1176/ajp.143.8.993. PMID 3487983. 148. ^ Schroeder SA (September 2007). "Shattuck Lecture. We can do better—improving the health of the American people". The New England Journal of Medicine. 357 (12): 1221–8. doi:10.1056/NEJMsa073350. PMID 17881753. S2CID 12299551. 149. ^ George T (2002-07-22). "Schizophrenia and Smoking". Health Report. ABC Radio National (Australian Broadcasting Corporation). Retrieved 2012-05-06. 150. ^ Sacco KA, Bannon KL, George TP (December 2004). "Nicotinic receptor mechanisms and cognition in normal states and neuropsychiatric disorders". Journal of Psychopharmacology. 18 (4): 457–74. doi:10.1177/0269881104047273. PMC 1201375. PMID 15582913. 151. ^ Kumari V, Postma P (2005). "Nicotine use in schizophrenia: the self medication hypotheses". Neuroscience and Biobehavioral Reviews. 29 (6): 1021–34. doi:10.1016/j.neubiorev.2005.02.006. PMID 15964073. S2CID 15581894. 152. ^ Gurillo P, Jauhar S, Murray RM, MacCabe JH (August 2015). "Does tobacco use cause psychosis? Systematic review and meta-analysis". The Lancet. Psychiatry. 2 (8): 718–725. doi:10.1016/S2215-0366(15)00152-2. PMC 4698800. PMID 26249303. 153. ^ Anda RF, Williamson DF, Escobedo LG, Mast EE, Giovino GA, Remington PL (September 1990). "Depression and the dynamics of smoking. A national perspective". JAMA. 264 (12): 1541–5. doi:10.1001/jama.1990.03450120053028. PMID 2395193. 154. ^ Glassman AH, Helzer JE, Covey LS, Cottler LB, Stetner F, Tipp JE, Johnson J (September 1990). "Smoking, smoking cessation, and major depression". JAMA. 264 (12): 1546–9. doi:10.1001/jama.1990.03450120058029. PMID 2395194. 155. ^ Covey LS, Glassman AH, Stetner F (1998). "Cigarette smoking and major depression". Journal of Addictive Diseases. 17 (1): 35–46. doi:10.1300/J069v17n01_04. PMID 9549601. 156. ^ Hall SM, Muñoz RF, Reus VI, Sees KL (October 1993). "Nicotine, negative affect, and depression". Journal of Consulting and Clinical Psychology. 61 (5): 761–7. doi:10.1037/0022-006X.61.5.761. PMID 7902368. 157. ^ Wang M, Wang ZP, Gong R, Zhao ZT (January 2014). "Maternal smoking during pregnancy and neural tube defects in offspring: a meta-analysis". Child's Nervous System. 30 (1): 83–9. doi:10.1007/s00381-013-2194-5. PMID 23760473. S2CID 40996359. 158. ^ Ward C, Lewis S, Coleman T (May 2007). "Prevalence of maternal smoking and environmental tobacco smoke exposure during pregnancy and impact on birth weight: retrospective study using Millennium Cohort". BMC Public Health. 7: 81. doi:10.1186/1471-2458-7-81. PMC 1884144. PMID 17506887. 159. ^ Kroon LA (September 2007). "Drug interactions with smoking". American Journal of Health-System Pharmacy. 64 (18): 1917–21. doi:10.2146/ajhp060414. PMID 17823102. S2CID 5397510. 160. ^ Ande A, McArthur C, Ayuk L, Awasom C, Achu PN, Njinda A, Sinha N, Rao PS, Agudelo M, Nookala AR, Simon S, Kumar A, Kumar S (2015). "Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals". PLOS ONE. 10 (4): e0122402. Bibcode:2015PLoSO..1022402A. doi:10.1371/journal.pone.0122402. PMC 4399877. PMID 25879453. 161. ^ Chen H, Vlahos R, Bozinovski S, Jones J, Anderson GP, Morris MJ (April 2005). "Effect of short-term cigarette smoke exposure on body weight, appetite and brain neuropeptide Y in mice". Neuropsychopharmacology. 30 (4): 713–9. doi:10.1038/sj.npp.1300597. PMID 15508020. Lay summary – News-Medical.Net. 162. ^ Vanni H, Kazeros A, Wang R, Harvey BG, Ferris B, De BP, Carolan BJ, Hübner RH, O'Connor TP, Crystal RG (May 2009). "Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human". Chest. 135 (5): 1197–1208. doi:10.1378/chest.08-1024. PMC 2679098. PMID 19188554. 163. ^ Leistikow BN, Martin DC, Milano CE (August 2000). "Fire injuries, disasters, and costs from cigarettes and cigarette lights: a global overview". Preventive Medicine. 31 (2 Pt 1): 91–9. doi:10.1006/pmed.2000.0680. PMID 10938207. S2CID 11722177. 164. ^ Leistikow BN, Martin DC, Samuels SJ (December 2000). "Injury death excesses in smokers: a 1990–95 United States national cohort study". Injury Prevention. 6 (4): 277–80. doi:10.1136/ip.6.4.277. PMC 1730660. PMID 11144627. 165. ^ Cosnes J, Carbonnel F, Carrat F, Beaugerie L, Cattan S, Gendre J (November 1999). "Effects of current and former cigarette smoking on the clinical course of Crohn's disease". Alimentary Pharmacology & Therapeutics. 13 (11): 1403–11. doi:10.1046/j.1365-2036.1999.00630.x. PMID 10571595. S2CID 6620451. 166. ^ Calkins BM (December 1989). "A meta-analysis of the role of smoking in inflammatory bowel disease". Digestive Diseases and Sciences. 34 (12): 1841–54. doi:10.1007/BF01536701. PMID 2598752. S2CID 5775169. 167. ^ Lakatos PL, Szamosi T, Lakatos L (December 2007). "Smoking in inflammatory bowel diseases: good, bad or ugly?". World Journal of Gastroenterology. 13 (46): 6134–9. doi:10.3748/wjg.13.6134. PMC 4171221. PMID 18069751. 168. ^ Mahid SS, Minor KS, Soto RE, Hornung CA, Galandiuk S (November 2006). "Smoking and inflammatory bowel disease: a meta-analysis". Mayo Clinic Proceedings. 81 (11): 1462–71. doi:10.4065/81.11.1462. PMID 17120402. 169. ^ Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM, Hunter DJ (October 2004). "Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors". American Journal of Epidemiology. 160 (8): 784–96. doi:10.1093/aje/kwh275. PMID 15466501. 170. ^ Calhaz-Jorge C, Mol BW, Nunes J, Costa AP (September 2004). "Clinical predictive factors for endometriosis in a Portuguese infertile population". Human Reproduction. 19 (9): 2126–31. doi:10.1093/humrep/deh374. PMID 15229202. 171. ^ Baron JA (January 1996). "Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious". British Medical Bulletin. 52 (1): 58–73. doi:10.1093/oxfordjournals.bmb.a011533. PMID 8746297. 172. ^ Schwartz SM, Marshall LM, Baird DD (October 2000). "Epidemiologic contributions to understanding the etiology of uterine leiomyomata". Environmental Health Perspectives. 108 Suppl 5: 821–7. doi:10.1289/ehp.00108s5821. JSTOR 3454313. PMID 11035989. 173. ^ Lubin JH, Steindorf K (January 1995). "Cigarette use and the estimation of lung cancer attributable to radon in the United States". Radiation Research. 141 (1): 79–85. Bibcode:1995RadR..141...79L. doi:10.2307/3579093. JSTOR 3579093. PMID 7997518. 174. ^ Reid A, de Klerk NH, Ambrosini GL, Berry G, Musk AW (August 2006). "The risk of lung cancer with increasing time since ceasing exposure to asbestos and quitting smoking". Occupational and Environmental Medicine. 63 (8): 509–12. doi:10.1136/oem.2005.025379. PMC 2078130. PMID 16849527. 175. ^ Lederle FA, Larson JC, Margolis KL, Allison MA, Freiberg MS, Cochrane BB, Graettinger WF, Curb JD (October 2008). "Abdominal aortic aneurysm events in the women's health initiative: cohort study". BMJ. 337: a1724. doi:10.1136/bmj.a1724. PMC 2658825. PMID 18854591. Lay summary – Medical News Today. 176. ^ Kanis JA, Johnell O, Oden A, Johansson H, De Laet C, Eisman JA, Fujiwara S, Kroger H, McCloskey EV, Mellstrom D, Melton LJ, Pols H, Reeve J, Silman A, Tenenhouse A (February 2005). "Smoking and fracture risk: a meta-analysis". Osteoporosis International. 16 (2): 155–62. doi:10.1007/s00198-004-1640-3. PMID 15175845. S2CID 19890259. 177. ^ Sørensen LT (April 2012). "Wound healing and infection in surgery. The clinical impact of smoking and smoking cessation: a systematic review and meta-analysis". Archives of Surgery. 147 (4): 373–83. doi:10.1001/archsurg.2012.5. PMID 22508785. 178. ^ "Smoking and Diabetes". Centers for Disease Control and Prevention. 23 April 2018. 179. ^ "2014 Surgeon General's Report: The Health Consequences of Smoking—50 Years of Progress". Centers for Disease Control and Prevention. 5 March 2018. 180. ^ Cohen DJ, Doucet M, Cutlip DE, Ho KK, Popma JJ, Kuntz RE (August 2001). "Impact of smoking on clinical and angiographic restenosis after percutaneous coronary intervention: another smoker's paradox?". Circulation. 104 (7): 773–8. doi:10.1161/hc3201.094225. PMID 11502701. 181. ^ Goldman SM (2014). "Environmental toxins and Parkinson's disease". Annual Review of Pharmacology and Toxicology. 54: 141–64. doi:10.1146/annurev-pharmtox-011613-135937. PMID 24050700. 182. ^ Pradhan P, Tirumala S, Liu X, Sayer JM, Jerina DM, Yeh HJ (May 2001). "Solution structure of a trans-opened (10S)-dA adduct of (+)-(7S,8R,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in a fully complementary DNA duplex: evidence for a major syn conformation". Biochemistry. 40 (20): 5870–81. doi:10.1021/bi002896q. PMID 11352722. 183. ^ Bray F, Tyczynski JE, Parkin DM (January 2004). "Going up or coming down? The changing phases of the lung cancer epidemic from 1967 to 1999 in the 15 European Union countries". European Journal of Cancer. 40 (1): 96–125. doi:10.1016/j.ejca.2003.08.005. PMID 14687795. 184. ^ Jones M, Fosbery R, Taylor D (2000). "Answers to self-assessment questions". Biology 1. Cambridge Advanced Sciences. p. 250. ISBN 978-0-521-78719-2. 185. ^ a b Feng Z, Hu W, Hu Y, Tang MS (October 2006). "Acrolein is a major cigarette-related lung cancer agent: Preferential binding at p53 mutational hotspots and inhibition of DNA repair". Proceedings of the National Academy of Sciences of the United States of America. 103 (42): 15404–9. Bibcode:2006PNAS..10315404F. doi:10.1073/pnas.0607031103. PMC 1592536. PMID 17030796. 186. ^ Dr. C. Everett Koop. "Smoking and smokeless tobacco". Archived from the original on July 23, 2006. Retrieved July 15, 2006. 187. ^ Hecht, S. S. (1999). "Tobacco Smoke Carcinogens and Lung Cancer". JNCI Journal of the National Cancer Institute. 91 (14): 1194–1210. doi:10.1093/jnci/91.14.1194. PMID 10413421. Retrieved 8 September 2014. 188. ^ "DNA interaction with Benzopyrene". DNA. Archived from the original on December 23, 2004. Retrieved March 5, 2005. 189. ^ Kataoka H, Sumida A, Makita M (1997). "Determination of aliphatic and aromatic aldehydes in cigarette smoke by gas chromatography with flame photometric detection". Chromatographia. 44 (9–10): 491–6. doi:10.1007/BF02466742. S2CID 97329744. 190. ^ Sumner PE, Moore JM, Boyette MD. "Retrofitting Tobacco Curing Barns" (PDF). Extension Engineering Publications. The University of Georgia College of Agricultural and Environmental Sciences. Retrieved 2012-05-06. 191. ^ NOVA. "Search for a Safer Cigarette". 192. ^ Godish T (2001). Indoor environmental quality. Chelsea, Michigan: Lewis Publishers. pp. 77–9. ISBN 978-1-56670-402-1. 193. ^ "Smoking, Health And Personality". REBEK. May 13, 2015. Archived from the original on 2015-05-18. Retrieved 2015-05-13. 194. ^ U.S. Army Center for Health Promotion and Preventive Medicine. "Radiological Sources of Potential Exposure and/or Contamination" (PDF). Archived from the original (PDF) on December 12, 2006. 195. ^ Martell EA (March 1983). "alpha-Radiation dose at bronchial bifurcations of smokers from indoor exposure to radon progeny". Proceedings of the National Academy of Sciences of the United States of America. 80 (5): 1285–9. Bibcode:1983PNAS...80.1285M. doi:10.1073/pnas.80.5.1285. PMC 393580. PMID 6572389. 196. ^ Muggli ME, Ebbert JO, Robertson C, Hurt RD (September 2008). "Waking a sleeping giant: the tobacco industry's response to the polonium-210 issue". American Journal of Public Health. 98 (9): 1643–50. doi:10.2105/AJPH.2007.130963. PMC 2509609. PMID 18633078. 197. ^ Rego B (September 2009). "The Polonium brief: a hidden history of cancer, radiation, and the tobacco industry" (PDF). Isis; an International Review Devoted to the History of Science and Its Cultural Influences. 100 (3): 453–84. doi:10.1086/644613. PMID 19960838. S2CID 26001557. Archived from the original (PDF) on 2016-03-04. Retrieved 2014-07-20. 198. ^ Office of Research Services, Division of Radiation Safety. "F. Typical Sources of Radiation Exposure". United States National Institutes of Health. Archived from the original on 2013-06-13. Retrieved 2012-05-06. 199. ^ "Radiation Risk for Xray and CT exams –". dosage chart. Associated Radiologists. Archived from the original on April 26, 2012. Retrieved 2012-05-06. 200. ^ "Radiation Risks and Realities" (PDF). United States Environmental Protection Agency. 2014-07-16. 201. ^ a b "Everyday exposures to radiation". Front Line. Public Broadcasting System. 202. ^ "Radiation fears after Japan blast". BBC. 2011-07-21. 203. ^ Proctor RN (2006-12-01). "Puffing on Polonium". The New York Times. 204. ^ "Tobacco Smoke \| Radiation Protection". United States Environmental Protection Agency. Retrieved 2012-05-06. 205. ^ Hecht SS (July 1999). "Tobacco smoke carcinogens and lung cancer". Journal of the National Cancer Institute. 91 (14): 1194–210. doi:10.1093/jnci/91.14.1194. PMID 10413421. 206. ^ Hecht, S. S. (2011). "Tobacco smoke carcinogens and lung cancer". In Penning, T. M. (ed.). Chemical Carcinogenesis. Totowa, NJ: Springer. p. 67. ISBN 9781617379949. 207. ^ a b c d Messner B, Bernhard D (2014). "Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis". Arteriosclerosis, Thrombosis, and Vascular Biology. 34 (3): 509–515. doi:10.1161/ATVBAHA.113.300156. PMID 24554606. 208. ^ Bonetti PO, Lerman LO, Lerman A (2003). "Endothelial dysfunction: a marker of atherosclerotic risk". Arteriosclerosis, Thrombosis, and Vascular Biology. 23 (2): 168–175. doi:10.1161/01.ATV.0000051384.43104.FC. PMID 12588755. S2CID 34213675. 209. ^ Talhout R, Opperhuizen A, van Amsterdam JG (October 2007). "Role of acetaldehyde in tobacco smoke addiction". European Neuropsychopharmacology. 17 (10): 627–36. doi:10.1016/j.euroneuro.2007.02.013. PMID 17382522. S2CID 25866206. 210. ^ Hilts PJ (1994-08-02). "Relative Addictiveness of Drugs". New York Times. Retrieved 2012-05-06. 211. ^ "The Henningfield-Benowitz substance comparison charts". Retrieved 2012-05-06. 212. ^ "AADAC\|Truth About Tobacco – Addiction". Alberta Health Services. Archived from the original on 2014-02-25. 213. ^ Gervais A, O'Loughlin J, Meshefedjian G, Bancej C, Tremblay M (August 2006). "Milestones in the natural course of onset of cigarette use among adolescents". CMAJ. 175 (3): 255–61. doi:10.1503/cmaj.051235. PMC 1513423. PMID 16880445. 214. ^ National Cancer Institute. "Harms of Smoking and Health Benefits of Quitting". Fact Sheet. United States National Institutes of Health. Retrieved 2012-05-06. 215. ^ Smith D (2000). "Smoking increases teen depression". Monitor on Psychology. American Psychological Association. Retrieved 2012-05-06. 216. ^ National Institute on Drug Abuse. "Mind Over Matter: Tobacco Addiction". United States National Institutes of Health. Archived from the original on 2012-05-05. Retrieved 2012-05-06. 217. ^ Parkin C, Fairweather DB, Shamsi Z, Stanley N, Hindmarch I (March 1998). "The effects of cigarette smoking on overnight performance". Psychopharmacology. 136 (2): 172–8. doi:10.1007/s002130050553. PMID 9551774. S2CID 22962937. 218. ^ Maneckjee R, Minna JD (October 1994). "Opioids induce while nicotine suppresses apoptosis in human lung cancer cells". Cell Growth & Differentiation. 5 (10): 1033–40. PMID 7848904. 219. ^ Guillem K, Vouillac C, Azar MR, Parsons LH, Koob GF, Cador M, Stinus L (September 2005). "Monoamine oxidase inhibition dramatically increases the motivation to self-administer nicotine in rats". The Journal of Neuroscience. 25 (38): 8593–600. doi:10.1523/JNEUROSCI.2139-05.2005. PMC 6725504. PMID 16177026. 220. ^ Villégier AS, Blanc G, Glowinski J, Tassin JP (September 2003). "Transient behavioral sensitization to nicotine becomes long-lasting with monoamine oxidases inhibitors". Pharmacology Biochemistry and Behavior. 76 (2): 267–74. doi:10.1016/S0091-3057(03)00223-5. PMID 14592678. S2CID 30370768. 221. ^ a b "Secondhand Smoke". American Lung Association. June 2007. Retrieved 2012-05-06. 222. ^ ""Tobacco-Free Florida", Centers for Disease Control & Prevention Fact Sheets". Retrieved 8 September 2014. 223. ^ a b IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2007). "Smokeless tobacco and some tobacco-specific N-nitrosamines" (PDF). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 89: 1–592. PMC 4781254. PMID 18335640. 224. ^ "What is cancer?". Detailed Guide. American Cancer Society. 2011-04-11. 225. ^ Dollar KM, Mix JM, Kozlowski LT (May 2008). "Little cigars, big cigars: omissions and commissions of harm and harm reduction information on the Internet". Nicotine & Tobacco Research. 10 (5): 819–26. CiteSeerX 10.1.1.1009.3126. doi:10.1080/14622200802027214. PMID 18569755. 226. ^ Shanks TG, Burns DM (February 1988). "Disease Consequences of Cigar Smoking" (PDF). In Shopland DR, Burns DM, Hoffmann D, Cummings KM, Amacher RH (eds.). Cigars: Health Effects and Trends. Smoking and Tobacco Control Monograph No. 9. National Cancer Institute. pp. 105–60. 227. ^ "Questions and answers about cigar smoking and cancer". National Cancer Institute. 2000-03-07. Retrieved 2008-10-21. 228. ^ Misner, Jared (November 18, 2009). "UF study finds more teens smoke hookah". The Independent Florida Alligator. 229. ^ Knishkowy B, Amitai Y (July 2005). "Water-pipe (narghile) smoking: an emerging health risk behavior". Pediatrics. 116 (1): e113–9. doi:10.1542/peds.2004-2173. PMID 15995011. 230. ^ Hurt RD (2010-02-20). "Hookah smoking: Is it safer than cigarettes?". Mayo Clinic. 231. ^ "EGYPT: Water pipe smoking a significant TB risk". IRIN. March 24, 2008. 232. ^ "Egyptians warned on pipe smoking". The Australian. Reuters. March 17, 2007. 233. ^ a b Shihadeh A, Azar S, Antonios C, Haddad A (September 2004). "Towards a topographical model of narghile water-pipe café smoking: a pilot study in a high socioeconomic status neighborhood of Beirut, Lebanon". Pharmacology Biochemistry and Behavior. 79 (1): 75–82. doi:10.1016/j.pbb.2004.06.005. PMID 15388286. S2CID 29182130. 234. ^ Djordjevic MV, Stellman SD, Zang E (January 2000). "Doses of nicotine and lung carcinogens delivered to cigarette smokers". Journal of the National Cancer Institute. 92 (2): 106–11. doi:10.1093/jnci/92.2.106. PMID 10639511. 235. ^ "WHO warns the hookah may pose same risk as cigarettes". USA Today. Associated Press. May 29, 2007. 236. ^ Natto SB (2005). "Tobacco smoking and periodontal health in a Saudi Arabian population". Swedish Dental Journal. Supplement (176): 8–52, table of contents. PMID 16223098. 237. ^ Koch W (2005-12-28). "Hookah trend is puffing along". USA Today. Retrieved 2010-05-04.[better source needed] 238. ^ Sajid KM, Chaouachi K, Mahmood R (May 2008). "Hookah smoking and cancer: carcinoembryonic antigen (CEA) levels in exclusive/ever hookah smokers". Harm Reduction Journal. 5: 19. doi:10.1186/1477-7517-5-19. PMC 2438352. PMID 18501010. 239. ^ Koul PA, Hajni MR, Sheikh MA, Khan UH, Shah A, Khan Y, Ahangar AG, Tasleem RA (2011). "Hookah smoking and lung cancer in the Kashmir valley of the Indian subcontinent". Asian Pacific Journal of Cancer Prevention. 12 (2): 519–24. PMID 21545223. 240. ^ Boffetta P, Hecht S, Gray N, Gupta P, Straif K (July 2008). "Smokeless tobacco and cancer". The Lancet. Oncology. 9 (7): 667–75. doi:10.1016/S1470-2045(08)70173-6. PMID 18598931. 241. ^ "Summaries for patients. Primary care interventions to prevent tobacco use in children and adolescents: U.S. Preventive Services Task Force recommendation statement". Annals of Internal Medicine. 159 (8): I–36. October 2013. doi:10.7326/0003-4819-159-8-201310150-00699. PMID 23974179. S2CID 28035258. 242. ^ "Average price of a pack of cigarettes". Our World in Data. Retrieved 5 March 2020. 243. ^ "Taxes as a share of cigarette price". Our World in Data. Retrieved 5 March 2020. 244. ^ "Enforcement of bans on tobacco advertising". Our World in Data. Retrieved 5 March 2020. 245. ^ "Support to help quit tobacco use". Our World in Data. Retrieved 5 March 2020. 246. ^ Guindon GE, Boisclair D (2003). Past, current and future trends in tobacco use (PDF). Washington DC: The International Bank for Reconstruction and Development / The World Bank. pp. 13–16. ISBN 978-1-932126-66-2. Retrieved 2009-03-22. 247. ^ a b "WHO/WPRO-Smoking Statistics". World Health Organization Regional Office for the Western Pacific. 2002-05-28. Archived from the original on 2009-11-08. Retrieved 2009-01-01. 248. ^ "Teens and E-Cigarettes". National Institute on Drug Abuse. 2016-02-01. Retrieved 2018-12-23. 249. ^ "Quick Facts on the Risks of E-cigarettes for Kids, Teens, and Young Adults". CDC. 2018-12-03. Retrieved 2018-12-23. 250. ^ Centers for Disease Control and Prevention (CDC) (November 2007). "Cigarette smoking among adults—United States, 2006". MMWR. Morbidity and Mortality Weekly Report. 56 (44): 1157–61. PMID 17989644. 251. ^ a b "The Global Burden of Disease 2004 Update" (PDF). World Health Organization. 2008. Retrieved 2008-01-01. 252. ^ a b "WHO/WPRO-Tobacco Fact sheet". World Health Organization Regional Office for the Western Pacific. 2007-05-29. Archived from the original on 2009-02-07. Retrieved 2009-01-01. 253. ^ Elementary and Secondary Education \| Environmental Tobacco Smoke \| Pro-Children Act of 2001 \| Non-Smoking Policy for Children’s Services \| Section 4303 254. ^ Colgrove J, Bayer R, Bachynski KE (June 2011). "Nowhere left to hide? The banishment of smoking from public spaces". The New England Journal of Medicine. 364 (25): 2375–7. doi:10.1056/NEJMp1104637. PMID 21612464. S2CID 205107540. ## Bibliography[edit] * "WHO REPORT on the global TOBACCO epidemic" (PDF). World Health Organization. 2008. Retrieved 2008-01-01. * "The Global Burden of Disease 2004 Update" (PDF). World Health Organization. 2008. Retrieved 2008-01-01. * "Chapter 1: Introduction and Approach to Causal Inference" (PDF). 2004 Surgeon General's Report—The Health Consequences of Smoking (PDF). Washington DC: Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2004. Retrieved 2009-05-24. * "The health consequences of involuntary exposure to tobacco smoke: a report of the Surgeon General" (PDF). Atlanta, U.S.: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2006. Retrieved 2009-02-15. * "Cancer Facts and Figures 2004: Basic Cancer Facts". American Cancer Society. Archived from the original on 2009-02-12. Retrieved 2009-01-21. * Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K (July 2000). "Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland". The New England Journal of Medicine. 343 (2): 78–85. doi:10.1056/NEJM200007133430201. PMID 10891514. * Montesano R, Hall J (October 2001). "Environmental causes of human cancers". European Journal of Cancer. 37 Suppl 8: S67–87. doi:10.1016/S0959-8049(01)00266-0. PMID 11602374. ## External links[edit] Tobaccoat Wikipedia's sister projects * Definitions from Wiktionary * Media from Wikimedia Commons * News from Wikinews * Quotations from Wikiquote * Texts from Wikisource * Textbooks from Wikibooks * Resources from Wikiversity * Tobacco Free awareness action – How many people smoke in cars * v * t * e Smoking Country and region Africa * Egypt * Nigeria * South Africa Asia * Afghanistan * East Timor * Hong Kong * India * Indonesia * Iran * Iraq * Japan * Korea * North * South * Macau * Mainland China * Malaysia * New Zealand * Tokelau * Pakistan * Philippines * Saudi Arabia * Singapore * Syria * Taiwan * Turkey * Vietnam Europe * Albania * Finland * France * Germany * Greece * Hungary * Iceland * Ireland * Italy * Latvia * Norway * Sweden * United Kingdom South America * Argentina * Brazil * Colombia * Ecuador * Uruguay North America * Canada * United States Religion * Smoking in Jewish law * Tobacco fatwa * Ceremonial pipe * Chanunpa * Kinnikinnick * Pipe bag Health * Health effects of tobacco (Nicotine poisoning * Nicotine withdrawal) * Passive smoking * Third-hand smoke * Prevalence of tobacco use * Schizophrenia and smoking * Sidestream smoke * Smokeless tobacco keratosis * Smoker's face * Smoker's melanosis * Stomatitis nicotina * Smoking age * Smoking and male infertility * Smoking cessation * Tobacco-Free Pharmacies * Tobacco packaging warning messages * WHO Framework Convention on Tobacco Control * Protocol to Eliminate Illicit Trade in Tobacco Products * World No Tobacco Day * Youth smoking Women and smoking * Breastfeeding difficulties * Breast cancer * Cervical cancer * Menopause * Ptosis of the breast * Smoking and female infertility * Smoking and pregnancy Smoking ban * Inflight smoking * List of smoking bans * Smoking bans in private vehicles * Tobacco-Free College Campuses Country and region * Australia * England * France * United States Other * Chain smoking * Cigarette consumption per capita * History of smoking * Smokeasy * Smoking fetishism * Smoking pipe * tobacco pipe * Tobacco advertising * Tobacco bowdlerization * Tobacco industry * Tobacco smoking * Category * v * t * e Health effects of food, drink, and use of natural substances Food * Chocolate * Honey * Sugar Drink * Alcohol * Coffee * Tea * Wine Phytochemicals * Caffeine * Natural phenols and polyphenols (including tannins) Other * Cannabis * Noise pollution * Pesticide exposure * Sun exposure * Tobacco * v * t * e Cigarettes Types * Fashion * Fire safe * Kretek * Lights * Menthol * Beedi Components * Tobacco * Rolling paper * Filter * Additives Peripherals * Ashtray * Case * Holder * Lighter * Pack * Receptacles * Vending machine Culture * Cigarette card * Cigarette smoking among college students * Loosie * Smoking fetishism * Tobacco smoking Health issues * Chain smoking * Cigarette smoking for weight loss * Nicotine poisoning * Passive smoking * Third-hand smoke * Schizophrenia and smoking * Sidestream smoke * Smoking cessation * Tobacco harm reduction Related products * Electronic cigarette * E-liquid * Candy cigarette * Herbal cigarette * Heated tobacco product * Nicotine patch * Nicotine gum * Nicotine inhaler * Nicotine lozenge * Nicotine pouch Tobacco industry * Cultivation of tobacco * Egyptian cigarette industry * History of commercial tobacco in the United States * Tobacco advertising Government and the law * Cigarette smuggling * Plain cigarette packaging * Smoking age * Smoking bans in private vehicles * Tobacco control movement * Tobacco Master Settlement Agreement * Tobacco packaging warning messages * Tobacco politics * WHO Framework Convention on Tobacco Control * Protocol to Eliminate Illicit Trade in Tobacco Products Lists * Cigarette brands * Cigarette smoke carcinogens * Countries by cigarette consumption per capita * Rolling papers * Smoking bans * v * t * e Electronic cigarettes General topics * Construction * Usage * Marketing * Regulation * Safety * Cloud-chasing * Composition of electronic cigarette aerosol * Composition of heated tobacco product emissions * Flavored tobacco * Heated tobacco product * Pod mod * Vape shop Brands and companies * Blu eCigs * Dragonite International * Juul * LOGIC * NJOY * Openvape * Pax Labs * R. J. Reynolds Vapor Company * Ten Motives * Vuse Controversy * Adverse effects of electronic cigarettes * Vaping-associated pulmonary injury * Effects of electronic cigarettes on human brain development * Positions of medical organizations on electronic cigarettes * List of vaping bans in the United States * 2019–20 vaping lung illness outbreak * Hospitalized cases in the vaping lung illness outbreak * Nicotine poisoning * Nicotine salt Lists * List of electronic cigarette and e-cigarette liquid brands * List of heated tobacco products * Category * Category * Commons [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Health effects of tobacco	None	28,640	wikipedia	https://en.wikipedia.org/wiki/Health_effects_of_tobacco	2021-01-18T18:45:54	{"wikidata": ["Q465016"]}
A rare genetic neurological disorder characterized by the association of congenital spastic paraplegia with global developmental delay and intellectual disability, ophthalmologic abnormalities (including nystagmus, reduced visual acuity, or hypermetropia), and obesity. Additional manifestations are brachyplagiocephaly and dysmorphic facial features. Brain imaging may show dilated ventricles, abnormal myelination, and mild generalized atrophy. Homozygous loss-of-function variants of KIDINS220 associated with a fetal lethal phenotype with ventriculomegaly and limb contractures 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 [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Spastic paraplegia-intellectual disability-nystagmus-obesity syndrome	c4284592	28,641	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=521390	2021-01-23T17:05:43	{"omim": ["617296"], "synonyms": ["SINO syndrome"]}
An axonal Charcot-Marie-Tooth (CMT) peripheral sensorimotor polyneuropathy. ## Epidemiology CMT2K is a rare form of CMT with only three families reported in the literature so far. ## Clinical description It is characterized by a mild phenotype with onset during the second decade of life and very slow progression. Walking ability is retained (one of the reported patients was still able to walk at 70 years of age). ## Etiology CMT2K is caused by mutations in the GDAP1 gene (8q13.3), encoding a protein required for mitochondrial fission. Mutations in the same gene are associated with severe early-onset forms of CMT: CMT4A (an autosomal recessive demyelinating form of CMT4) and CMT4C4 (another autosomal recessive form of CMT4 with an axonal phenotype and an association with vocal cord paralysis; 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 [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autosomal dominant Charcot-Marie-Tooth disease type 2K	c1842983	28,642	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99944	2021-01-23T17:26:31	{"gard": ["9199"], "mesh": ["C535418"], "omim": ["607831"], "umls": ["C1842983", "C1842984"], "icd-10": ["G60.0"], "synonyms": ["CMT2K"]}
Angiolathyrism SpecialtyNeurology SymptomsWeakness, fatigue, paralysis of the legs, atrophy of leg muscles Usual onsetGradual DurationPermanent TypesNeurolathyrism Diagnostic methodBased on symptoms and diet FrequencyRare Angiolathyrism is a form of Lathyrism disease. It is mainly caused the consumption of Lathyrus sativus (also known as grass pea) and to a lesser degree by Lathyrus cicera, Lathyrus ochrus and Lathyrus clymenum[1] containing the toxin ODAP.[2] The main chemical responsible is β-Aminopropionitrile, which prevents collagen cross-linking, thus making the blood vessel, especially the tunica media, weak. This can result in Cystic medial necrosis or a picture similar to Marfan syndrome. The damaged vessels are at an increased risk of dissection. Unlike osteolathyrism, the blood vessels are affected instead of bone. However it is caused by similar action and is typically associated with the other forms of lathyrism. ## References[edit] 1. ^ "Medical problems caused by plants: Lathyrism" at Prince Leopold Institute of Tropical Medicine online database 2. ^ "Lathyrism". Egton Medical Information Systems Limited. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Angiolathyrism	None	28,643	wikipedia	https://en.wikipedia.org/wiki/Angiolathyrism	2021-01-18T18:51:55	{"wikidata": ["Q4763268"]}
A number sign (#) is used with this entry because megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-1 (MPPH1) is caused by heterozygous mutation in the PIK3R2 gene (603157) on chromosome 19p13. Description This disorder comprises megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome (MCAP; 602501) (summary by Gripp et al., 2009). ### Genetic Heterogeneity of the Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome See also MPPH2 (615937), caused by mutation in the AKT3 gene (611223) on chromosome 1q43-q44; and MPPH3 (615938), caused by mutation in the CCND2 gene (123833) on chromosome 12p13. Clinical Features Gohlich-Ratmann et al. (1998) reported 3 sporadic cases of in utero-onset megalencephaly. The children were born to healthy nonconsanguineous parents after uneventful pregnancies. Head circumferences were just above the 97th centile at birth in 2 patients, 2 cm above the 97th centile in 1 patient, and subsequently increased to 4.5 to 6.5 cm above the 97th centile at age 5 years. All patients completely lacked motor and speech development and showed very little intellectual progress. There was a distinctive facial aspect with frontal bossing, low nasal bridge, and large eyes, but no cutaneous abnormalities and no signs of other organ involvement. Magnetic resonance imaging showed bilateral megalencephaly with a broad corpus callosum, enlarged white matter, and focally thick gray matter, resulting in pachygyric appearance of the cortex. Formation of the frontoparietal operculum was incomplete, and the Sylvian fissures were wide. Gohlich-Ratmann et al. (1998) knew of no reports of similar cases. On review of the MRI figures in the paper by Gohlich-Ratmann et al. (1998), Mirzaa et al. (2004) concluded that the cortical dysplasia suggested polymicrogyria rather than typical pachygyria, a point with which the authors of the 1998 paper agreed. Mirzaa et al. (2004) thus suggested the designation megalencephaly-polymicrogyria-mega-corpus callosum (MEG-PMG-MegaCC) syndrome. Postaxial polydactyly was also seen in the patients reported by Mirzaa et al. (2004). Tohyama et al. (2007) reported a Japanese girl with MPPH. She was noted to have enlarged ventricles on prenatal ultrasound at 30 weeks' gestational age. At birth, she had macrocephaly (+3.5 SD) and polydactyly of the lower limbs. She developed partially refractory seizures at age 3 months, and showed global developmental delay. Dysmorphic features included prominent forehead, hypertelorism, telecanthus, and depressed nasal bridge. Se also had visual impairment, but ophthalmic examination was normal. Brain MRI showed polymicrogyria, decreased white matter volume, and signal abnormalities in the occipital lobe. Dagli et al. (2008) reported a female infant with a phenotype similar to that described by Gohlich-Ratmann et al. (1998). At birth, she had macrocephaly, hypotonia, frontal bossing, depressed nasal bridge, and normal brain MRI. Features noted later included open anterior fontanel, wide palpebral fissures, ptosis, and profound mental retardation with no psychomotor development. Brain MRI at age 15 months showed bilateral megalencephaly with generalized thickening of the cortex, severe enlargement of the corpus callosum, and a cavum septum pellucidum. There was abnormal sulcation, which may be seen with polymicrogyria. The ventricles were normal in size, and the Sylvian fissures were not wide. The patient died at home at 21 months of age from respiratory complications associated with a flu-like illness. Hengst et al. (2010) reported a 3-year-old girl who was born with macrocephaly and showed hypotonia, reduced spontaneous movements, and severely delayed motor development. Brain MRI at age 8 months showed extensive polymicrogyria sparing the midline cortical structures and the visual cortex, a markedly enlarged corpus callosum, and megalencephaly of the hemispheres and cerebellum. There was increased diameter of the internal cerebral vein, the vein of Galen, and the straight sinus. By age 2 years, she had learned to control her head for a short time and to roll around, but could not sit or grasp. She had hypotonia, with salivation, mental retardation, and lack of speech. There was no facial dysmorphism and she did not have seizures. Hengst et al. (2010) suggested the term 'megalencephaly-mega corpus callosum-motor retardation syndrome (MMM)' as a more accurate designation. Diagnosis Mirzaa et al. (2012) reviewed the phenotypic features of 42 patients with a megalencephalic syndrome in an attempt to clarify and simplify the categorization and diagnosis of these disorders. Statistical analysis of particular features yielded 2 main groups: 21 patients with a vascular malformation consistent with MCAP and 19 with no vascular malformation consistent with MPPH; 2 patients were in an overlap group. Vascular malformations were significantly associated with syndactyly and somatic overgrowth at birth, and lack of vascular malformations was associated with polydactyly. The various features were assigned to 5 major classes of developmental abnormalities. Both MCAP and MPPH had (1) megalencephaly and variable somatic overgrowth (particularly in MCAP); (2) distal limb malformations, syndactyly being more associated with MCAP and polydactyly with MPPH; and (3) similar cortical brain malformations (mainly polymicrogyria). In addition, MCAP included (4) developmental vascular abnormalities and (5) occasional connective tissue dysplasia, such as hyperelasticity or thick skin. MPPH lacks vascular malformations, connective tissue dysplasia, and heterotopia. Based on these findings, Mirzaa et al. (2012) proposed diagnostic criteria for the MCAP and MPPH syndromes, and postulated that the 2 disorders represent different, although overlapping, syndromes that may be caused by different genes involved in the same biologic pathway. Molecular Genetics Riviere et al. (2012) performed exome sequencing in the oldest of 3 affected sibs with MPPH and identified a heterozygous mutation in the PIK3R2 gene (G373R; 603157.0001), which encodes the p85B regulatory subunit of class IA PI3K. Sanger sequencing confirmed the presence of the mutation in all 3 affected sibs and its absence in the saliva and blood of both parents and the unaffected sister, showing germline mosaicism in 1 parent. Sequencing of the PIK3R2 gene in 40 individuals with megalencephaly identified the same nucleotide change in 10 additional subjects with MPPH, and this mutation was shown to be de novo in all subjects for whom parental DNA was available. The mutation occurred at a CpG dinucleotide, which might explain its recurrence. In a Japanese girl with MPPH originally reported by Tohyama et al. (2007), Nakamura et al. (2014) identified a de novo heterozygous missense mutation in the PIK3R2 gene (L401P; 603157.0002). Functional studies of the variant were not performed. INHERITANCE \- Autosomal dominant GROWTH Height \- Small birth length HEAD & NECK Head \- Macrocephaly Face \- Frontal bossing Eyes \- Large eyes \- Blindness \- Pale optic nerves \- Wide palpebral fissures \- Eyelid ptosis Nose \- Low bridge Mouth \- Tent-shaped mouth \- Prominent philtral groove \- Submucous cleft palate (rare) CARDIOVASCULAR Heart \- Atrial septal defect \- Ventricular septal defect \- Vascular ring \- Mitral regurgitation, mild GENITOURINARY Kidneys \- Duplicated kidneys (rare) SKELETAL Spine \- Kyphosis \- S-scoliosis of thoracic spine Limbs \- Flexion contractures at both knees Hands \- Postaxial polydactyly MUSCLE, SOFT TISSUES \- Muscle atrophy NEUROLOGIC Central Nervous System \- Diffuse hypotonia \- Axial hypotonia \- Developmental delay \- Mental retardation, profound \- No language \- Increased tendon reflex \- Seizures \- Megalencephaly \- Thick corpus callosum \- Mildly thin corpus callosum \- Enlarged white matter \- Focal pachygyria \- Polymicrogyria \- Wide Sylvian fissures with incomplete opercularization \- Ventricles slightly enlarged \- Hydrocephalus \- Cavum septi pellucidi \- Cavum vergae \- Small cavum septum Behavioral Psychiatric Manifestations \- Asperger-like features NEOPLASIA \- Increased risk of medulloblastoma (rare) MOLECULAR BASIS \- Caused by mutation in the phosphatidylinositol 3-kinase, regulatory subunit 2 gene (PIK3R2, 603157.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1	c1863924	28,644	omim	https://www.omim.org/entry/603387	2019-09-22T16:13:05	{"mesh": ["C566381"], "omim": ["603387"], "orphanet": ["83473"], "synonyms": ["Alternative titles", "MEGALENCEPHALY, POLYMICROGYRIA, MEGA CORPUS CALLOSUM SYNDROME", "MEG-PMG-MEGACC SYNDROME", "MEGALENCEPHALY, MEGA CORPUS CALLOSUM, AND COMPLETE LACK OF MOTOR DEVELOPMENT"], "genereviews": ["NBK396098"]}
A number sign (#) is used with this entry because of evidence that primary hypoalphalipoproteinemia-1 is caused by heterozygous mutation in the ABC1 gene (ABCA1; 600046) on chromosome 9q31, which is also the site of mutations causing Tangier disease (205400). Description Twenty to 30% of early familial coronary heart disease (CHD) is ascribed to hypoalphalipoproteinemia, or high density lipoprotein deficiency. Although not initially recognized as a predisposing dyslipidemia, extensive epidemiologic work has implicated low high-density lipoprotein cholesterol (HDLC) levels in increased risk of cardiovascular disease, and low HDLC is considered to be a true dyslipidemic syndrome (Warnick and Wood, 1995). Primary hypoalphalipoproteinemia-2 (618463) is caused by mtation in the APOA1 gene (107680) on chromosome 11q23. Clinical Features As in Tangier disease, an autosomal recessive disorder, the dominantly inherited disorder familial hypoalphalipoproteinemia shows a reduction in cellular cholesterol efflux (Marcil et al., 1999). Mapping After demonstrating mutations in the ABC1 gene in patients with Tangier disease, Brooks-Wilson et al. (1999) studied 4 French Canadian families with familial hypoalphalipoproteinemia. Linkage analysis revealed a maximum lod score of 9.67 at a recombination fraction of 0.0 at D9S277, the region to which Tangier disease had been mapped. These 2 diseases had hitherto been considered distinct, with different clinical and biochemical characteristics. Molecular Genetics In affected members of French Canadian families with hypoalphalipoproteinemia, Brooks-Wilson et al. (1999) identified heterozygous mutations in the ABC1 gene (600046.0001-600046.0004). One of the families had previously been studied by Marcil et al. (1995). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	HYPOALPHALIPOPROTEINEMIA, PRIMARY, 1	c0342898	28,645	omim	https://www.omim.org/entry/604091	2019-09-22T16:12:30	{"omim": ["604091"], "orphanet": ["425"], "synonyms": ["Alternative titles", "HYPOALPHALIPOPROTEINEMIA, FAMILIAL", "HIGH DENSITY LIPOPROTEIN DEFICIENCY", "FAMILIAL HDL DEFICIENCY", "HDL CHOLESTEROL, LOW SERUM"]}
A number sign (#) is used with this entry because episodic kinesigenic dyskinesia-1 (EKD1), also known as paroxysmal kinesigenic dyskinesia, is caused by heterozygous mutation in the PRRT2 gene (614386) on chromosome 16p11. Description Paroxysmal kinesigenic choreoathetosis (PKC) is an autosomal dominant neurologic condition characterized by recurrent and brief attacks of involuntary movement triggered by sudden voluntary movement. These attacks usually have onset during childhood or early adulthood and can involve dystonic postures, chorea, or athetosis. Symptoms become less severe with age and show favorable response to anticonvulsant medications such as carbamazepine or phenytoin. It is the most common type of paroxysmal movement disorder. The condition is often misdiagnosed as an epileptic manifestation (summary by Chen et al., 2011). PKC shares some clinical features with benign familial infantile convulsions (BFIC2; 605751) and infantile convulsions and paroxysmal choreoathetosis (ICCA; 602066), which are allelic disorders. See also rolandic epilepsy with paroxysmal exercise-induced dystonia and writer's cramp (608105), which maps to chromosome 16p12-p11.2. ### Genetic Heterogeneity of Episodic Kinesigenic Dyskinesia See also EKD2 (611031), which maps to chromosome 16q13-q22.1. Clinical Features Familial paroxysmal dystonia was reported as a 'pure entity' in mother and 3 sons by Weber (1967). He claimed that only 1 family had previously been reported (Lance, 1963) and that the disorder is distinct from familial paroxysmal choreoathetosis (see PNKD1, 118800). It may be the same as the periodic dystonia reported by Smith and Heersema (1941) in which 3 unrelated sibships of Polish and Lithuanian extraction demonstrated episodic dystonic movements of 5 to 10 seconds duration induced by movement. Kertesz (1967) called the condition paroxysmal kinesigenic choreoathetosis. Goodenough et al. (1978) divided familial paroxysmal dyskinesias into kinesigenic and nonkinesigenic forms according to whether or not paroxysms are precipitated by sudden movements. The kinesigenic form differs from the nonkinesigenic form by later onset in many cases, briefer duration of attacks (seconds to minutes) which usually occur daily, and good response to anticonvulsants. Goodenough et al. (1978) pointed out that there are also acquired forms of paroxysmal dyskinesias, e.g., with multiple sclerosis, cerebral palsy or idiopathic hypoparathyroidism. The family first reported by Mount and Reback (1940) is an example of familial nonkinesigenic paroxysmal dyskinesia. In the familial nonkinesigenic form, the movements are of longer duration, occur less frequently, and rarely respond to anticonvulsants. So-called incompletely atonic attacks of PKC appear to be especially frequent in Japanese. Fukuda et al. (1999) described this form in a woman, her brother, and their mother. The woman first presented at the age of 22 years with attacks of muscle weakness mainly in her limbs. The attacks of muscle weakness resembled the choreoathetotic attacks that occur in PKC in terms of their kinesigenicity and duration, clarity of consciousness during the attacks, good therapeutic response to low doses of phenytoin, and familial transmission. All 3 individuals reported by Fukuda et al. (1999) had hypercalcitoninemia which was unexplained. They were not thought to have multiple endocrine neoplasia type IIA (MEN2; 171400) or IIB (MEN2B; 162300), both of which are associated with hypercalcitoninemia. Sadamatsu et al. (1999) performed video-monitoring EEG in 2 patients with PKC during attacks elicited by movements of the lower extremities. Findings strongly suggested that the etiology should be considered distinct from that of reflex epilepsy. However, the patients in this pedigree had experienced generalized convulsions in infancy; thus, Sadamatsu et al. (1999) could not rule out the possibility of an epileptogenic basis for the condition. No evidence for linkage was found with any 1 of 5 candidate regions. In a comprehensive review of clinical and molecular genetics of primary dystonias, Muller et al. (1998) referred to this disorder as dystonia-10 and pointed to the reports of Kertesz (1967) and Walker (1981) as examples. In an extensive linkage study of patients with PKC, Tomita et al. (1999) reported that 42% of their patients had afebrile, general convulsions in infancy (see, e.g., BFIC2, 605751). Spacey et al. (2002) reported a Caucasian English family in which 8 members had either PKC or seizure. Four family members with PKC had attacks that were choreic and lasted less than a minute, and four family members had generalized and/or partial seizures without PKC, including 2 with infantile seizures. There was suggestive linkage to chromosome 16 if the phenotype considered was PKC plus seizures. Chen et al. (2011) reported 8 unrelated Han Chinese families with EKD1 confirmed by genetic analysis (614386.0001-614386.0003). The transmission pattern in each family was consistent with autosomal dominant inheritance. The proband of 1 family was described in detail. He had onset at age 6 years of dystonic posturing of the head and arm, usually triggered by standing up quickly. This occurred up to 10 times per day, and lasted about 5 to 10 minutes. Brain MRI and EEG were normal at age 9 years. Treatment with carbamazepine resulted in complete symptom resolution. Clinical Management In a 2-stage study, Li et al. (2013) found that all (100%) of 25 patients with EKD1 due to mutations in the PRRT2 gene responded favorably to treatment with carbamazepine, whereas 31 (94%) of 33 patients with a similar phenotype who did not carry PRRT2 mutations had no or only partial response to this medication. The study provided Class IV evidence of a correlation between genotype and phenotype in patients with EKD1 due to a PRRT2 mutation and response to carbamazepine. Inheritance Both autosomal dominant and autosomal recessive modes of inheritance of the kinesigenic form were proposed by Goodenough et al. (1978). The cases interpreted as autosomal recessive may have been instances of reduced penetrance in an affected parent or new mutation. Autosomal dominant inheritance is well established in the familial nonkinesigenic form. Sadamatsu et al. (1999) studied a pedigree in which 5 members in 3 generations had PKC; 1 individual in the second generation was not affected. Mapping Tomita et al. (1999) performed genomewide linkage analysis on 8 Japanese families with PKC. Two-point linkage analysis provided a maximum lod score of 10.27 (recombination fraction of 0.00; penetrance of 0.7) at marker D16S3081, and a maximum multipoint lod score for a subset of markers was calculated to be 11.51 (penetrance of 0.8) at D16S3080. Haplotype analysis defined the disease locus within a region of approximately 12.4 cM between D16S3093 and D16S416. P1-derived artificial chromosome clones containing D16S3093 and D16S416 were mapped by FISH to 16p11.2 and 16q12.1, respectively. Thus, in the 8 families studied, the chromosomal location of the PKC critical region (PKCCR) is 16p11.2-q12.1. The same region was implicated in a study of an African American family with PKC in which linkage analysis localized the gene to an 18-cM interval between D16S3100 and D16S771 (Bennett et al., 2000). Tomita et al. (2002) showed that wet ear wax (117800) cosegregated with PKC in 8 Japanese families and indeed maps to the same region of chromosome 16. Kikuchi et al. (2007) reported 4 new families in which a total of 16 members had autosomal dominant PKC. Haplotype analysis showed that affected individuals shared a 24-cM segment between D16S3131 and D16S408. Molecular analysis of coding regions of 157 genes within the PKCCR in these 4 families and 3 additional PKC families did not show any clear pathogenic mutations. ### Genetic Heterogeneity Spacey et al. (2002) reported a 3-generation Caucasian English family in which 4 individuals had PKC inherited in an autosomal dominant pattern. Age of onset ranged from 6 to 13 years, and dystonic episodes lasted only 5 to 20 seconds. None had epilepsy or migraine. Three patients showed remission of PKC at ages 28 to 31 years. Linkage analysis excluded the pericentromeric region of chromosome 16, indicating genetic heterogeneity. Cytogenetics Lipton and Rivkin (2009) reported a 17-year-old boy with a history of carbamazepine-responsive paroxysmal kinesigenic dyskinesia, possible infantile-onset convulsions, and verbal learning disabilities, who presented with acute-onset gait ataxia. Motor development was normal prior to onset. Neurologic examination showed features of parkinsonism, including masked facies, monotonous prosody, and decreased spontaneous movement in all 4 limbs with poor initiation. There was also mild extrapyramidal rigidity, cogwheeling in the upper extremities, and truncal instability. Brain MRI showed mild cerebellar atrophy. Chromosomal microarray analysis detected a de novo 544-kb deletion on chromosome 16p11.2. Treatment with L-DOPA resulted in rapid resolution of parkinsonism. Lipton and Rivkin (2009) noted that parkinsonism is usually not described in this condition, and suggested that a disturbance in dopaminergic neurotransmission may underlie the disorder. Molecular Genetics In affected members of 8 unrelated Han Chinese families with episodic kinesigenic dyskinesia-1, Chen et al. (2011) identified 3 different heterozygous truncating mutations in the PRRT2 gene (614386.0001-614386.0003). The first mutation was found by exome sequencing of a large 4-generation family with 17 affected individuals. The protein was found to be highly expressed in various regions of the mouse developing central nervous system. Expression of a truncated form of PRRT2 in COS-7 cells showed loss of membrane targeting and localization of the truncated protein in the cytoplasm, suggesting interruption of protein function. Using a combination of exome sequencing and linkage analysis in 2 large Han Chinese families with EKD1, Wang et al. (2011) independently and simultaneously identified 2 different heterozygous truncating mutations in the PRRT2 gene (649dupC; 614386.0001 and 614386.0009, respectively) that completely segregated with the phenotype in each family. Two patients in each family also had infantile convulsion and choreoathetosis syndrome (ICCA; 602066), indicating intrafamilial variability. Analysis of 3 additional Han Chinese families with EKD1 revealed that 2 carried the 649dupC mutation and 1 had a different PRRT2 mutation (614386.0010). Meneret et al. (2012) identified heterozygous mutations in the PRRT2 gene (see, e.g., 614386.0001; 614386.0011-614386.0012) in 22 (65%) of 34 patients of European descent with EKD1 (20 patients) or ICCA (2 patients). Mutations were found in 13 (93%) of 14 familial cases and in 9 (45%) of 20 sporadic cases. There was evidence for incomplete penetrance. The most common mutation was 649dupC, which was found in 17 of the 22 patients with PRRT2 mutations, although this was not due to a founder effect. Compared to patients without PRRT2 mutations, those with mutations had a slightly earlier age at onset (median age of 15 years and 9 years, respectively), but otherwise there were no phenotypic differences between the 2 groups. Most of the mutations caused premature termination, leading Meneret et al. (2012) to suggest that the disorders result from PRRT2 haploinsufficiency. Ono et al. (2012) identified the 649dupC mutation in 14 of 15 Japanese families with EKD1, some of whom also had ICCA, and in 2 Japanese families with BFIS2. The mutation was shown to occur de novo in at least 1 family, suggesting that it is a mutational hotspot. EKD1, ICCA, and BFIS2 segregated with the mutation even within the same family. The findings indicated that all 3 disorders are allelic and are likely caused by a similar mechanism. In 1 family, a Japanese mother and daughter both carried a heterozygous mutation (Q250X; 614386.0015). The mother had EKD1 and her daughter had BFIS2. Population Genetics Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal movement disorder, with a prevalence of 1 in 150,000 individuals (Chen et al., 2011). INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Orofacial dyskinesia NEUROLOGIC Central Nervous System \- Dyskinesia, episodic \- Choreoathetosis, episodic \- Dystonia, episodic \- Abnormal involuntary movements \- Infantile seizures, afebrile, with no neurologic sequelae (in 40% of patients) MISCELLANEOUS \- Onset in childhood or adolescence (median age of 9 years) \- Increased male-to-female ratio (3-4 to 1) \- Symptoms precipitated by sudden movements \- Favorable response to anticonvulsants \- Symptoms often decrease or remit with age \- Incomplete penetrance \- Prevalence of 1 in 150,000 MOLECULAR BASIS \- Caused by mutation in the proline-rich transmembrane protein 2 gene (PRRT2, 614386.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	EPISODIC KINESIGENIC DYSKINESIA 1	c1868682	28,646	omim	https://www.omim.org/entry/128200	2019-09-22T16:42:03	{"doid": ["0090053"], "omim": ["128200"], "orphanet": ["98809"], "synonyms": ["Alternative titles", "PAROXYSMAL KINESIGENIC CHOREOATHETOSIS", "PAROXYSMAL KINESIGENIC DYSKINESIA", "DYSTONIA, FAMILIAL PAROXYSMAL", "DYSTONIA 10"], "genereviews": ["NBK475803"]}
A group of rare renal diseases, characterized by amyloid fibril deposition of apolipoprotein A-I or A-II (AApoAI or AApoAII amyloidosis), lysozyme (ALys amyloidosis) or fibrinogen A-alpha chain (AFib amyloidosis) in one or several organs. Renal involvement leading to chronic renal disease and renal failure is a common sign. Additional manifestations depend on the organ involved and the type of amyloid fibrils deposited. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hereditary amyloidosis with primary renal involvement	c0268389	28,647	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85450	2021-01-23T19:04:51	{"gard": ["8282"], "mesh": ["C538249"], "omim": ["105200"], "icd-10": ["E85.0"], "synonyms": ["Amyloidosis, Ostertag type", "Familial amyloid nephropathy", "Familial renal amyloidosis", "Hereditary amyloid nephropathy", "Hereditary renal amyloidosis"]}
Corticobasal degeneration is characterized by the break down (degeneration) of parts of the brain, including the cerebral cortex and basal ganglia. The cerebral cortex is responsible for most of the brain's processing of information, and the basal ganglia are deep brain structures that help start and control movement. Signs and symptoms of corticobasal degeneration include poor coordination, loss of movement, rigidity, poor balance, unnatural posturing of the muscles, intellectual (cognitive) impairment, speech impairment, muscular jerks, and difficulty swallowing. These symptoms develop and worsen over time. Currently the cause of corticobasal degeneration is not known. Treatment depends on the symptoms in each person. People with corticobasal degeneration usually do not survive beyond an average of 7 years after symptoms begin. Aspiration pneumonia or other complications are usually the cause of death. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Corticobasal degeneration	c0393570	28,648	gard	https://rarediseases.info.nih.gov/diseases/46/corticobasal-degeneration	2021-01-18T18:01:04	{"umls": ["C0393570"], "orphanet": ["454887"], "synonyms": ["Cortical-Basal Ganglionic degeneration", "Cortico-Basal Ganglionic Degeneration (CBGD)", "CBGD", "Corticobasal syndrome"]}
Bamforth–Lazarus syndrome Other namesAthyroidal hypothyroidism-spiky hair-cleft palate syndrome Bamforth–Lazarus syndrome is a genetic condition that results in thyroid dysgenesis.[1][2] It is due to recessive mutations in forkhead/winged-helix domain transcription factor (FKLH15 or TTF2).[3] It is associated with FOXE1.[4] ## References[edit] 1. ^ Bamforth JS, Hughes I, Lazarus J, John R (June 1986). "Congenital anomalies associated with hypothyroidism". Arch. Dis. Child. 61 (6): 608–9. doi:10.1136/adc.61.6.608. PMC 1777822. PMID 3729532. 2. ^ Bamforth JS, Hughes IA, Lazarus JH, Weaver CM, Harper PS (January 1989). "Congenital hypothyroidism, spiky hair, and cleft palate". J. Med. Genet. 26 (1): 49–51. doi:10.1136/jmg.26.1.49. PMC 1015536. PMID 2918525. 3. ^ Kopp P (June 2002). "Perspective: genetic defects in the etiology of congenital hypothyroidism". Endocrinology. 143 (6): 2019–24. doi:10.1210/en.143.6.2019. PMID 12021164. 4. ^ Venza I, Visalli M, Parrillo L, De Felice M, Teti D, Venza M (March 2011). "MSX1 and TGF-beta3 are novel target genes functionally regulated by FOXE1". Hum. Mol. Genet. 20 (5): 1016–25. doi:10.1093/hmg/ddq547. PMID 21177256. ## External links[edit] Classification D * ICD-10: E03.1 * OMIM: 241850 * MeSH: C537901 External resources * Orphanet: 1226 * v * t * e Congenital endocrine disorders Pituitary * Congenital hypopituitarism Thyroid * Thyroid disease * Persistent thyroglossal duct * Thyroglossal cyst * Congenital hypothyroidism * Thyroid dysgenesis * Thyroid dyshormonogenesis * Pendred syndrome Parathyroid * Congenital absence of parathyroid Adrenal * Absent adrenal gland * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Bamforth–Lazarus syndrome	c1855794	28,649	wikipedia	https://en.wikipedia.org/wiki/Bamforth%E2%80%93Lazarus_syndrome	2021-01-18T18:38:45	{"gard": ["414"], "mesh": ["C537901"], "umls": ["C1855794"], "orphanet": ["1226"], "wikidata": ["Q4853488"]}
## Clinical Features Rosenthal and Kloepfer (1962) described a 'new' syndrome with these three features in 13 persons of 4 generations of a Louisiana black family. Through the courtesy of Kloepfer, McKusick (1971) examined affected members of this family. The corneal leukoma is an epithelial change. The hands, feet, and chin are very large, and the affected persons unusually tall. Although growth hormone assays had not been done, other endocrine studies and x-ray views of the sella turcica gave no indication of pituitary dysfunction. One of the affected females examined had 9 living children. The skin of the hands is unusually soft and has an abnormal dermal ridge pattern, referred to as 'split ridges,' which permits identification of the disorder in children of preclinical age. A possible difference from the usual cutis verticis gyrata is a longitudinal orientation of the skin folds rather than transverse orientation. X-ray features were reported by Harbison and Nice (1971). INHERITANCE \- Autosomal dominant GROWTH Height \- Tall stature HEAD & NECK Face \- Large chin Eyes \- Corneal leukoma SKELETAL \- Periostosis Hands \- Large hands Feet \- Large feet SKIN, NAILS, & HAIR Skin \- Soft skin \- Split ridge dermal ridge pattern \- Cutis verticis gyrata with longitudinal folding ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ACROMEGALOID CHANGES, CUTIS VERTICIS GYRATA, AND CORNEAL LEUKOMA	c1321495	28,650	omim	https://www.omim.org/entry/102100	2019-09-22T16:45:27	{"mesh": ["C535654"], "omim": ["102100"], "orphanet": ["964"], "synonyms": ["ROSENTHAL-KLOEPFER SYNDROME", "Alternative titles"]}
Steroid dehydrogenase deficiency-dental anomalies syndrome is an autosomal recessive liver disease which was associated with numerical dental aberrations in a consanguineous Arabi Saudi family. This association suggests that the same gene is involved in both defects. General hypomineralisation and enamel hypoplasia found in this family is thought to be secondary to malabsorption due to liver disease. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Steroid dehydrogenase deficiency-dental anomalies syndrome	c2931508	28,651	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3196	2021-01-23T17:27:00	{"gard": ["5015"], "mesh": ["C537490"], "umls": ["C2931508"], "icd-10": ["K76.8"], "synonyms": ["Lyngstadaas syndrome"]}
## Description Tufted angioma is a rare benign vascular lesion that predominantly affects children under 5 years of age but may occur in adulthood. Some cases of tufted angioma have been reported in the mother during pregnancy, whereas in other cases the tufted angioma may be congenital. The lesions occur predominantly on the neck, shoulders, and trunk and appear histologically in a 'cannonball' distribution of rounded nodules or tufts of capillary-sized vessels in the dermis, with lymphatic vessels present at the periphery. The natural history is slow progressive growth, after which it tends to remain stable in size. Regression has been reported in some cases. Tufted angioma should be distinguished from kaposiform hemangioendothelioma (KHE). Multiple tufted angioma and KHE may be associated with Kasabach-Merritt syndrome (141000), which is characterized by severe thrombocytopenia and consumption of coagulation factors (summary by Tille et al., 2003). Clinical Features Tille et al. (2003) described a family with a 2-year-old boy with a single tufted angioma and 4 relatives with single lesions in 5 generations. The proband presented with a red exophytic lesion on the upper left back that was not present at birth. Histologic studies of the lesion in the proband demonstrated the existence of both blood and lymphatic vascular elements. Clinical Management Tille et al. (2003) stated that because the tufted angioma lesions are stable and can regress spontaneously, no treatment is recommended. Surgical excision or interferon-alpha (147660) treatment may be required to reduce the mass. Inheritance Heagerty et al. (1992) reported a patient with tufted angioma who had a strong family history of similar lesions in a pattern suggesting a monogenic, autosomal dominant predisposition. The transmission pattern of tufted angioma in the family reported by Tille et al. (2003) was consistent with autosomal dominant inheritance with reduced penetrance. Mapping In a preliminary analysis, Tille et al. (2003) found that 3 candidate genes, KDR (191306), ENG (131195), and FLT4 (136352), were compatible with linkage, with haplotypes being shared between 3 affected individuals and the 1 obligate carrier available for testing. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Vascular \- Vascular abnormalities restricted to skin SKIN, NAILS, & HAIR Skin \- Exophytic, red lesion \- Usually present on skin of neck, shoulders, or trunk \- Frequent bleeding may occur with trauma \- Histology shows 'cannonball' distribution of capillary-sized vessels in the dermis \- Vessels may form rounded nodules ('tufts') \- Lymphatic vessels present at the periphery of lesion MISCELLANEOUS \- Usually occurs in children younger than 5 years \- May occur in adults (also in pregnancy) \- Slow, progressive growth, then stable \- May regress \- Reduced penetrance ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ANGIOMA, TUFTED	c0346073	28,652	omim	https://www.omim.org/entry/607859	2019-09-22T16:08:42	{"mesh": ["C536924"], "omim": ["607859"], "orphanet": ["1063"], "synonyms": ["Alternative titles", "TUFTED ANGIOMA"]}
A rare, acute myeloid leukemia characterized by no significant myeloid maturation and more than 90% blast cells in the non-erythroid population. Various degrees of anemia, thrombocytopenia, or pancytopenia are present. Frequent clinical manifestations include fatigue, fever, bleeding disorders, and organomegaly, especially hepatosplenomegaly. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Acute myeloblastic leukemia without maturation	c0026998	28,653	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98833	2021-01-23T18:36:39	{"gard": ["526"], "mesh": ["D015470"], "umls": ["C0026998"], "icd-10": ["C92.0"], "synonyms": ["AML M1", "Acute myeloblastic leukemia M1"]}
Intestinal atresia Radiograph with double bubble sign indicating duodenal atresia SpecialtyGastroenterology Intestinal atresia is any congenital malformation of the structure of the intestine that causes bowel obstruction. The malformation can be a narrowing (stenosis), absence or malrotation of a portion of the intestine. These defects can either occur in the small or large intestine. ## Contents * 1 Symptoms and signs * 2 Cause * 3 Diagnosis * 3.1 Classification * 3.1.1 By location * 3.1.2 By malformation * 3.1.2.1 Type I * 3.1.2.2 Type II * 3.1.2.3 Type IIIa * 3.1.2.4 Type IIIb * 3.1.2.5 Type IV * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 History * 8 See also * 9 References * 10 External links ## Symptoms and signs[edit] The most prominent symptom of intestinal atresia is bilious vomiting soon after birth.[1] This is most common in jejunal atresia.[2] Other features include abdominal distension and failure to pass meconium. The distension is more generalised the further down the bowel the atresia is located and is thus most prominent with ileal atresia.[1][2] Inability to pass stool is most common with duodenal or jejunal atresia;[2] if stool is passed, it may be small, mucus-like and grey.[1] Occasionally, there may be jaundice, which is most common in jejunal atresia.[2] Abdominal tenderness or an abdominal mass are not generally seen as symptoms of intestinal atresia. Rather, abdominal tenderness is a symptom of the late complication meconium peritonitis.[1] Before birth, excess amniotic fluid (polyhydramnios) is a possible symptom. This is more common in duodenal and oesophageal atresia.[1] ## Cause[edit] The most common cause of non-duodenal intestinal atresia is a vascular accident in utero that leads to decreased intestinal perfusion and ischemia of the respective segment of bowel.[3] This leads to narrowing, or in the most severe cases, complete obliteration of the intestinal lumen.[citation needed] In the case that the superior mesenteric artery, or another major intestinal artery, is occluded, large segments of bowel can be entirely underdeveloped (Type III). Classically, the affected area of bowel assumes a spiral configuration and is described to have an "apple peel" like appearance; this is accompanied by lack of a dorsal mesentery (Type IIIb).[citation needed] An inherited form – familial multiple intestinal atresia – has also been described. This disorder was first reported in 1971.[4] It is due to a mutation in the gene TTC7A on short arm of chromosome 2 (2p16). It is inherited as an autosomal recessive gene and is usually fatal in infancy. Ileal atresia can also result as a complication of meconium ileus.[citation needed] A third of infants with intestinal atresia are born prematurely[1] or with low birth weight.[2] ## Diagnosis[edit] Intestinal atresias are often discovered before birth; either during a routine sonogram which shows a dilated intestinal segment due to the blockage, or by the development of polyhydramnios (the buildup of too much amniotic fluid in the uterus). These abnormalities are indications that the fetus may have a bowel obstruction which a more detailed ultrasound study can confirm.[5] Infants with stenosis instead of atresia are often not discovered until several days after birth.[1] Some fetuses with bowel obstruction have abnormal chromosomes. An amniocentesis is recommended because it can determine not only the sex of the baby, but whether or not there is a problem with the chromosomes.[citation needed] If not diagnosed in utero, infants with intestinal atresia are typically diagnosed at day 1 or day 2 after presenting with eating problems, vomiting, and/or failure to have a bowel movement.[3] Diagnosis can be confirmed with an X-ray, and typically followed with an upper gastrointestinal series, lower gastrointestinal series, and ultrasound.[5][3] ### Classification[edit] Sites of small bowel atresia: duodenum, jejunum and ileum #### By location[edit] Intestinal atresia may be classified by its location. Patients may have intestinal atresia in multiple locations.[6] * Duodenal atresia – malformation of the duodenum, part of the intestine that empties from the stomach, and first section of the small intestine * Jejunal atresia – malformation of the jejunum, the second part of the small intestine extending from the duodenum to the ileum, that causes the jejunum to block blood flow to the colon [7] * Ileal atresia – malformation of the ileum, the lower part of the small intestine * Colon atresia – malformation of the colon Malformations may also occur along multiple portions of the intestinal tract; for instance a malformation that occurs along or spans the length of the jejunum and the ileum is termed jejunoileal atresia.[5][3] #### By malformation[edit] Intestinal atresia can also by classified by the type of malformation.[8] The classification system by Bland-Sutton and Louw and Barnard (1955)[9] initially divided them into three types.[8][5] This was later expanded to five by Zerella and Grosfeld et al.[2] ##### Type I[edit] In type I, there is a wall (septum) or membrane at some point in the bowel, leading to dilation of the bowel on the nearer side and a collapse of the bowel on the latter side. Bowel length is not usually affected in this type.[1] ##### Type II[edit] In type II, there is a gap in the bowel, and either end of the remaining intestine is closed off and connected to the other by a fibrous cord that runs along the edge of the mesentery. The mesentery remains intact.[1] ##### Type IIIa[edit] Type IIIa is similar to type II, but the mesentery is defective (there is a V-shaped gap),[10] and the bowel length may be shortened.[1] ##### Type IIIb[edit] In type IIIb, also known as the "apple peel" or "Christmas tree" deformity, the atresia affects the jejunum, and the intestine is often malrotated with most of the mesenteric arteries absent. The remaining ileum, which is of varying length, survives on a single mesenteric artery, which it is twisted around in a spiral form.[1] The term apple-peel intestinal atresia is generally reserved for when it affects the jejunum,[11][12] while Christmas tree intestinal atresia is used if it affects the duodenum. It may affect both, however.[6] ##### Type IV[edit] Type IV involves a combination of all the other types and takes the appearance of a string of sausages. The length of the bowel is always shortened, but the last part of the ileum is usually not affected, as in type III.[1] This type usually affects the nearest end of the jejunum, but the far end of the ileum may instead be affected.[13] ## Treatment[edit] Fetal and neonatal intestinal atresia are treated using laparotomy after birth. If the area affected is small, the surgeon may be able to remove the damaged portion and join the intestine back together. In instances where the narrowing is longer, or the area is damaged and cannot be used for period of time, a temporary stoma may be placed.[citation needed] The infant is usually given intravenous fluid hydration, and a nasogastric or orogastric tube may be used to aspirate the contents of the stomach. The nutritional administration is maintained after surgery until the bowel can resume normal function.[1] ## Prognosis[edit] Complication of ileal atresia, meconium peritonitis, in which the bowel perforated before birth. X-ray shows meconium pseudocyst. Prognosis is usually good if treated with surgery in infancy. The main factor in mortality is the availability of care and appropriate parenteral nutrition after surgery until the bowel can resume normal function.[1] The most common complication is pseudo-obstruction at the site of surgery due to pre-existing intestinal dysmotility. This can usually only be treated by non-surgical methods.[1] If the atresia is not treated, the bowel may become perforated or ischemic. This can lead to abdominal tenderness and meconium peritonitis, which can be fatal.[1] ## Epidemiology[edit] Intestinal atresia occurs in around 1 in 3,000 births in the United States.[1] The most common form of intestinal atresia is duodenal atresia. It has a strong association with Down syndrome.[14] The second-most common type is ileal atresia. 95% of congenital jejunoileal obstructions are atresias; only 5% are stenoses.[2] Prevalence of jejunoileal atresia is 1 to 3 in 10,000 live births. It is weakly associated with cystic fibrosis, intestinal malrotation, and gastroschisis.[3] The frequencies of each type from Louw and Barnard's classification are as follows:[1][15][2] * Type I: 19–23% of cases (mean: 20.6%) * Type II:10–35% of cases (mean: 25.3%) * Type IIIa: 15%–46% of cases (mean: 30%) * Type IIIb ("apple-peel" type): 4–19% of cases (mean: 8.8%) * Type IV: 6–32% of cases (mean: 15.9%). (Note: the mean percentages total higher than 100% due to rounding.) ## History[edit] Ileal atresia was first described in 1684 by Goeller. In 1812, Johann Friedrich Meckel reviewed the topic and speculated on an explanation. In 1889, English surgeon John Bland-Sutton proposed a classification system for intestinal atresia and suggested that it occurs at areas that are obliterated as part of normal development. In 1900, Austrian physician Julius Tandler first put forward the theory that it may be caused by lack of recanalisation during development.[2] The vascular ischemic cause of non-duodenal atresia was confirmed by Louw and Barnard in 1955 and was repeated in later studies. It had first been proposed by N. I. Spriggs in 1912.[2] ## See also[edit] * Atresia * Bowel obstruction * Ileus * Pediatric surgery ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r Alastair John Ward Millar, John R. Gosche, Kokila Lakhoo (2011). "Chapter 63 - Intestinal Atresia and Stenosis" (PDF).CS1 maint: multiple names: authors list (link) 2. ^ a b c d e f g h i j Prasad, T. R. Sai; Bajpai, M. (2000-09-01). "Intestinal atresia". The Indian Journal of Pediatrics. 67 (9): 671–678. doi:10.1007/BF02762182. ISSN 0973-7693. PMID 11028122. S2CID 45391970. 3. ^ a b c d e William J. Cochran, MD. "Jejunoileal Atresia - Pediatrics". MSD Manual Professional Edition. Retrieved 2019-02-03. 4. ^ Mishalany, Henry G.; Der Kaloustian, Vazken M. (July 1971). "Familial multiple-level intestinal atresias: Report of two siblings". The Journal of Pediatrics. 79 (1): 124–125. doi:10.1016/s0022-3476(71)80072-0. ISSN 0022-3476. PMID 5091250. 5. ^ a b c d "Jejunoileal Atresia". Short Bowel Foundation. Retrieved 2019-02-03. 6. ^ a b Federici, S.; Domenichelli, V.; Antonellini, C.; Dòmini, R. (August 2003). "Multiple intestinal atresia with apple peel syndrome: successful treatment by five end-to-end anastomoses, jejunostomy, and transanastomotic silicone stent". Journal of Pediatric Surgery. 38 (8): 1250–1252. doi:10.1016/S0022-3468(03)00281-1. ISSN 1531-5037. PMID 12891506. 7. ^ Jejunal Atresia. Genetic and Rare Diseases Information Center (GARD) https://rarediseases.info.nih.gov/diseases/6799/jejunal-atresia 8. ^ a b Shorter, Nicholas A.; Georges, Anthony; Perenyi, Agnes; Garrow, Eugene (Nov 2006). "A proposed classification system for familial intestinal atresia and its relevance to the understanding of the etiology of jejunoileal atresia". Journal of Pediatric Surgery. 41 (11): 1822–1825. doi:10.1016/j.jpedsurg.2006.06.008. ISSN 0022-3468. PMID 17101351. 9. ^ Louw, J.H.; Barnard, C.N. (Nov 1955). "Congenital Intestinal Atresia Observations on ITS Origin". The Lancet. 266 (6899): 1065–1067. doi:10.1016/s0140-6736(55)92852-x. ISSN 0140-6736. PMID 13272331. 10. ^ Prasad, T. R. Sai; Bajpai, M. (2000-09-01). "Intestinal atresia". The Indian Journal of Pediatrics. 67 (9): 671–678. doi:10.1007/BF02762182. ISSN 0973-7693. PMID 11028122. S2CID 45391970. 11. ^ Blyth, H; Dickson, J A (September 1969). "Apple peel syndrome (congenital intestinal atresia): a family study of seven index patients". Journal of Medical Genetics. 6 (3): 275–277. doi:10.1136/jmg.6.3.275. ISSN 0022-2593. PMC 1468754. PMID 5345098. 12. ^ Gaillard, Frank. "Apple-peel intestinal atresia". Radiopaedia. Retrieved 2019-02-01. 13. ^ Prasad, T. R. Sai; Bajpai, M. (2000-09-01). "Intestinal atresia". The Indian Journal of Pediatrics. 67 (9): 671–678. doi:10.1007/BF02762182. ISSN 0973-7693. PMID 11028122. S2CID 45391970. 14. ^ Le, Tao (2013). First Aid for the USMLE STEP. New York: Mc Graw Hill. p. 308. ISBN 978-0-07-180232-1. 15. ^ Federici, S.; Domenichelli, V.; Antonellini, C.; Dòmini, R. (2003-08-01). "Multiple intestinal atresia with apple peel syndrome: successful treatment by five end-to-end anastomoses, jejunostomy, and transanastomotic silicone stent". Journal of Pediatric Surgery. 38 (8): 1250–1252. doi:10.1016/S0022-3468(03)00281-1. ISSN 0022-3468. PMID 12891506. ## External links[edit] Classification D * ICD-10: Q41, Q42 * ICD-9-CM: 751.1 751.2 * OMIM: 223400 243600 * MeSH: D007409 * DiseasesDB: 31514 * v * t * e Congenital malformations and deformations of digestive system Upper GI tract Tongue, mouth and pharynx * Cleft lip and palate * Van der Woude syndrome * tongue * Ankyloglossia * Macroglossia * Hypoglossia Esophagus * EA/TEF * Esophageal atresia: types A, B, C, and D * Tracheoesophageal fistula: types B, C, D and E * esophageal rings * Esophageal web (upper) * Schatzki ring (lower) Stomach * Pyloric stenosis * Hiatus hernia Lower GI tract Intestines * Intestinal atresia * Duodenal atresia * Meckel's diverticulum * Hirschsprung's disease * Intestinal malrotation * Dolichocolon * Enteric duplication cyst Rectum/anal canal * Imperforate anus * Rectovestibular fistula * Persistent cloaca * Rectal atresia Accessory Pancreas * Annular pancreas * Accessory pancreas * Johanson–Blizzard syndrome * Pancreas divisum Bile duct * Choledochal cysts * Caroli disease * Biliary atresia Liver * Alagille syndrome * Polycystic liver disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Intestinal atresia	c0021828	28,654	wikipedia	https://en.wikipedia.org/wiki/Intestinal_atresia	2021-01-18T18:55:19	{"mesh": ["D007409"], "umls": ["C0021828"], "icd-9": ["751.2", "751.1"], "wikidata": ["Q4597494"]}
Autosomal spastic paraplegia type 30 is a form of hereditary spastic paraplegia characterized by either a pure spastic paraplegia phenotype, usually presenting in the first or second decade of life, with spastic lower extremities, unsteady spastic gait, hyperreflexia and extensor plantar responses, or as a complicated phenotype with the additional manifestations of distal wasting, saccadic ocular movements, mild cerebellar ataxia and mild, distal, axonal neuropathy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autosomal spastic paraplegia type 30	c1835896	28,655	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101010	2021-01-23T17:02:02	{"mesh": ["C563677"], "omim": ["610357"], "umls": ["C1835896"], "icd-10": ["G11.4"], "synonyms": ["SPG30"]}
Methanol poisoning is a rare poisoning resulting in elevated anion gap metabolic acidosis, due to the alcohol dehydrogenase (ADH)-mediated production of formic acid (which is poisonous to the central nervous system), and characterized by dizziness, nausea, vomiting, confusion, metabolic acidosis, visual disturbances (which if left untreated can lead to blindness), coma, and death (due to respiratory failure). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Methanol poisoning	c0392621	28,656	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=31825	2021-01-23T17:36:15	{"icd-10": ["T51.1"]}
A developmental disorder affecting premature infants, likely secondary to an immaturity of respiratory control resulting in idiopathic pauses in breathing often associated with reduced heart rate and arterial blood oxygen levels. It may be exacerbated by concurrent neonatal diseases. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Apnea of prematurity	c0475715	28,657	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99981	2021-01-23T17:23:27	{"umls": ["C0475715"], "icd-10": ["P28.4"]}
Hypogonadotropic hypogonadism Other namesSecondary hypogonadism Hypogonadotropic hypogonadism (HH), is due to problems with either the hypothalamus or pituitary gland affecting the hypothalamic-pituitary-gonadal axis (HPG axis).[1] Hypothalamic disorders result from a deficiency in the release of gonadotropic releasing hormone (GnRH), while pituitary gland disorders are due to a deficiency in the release of gonadotropins from the anterior pituitary.[1] GnRH is the central regulator in reproductive function and sexual development via the HPG axis. GnRH is released by hypothalamic neuroendocrine cells into the hypophyseal portal system acting on gonadotrophs in the anterior pituitary. [1] The release of gonadotropins, LH and FSH, act on the gonads for the development and maintenance of proper adult reproductive physiology. LH acts on Leydig cells in the male testes and theca cells in the female. FSH acts on Sertoli cells in the male and follicular cells in the female. Combined this causes the secretion of gonadal sex steroids and the initiation of folliculogenesis and spermatogenesis. The production of sex steroids forms a negative feedback loop acting on both the anterior pituitary and hypothalamus causing a pulsatile secretion of GnRH. [1] GnRH neurons lack sex steroid receptors and mediators such as kisspeptin stimulate GnRH neurons for pulsatile secretion of GnRH. [2] ## Contents * 1 Types * 2 Pathogenesis * 3 Diagnosis * 4 Management * 5 See also * 6 References * 7 External links ## Types[edit] There are two subtypes of HH, congenital HH (CHH) and acquired HH (AHH).[3] CHH is due to genetic abnormalities resulting in non-functional GnRH secreting neurons or gonadotropic cell dysfunction in the anterior pituitary. CHH is divided into 2 subtypes depending on the condition of the olfactory system, anosmic HH (Kallman syndrome) and normosmic HH. [4] AHH is an acquired form of the disease often occurring after sexual maturation and is not related to genetic defects. [3] ## Pathogenesis[edit] CHH is a type of HH resulting from the abnormal migration of GnRH neurons during embryonic development. GnRH neurons are derived from the olfactory placode and migrate into the central nervous system (CNS) during embryonic development. Embryonic migration can be affected by several gene mutations including but not limited to, KAL1, fibroblast growth factor (FGF8), sex determining region Y-Box 10 (SOX10), GNRHR, GNRH1 and KISS1R .[3] Kallmann syndrome results in a loss of smell (anosmia) and is associated with KAL1 mutations. The KAL1 gene encodes anosmin-1, an extracellular adhesion molecule that plays a role in GnRH neuronal migration and adhesion.[3] Mutated KAL1 genes leads to ill GnRH neuronal migration as well as olfactory neuron disorder causing anosmia and non-functional GnRH releasing neurons. Mutations of KAL1 are mostly nucleotide insertion or deletion causing frame shifts in the translation of anosmin-1 resulting in a faulty protein. [4] Inactivating mutations in the genes encoding GNRH1 or its receptor will result in the failure of the HPG axis and give rise to normosmic CHH. [2] Inactivating mutations of KISS1 or KISS1R causes normosmic CHH in humans [2] This is because KISS1 is the mediator for the feedback loop in the HPG axis allowing low levels of sex steroid to stimulate GnRH secretion from the hypothalamus.[citation needed] CHH is a genetically heterogenous disorder with cases reported as being X-linked, recessive and autosomally inherited. [5] The prevalence has been estimated to be 1/4000 to 1/10000 in males and 2 to 5 times less frequent in females. The prevalence difference between male and females is unknown, and is likely to be underreported for females. [5] Acquired hypogonadotropic hypogonadism (AHH) is a postnatal onset of a GnRH releasing disorder and/or pituitary gonadotroph cell disorder. [3] There are many causes of AHH, mostly due to structural or functional abnormalities involving the HPG axis such as sarcoidosis, lymphocytic hypophysitis, pituitary adenomas, craniopharyngiomas and other CNS tumours. Most of these patients have multiple pituitary hormone deficiencies. [5] Hyperprolactinaemia is the most common cause of AHH. It is a well-established cause of infertility in both male and female mammals.[6] Prolactin inhibits GnRH neurons and therefore inhibits the subsequent release of LH, FSH and sex steroids. The mechanism of prolactin induced inhibition of GnRH release is poorly understood. [6] It is suspected that the prolactin receptor is expressed on a small subset of GnRH neurons in mice and thus has a direct inhibitory effect on GnRH release. There is evidence to suggest indirect inhibition of GnRH neurons mediated by other neurotransmitters such as dopamine, opioid, neuropeptide Y and γ-aminobutyric acid. [6] Drug usage of glucocorticoids and opioid analgesics in high dosages can lead to the inhibition of GnRH synthesis. [7] Opioid receptors reside in the hypothalamus and when bound to opioids they decrease the normal pulsatile secretion of GnRH and therefore result in HH. [7] Chronic treatment with supraphysiological doses of glucocorticoids results in a marked decrease in testosterone without an increase of LH levels, suggestive of a central mechanism of induced HH. [7] ## Diagnosis[edit] The clinical presentation of HH depend on the time of onset as well as the severity of the defect. [5] Diagnostic tests to measure GnRH levels are difficult. This is because GnRH is confined within hypophyseal portal system and has a short half-life of 2–4 minutes. [4] GnRH levels are thus checked indirectly via LH and FSH levels which will be totally or partially absent in HH. Exogenous GnRH can be used as a diagnostic tool. If the patient has hypothalamic GnRH deficiency, LH and FSH will gradually appear in response to the exogenous GnRH but in pituitary cases of HH, a minimal response will be generated. [8] Typically, CHH is diagnosed in adolescence due to a lack of pubertal development, but it can be possible to diagnose in male neonates. Clinical presentations of CHH involve an absence of puberty by 18 years of age, poorly developed secondary sexual characteristics, or infertility. [5] In men with CHH, serum levels of inhibin B are typically very low as inhibin B is a marker of Sertoli cell number. [3] For females, CHH is most commonly revealed by primary amenorrhea. Breast development is variable and pubic hair may or may not be present. [8] CHH can be diagnosed in the male neonate with cryptorchidism (maldescended testes) and a micropenis as signs of GnRH deficiency. [3] There are no clear signs of CHH in female neonates. [3] Another clinical sign of CHH, more specifically Kallmann syndrome, is a lack of a sense of smell due to the altered migration of GnRH neurons on the olfactory placode. Kallmann syndrome can also be shown through MRI imaging with irregular morphology or aplasia of the olfactory bulb and olfactory sulci. Anterior pituitary function must be normal for all other axes in CHH as it is an isolated disorder. [5] Testing anterior pituitary function is helpful to identify if the HH is due to hyperprolactinemia. [8] ## Management[edit] The goal for HH therapy is to induce pubertal development, sexual function, fertility, bone health, and psychological wellbeing [3] Testosterone therapy for males and estradiol therapy for females is used to improve genital development, develop secondary sexual characteristics, allow for the growth and closure of the epiphyseal plate, as well as improving sexual function. [5] This therapy does not restore fertility as gonadotropins are required for spermatogenesis and folliculogenesis. If fertility is desired, pulsatile GnRH therapy or gonadotropin therapy is necessary.[5] Gonadotropin therapy involves the use of human chorionic gonadotropin (hCG) and FSH. In the male, hCG stimulates Leydig cells to produce testosterone so that plasma and testicular levels increase. With the increased levels of testosterone, sexual activity, libido and overall wellbeing should improve. [1] Administration of FSH is required to induce spermatogenesis by acting on Sertoli cells. FSH is required for maintaining the production of high numbers of good quality sperm. Gonadotropin therapy in HH men usually is able to generate enough sperm for fertility to occur, however sperm count is still lower than normal. [1] In the female, the goal for gonadotropin therapy is to obtain ovulation. This is obtained with FSH treatment followed by hCG or LH to trigger ovulation. FSH will stimulate granulosa cells for follicular maturation while LH will act on luteal cells to produce steroids aiding follicular maturation and preparing the endometrium for pregnancy.[citation needed] For hyperprolactinaemia-caused AHH, dopamine agonists are used to improve GnRH secretion. Dopamine binds to D2 receptors on lactotrophs within the anterior pituitary [6] This results in the inhibition of secretion of prolactin resulting in less direct and indirect inhibition of GnRH secretion.[citation needed] In up to 10-20% of cases, patients can exhibit sustained fertility and steroid production after therapy, resulting in hypogonadotropic hypogonadism reversal. The mechanism for this reversal is unknown but there is believed to be some neuronal plasticity within GnRH releasing cells. [4] ## See also[edit] * Isolated hypogonadotropic hypogonadism * Hypergonadotropic hypogonadism * Kallmann syndrome * Hypothalamic–pituitary–gonadal axis * GnRH and gonadotropins (FSH and LH) * androgens and estrogens ## References[edit] 1. ^ a b c d e f Basaria S (2014). "Male hypogonadism". The Lancet. 383 (9924): 1250–1263. doi:10.1016/S0140-6736(13)61126-5. PMID 24119423. S2CID 30479724. 2. ^ a b c Topaloglu AK, Tello JA, Kotan LD, Ozbek MN, Yilmaz MB, Erdogan S, Gurbuz F, Temiz F, Millar RP, Yuksel B (2012). "Inactivating KISS1 Mutation and Hypogonadotropic Hypogonadism" (PDF). The New England Journal of Medicine. 366 (7): 629–635. doi:10.1056/NEJMoa1111184. hdl:2263/18519. PMID 22335740. 3. ^ a b c d e f g h i Boehm U, Bouloux P, Dattani M, de Roux N, Dodé C, Dunkel L, Dwyer A, Giacobini P, Hardelin J, Juul A, Maghnie M, Pitteloud N, Prevot V, Raivio T, Tena-Sempere M, Quinton R, Young J (2015). "European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment". Nature Reviews Endocrinology. 11 (9): 158–162. doi:10.1038/nrendo.2015.112. PMID 26194704. 4. ^ a b c d Fraietta R, Zylberstejn D, Esteves S (2013). "Hypogonadotropic Hypogonadism Revisited". Clinics. 68 (S1): 81–88. doi:10.6061/clinics/2013(Sup01)09. PMC 3583156. PMID 23503957. 5. ^ a b c d e f g h Silveira L, Latronico A (2013). "Approach to the Patient With Hypogonadotropic Hypogonadism". The Journal of Clinical Endocrinology & Metabolism. 98 (5): 1781–1788. doi:10.1210/jc.2012-3550. PMID 23650335. 6. ^ a b c d Grattan DR, Jasoni CL, Liu X, Anderson GM, Herbison, AE (2007). "Prolactin regulation of gonadotropin-releasing hormone neurons to suppress luteinizing hormone secretion in mice". Endocrinology. 148 (9): 4344–4351. doi:10.1210/en.2007-0403. PMID 17569755. 7. ^ a b c Lenzi A, Balercia G, Bellastella A, Colao A, Fabbri A, Foresta C, Galdiero M, Gandini L, Krausz C, Lombardi G, Lombardo F, Maggi M, Radicioni A, Selice R, Sinisi A, Forti G (2009). "Epidemiology; diagnosis, and treatment of male hypogonadotropic hypogonadism". Journal of Endocrinological Investigation. 32 (11): 934–938. doi:10.1007/BF03345775. PMID 19955846. S2CID 72632426. 8. ^ a b c Bry-Gauillard H, Trabado S, Bouligand J, Sarfati J, Francou B, Salenave S, Chanson P, Brailly-Tabard S, Guiochon-Mantel A, Young J (2010). "Congenital hypogonadotropic hypogonadism in females: Clinical spectrum, evaluation and genetics". Annales d'Endocrinologie. 71 (3): 158–162. doi:10.1016/j.ando.2010.02.024. PMID 20363464. ## External links[edit] Classification D * ICD-10: N91.1 External resources * MedlinePlus: 000390 * v * t * e Gonadal disorder Ovarian * Polycystic ovary syndrome * Premature ovarian failure * Estrogen insensitivity syndrome * Hyperthecosis Testicular Enzymatic * 5α-reductase deficiency * 17β-hydroxysteroid dehydrogenase deficiency * aromatase excess syndrome Androgen receptor * Androgen insensitivity syndrome * Familial male-limited precocious puberty * Partial androgen insensitivity syndrome Other * Sertoli cell-only syndrome General * Hypogonadism * Delayed puberty * Hypergonadism * Precocious puberty * Hypoandrogenism * Hypoestrogenism * Hyperandrogenism * Hyperestrogenism * Postorgasmic illness syndrome * Cytochrome P450 oxidoreductase deficiency * Cytochrome b5 deficiency * Androgen-dependent condition * Aromatase deficiency * Complete androgen insensitivity syndrome * Mild androgen insensitivity syndrome * Hypergonadotropic hypogonadism * Hypogonadotropic hypogonadism * Fertile eunuch syndrome * Estrogen-dependent condition * Premature thelarche * Gonadotropin insensitivity * Hypergonadotropic hypergonadism [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hypogonadotropic hypogonadism	c0271623	28,658	wikipedia	https://en.wikipedia.org/wiki/Hypogonadotropic_hypogonadism	2021-01-18T18:33:22	{"mesh": ["D007006"], "wikidata": ["Q1641332"]}
PTEN hamartoma tumor syndrome (PHTS) is a term defining a group of clinically heterogeneous disorders united by a germline PTEN mutation and the involvement of derivatives of all 3 germ cell layers, manifesting with hamartomas, overgrowth and neoplasia. Currently, subsets carrying clinical diagnoses of Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus and Proteus-like syndromes and SOLAMEN syndrome (see these terms) belong to PHTS. ## Epidemiology The prevalence is unknown. ## Clinical description Disease onset depends on the specific disorder. The most important component seen in this group are malignancies and include breast carcinomas in women with an 85% lifetime risk, epithelial thyroid carcinomas with a 35% lifetime risk, endometrial carcinomas with a 28% lifetime risk, renal cell carcinomas with a 32% lifetime risk and colorectal carcinoma with a 10% lifetime risk. Epithelial thyroid cancer has been diagnosed before the age of 18 years and as early as 6 years of age. Non-malignant components of PHTS vary but include macrocephaly (in >90% of individuals), benign thyroid pathology (especially Hashimoto thyroiditis), mucocutaneous hamartomas, colonic polyps (in >90% of individuals who have received a colonoscopy) and vascular malformations. ## Etiology By definition, all individuals with PHTS carry germline mutations in the phosphatase and tensin homolog PTEN gene. The canonical PTEN pathway antagonizes phosphoinositide 3-kinase (PI3K) and downregulates P-AKT resulting in control of the cell cycle, apoptosis, migration and genome stability. There are other additional non-canonical functions of PTEN. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	PTEN hamartoma tumor syndrome	c1959582	28,659	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=306498	2021-01-23T17:08:49	{"gard": ["12800"], "mesh": ["D006223"], "umls": ["C1959582"], "synonyms": ["PHTS"]}
A rare, genetic, primary lipodystrophy syndrome characterized by severe developmental delay and intellectual disability, hypertonia, hyperreflexia, microcephaly, tightly adherent skin, an aged appearance, severe generalized lipodystrophy, and distinct facial dysmorphism which includes large prominent eyes, narrow nasal bridge, tented upper lip vermilion, an open mouth, and high-arched palate. Laboratory analysis of serum and urine are normal. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Keppen-Lubinsky syndrome	c3279800	28,660	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=435628	2021-01-23T18:54:33	{"omim": ["614098"], "icd-10": ["E88.1"], "synonyms": ["Generalized lipodystrophy-progeroid features-severe intellectual disability syndrome"]}
Steatocystoma multiplex Other namesEpidermal polycystic disease and Sebocystomatosis[1]:781 SpecialtyDermatology Steatocystoma multiplex, is a benign, autosomal dominant congenital condition resulting in multiple cysts on a person's body. Steatocystoma simplex is the solitary counterpart to steatocystoma multiplex.[2] In steatocystoma multiplex, the tendency to develop cysts is inherited in an autosomal dominant fashion, so one parent can be expected to also have steatocystoma multiplex. It may also occur sporadically. Both males and females may be affected. The onset at puberty is presumably due to hormonal stimulus of the pilosebaceous unit. They most often arise on the chest and may also occur on the abdomen, upper arms, armpits and face. In some cases cysts may develop all over the body. The cysts are mostly small (2-20 mm) but they may be several centimetres in diameter. They tend to be soft to firm semi-translucent bumps, and contain an oily, yellow liquid. Sometimes a small central punctum can be identified and they may contain one or more hairs (eruptive vellus hair cysts). They may become inflamed and heal with scarring, like acne nodules (see nodulocystic acne and hidradenitis suppurativa). Steatocystomas are thought to come from an abnormal lining of the passageway to the oil glands (sebaceous duct). Localised, generalised, facial, acral, and suppurative types of steatocystoma multiplex have been described. ## Contents * 1 Causes * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 External links ## Causes[edit] Relative incidence of cutaneous cysts. Steatocystoma is labeled at right. It is associated with defects in Keratin 17.[3] The condition is inherited in an autosomal dominant manner. This indicates that the defective gene responsible for a disorder is located on an autosome, and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. However, a solitary case can also emerge in a family with no prior history of the disorder due to the occurrence of a mutation (often referred to as a sporadic or spontaneous mutation).[citation needed] ## Diagnosis[edit] It is difficult to diagnose genetic and rare diseases. Healthcare professionals would look at a combination of a patient's medical history, symptoms, physical exam and other laboratory tests to inform their diagnosis.[4] ## Treatment[edit] The cysts can be removed via excision, though conventional cyst excision techniques have proven impractical, and a specialized regimen is required.[5] Cryotherapy and electrosessication may also be tried, but since it is genetic disorder so all the modalties have very little effect. Individual cysts can be removed surgically. In most cases, small incisions (cuts into the skin) allow the cyst and its contents to be extracted through the opening. If it is tethered to the underlying skin, excision biopsy may be necessary. Cysts can also be removed by laser, electrosurgery or cryotherapy. Inflammation can be reduced with oral antibiotics. Oral isotretinoin is not curative but may temporarily shrink the cysts and reduce inflammation.[6] ## See also[edit] * Keratin disease * Steatocystoma simplex * List of cutaneous conditions * List of cutaneous conditions caused by mutations in keratins ## References[edit] 1. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 2. ^ Davey, Mathew. "Steatocystoma Multiplex". Retrieved 25 May 2011. 3. ^ Smith FJ, Corden LD, Rugg EL, et al. (1997). "Missense mutations in keratin 17 cause either pachyonychia congenita type 2 or a phenotype resembling steatocystoma multiplex". J. Invest. Dermatol. 108 (2): 220–3. doi:10.1111/1523-1747.ep12335315. PMID 9008238. 4. ^ "Steatocystoma multiplex \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2021-01-02. 5. ^ Pamoukian VN, Westreich M (1997). "Five generations with steatocystoma multiplex congenita: a treatment regimen". Plast. Reconstr. Surg. 99 (4): 1142–6. doi:10.1097/00006534-199704000-00036. PMID 9091916. 6. ^ "Steatocystoma multiplex \| DermNet NZ". dermnetnz.org. Retrieved 2020-07-10. ## External links[edit] Classification D * ICD-10: L72.2 * ICD-9-CM: 706.2 * OMIM: 184500 * MeSH: D062685 * DiseasesDB: 29808 External resources * eMedicine: derm/404 * v * t * e Disorders of skin appendages Nail * thickness: Onychogryphosis * Onychauxis * color: Beau's lines * Yellow nail syndrome * Leukonychia * Azure lunula * shape: Koilonychia * Nail clubbing * behavior: Onychotillomania * Onychophagia * other: Ingrown nail * Anonychia * ungrouped: Paronychia * Acute * Chronic * Chevron nail * Congenital onychodysplasia of the index fingers * Green nails * Half and half nails * Hangnail * Hapalonychia * Hook nail * Ingrown nail * Lichen planus of the nails * Longitudinal erythronychia * Malalignment of the nail plate * Median nail dystrophy * Mees' lines * Melanonychia * Muehrcke's lines * Nail–patella syndrome * Onychoatrophy * Onycholysis * Onychomadesis * Onychomatricoma * Onychomycosis * Onychophosis * Onychoptosis defluvium * Onychorrhexis * Onychoschizia * Platonychia * Pincer nails * Plummer's nail * Psoriatic nails * Pterygium inversum unguis * Pterygium unguis * Purpura of the nail bed * Racquet nail * Red lunulae * Shell nail syndrome * Splinter hemorrhage * Spotted lunulae * Staining of the nail plate * Stippled nails * Subungual hematoma * Terry's nails * Twenty-nail dystrophy Hair Hair loss/ Baldness * noncicatricial alopecia: Alopecia * areata * totalis * universalis * Ophiasis * Androgenic alopecia (male-pattern baldness) * Hypotrichosis * Telogen effluvium * Traction alopecia * Lichen planopilaris * Trichorrhexis nodosa * Alopecia neoplastica * Anagen effluvium * Alopecia mucinosa * cicatricial alopecia: Pseudopelade of Brocq * Central centrifugal cicatricial alopecia * Pressure alopecia * Traumatic alopecia * Tumor alopecia * Hot comb alopecia * Perifolliculitis capitis abscedens et suffodiens * Graham-Little syndrome * Folliculitis decalvans * ungrouped: Triangular alopecia * Frontal fibrosing alopecia * Marie Unna hereditary hypotrichosis Hypertrichosis * Hirsutism * Acquired * localised * generalised * patterned * Congenital * generalised * localised * X-linked * Prepubertal Acneiform eruption Acne * Acne vulgaris * Acne conglobata * Acne miliaris necrotica * Tropical acne * Infantile acne/Neonatal acne * Excoriated acne * Acne fulminans * Acne medicamentosa (e.g., steroid acne) * Halogen acne * Iododerma * Bromoderma * Chloracne * Oil acne * Tar acne * Acne cosmetica * Occupational acne * Acne aestivalis * Acne keloidalis nuchae * Acne mechanica * Acne with facial edema * Pomade acne * Acne necrotica * Blackhead * Lupus miliaris disseminatus faciei Rosacea * Perioral dermatitis * Granulomatous perioral dermatitis * Phymatous rosacea * Rhinophyma * Blepharophyma * Gnathophyma * Metophyma * Otophyma * Papulopustular rosacea * Lupoid rosacea * Erythrotelangiectatic rosacea * Glandular rosacea * Gram-negative rosacea * Steroid rosacea * Ocular rosacea * Persistent edema of rosacea * Rosacea conglobata * variants * Periorificial dermatitis * Pyoderma faciale Ungrouped * Granulomatous facial dermatitis * Idiopathic facial aseptic granuloma * Periorbital dermatitis * SAPHO syndrome Follicular cysts * "Sebaceous cyst" * Epidermoid cyst * Trichilemmal cyst * Steatocystoma * simplex * multiplex * Milia Inflammation * Folliculitis * Folliculitis nares perforans * Tufted folliculitis * Pseudofolliculitis barbae * Hidradenitis * Hidradenitis suppurativa * Recurrent palmoplantar hidradenitis * Neutrophilic eccrine hidradenitis Ungrouped * Acrokeratosis paraneoplastica of Bazex * Acroosteolysis * Bubble hair deformity * Disseminate and recurrent infundibulofolliculitis * Erosive pustular dermatitis of the scalp * Erythromelanosis follicularis faciei et colli * Hair casts * Hair follicle nevus * Intermittent hair–follicle dystrophy * Keratosis pilaris atropicans * Kinking hair * Koenen's tumor * Lichen planopilaris * Lichen spinulosus * Loose anagen syndrome * Menkes kinky hair syndrome * Monilethrix * Parakeratosis pustulosa * Pili (Pili annulati * Pili bifurcati * Pili multigemini * Pili pseudoannulati * Pili torti) * Pityriasis amiantacea * Plica neuropathica * Poliosis * Rubinstein–Taybi syndrome * Setleis syndrome * Traumatic anserine folliculosis * Trichomegaly * Trichomycosis axillaris * Trichorrhexis (Trichorrhexis invaginata * Trichorrhexis nodosa) * Trichostasis spinulosa * Uncombable hair syndrome * Wooly hair nevus Sweat glands Eccrine * Miliaria * Colloid milium * Miliaria crystalline * Miliaria profunda * Miliaria pustulosa * Miliaria rubra * Occlusion miliaria * Postmiliarial hypohidrosis * Granulosis rubra nasi * Ross’ syndrome * Anhidrosis * Hyperhidrosis * Generalized * Gustatory * Palmoplantar Apocrine * Body odor * Chromhidrosis * Fox–Fordyce disease Sebaceous * Sebaceous hyperplasia * v * t * e Cytoskeletal defects Microfilaments Myofilament Actin * Hypertrophic cardiomyopathy 11 * Dilated cardiomyopathy 1AA * DFNA20 * Nemaline myopathy 3 Myosin * Elejalde syndrome * Hypertrophic cardiomyopathy 1, 8, 10 * Usher syndrome 1B * Freeman–Sheldon syndrome * DFN A3, 4, 11, 17, 22; B2, 30, 37, 48 * May–Hegglin anomaly Troponin * Hypertrophic cardiomyopathy 7, 2 * Nemaline myopathy 4, 5 Tropomyosin * Hypertrophic cardiomyopathy 3 * Nemaline myopathy 1 Titin * Hypertrophic cardiomyopathy 9 Other * Fibrillin * Marfan syndrome * Weill–Marchesani syndrome * Filamin * FG syndrome 2 * Boomerang dysplasia * Larsen syndrome * Terminal osseous dysplasia with pigmentary defects IF 1/2 * Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1 * Striate palmoplantar keratoderma 3 * Epidermolytic hyperkeratosis * IHCM * KRT2E (Ichthyosis bullosa of Siemens) * KRT3 (Meesmann juvenile epithelial corneal dystrophy) * KRT4 (White sponge nevus) * KRT5 (Epidermolysis bullosa simplex) * KRT8 (Familial cirrhosis) * KRT10 (Epidermolytic hyperkeratosis) * KRT12 (Meesmann juvenile epithelial corneal dystrophy) * KRT13 (White sponge nevus) * KRT14 (Epidermolysis bullosa simplex) * KRT17 (Steatocystoma multiplex) * KRT18 (Familial cirrhosis) * KRT81/KRT83/KRT86 (Monilethrix) * Naegeli–Franceschetti–Jadassohn syndrome * Reticular pigmented anomaly of the flexures 3 * Desmin: Desmin-related myofibrillar myopathy * Dilated cardiomyopathy 1I * GFAP: Alexander disease * Peripherin: Amyotrophic lateral sclerosis 4 * Neurofilament: Parkinson's disease * Charcot–Marie–Tooth disease 1F, 2E * Amyotrophic lateral sclerosis 5 * Laminopathy: LMNA * Mandibuloacral dysplasia * Dunnigan Familial partial lipodystrophy * Emery–Dreifuss muscular dystrophy 2 * Limb-girdle muscular dystrophy 1B * Charcot–Marie–Tooth disease 2B1 * LMNB * Barraquer–Simons syndrome * LEMD3 * Buschke–Ollendorff syndrome * Osteopoikilosis * LBR * Pelger–Huet anomaly * Hydrops-ectopic calcification-moth-eaten skeletal dysplasia Microtubules Kinesin * Charcot–Marie–Tooth disease 2A * Hereditary spastic paraplegia 10 Dynein * Primary ciliary dyskinesia * Short rib-polydactyly syndrome 3 * Asphyxiating thoracic dysplasia 3 Other * Tauopathy * Cavernous venous malformation Membrane * Spectrin: Spinocerebellar ataxia 5 * Hereditary spherocytosis 2, 3 * Hereditary elliptocytosis 2, 3 Ankyrin: Long QT syndrome 4 * Hereditary spherocytosis 1 Catenin * APC * Gardner's syndrome * Familial adenomatous polyposis * plakoglobin (Naxos syndrome) * GAN (Giant axonal neuropathy) Other * desmoplakin: Striate palmoplantar keratoderma 2 * Carvajal syndrome * Arrhythmogenic right ventricular dysplasia 8 * plectin: Epidermolysis bullosa simplex with muscular dystrophy * Epidermolysis bullosa simplex of Ogna * plakophilin: Skin fragility syndrome * Arrhythmogenic right ventricular dysplasia 9 * centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II) Related topics: Cytoskeletal proteins [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Steatocystoma multiplex	c3671377	28,661	wikipedia	https://en.wikipedia.org/wiki/Steatocystoma_multiplex	2021-01-18T18:44:44	{"gard": ["5003"], "mesh": ["C580471", "D062685"], "umls": ["C3671377"], "icd-9": ["706.2"], "icd-10": ["L72.2"], "orphanet": ["841"], "wikidata": ["Q3972207"]}
Orofaciodigital syndrome 1 Other namesOFDI, OFDSI, Oral-facial-digital syndrome type 1 This condition is inherited in an X-linked dominant manner. SpecialtyMedical genetics Orofaciodigital syndrome 1 (OFD1), also called Papillon-League and Psaume syndrome,[1] is an X-linked congenital disorder characterized by malformations of the face, oral cavity, and digits with polycystic kidney disease and variable involvement of the central nervous system.[2] ## Contents * 1 Cause * 1.1 Relation to other rare genetic disorders * 2 Diagnosis * 3 Management * 4 See also * 5 References * 6 Further reading * 7 External links ## Cause[edit] Orofaciodigital syndrome type 1 is caused by mutations in the OFD1 gene. OFD1 localizes to both centrosomes and basal bodies within the human genetic cellular structure. This suggests that this syndrome may fall into a broad category of ciliary diseases. The ciliary organelles are present in many cellular types throughout the human body. Cilia defects adversely affect numerous critical developmental signaling pathways essential to cellular development.[2] Other types include: * OMIM: 252100 Mohr syndrome; Orofaciodigital syndrome 2 at NIH's Office of Rare Diseases * OMIM: 258860 Orofaciodigital syndrome 4 at NIH's Office of Rare Diseases * OMIM: 300238 Orofaciodigital syndrome, Shashi type at NIH's Office of Rare Diseases * OMIM: 277170 Varadi Papp syndrome; OFD6 at NIH's Office of Rare Diseases ### Relation to other rare genetic disorders[edit] Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genotypical root cause of these widely varying, phenotypically-observed disorders. Orofaciodigital syndrome has been found to be a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney disease and polycystic liver disease, nephronophthisis, Alström syndrome, Meckel–Gruber syndrome and some forms of retinal degeneration.[2] ## Diagnosis[edit] Orofaciodigital syndrome type 1 is diagnosed through genetic testing. Some symptoms of Orofaciodigital syndrome type 1 are oral features such as, split tongue, benign tumors on the tongue, cleft palate, hypodontia and other dental abnormalities. Other symptoms of the face include hypertelorism and micrognathia. Bodily abnormalities such as webbed, short, joined, or abnormally curved fingers and toes are also symptoms of Orofaciodigital syndrome type 1. The most frequent symptoms are accessory oral frenulum, broad alveolar ridges, frontal bossing, high palate, hypertelorism, lobulated tongue, median cleft lip, and wide nasal bridge. Genetic screening of the OFD1 gene is used to officially diagnose a patient who has the syndrome, this is detected in 85% of individuals who are suspected to have Orofaciodigital syndrome type 1.[3][4] ## Management[edit] Orofaciodigital syndrome type 1 can be treated with reconstructive surgery or the affected parts of the body. Surgery of cleft palate, tongue nodules, additional teeth, accessory frenulae, and orthodontia for malocclusion. Routine treatment for patients with renal disease and seizures may also be necessary. Speech therapy and special education in the later development may also be used as management.[5] ## See also[edit] * OFD1 ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): 311200 2. ^ a b c Badano JL, Mitsuma N, Beales PL, Katsanis N (2006). "The ciliopathies: an emerging class of human genetic disorders". Annu Rev Genom Hum Genet. 7: 125–48. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. 3. ^ "Orofaciodigital syndrome 1 \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-07-07. 4. ^ Poretti, Andrea; Vitiello, Giuseppina; Hennekam, Raoul CM; Arrigoni, Filippo; Bertini, Enrico; Borgatti, Renato; Brancati, Francesco; D'Arrigo, Stefano; Faravelli, Francesca (2012-01-11). "Delineation and Diagnostic Criteria of Oral-Facial-Digital Syndrome Type VI". Orphanet Journal of Rare Diseases. 7: 4. doi:10.1186/1750-1172-7-4. ISSN 1750-1172. PMC 3313869. PMID 22236771. 5. ^ Toriello, Helga V.; Franco, Brunella; Bruel, Ange-Line; Thauvin-Robinet, Christel (1993). "Oral-Facial-Digital Syndrome Type I". In Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora J.H.; Bird, Thomas D.; Ledbetter, Nikki; Mefford, Heather C. (eds.). GeneReviews. Seattle (WA): University of Washington, Seattle. PMID 20301367. ## Further reading[edit] * GeneReview/NCBI/NIH/UW entry on Oral-Facial-Digital Syndrome Type I * Orofaciodigital syndrome Thurston type at NIH's Office of Rare Diseases * Orofaciodigital syndrome type 2 at NIH's Office of Rare Diseases * Orofaciodigital syndrome Gabrielli type at NIH's Office of Rare Diseases * OFD syndrome type Figuera at NIH's Office of Rare Diseases * OFD syndrome type 8 at NIH's Office of Rare Diseases ## External links[edit] Classification D * OMIM: 311200 * MeSH: D009958 * DiseasesDB: 29898 External resources * Orphanet: 2750 * v * t * e Diseases of cilia Structural * receptor: Polycystic kidney disease * cargo: Asphyxiating thoracic dysplasia * basal body: Bardet–Biedl syndrome * mitotic spindle: Meckel syndrome * centrosome: Joubert syndrome Signaling * Nephronophthisis Other/ungrouped * Alström syndrome * Primary ciliary dyskinesia * Senior–Løken syndrome * Orofaciodigital syndrome 1 * McKusick–Kaufman syndrome * Autosomal recessive polycystic kidney See also: ciliary proteins * v * t * e X-linked disorders X-linked recessive Immune * Chronic granulomatous disease (CYBB) * Wiskott–Aldrich syndrome * X-linked severe combined immunodeficiency * X-linked agammaglobulinemia * Hyper-IgM syndrome type 1 * IPEX * X-linked lymphoproliferative disease * Properdin deficiency Hematologic * Haemophilia A * Haemophilia B * X-linked sideroblastic anemia Endocrine * Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy * KAL1 Kallmann syndrome * X-linked adrenal hypoplasia congenita Metabolic * Amino acid: Ornithine transcarbamylase deficiency * Oculocerebrorenal syndrome * Dyslipidemia: Adrenoleukodystrophy * Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency * Pyruvate dehydrogenase deficiency * Danon disease/glycogen storage disease Type IIb * Lipid storage disorder: Fabry's disease * Mucopolysaccharidosis: Hunter syndrome * Purine–pyrimidine metabolism: Lesch–Nyhan syndrome * Mineral: Menkes disease/Occipital horn syndrome Nervous system * X-linked intellectual disability: Coffin–Lowry syndrome * MASA syndrome * Alpha-thalassemia mental retardation syndrome * Siderius X-linked mental retardation syndrome * Eye disorders: Color blindness (red and green, but not blue) * Ocular albinism (1) * Norrie disease * Choroideremia * Other: Charcot–Marie–Tooth disease (CMTX2-3) * Pelizaeus–Merzbacher disease * SMAX2 Skin and related tissue * Dyskeratosis congenita * Hypohidrotic ectodermal dysplasia (EDA) * X-linked ichthyosis * X-linked endothelial corneal dystrophy Neuromuscular * Becker's muscular dystrophy/Duchenne * Centronuclear myopathy (MTM1) * Conradi–Hünermann syndrome * Emery–Dreifuss muscular dystrophy 1 Urologic * Alport syndrome * Dent's disease * X-linked nephrogenic diabetes insipidus Bone/tooth * AMELX Amelogenesis imperfecta No primary system * Barth syndrome * McLeod syndrome * Smith–Fineman–Myers syndrome * Simpson–Golabi–Behmel syndrome * Mohr–Tranebjærg syndrome * Nasodigitoacoustic syndrome X-linked dominant * X-linked hypophosphatemia * Focal dermal hypoplasia * Fragile X syndrome * Aicardi syndrome * Incontinentia pigmenti * Rett syndrome * CHILD syndrome * Lujan–Fryns syndrome * Orofaciodigital syndrome 1 * Craniofrontonasal dysplasia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Orofaciodigital syndrome 1	c0029294	28,662	wikipedia	https://en.wikipedia.org/wiki/Orofaciodigital_syndrome_1	2021-01-18T18:36:38	{"gard": ["4121"], "mesh": ["D009958"], "umls": ["C0029294", "C0026363", "C1510460"], "orphanet": ["2750"], "wikidata": ["Q3508786"]}
A rare vascular liver disease characterized by widespread or focal cystic dilatation of sinusoidal blood-filled spaces of the liver without any known cause. Lesions can vary in diameter between few millimeters and several centimeters. The condition may remain asymptomatic or manifest with complications including rupture and intraperitoneal hemorrhage, hepatomegaly, portal hypertension, cholestasis, and liver failure. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Idiopathic peliosis hepatis	None	28,663	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=480524	2021-01-23T18:15:50	{"synonyms": ["Idiopathic peliosis hepatitis"]}
For the 2014 novel, see Echopraxia (novel). Echopraxia (also known as echokinesis[1]) is the involuntary repetition or imitation of another person's actions.[1] Similar to echolalia, the involuntary repetition of sounds and language, it is one of the echophenomena ("automatic imitative actions without explicit awareness").[1] It has long been recognized as a core feature of Tourette syndrome,[1] and is considered a complex tic, but it also occurs in autism spectrum disorders,[1][2] schizophrenia and catatonia,[1][3] aphasia, and disorders involving the startle reflex such as latah.[1][4] Echopraxia has also been observed in individuals with frontal lobe damage,[5] epilepsy, dementia and autoimmune disorders;[1] the causes of and the link between echopraxia and these disorders is undetermined.[6] The etymology of the term is from Ancient Greek: "ἠχώ (ēkhō) from ἠχή (ēkhē "sound") and "πρᾶξις (praksis, "action, activity, practice)".[7] ## Contents * 1 Characteristics * 2 Causes and pathophysiology * 3 Diagnosis * 4 References ## Characteristics[edit] Echopraxia is the involuntary mirroring of an observed action. Imitated actions can range from simple motor tasks such as picking up a phone to violent actions such as hitting another person. Imitative learning and emulation of physical and verbal actions are critical to early development (up to the age of two or three), but when these behaviors become reactions rather than a means for learning, they are considered echophenomena (copying behaviors).[1] ## Causes and pathophysiology[edit] Echopraxia is a typical symptom of Tourette syndrome but causes are not well elucidated.[1] Frontal lobe animation One theoretical cause subject to ongoing debate surrounds the role of the mirror neuron system (MNS), a group of neurons in the inferior frontal gyrus (F5 region) of the brain that may influence imitative behaviors,[1] but no widely accepted neural or computational models have been put forward to describe how mirror neuron activity supports cognitive functions such as imitation.[8] ## Diagnosis[edit] There is no formal test for diagnosing echopraxia. It is easier to distinguish in individuals over the age of five, because younger children frequently imitate others' actions. Imitation can be divided into two types: imitative learning and automatic imitation.[1] Imitative learning occurs when a person consciously mimics an observed action in order to learn the mechanism behind that action and perform it themselves. Babies begin copying movements soon after birth; this behavior begins to diminish around the age of three. Before that, it is not possible to diagnose echopraxia, because it is difficult to differentiate between imitative learning and automatic imitation. If the imitative behavior continues beyond infanthood, it may be considered echopraxia.[1] Echopraxia may be more easily distinguished in older individuals, because their behaviors in relation to prior behaviors can be differentiated. They report feeling an uncontrollable urge to perform an action after seeing it being performed. Automatic behavior is occasionally present in healthy adults (for example, when a person observes someone yawning, he or she may do the same); these behaviors are not considered echopraxia. ## References[edit] 1. ^ a b c d e f g h i j k l m Ganos C, Ogrzal T, Schnitzler A, Münchau A (September 2012). "The pathophysiology of echopraxia/echolalia: relevance to Gilles de la Tourette syndrome". Mov. Disord. 27 (10): 1222–9. doi:10.1002/mds.25103. PMID 22807284. 2. ^ Realmuto GM, August GJ (December 1991). "Catatonia in autistic disorder: a sign of comorbidity or variable expression?". J Autism Dev Disord. 21 (4): 517–28. doi:10.1007/BF02206874. PMID 1778964. 3. ^ Pridmore S, Brüne M, Ahmadi J, Dale J (July 2008). "Echopraxia in schizophrenia: possible mechanisms" (PDF). Aust N Z J Psychiatry. 42 (7): 565–71. doi:10.1080/00048670802119747. PMID 18612859. 4. ^ Tanner CM, Chamberland J (May 2001). "Latah in Jakarta, Indonesia". Mov. Disord. 16 (3): 526–9. doi:10.1002/mds.1088. PMID 11391750. 5. ^ [unreliable medical source?] Aziz-Zadeh L, Koski L, Zaidel E, Mazziotta J, Iacoboni M (March 2006). "Lateralization of the human mirror neuron system". J. Neurosci. 26 (11): 2964–70. doi:10.1523/JNEUROSCI.2921-05.2006. PMID 16540574. 6. ^ Cho YJ, Han SD, Song SK, Lee BI, Heo K (June 2009). "Palilalia, echolalia, and echopraxia-palipraxia as ictal manifestations in a patient with left frontal lobe epilepsy". Epilepsia. 50 (6): 1616–9. doi:10.1111/j.1528-1167.2008.01980.x. PMID 19175395. 7. ^ "Medical Dictionary Medilexicon". 8. ^ Dinstein I, Thomas C, Behrmann M, Heeger DJ (2008). "A mirror up to nature". Curr Biol. 18 (1): R13–8. doi:10.1016/j.cub.2007.11.004. PMC 2517574. PMID 18177704. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Echopraxia	c0233613	28,664	wikipedia	https://en.wikipedia.org/wiki/Echopraxia	2021-01-18T18:32:04	{"umls": ["C0233613"], "wikidata": ["Q1280852"]}
This article is about the subtype of pseudohypoparathyroidism known as Albright's hereditary osteodystrophy. For the genetically-related condition, see McCune-Albright Syndrome. Albright's hereditary osteodystrophy Albright's hereditary osteodystrophy has an autosomal dominant pattern of inheritance SpecialtyEndocrinology SymptomsChoroid plexus calcification, Full cheeks[1] CausesGs alpha subunit deficiency[2] Diagnostic methodCBC, Urine test[3] TreatmentPhosphate binders, supplementary calcium [4] Albright's hereditary osteodystrophy is a form of osteodystrophy,[5] and is classified as the phenotype of pseudohypoparathyroidism type 1A; this is a condition in which the body does not respond to parathyroid hormone.[1] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 History * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] The disorder is characterized by the following:[1] * Hypogonadism * Brachydactyly syndrome * Choroid plexus calcification * Hypoplasia of dental enamel * Full cheeks * Hypocalcemic tetany Choroid plexus(bottom left) Individuals with Albright hereditary osteodystrophy exhibit short stature, characteristically shortened fourth and fifth metacarpals, rounded facies, and often mild intellectual deficiency.[6] Albright hereditary osteodystrophy is commonly known as pseudohypoparathyroidism because the kidney responds as if parathyroid hormone were absent. Blood levels of parathyroid hormone are elevated in pseudohypoparathyroidism due to the hypocalcemia[medical citation needed] ## Genetics[edit] This condition is associated with genetic imprinting. It is thought to be inherited in an autosomal dominant pattern, and seems to be associated with a Gs alpha subunit deficiency.[2] ## Mechanism[edit] The mechanism of this condition is due to Gs signaling decrease in hormones having to do with signal transduction which is when a signal from outside cell causes change within the cell (in function). Renal tubule cells only express maternal alleles (variant form of a gene).[7][8][9] ## Diagnosis[edit] Complete blood count The diagnosis of Albright's hereditary osteodystrophy is based on the following exams below:[3] * CBC * Urine test * MRI ## Treatment[edit] Treatment consists of maintaining normal levels of calcium, phosphorus, and vitamin D. Phosphate binders, supplementary calcium and vitamin D will be used as required.[4] ## History[edit] The disorder bears the name of Fuller Albright, who characterized it in 1942.[10] He was also responsible for naming it "Sebright bantam syndrome," after the Sebright bantam chicken, which demonstrates an analogous hormone insensitivity. Much less commonly, the term Martin-Albright syndrome is used, this refers to Eric Martin.[11] ## See also[edit] * Pseudopseudohypoparathyroidism ## References[edit] 1. ^ a b c "Albright's hereditary osteodystrophy". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. Retrieved 9 February 2017. 2. ^ a b Kottler, Marie (2004). "Alpha hereditary Osteodystrophy" (PDF). Orphanet. 3. ^ a b "Pseudohypoparathyroidism: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 12 February 2017. 4. ^ a b Kliegman, Robert (2016). Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Elsevier. pp. chap 572. ISBN 978-1-4557-7566-8. 5. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 657. ISBN 978-1-4160-2999-1. 6. ^ Garavelli L; Pedori S; Zanacca C; et al. (April 2005). "Albright's hereditary osteodystrophy (pseudohypoparathyroidism type Ia): clinical case with a novel mutation of GNAS1". Acta Biomed. 76 (1): 45–8. PMID 16116826. 7. ^ "OMIM Entry - # 103580 - PSEUDOHYPOPARATHYROIDISM, TYPE IA; PHP1A". omim.org. Retrieved 12 February 2017. 8. ^ Cooper, Geoffrey M. (1 January 2000). "Pathways of Intracellular Signal Transduction". Retrieved 12 February 2017. Cite journal requires `\|journal=` (help) 9. ^ Reference, Genetics Home. "What is a gene?". Genetics Home Reference. Retrieved 2017-02-12. 10. ^ F. Albright, C. H. Burnett, P. H. Smith, et al. Pseudo-hypoparathyroidism-example of 'Seabright-Bantam syndrome'; report of three cases. Endocrinology, Baltimore, 1942, 30: 922-932. 11. ^ D. Martin, J. Bourdillon. Un cas de tétanie idiopathique chronique. Échec thérapeutique de la graffe d’un adénome parathyroïdien. Revue médicale de la Suisse romande, Lausanne, 1940, 60: 1166-1177. ## Further reading[edit] * Thakker, Rajesh V.; Whyte, Michael P.; Eisman, John; Igarashi, Takashi (2013). Genetics of Bone Biology and Skeletal Disease. Academic Press. ISBN 9780123878304. Retrieved 12 February 2017. * Henderson, Katherine E.; Baranski, Thomas J.; Bickel, Perry E.; Clutter, William E. (2009). The Washington Manual Endocrinology Subspecialty Consult. Lippincott Williams & Wilkins. ISBN 9780781791540. Retrieved 12 February 2017. ## External links[edit] Classification D * ICD-10: E20.1 * ICD-9-CM: 275.49 * OMIM: 103580 * MeSH: C537045 * DiseasesDB: 10835 Scholia has a topic profile for Albright's hereditary osteodystrophy. * 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 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Albright's hereditary osteodystrophy	c3494506	28,665	wikipedia	https://en.wikipedia.org/wiki/Albright%27s_hereditary_osteodystrophy	2021-01-18T18:54:12	{"gard": ["7486", "5770"], "mesh": ["D011547", "C537045"], "umls": ["C3494506"], "icd-9": ["275.49"], "icd-10": ["E20.1"], "orphanet": ["79443", "665"], "wikidata": ["Q4712685"]}
Complex regional pain syndrome type 1 (CRPS1) is a form of complex regional pain syndrome (see this term) in which the pain is disproportionate to any known inciting event and is characterized by continuous pain, allodynia, or hyperalgesia as well as edema, coloration (changes in skin blood flow), or abnormal sudomotor activity in the region of pain. Onset of CRPS1 symptoms may occur within a few days to a month after an injury or trauma to the affected limb. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Complex regional pain syndrome type 1	c0034931	28,666	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99995	2021-01-23T17:56:05	{"mesh": ["D012019"], "omim": ["604335"], "umls": ["C0034931", "C1527353"], "icd-10": ["M89.0"], "synonyms": ["Algodystrophy", "Reflex sympathetic dystrophy"]}
## Summary ### Clinical characteristics. Individuals with the 15q13.3 microdeletion are at increased risk for a wide range of clinical manifestations including intellectual disability, seizures, autism spectrum disorders, and schizophrenia; however, the microdeletion itself does not appear to lead to a clinically recognizable syndrome and a subset of persons with the deletion have no obvious clinical findings. Behavioral problems are common and mainly comprise poor attention span, hyperactivity, mood disorder, and aggressive and/or impulsive behavior. Intellectual disability, observed in about half of the individuals with this recurrent deletion, is usually mild but can be moderate to severe. ### Diagnosis/testing. The 15q13.3 microdeletion is defined as the presence of a common 2.0-Mb deletion at the approximate position of 30.5-32.5 Mb in the reference genome, which includes deletion of 1.5 Mb of unique sequence as well as an additional 500 kb or more of segmental duplications. No single gene within the deletion has been associated with disease findings. Genomic testing methods that determine the copy number of sequences, such as chromosomal microarray (CMA) using oligonucleotide arrays or SNP genotyping arrays, can detect the 15q13.3 microdeletion in a proband. ### Management. Treatment of manifestations: Ideally treatment is tailored to the specific needs of the individual. It is suggested that treatment for neurodevelopmental disability be based on a neuropsychological and/or developmental assessment by a clinical psychologist. Medical treatment for cardiac defects, epilepsy, autism spectrum disorders, and schizophrenia should follow standard practice for these disorders, considering the age of the individual and the specific manifestations. Surveillance: Close assessment/monitoring of developmental milestones is recommended during childhood, with referral to early intervention programs if required. ### Genetic counseling. The 15q13.3 microdeletion is a contiguous gene deletion inherited in an autosomal dominant manner. Approximately 15% are de novo and approximately 85% are inherited. Offspring of an individual with this deletion have a 50% chance of inheriting the deletion. Although prenatal testing is technically feasible, it is not possible to reliably predict the phenotype based on the laboratory finding of the 15q13.3 microdeletion. ## Diagnosis Individuals with the 15q13.3 microdeletion may have a wide range of clinical manifestations. The deletion itself may not lead to a clinically recognizable syndrome and a subset of persons with the deletion have no obvious clinical findings, implying that penetrance for the deletion is incomplete. ### Suggestive Findings 15q13.3 microdeletion should be considered in individuals with the following clinical findings: * Intellectual disability * Speech delay * Seizures * Autism * Schizophrenia * Behavioral problems (poor attention span, hyperactivity, mood disorder, and aggressive and/or impulsive behavior) Some affected individuals have combinations of these findings, such as intellectual disability and seizures. ### Establishing the Diagnosis The diagnosis of the 15q13.3 microdeletion is established by detection of the 2.0-Mb heterozygous microdeletion at chromosome 15q13.3. For this GeneReview, the 15q13.3 microdeletion is defined as the presence of a recurrent 2.0-Mb deletion at the approximate position of 30.5-32.5 Mb in the reference genome, which includes deletion of 1.5 Mb of unique sequence as well as an additional 500 kb or more of segmental duplications (NCBI Build [hg38]). Note: The phenotype of significantly larger or smaller deletions within this region may be clinically distinct from the 15q13.3 microdeletion (see Genetically Related Disorders). Although several genes of interest (e.g., CHRNA) are within the 2.0-Mb deletion, no single gene has been associated with the disease findings (see Molecular Genetics for genes of interest in the deleted region). Genomic testing methods that determine the copy number of sequences can include chromosomal microarray (CMA) or targeted deletion analysis by fluorescence in situ hybridization (FISH) or multiplex ligation dependent probe amplification (MLPA). Note: The 15q13.3 microdeletion cannot be identified by routine analysis of G-banded chromosomes or other conventional cytogenetic banding techniques. * Chromosomal microarray (CMA) using oligonucleotide arrays or SNP genotyping arrays can detect the common deletion in a proband. The ability to size the deletion depends on the type of microarray used and the density of probes in the 15q13.3 region. Note: (1) Most individuals with the 15q13.3 microdeletion are identified by CMA performed in the context of developmental delay, intellectual disability, or autism spectrum disorders. (2) Prior to 2008 some CMA platforms did not include coverage for this region and thus may not have detected this deletion. * Targeted deletion analysis. FISH analysis and MLPA may be used to test at-risk relatives of a proband known to have the 15q13.3 microdeletion. Note: (1) Targeted deletion testing by FISH or MLPA is not appropriate for an individual in whom the microdeletion was not detected by CMA designed to target 15q13.3. (2) It is not possible to size the microdeletion routinely by use of FISH or MLPA. ### Table 1. Genomic Testing Used in 15q13.3 Microdeletion View in own window Deletion 1ISCA ID 2Region Location 3, 4MethodSensitivity ProbandAt-risk family members ~2.0-Mb heterozygous deletion at 15q13.3ISCA-37411GRCh38/hg38 chr15: 30.5-32.5CMA 5100%100% FISH or MLPANot applicable 6100% 1\. See Molecular Genetics for details of deletion. 2\. Standardized clinical annotation and interpretation for genomic variants from the Clinical Genome Resource (ClinGen) project; formerly the International Standards for Cytogenomic Arrays (ISCA) Consortium 3\. Genomic coordinates represent the minimum deletion size associated with 15q13.3 microdeletion as designated by ClinGen. Deletion coordinates may vary slightly based on array design used by the testing laboratory. Note that the size of the microdeletion as calculated from these genomic positions may differ from the expected microdeletion size due to the presence of segmental duplications near breakpoints. The phenotype of significantly larger or smaller microdeletions within this region may be clinically distinct from the 15q13.3 microdeletion (see Genetically Related Disorders). 4\. See Molecular Genetics for genes of interest included in the deleted region. 5\. Chromosome microarray analysis (CMA) using oligonucleotide arrays or SNP genotyping arrays. CMA designs in current clinical use target the 15q13.3 region. Note: The 15q13.3 microdeletion may not have been detectable by older oligonucleotide or BAC platforms. 6\. FISH and MLPA are not appropriate as a diagnostic method for an individual in whom the 15q13.3 microdeletion was not detected by CMA designed to target this region. Evaluating at-risk relatives. FISH can be used to identify 15q13.3 microdeletion in at-risk relatives of the proband. Testing of parental samples is important in determining recurrence risk (see Genetic Counseling). ## Clinical Characteristics ### Clinical Description The 15q13.3 microdeletion was first reported in nine individuals with intellectual disability [Sharp et al 2008]. Later studies reported not only a higher prevalence of this microdeletion in persons with intellectual disability (0.3%), but also in individuals with seizures (1%-2%), schizophrenia (0.2%), and autism spectrum disorders (0.2%). In addition, the microdeletion has occasionally been found in healthy controls (0.02%) and frequently in healthy relatives of affected individuals [International Schizophrenia Consortium 2008, Sharp et al 2008, Stefansson et al 2008, Ben-Shachar et al 2009, Dibbens et al 2009, Helbig et al 2009, Miller et al 2009, van Bon et al 2009, de Kovel et al 2010, Masurel-Paulet et al 2010]. Data on 23,838 adult controls detected no 15q13.3 microdeletions [Lowther et al 2015]. However, another study reporting on a population-based sample (n=101,655) identified 25 such microdeletions (0.025%) [Stefansson et al 2014]. Intellectual disability and developmental delay. Accounting for ascertainment, intellectual or developmental disability has been observed in 58% of the individuals with the 15q13.3 microdeletion [Lowther et al 2015]. Developmental delays are mainly delays in speech acquisition and cognitive function rather than motor disability. In the majority of individuals, cognitive impairment is mild. However, a subset of individuals with moderate to severe disability has been reported [Ben-Shachar et al 2009, van Bon et al 2009, Lowther et al 2015]. Epilepsy. The 15q13.3 microdeletion has been shown to represent a major risk factor for epilepsy, found in 1%-2% of individuals with generalized epilepsy. Accounting for ascertainment, epilepsy/seizures are present in 28% of individuals [Lowther et al 2015]. The types of epilepsy include juvenile myoclonic epilepsy, childhood absence epilepsy, and juvenile absence epilepsy [Dibbens et al 2009, Helbig et al 2009, de Kovel et al 2010, Mefford et al 2010]. Seizure types include typical absence seizures, myoclonic seizures, and primary generalized tonic-clonic seizures. 15q13.3 microdeletion has not been found in individuals with a primary diagnosis of partial epilepsy [Heinzen et al 2010]. Neuropsychiatric disorders. Behavioral problems are relatively common (35%) and mainly include poor attention span, hyperactivity, mood disorder, self-mutilation and aggressive and/or impulsive behavior. Accounting for ascertainment, ADHD is present in 6.5% of individuals [Lowther et al 2015]. In three studies, the 15q13.3 microdeletion was found to be enriched in cohorts of individuals with schizophrenia compared to controls [International Schizophrenia Consortium 2008, Stefansson et al 2008, Lowther et al 2015]. Accounting for ascertainment bias, schizophrenia could be diagnosed in 11% of individuals and mood disorder in 10% of individuals [Lowther et al 2015]. Autism spectrum disorder has been reported in 11% of persons with the 15q13.3 microdeletion and can be present in both intellectually disabled and non-disabled individuals [Lowther et al 2015]. Non-disabled individuals with the microdeletion with an autism spectrum disorder may show impaired expressive and written language, poor eye contact, repetitive movements, obsessive and hyperactive behavior, and disturbed social interactions [Miller et al 2009, Pagnamenta et al 2009]. Dysmorphisms and congenital anomalies. In general, individuals with the 15q13.3 microdeletion have no specific pattern of dysmorphic features. Although cardiac defects were previously reported in a subset of individuals with the microdeletion [Sharp et al 2008, van Bon et al 2009, Masurel-Paulet et al 2010], a recent systematic review including all currently reported cases (n=246), emphasized the low penetrance (2.4%) for structural cardiac defects. No other frequently occurring congenital anomalies have been reported. ### Genotype-Phenotype Correlations No phenotype-genotype correlations are known as the phenotypic findings in individuals with the 15q13.3 microdeletion ranges from normal to significantly impaired. ### Penetrance The penetrance of the 15q13.3 microdeletion is highly variable. In total, 80.5% of individuals with the microdeletion have at least one of the following neurodevelopmental or neuropsychiatric diagnoses: intellectual disability/developmental delay, speech problems, epilepsy, autism spectrum disorder, schizophrenia, mood disorder, and ADHD [Lowther et al 2015]. ### Nomenclature Owing to the lack of a recognizable phenotype in persons with the 15q13.3 microdeletion, it has not been described eponymously. Although the 15q13.3 region includes other segmental duplication break points [Makoff & Flomen 2007, Shinawi et al 2009], the 15q13.3 microdeletion specifically refers to deletion of the 2.0-Mb region at the approximate position of 30.5-32.5 Mb in the reference genome (NCBI Build [hg38]). ### Prevalence Estimates of prevalence depend on the subset of individuals tested. In control cohorts, the 15q13.3 microdeletion has been found in 0.02% of individuals. It has been found in approximately 0.3% of individuals with intellectual disability, 1%-2% of persons with epilepsy, approximately 0.2% of individuals with schizophrenia, and approximately 0.2% of persons with autism. ## Differential Diagnosis The differential diagnosis of the 15q13.3 microdeletion comprises an extensive and broad spectrum of diseases. It includes any cause of developmental delay, schizophrenia, autism spectrum disorders, and epilepsy without additional distinguishing clinical features. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with the 15q13.3 microdeletion, the following evaluations are recommended: * General clinical examination * Cognitive assessment including speech assessment * Neuropsychological and developmental evaluation by a clinical psychologist to help determine needs for subsequent treatment * EEG and neurologic examination if epilepsy is suspected * Cardiac ultrasound evaluation * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Ideally treatment is tailored to the specific needs of the individual. Because of the high incidence of neurodevelopmental disability, referral to a clinical psychologist for neuropsychological and/or developmental assessment for treatment recommendations is suggested. Medical treatment for persons with cardiac defects, epilepsy, autism spectrum disorders, and schizophrenia should follow standard practice for these disorders, considering the age of the patient and the specific manifestations. Additional management in healthy adults who have the 15q13.3 microdeletion is not necessary, although their medical care providers may benefit from being alerted to the possible increased risk for late-onset manifestations (e.g., schizophrenia). ### Surveillance Close assessment/monitoring of neurocognitive development and developmental milestones are recommended during childhood for all children who have the 15q13.3 microdeletion, with referral to early intervention programs if required. Medical surveillance for persons with cardiac defects, epilepsy, autism spectrum disorders, and schizophrenia should follow standard practice for these disorders, considering the age of the patient and the specific manifestations. ### Agents/Circumstances to Avoid About 10% of the individuals with the 15q13.3 microdeletion develop schizophrenia. The use of cannabis has been reported as a risk factor for development of schizophrenia. Although no studies have been performed on the possible additional risk of the use of cannabis by persons with the 15q13.3 microdeletion, discouraging the use of cannabis may be considered. ### Evaluation of Relatives at Risk Using genomic testing that will detect the 15q13.3 microdeletion found in the proband, it is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those who would benefit from close assessment/monitoring of developmental milestones in childhood. 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. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	15q13.3 Microdeletion	c2677613	28,667	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK50780/	2021-01-18T21:46:11	{"mesh": ["C567439"], "synonyms": []}
A severe form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, with onset in the 2nd or 3rd decade, characterized by ulcerations and infections of feet. Symmetric and distal weakness develops mostly in the legs together with a severe symmetric distal sensory loss, tendon reflexes are only reduced at ankles and foot deformities, including pes cavus or planus and hammer toes, appear in childhood. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autosomal dominant Charcot-Marie-Tooth disease type 2B	c1833219	28,668	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99936	2021-01-23T17:30:14	{"gard": ["9192"], "mesh": ["C537989"], "omim": ["600882"], "umls": ["C1833219"], "icd-10": ["G60.0"], "synonyms": ["CMT2B"]}
Lethal congenital contracture syndrome type 1 is a rare, genetic arthrogryposis syndrome characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Lethal congenital contracture syndrome type 1	c1854664	28,669	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1486	2021-01-23T18:14:53	{"gard": ["3227"], "mesh": ["C537194"], "omim": ["253310"], "umls": ["C1854664"], "icd-10": ["Q68.8"], "synonyms": ["Herva disease", "LCCS1", "Multiple contracture syndrome, Finnish type"]}
## Clinical Features Chung et al. (2003) described an extensive, 4-generation African American family, residing in western Pennsylvania, with an autosomal dominant nephropathy. The disorder was clinically diagnosed as hypertensive nephropathy in multiple family members. Of the 18 affected individuals studied, 7 had end-stage renal disease, including the 13-year-old proband. The proband presented with hypertension and proteinuria and underwent a kidney biopsy that revealed focal segmental glomerular sclerosis (FSGS; 603278)-like lesions with arteriolar thickening. Mapping By linkage analysis in an African American family segregating hypertensive nephropathy, Chung et al. (2003) found a maximum multipoint lod score of 5.4 in the 9q31-q32 region under an autosomal dominant model with 99% penetrance. The locus, which the authors termed HNP1, was narrowed to an 8-cM region. Candidate gene sequencing studies excluded the coding regions of the ACTL7A (604303), ACTL7B (604304), and CTNNAL1 (604785) genes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	HYPERTENSIVE NEPHROPATHY	c0848548	28,670	omim	https://www.omim.org/entry/608026	2019-09-22T16:08:27	{"mesh": ["C563161"], "omim": ["608026"], "icd-9": ["403.9"], "icd-10": ["I12", "I12.9"]}
A number sign (#) is used with this entry because hypogonadotropic hypogonadism-2 with or without anosmia (HH2) is caused by heterozygous mutation in the gene encoding fibroblast growth factor receptor-1 (FGFR1; 136350) on chromosome 8p11, sometimes in association with mutation in other genes, e.g., FGF8 (600483) and GNRHR (138850). Description Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' Although HH was initially considered to be a monogenic disorder, the presence of marked locus heterogeneity, incomplete penetrance within pedigrees, and variable expressivity of pathogenic alleles, together with evidence for mutations in multiple genes in some affected individuals, resulted in a conceptual shift from monogenicity to an oligogenic framework in which a limited number of genes contribute pathogenic alleles to the genetic network responsible for the neuroendocrine control of human reproduction (Sykiotis et al., 2010). ### Genetic Heterogeneity of Hypogonadotropic Hypogonadism with or without Anosmia Other forms of autosomal hypogonadotropic hypogonadism with or without anosmia include HH3 (244200), caused by mutation in the PROKR2 gene (607123); HH4 (610628), caused by mutation in the PROK2 gene (607002); HH5 (612370), caused by mutation in the CHD7 gene (608892); HH6 (612702), caused by mutation in the FGF8 gene (600483); HH7 (146110), caused by mutation in the GNRHR gene (138850); HH8 (614837), caused by mutation in the KISS1R gene (604161); HH9 (614838), caused by mutation in the NELF gene (608137); HH10 (614839), caused by mutation in the TAC3 gene (162330); HH11 (614840), caused by mutation in the TACR3 gene (162332); HH12 (614841), caused by mutation in the GNRH1 gene (152760); HH13 (614842), caused by mutation in the KISS1 gene (603286); HH14 (614858), caused by mutation in the WDR11 gene (606417); HH15 (614880), caused by mutation in the HS6ST1 gene (604846); HH16 (614897), caused by mutation in the SEMA3A gene (603961); HH17 (615266), caused by mutation in the SPRY4 gene (607984); HH18 (615267), caused by mutation in the IL17RD gene (606807); HH19 (615269), caused by mutation in the DUSP6 gene (602748); HH20 (615270), caused by mutation in the FGF17 gene (603725); HH21 (615271), caused by mutation in the FLRT3 gene (604808); HH22 (616030), caused by mutation in the FEZF1 gene (613301); HH23 (228300), caused by mutation in the LHB gene (152780); and HH24 (229070), caused by mutation in the FSHB gene (136530). There is also an X-linked form of the disorder (HH1; 308700), caused by mutation in the KAL1 gene (300836). There is evidence that mutation in 2 or more of these genes can work in combination (oligogenicity) to produce GnRH-deficient conditions (summary by Chan, 2011). Sykiotis et al. (2010), for example, demonstrated that of patients with an identifiable coding sequence mutation in 1 of 8 genes responsible for isolated GnRH deficiency, 11% carried mutations in at least one other of these genes as well. To assess oligogenicity in hypogonadotropic hypogonadism, Miraoui et al. (2013) analyzed 350 HH probands of European descent for mutation in 17 HH-associated genes. Mutations were identified in 124 (35%) of the probands, and 24 (19%) of the mutation-positive probands carried at least 2 mutant alleles from different genes. Miraoui et al. (2013) noted that 23 of the 24 oligogenic cases involved at least 1 gene associated with the fibroblast growth factor (FGF) network (see 601513). Dode et al. (2006) stated that loss-of-function mutations in the KAL1 (300836) and FGFR1 genes account for approximately 20% of all cases of Kallmann syndrome and that mutations in the PROKR2 and PROK2 genes account for an additional 10%. Gurbuz et al. (2012) reviewed all causative mutations detected in multiplex families with normosmic hypogonadotropic hypogonadism over a 7-year period in Turkey. Mutations that segregated with disease were identified in 17 (77.2%) of 22 families studied, including mutations of the GNRHR gene in 7 (31.8%) of the families, TACR3 in 6 (27.2%), KISSR in 2 (9%), TAC3 in 1 (4.5%), and KISS1 in 1 (4.5%). Inheritance was autosomal recessive in all 17 families. Valdes-Socin et al. (2014) reviewed the reproductive, neurodevelopmental, and genetic aspects of hypogonadotropic hypogonadism in human pathology. Clinical Features In some cases of hypogonadotropic hypogonadism and anosmia, midline cranial anomalies (cleft lip, cleft palate and imperfect fusion) are present. In a large kindred with a high rate of consanguinity, Rosen (1965) found 5 cases of hypogonadism, 3 of anosmia, and 6 of midline cranial anomalies. Both males and females were affected; 2 persons had 2 defects and 2 others showed all 3. Tagatz et al. (1970) described 3 unrelated females with hypogonadotropic hypogonadism and anosmia. No relative was affected and the parents in each case were unrelated. Induction of ovulation with resulting normal term pregnancy was achieved in 2 of the patients with exogenous gonadotropins. Hintz et al. (1968) may have described the same or a related disorder. Merriam et al. (1977) reported the instructive case of a father with cryptorchidism, hypogonadism, and hyposmia who was rendered fertile by treatment with chorionic gonadotropin and had 3 children. One of the 3, a son, also had the triad mentioned. A brother and sister were apparently normal. Soules and Hammond (1980) reported the fully studied case of a female. In a study of 23 patients, Lieblich et al. (1982) found subtle abnormalities of hypothalamic-pituitary function, although hypogonadism was the only endocrine deficit evident clinically. Some relatives had only anosmia or had hypogonadotropic hypogonadism with normal sense of smell. Among 18 probands with anosmia and hypogonadotropic hypogonadism studied at the National Institutes of Health, White et al. (1983) found that 7 had affected relatives and 3 had consanguineous parents. Both sexes were equally affected and parents were phenotypically normal. Cleft lip and palate occurred in both eugonadal and hypogonadal persons with anosmia. Segregation analysis was consistent with autosomal recessive inheritance with variable expression. They suggested that association of unilateral renal agenesis, mental retardation, and hypotelorism (e.g., families reported by Turner et al., 1974 and Wegenke et al., 1975) may indicate a distinct X-linked or male-limited autosomal dominant form (see 308700). Evain-Brion et al. (1982) suspected hypogonadotropic hypogonadism in 3 male newborns on the basis of a very small penis, cryptorchidism, and a family history of Kallmann syndrome in 1 and isolated anosmia in the other 2. The diagnosis was confirmed in early infancy by lack of the postnatal rise of LH and testosterone and a blunted response to LHRH and HCG stimulation. In 1 case the mother had anosmia, primary amenorrhea, low gonadotropin and lack of response to LHRH; she had been successfully treated with HMG and HCG to induce ovulation (Gorins et al., 1977). In the second case, 'the father was hyposmic with normal gonadal function, and his grandmother had been anosmic.' In the third case, although the parents were normal, a maternal uncle had cryptorchidism with anosmia. Klein et al. (1987) described the association of Kallmann syndrome with choanal atresia. The Kallmann syndrome occurred in an aunt and niece; the niece also had choanal atresia as did her newborn child. The olfactory capacity and gonadal or hormonal status of the infant could not be determined at her age. Klein et al. (1987) suggested that this may be further evidence that Kallmann syndrome represents the least severe form of the holoprosencephaly-hypopituitarism complex, a group of developmental field defects. Kallmann syndrome associated with congenital heart disease may be a distinct entity. Cortez et al. (1993) described the case of a 17-year-old boy with Kallmann syndrome and a complex congenital heart malformation. He also had neurosensory hearing loss and mental retardation. They noted that 7 previously reported patients with Kallmann syndrome and cardiac abnormalities were short with heights more than 2 standard deviations below the mean for age, lacked a family history of Kallmann syndrome, and were mentally retarded. Levy and Knudtzon (1993) reported a family in which 2 sisters, aged 13 and 19 years, had hypogonadotropic hypogonadism and anosmia. In addition, they had bilateral vesicoureteral reflux and unilateral hearing loss. One of the girls had unilateral coloboma of the optic nerve. The father had no clinical signs of either hypogonadism or anosmia. However, he had unilateral hearing loss and duplication of the left ureter and died suddenly at the age of 40 from myocardial infarction and undiagnosed coarctation of the aorta. The mother was normal. Levy and Knudtzon (1993) postulated dominant inheritance in this family. The European Recombinant Human LH Study Group (1998) evaluated the efficacy of recombinant human luteinizing hormone (rhLH; see 152780) for supporting human recombinant follicle-stimulating hormone (rhFSH)-induced follicular development in hypogonadotropic hypogonadal women (WHO group I anovulation). Thirty-eight patients were randomized to receive rhLH (0, 25, 75, or 225 IU per day) in addition to a fixed dose of rhFSH (150 IU per day). RhLH was found to promote dose-related increases in estradiol (E2) and androstenedione secretion by rhFSH-induced follicles, increase ovarian sensitivity to FSH, and enhance the ability of these follicles to luteinize when exposed to human chorionic gonadotropin (CG; see 118850). A daily dose of 75 IU rhLH was effective in the majority of women in promoting optimal follicular development and maximal endometrial growth. The authors concluded that a minority of patients may require up to 225 IU per day and that rhLH given subcutaneously at a dose up to 225 IU per day was not immunogenic and was well tolerated. Young et al. (1999) measured the serum anti-mullerian hormone (AMH; 600957) levels in 20 normal men, aged 20 to 60 years, 12 patients with congenital hypogonadotropic hypogonadism (CHH), aged 19 to 30 years, and 18 patients with acquired hypogonadotropic hypogonadism (AHH), aged 19 to 65 years, either untreated or during testosterone (T) or human CG therapy. Mean serum AMH levels in normal adult men were low (20 +/- 4.9 pmol/L). In untreated CHH patients, mean serum AMH levels were significantly higher than in normal men (292 +/- 86 pmol/L; p less than 0.001) and were similar to those previously reported in prepubertal boys. In men with AHH, mean serum AMH levels were also significantly increased (107 +/- 50 pmol/L; p less than 0.01) when compared with healthy men, but were less than in men with CHH. In addition, in 10 patients treated for prostate cancer, a modest but significant increase of serum AMH (from 11.4 +/- 5.7 pmol/L to 49 +/- 9.9 pmol/L; p less than 0.01) was observed 12 months after suppression of the gonadal axis with the GNRH agonist Triptorelin (3.75 mg IM once a month). Plasma T and serum AMH levels were measured at baseline and at 3 and 6 months in 10 HH patients (6 CHH and 4 AHH) treated with human CG (1,500 IU/twice weekly for 6 months) and in 8 HH patients (4 CHH and 4 AHH) treated with T (T enanthate, 250 mg/3 weeks for 6 months). Human CG treatment induced an increase of plasma T (from 1.0 +/- 0.7 to 11 +/- 2.4 and 19 +/- 4.8 nmol/L, at 3 and 6 months, respectively) associated with a dramatic decrease of serum AMH (from 314 +/- 93 to 56 +/- 30 and 17 +/- 4.3 pmol/L). The similar increase in plasma T levels (from 1.4 +/- 1.0 to 15.6 +/- 4.2 and 23 +/- 6.2 ng/ml) obtained with exogenous T induced a lesser decrease of serum AMH (from 221 +/- 107 to 114 +/- 50 and 66 +/- 17 pmol/L). The authors concluded that (1) high plasma AMH levels in CHH patients are related to the absence of pubertal maturation of Sertoli cells; (2) high AMH levels in AHH and its increase after Triptorelin-induced gonadotropin deficiency suggested that the suppression of AMH is a reversible phenomenon; and (3) inhibition of AMH production by Sertoli cells is induced by intratesticular T. To test the hypothesis that follicle-stimulating hormone (FSH; see 136530) might be responsible for AMH upregulation in the absence of androgen inhibition, Young et al. (2005) administered recombinant human FSH to 8 male patients aged 18 to 31 years with untreated congenital hypogonadotropic hypogonadism. Although LH and T did not vary, AMH and inhibin B (see 147290) levels gradually increased after 20 days of FSH administration. However, in contrast to FSH alone, combined FSH plus CG stimulation of the testis dramatically suppressed the secretion of AMH and induced a modest but significant reduction of circulating inhibin B levels. The authors concluded that FSH stimulates AMH production in the testis when it is at a prepubertal stage. Gasztonyi et al. (2000) described 3 unrelated women with hypogonadotropic hypogonadism and anosmia. Absence of olfactory bulbs and tracts and different degrees of asymmetric dysplasia of olfactory sulci were demonstrated by MRI. The father of 1 patient and the maternal aunt of another had anosmia, making autosomal dominant inheritance likely. The last patient had Kallmann syndrome and femur-fibula-ulna syndrome (228200) as a sporadic occurrence in her family. ### Clinical Variability Dean et al. (1990) suggested autosomal dominant inheritance with variable expression as the basis for aggregation of isolated hypogonadotropic hypogonadism in the family that they studied. A brother and sister had been most fully studied. Limited examination was performed on 2 aunts and the son of one of the aunts. The sister presented at age 17 with primary amenorrhea. She did not have anosmia. Ovulation was subsequently induced by pulsatile infusion of gonadotropin-releasing hormone (GNRH1; 152760). The brother presented at age 21 with delayed puberty. He likewise denied anosmia. Both testes were small but were in the scrotum. One paternal aunt had primary amenorrhea and an adopted son, whereas another paternal aunt had menarche at age 23, following which she had 5 or 6 menstrual periods. Six years after her last period, she became pregnant and delivered an apparently normal male infant. In the subsequent 21 years she did not menstruate. The son had immature genitalia and an unbroken voice at age 16 but refused examinations. The father of the brother and sister had died from thromboembolism and was not available for study. Pitteloud et al. (2002) examined historical, clinical, biochemical, histologic, and genetic features in 78 men with IHH to gain further insight into the phenotypic heterogeneity of the syndrome. They hypothesized that at least some of the spectrum of phenotypes could be explained by placing the disorder into a developmental and genetic context. Thirty-eight percent of the population had Kallmann syndrome, 54% had normosmic IHH, and 8% had acquired IHH after completion of puberty. Phenotypically, Kallmann syndrome represented the most severe subtype (87% with complete absence of any history or signs of spontaneous pubertal development), normosmic IHH displayed the most heterogeneity (41% with some evidence of spontaneous puberty), and acquired IHH after completion of puberty clustered at the mildest end (all had complete puberty). Classification based on historical or clinical evidence of prior pubertal development, rather than the presence or absence of sense of smell, served to distinguish the population more clearly with respect to other clinical and biochemical features. Mean gonadotropin levels and the finding of apulsatile LH secretion based on frequent sampling (80% vs 55%; p less than 0.05) were statistically different between patients lacking and those exhibiting partial pubertal development, but the overlap was extensive. The authors concluded that use of clinical parameters (presence or absence of some evidence of prior pubertal development, cryptorchidism (219050), and microphallus), biochemical markers of testicular growth and differentiation (inhibin B, mullerian inhibitory substance), and genetic evidence provides insight into the time of onset and the severity of GnRH deficiency. The authors further concluded viewing IHH in the full context of its developmental, genetic, and biochemical complexity permits greatest insight into its phenotypic variability. Bhagavath et al. (2006) studied 315 probands with HH, 185 of whom had previously been studied by Bhagavath et al. (2005); the 315 probands included 258 males and 57 females, and 20 (6.3%) of the probands had 1 or more affected relatives. Of patients in whom information was available, 67 (31.5%) of 213 males and 12 (27.9%) of 43 females were anosmic, and 124 (62%) of 200 males and 16 (45.7%) of 35 females had complete HH. In the 20 HH families, 3 (15%) demonstrated vertical transmission, whereas 2 (5%) had only affected males inherited through presumptive carrier females, suggesting X-linked recessive inheritance. In 10 of the families, including both families that appeared to be X-linked recessive, affected individuals had anosmia (Kallmann syndrome). Bhagavath et al. (2006) noted that in contrast to previous reports of cryptorchidism being more common in Kallmann syndrome than in normosmic HH, cryptorchidism was present in 5 to 6% of both normosmic and hyposmic/anosmic HH patients in their cohort; however, in keeping with previous findings (Pitteloud et al., 2002), cryptorchidism was 4 times more common in cases of complete HH (16%) than in cases of incomplete HH (4%). Additional anomalies included visual abnormalities in 8 (2.5%) of 315 patients, neurologic abnormalities in 7 (2.2%), and renal agenesis in 1 (0.3%). Inheritance Hockaday (1966) described 2 cases. In the second case, the father was found to have 'complete anosmia on testing.' Thus, this may have been an autosomal dominant form of the disorder. On the basis of cases in which the father of affected individuals showed anosmia, Santen and Paulsen (1973) concluded that autosomal dominant inheritance is most likely. ### Oligogenic Inheritance Tornberg et al. (2011) studied a large French Canadian pedigree with several consanguineous loops, previously reported by White et al. (1983), in which affected individuals variably presented with hypogonadotropic hypogonadism, anosmia, and cleft palate. In 4 affected family members, Tornberg et al. (2011) identified homozygosity or heterozygosity for a missense mutation in the HS6ST1 gene (604846.0002; see HH15, 614880). Because of the phenotypic variability and reduced penetrance displayed in the family, the authors screened 8 additional known HH-associated genes and detected a missense mutation in FGFR1 that was also present in the 4 affected members as well as 1 unaffected individual (136350.0025). In another family in which a man with anosmic HH and his unaffected brother both carried a missense mutation in HS6ST1 (604846.0001), screening revealed an additional missense mutation in the NELF gene (608137.0001; see HH9, 614838) in the proband. Tornberg et al. (2011) concluded that HH is an oligogenic disorder in which a limited number of genes contribute pathogenic alleles to the genetic network responsible for neuroendocrine control of human reproduction. In the large consanguineous 10-generation French Canadian family with anosmic HH and cleft palate, previously reported by White et al. (1983) and in which Tornberg et al. (2011) had identified mutations in both the FGFR1 (136350.0025) and HS6ST1 (604846.0002) genes, Miraoui et al. (2013) identified additional mutations in 2 more genes in the FGF network, FGF17 (603725.0001) and FLRT3 (604808.0001 and 604808.0002). In 4 more unrelated probands with anosmic HH, Miraoui et al. (2013) identified heterozygosity for missense mutations in FGFR1 (e.g., 136350.0026) as well as heterozygosity for 4 other genes in the FGF network: IL17RD (606807.0002), SPRY4 (607984.0002), DUSP6 (602748.0002), and FLRT3 (604808.0003). Miraoui et al. (2013) concluded that mutations in genes encoding components of the FGF pathway are associated with complex modes of congenital hypogonadotropic hypogonadism (CHH) inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH. Cytogenetics In a man with Kallmann syndrome, Bergstrom et al. (1987) found a consistent extra small marker chromosome, seemingly derived from chromosome group D or G, with satellites at each end. Best et al. (1990) described a balanced de novo translocation (7;12)(q22;q24) in an individual with Kallmann syndrome. In a male patient with hypogonadotropic hypogonadism and cleft lip and palate, Kim et al. (2005) identified a balanced reciprocal translocation, t(7;8)(p12.3;p11.2). Positional cloning of the breakpoints revealed that the translocation disrupts the FGFR1 gene between exons 2 and 3 and predicts a novel fusion gene product. Molecular Genetics Of 59 Kallmann syndrome patients analyzed by Oliveira et al. (2001), 21 were familial and 38 were sporadic cases. Mutations in the coding sequence of KAL1 (300836) were identified in only 3 familial cases (14%) and 4 of the sporadic cases (11%). Oliveira et al. (2001) concluded that confirmed mutations in the coding sequence of the KAL1 gene occur in the minority of Kallmann syndrome cases, and that the majority of familial (and presumably sporadic) cases of Kallmann syndrome are caused by defects in at least 2 autosomal genes. Dode et al. (2003) took advantage of overlapping interstitial deletions at 8p12-p11 in 2 individuals who were affected by different contiguous gene syndromes that both included Kallmann syndrome. The gene encoding fibroblast growth factor receptor-1 (FGFR1; 136350) was in the critical interval. By determining the nucleotide sequence of the 18 coding exons and splice sites of FGFR1 in 129 unrelated individuals with Kallmann syndrome (91 males and 38 females), they detected heterozygous mutations in 4 familial cases and 8 sporadic cases (see, e.g., 136350.0002-136350.0006). In addition, they found that 1 individual, who was born to consanguineous parents and was affected by Kallmann syndrome with cleft palate, agenesis of the corpus callosum, unilateral hearing loss, and fusion of the fourth and fifth metacarpal bones, was homozygous with respect to a deleterious missense mutation (136350.0007). Moreover, cleft palate or lip and selective tooth agenesis, 2 anomalies that are occasionally associated with Kallmann syndrome (White et al., 1983; Hardelin, 2001) and were present in 5 individuals with mutations in FGFR1, can now be ascribed to this disease. In 1 family with an FGFR1 mutation, bimanual synkinesia was identified, indicating that it can occur in autosomal Kallmann syndrome, although it had previously been considered to be specific to the X-linked form of the disorder. The results of these studies suggested that olfactory bulb development in humans is crucially sensitive to reduced dosage of FGFR1. Sato et al. (2004) studied 25 male and 3 female Japanese individuals, aged 10 to 53 years, with Kallmann syndrome. Ten males were from 5 families, and the remaining 15 males and 3 females were apparently sporadic cases. The authors found 2 novel intragenic FGFR1 mutations in 2 sporadic male cases. The 2 males with FGFR1 mutations had hypogonadotropic hypogonadism and anosmia and lacked other features. Clinical features in the remaining 11 cases with no demonstrable KAL1 or FGFR1 mutations included right renal aplasia in 1 female and cleft palate, cleft palate with perceptive deafness, and selective tooth agenesis with perceptive deafness in 1 male each, in addition to a variable extent of hypogonadotropic hypogonadism and olfactory dysfunction. Pitteloud et al. (2006) examined the FGFR1 gene in 7 unrelated patients with normosmic IHH and identified heterozygous mutations in 3 individuals. An 18-year-old female diagnosed with partial IHH and her brother, who had Kallmann syndrome, were found to have a heterozygous missense mutation in the FGFR1 gene (136350.0013); their father, who was also heterozygous for the mutation, had congenital anosmia. In a 25-year-old Hispanic male with normosmic IHH and unilateral cryptorchidism who also had 2 congenitally missing teeth, Pitteloud et al. (2006) identified complex heterozygosity for 2 mutations of the FGFR1 gene on the same allele (136350.0014). The patient's mother, who was also heterozygous for the mutations, had congenital anosmia and normal puberty. In 2 brothers with normosmic IHH, 1 of whom also had cleft lip and palate and 3 missing teeth, Pitteloud et al. (2006) identified heterozygosity for a nonsense mutation in the FGFR1 gene (136350.0015). The sibs' father, who was also heterozygous for the mutation, reported having delayed puberty. Structural and biochemical analysis of the mutations revealed that all resulted in receptor loss of function. Noting the mixed pedigrees caused by mutation in FGFR1, Pitteloud et al. (2006) suggested that Kallmann syndrome and normosmic IHH are part of the same spectrum of disease. In a 16-year-old female with cleft lip and palate who presented with anosmia, irregular menstrual periods, and agenesis of 2 teeth, Riley et al. (2007) identified a nonsense mutation in the FGFR1 gene (136350.0018). Her father, who also carried the mutation, had isolated cleft lip and palate and a normal sense of smell and was fertile. The mutation was not found in the unaffected mother or brother; a deceased paternal great aunt was also reported to have cleft lip. Raivio et al. (2009) sequenced the FGFR1 gene in 134 patients with normosmic IHH and identified heterozygous loss-of-function mutations in 9 (7%). Screening of 5 more HH-associated genes in the 9 mutation-positive patients revealed additional mutations in 5 patients, including mutations in the GNRHR (138850), PROKR2 (607123), and FGF8 (600483) genes. Villanueva et al. (2015) studied 7 probands with mutations in the FGFR1 gene (see, e.g., 136350.0026) who exhibited HH as well as split hand/foot malformations (SHFM). In 6 families that were screened for mutation in 4 to 6 known HH-associated genes, the probands were heterozygous for FGFR1 mutations and exhibited SHFM limited to one or both feet. Other features exhibited by affected individuals included dental anomalies and cleft lip and/or palate. In 2 of these families, Incomplete penetrance was demonstrated by unaffected female carriers, and in 3 of the families, parental mutation status was not reported. In a consanguineous Turkish family, screened for mutation in 13 known HH-associated genes, the proband was homozygous for an FGFR1 missense mutation and had SHFM involving both hands and both feet as well as absent septum pellucidum and hypoplastic anterior corpus callosum on MRI. His unaffected parents and an anosmic sister were heterozygous for the mutation; in addition, 3 sibs with reportedly severe skeletal anomalies had died as neonates. ### Possible Association with Functional Hypothalamic Amenorrhea in Carrier Females Caronia et al. (2011) studied 55 women with functional hypothalamic amenorrhea, all of whom completed puberty spontaneously and had a history of secondary amenorrhea for 6 months or more, with low or normal gonadotropin levels and low serum estradiol levels. All had 1 or more predisposing factors, including excessive exercise, loss of more than 15% of body weight, and/or a subclinical eating disorder, and all had normal results on neuroimaging. The authors screened 7 HH-associated genes in the 55 affected women and identified 7 patients from 6 families who carried heterozygous mutations, including 1 in KAL1, 2 in FGFR1, 2 in PROKR2, and 1 in the GNRHR gene. Since these women with mutations resumed regular menses after discontinuing hormone-replacement therapy, Caronia et al. (2011) concluded that the genetic component of hypothalamic amenorrhea predisposes patients to, but is not sufficient to cause, GnRH deficiency. Genotype/Phenotype Correlations In 2 sisters with primary amenorrhea and no breast development at 25 and 18 years of age, respectively, Seminara et al. (2000) identified compound heterozygosity for mutations in the GNRHR gene: Q106R (138850.0001) on one allele and R262Q (138850.0002) on the other. The apparently unaffected parents were heterozygous for the mutations. The older sister conceived 3 times on pulsatile GnRH and twice on exogenous gonadotropin therapy, but suffered recurrent pregnancy loss; an embryo/trophoblast toxic factor was identified. The younger sister was treated with exogenous gonadotropins and gave birth to 3 children, with 1 singleton and 1 twin pregnancy. Pitteloud et al. (2007) reexamined the family studied by Seminara et al. (2000) and identified heterozygosity for an additional missense mutation in the FGFR1 gene (136350.0016) in the 2 sisters and in their father, who had a history of delayed puberty. Mutation analysis of the children of the younger sister revealed that her unaffected daughter who had undergone normal puberty was heterozygous for the mutation in FGFR1 but had no mutations in the GNRHR gene; and her prepubertal 10-year-old twin sons, born without cryptorchidism or microphallus, were each heterozygous for 1 of the mutations in GNRHR but did not have any mutations in the FGFR1 gene. In another family in which the proband had severe Kallmann syndrome, his father had a history of delayed puberty and congenital anosmia, his mother had clinodactyly and Duane ocular retraction syndrome, his sister had midline defects with a bifid nose and high-arched palate, and his brother had clinodactyly alone, Pitteloud et al. (2007) identified heterozygosity for a missense mutation in the FGFR1 gene (L342S; 136350.0017) in the proband, his father, and his sister. Heterozygosity for an additional mutation, an 8-bp deletion in the NELF gene (608137.0002), was identified in the proband, his mother, and his brother. The mother and both sibs of the proband had normal puberty and a normal sense of smell by formal testing. Pitteloud et al. (2007) concluded that mutations in 2 different genes can synergize to produce a more severe phenotype in families with hypogonadotropic hypogonadism than either alone, and that this digenic model may account for some of the phenotypic heterogeneity seen in GnRH deficiency. Salenave et al. (2008) studied the endocrine features reflecting gonadotropic-testicular axis function in 39 men; 21 had mutations in KAL1 (300836) and 18 in FGFR1, but none had additional mutations in PROK2 (607002) or PROKR2 (607123) genes. Puberty failed to occur in the patients with KAL1 mutations, all of whom had complete congenital hypogonadotropic hypogonadism. The fathers of 3 unrelated men with KS, who also carried the respective FGFR1 mutations, had normal puberty, were eugonadal, and had normal testosterone and gonadotropin levels. Cryptorchidism was more frequent and testicular volume was smaller in HH subjects with KAL1 mutations than in subjects with FGFR1 mutations. The mean basal plasma FSH (see 136530) level, serum inhibin B (see 147290) level, basal LH (see 152780) plasma level, and GnRH-stimulated LH plasma level were significantly lower in the subjects with KAL1 mutations. LH pulsatility was studied in 13 complete HH subjects with KAL1 mutations and 7 subjects with FGFR1 mutations; LH secretion was nonpulsatile in all the subjects, but mean LH levels were lower in those with KAL1 mutations. Salenave et al. (2008) concluded that men with KS and documented KAL1 mutations have a more severe reproductive phenotype than men with FGFR1 mutations, which are associated with a broad spectrum of phenotypes, ranging from complete HH to normality. Sykiotis et al. (2010) analyzed 8 known HH-associated genes, including KAL1, FGFR1, PROKR2, PROK2, FGF8, GNRHR, KISS1R, and NELF, in 397 well-phenotyped HH patients, of whom 44 women and 155 men had anosmia/hyposmia, and 52 women and 146 men were normosmic. Compared to 179 controls tested, HH patients were significantly more likely to harbor rare protein-altering variants (22% vs 10%; p = 0.001). A single variant allele was identified in 68 (17%) of the patients, and oligogenicity was found as frequently as homozygosity or compound heterozygosity in this cohort: 10 (2.5%) of the patients had rare variants in both alleles of a single gene, and 10 (2.5%) had variants in 2 or more alleles of different genes. Among the 22% of patients with detectable rare protein-altering variants, the likelihood of oligogenicity was 11.3%; no oligogenicity was detected among the controls (p less than 0.05), even though deleterious alleles were present. In the 10 oligogenic pedigrees, 3 of which were new and 7 of which had previously been reported (Pitteloud et al., 2007; Falardeau et al., 2008; Cole et al., 2008; Raivio et al., 2009; Chan et al., 2009), the higher the number of affected genes and alleles that an individual harbored, the more likely he or she was to have HH as opposed to a milder or partial phenotype, such as delayed puberty, isolated anosmia, or isolated cleft lip/palate. Sykiotis et al. (2010) concluded that GnRH deficiency should be considered to be an oligogenic disorder, and noted that the fact that no rare protein-altering variants were found in the majority (78%) of patients indicated that the 8 genes sequenced accounted for only a fraction of the genetic etiology of the disease. History In a family with Kallmann syndrome inherited presumably as an autosomal recessive, Dornan et al. (1980) excluded close linkage with HLA. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, unilateral (rare) Eyes \- Iris coloboma (rare) Nose \- Hyposmia/anosmia (in some patients) \- Absence of nasal cartilage, unilateral (rare) Mouth \- Cleft lip \- Cleft palate Teeth \- Tooth agenesis, variable in number (in some patients) CHEST Breasts \- Delayed or absent thelarche \- Gynecomastia (in untreated males) GENITOURINARY External Genitalia (Male) \- Micropenis \- Cryptorchidism Internal Genitalia (Female) \- Primary amenorrhea SKELETAL \- Osteopenia (in some patients) Hands \- Clinodactyly (rare) \- Fusion of fourth and fifth metacarpal bones (rare) \- Ectrodactyly (rare) Feet \- Ectrodactyly (rare) NEUROLOGIC Central Nervous System \- Mirror hand movements (bimanual synkinesis, in some patients) \- Corpus callosum agenesis (rare) ENDOCRINE FEATURES \- Hypogonadotropic hypogonadism \- Delayed or absent puberty \- Low to undetectable gonadotropin levels \- Low testosterone level \- Low estradiol level MISCELLANEOUS \- Incomplete penetrance \- Some patients experience later reversal of hypogonadotropic hypogonadism \- Phenotype may be oligogenic in some patients who carry mutations in more than one HH-associated gene MOLECULAR BASIS \- Caused by mutation in the fibroblast growth factor receptor-1 gene ({FGFR1, 136350.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	HYPOGONADOTROPIC HYPOGONADISM 2 WITH OR WITHOUT ANOSMIA	c0162809	28,671	omim	https://www.omim.org/entry/147950	2019-09-22T16:39:21	{"doid": ["0090083"], "mesh": ["D017436"], "omim": ["147950"], "orphanet": ["432", "478"], "synonyms": ["Gonadotropic deficiency", "Isolated congenital gonadotropin deficiency", "KALLMANN SYNDROME 2", "Alternative titles", "Normosmic idiopathic hypogonadotropic hypogonadism", "nIHH"], "genereviews": ["NBK1334"]}
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: "Tetra-amelia syndrome" – news · newspapers · books · scholar · JSTOR (January 2019) (Learn how and when to remove this template message) Tetra-amelia syndrome Other namesAutosomal recessive tetraamelia Violetta, a performer from the 1920s with tetra-amelia syndrome Tetra-amelia syndrome (tetra- \+ amelia), also called autosomal recessive tetraamelia,[1] is an extremely rare autosomal recessive[2] congenital disorder characterized by the absence of all four limbs. Other areas of the body are also affected by malformations, such as the face, skull, reproductive organs, anus and pelvis.[1] The disorder is caused by mutations in the WNT3 gene.[2] ## Contents * 1 Presentation * 2 Cause * 2.1 WNT3 gene * 2.2 Genetics within families * 3 Epidemiology * 4 People with tetra-amelia syndrome * 5 References * 6 External links ## Presentation[edit] Tetra-amelia syndrome is characterized by the complete absence of all four limbs. The syndrome causes severe malformations of various parts of the body, including the face and head, heart, nervous system, skeleton, and genitalia.[1] In many cases, the lungs are underdeveloped, which makes breathing difficult or impossible. Because children with tetra-amelia syndrome have such serious medical problems, most are stillborn or die shortly after birth. ## Cause[edit] Tetra-amelia syndrome has an autosomal recessive pattern of inheritance. ### WNT3 gene[edit] Researchers have found a mutation in the WNT3 gene in people with tetra-amelia syndrome from one large family. This gene is part of a family of WNT genes that play critical roles in development before birth. The WNT3 gene is located at human chromosome 17q21.[3] The protein produced from the WNT3 gene is involved in the formation of the limbs and other body systems during embryonic development. Mutations in the WNT3 gene prevent cells from producing functional WNT3 protein, which disrupts normal limb formation and leads to the other serious birth defects associated with tetra-amelia syndrome. ### Genetics within families[edit] In some affected families, the cause of tetra-amelia syndrome has not been determined. Some researchers believe that unidentified mutations in WNT3 or other genes involved in limb development may be responsible for the disorder. In most of the families reported so far, tetra-amelia syndrome appears to have an autosomal recessive pattern of inheritance.[1][2] This means the defective gene responsible for the disorder is located on an autosome (chromosome 17 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. ## Epidemiology[edit] Tetra-amelia syndrome has been reported in only a few families worldwide. According to a 2011 study by Bermejo-Sanchez, amelia – that is, the lacking of one or more limbs – occurs in roughly 1 out of every 71,000 pregnancies.[1] ## People with tetra-amelia syndrome[edit] Nick Vujicic, a motivational speaker who was born with tetra-amelia syndrome, speaking during the session "Inspired for a Lifetime" at the Annual Meeting 2011 of the World Economic Forum in Davos, Switzerland, on 30 January 2011 [4][5] * Joanne O'Riordan of Millstreet, Cork, Ireland. At the age of 16 she addressed the United Nations in New York. She appeared before the International Telecommunication Union’s conference ‘Girls in Technology’, receiving a standing ovation after delivering the keynote speech. * Hirotada Ototake * Nick Vujicic, founder of Life Without Limbs.[6] * Prince Randian * Violetta (entertainer) * Kent Bell (1965-2015) of Jacksonville, FL, scoreboard operator and disabled rights advocate, appeared on Oprah Winfrey show and in numerous print articles over the course of his life. * Rob Mendez, JV football coach at Prospect High School (Saratoga, California).[7] * Christian Arndt of Germany, media presenter. ## References[edit] 1. ^ a b c d e Online Mendelian Inheritance in Man (OMIM): 273395 2. ^ a b c Niemann, S.; Zhao, C.; Pascu, F.; Stahl, U.; Aulepp, U.; Niswander, L.; Weber, J.; Muller, U. (Mar 2004). "Homozygous WNT3 Mutation Causes Tetra-Amelia in a Large Consanguineous Family". The American Journal of Human Genetics (Free full text). 74 (3): 558–563. doi:10.1086/382196. PMC 1182269. PMID 14872406. 3. ^ Online Mendelian Inheritance in Man (OMIM): 165330 4. ^ Overcoming hopelessness \| Nick Vujicic \| TEDxNoviSad, retrieved 2019-08-15 5. ^ "TED Prize winner Sugata Mitra to speak at conference in Kuala Lumpur". The Star Online. 2013-11-12. Retrieved 2019-08-15. 6. ^ VUJICIC, NICK. "Life Without Limbs // Nick Vujicic". Life Without Limbs. Retrieved 2019-07-30. 7. ^ "Rob Mendez has never held a football. Who says he can't be a head coach?". ESPN.com. Retrieved 2019-02-16. ## External links[edit] Classification D * OMIM: 273395 * MeSH: C536498 C536498, C536498 * DiseasesDB: 34469 * "Tetra-amelia syndrome - Genetics Home Reference". U.S. National Library of Medicine. Retrieved 2009-01-09. * v * t * e Extracellular ligand disorders Cytokine * EDA Hypohidrotic ectodermal dysplasia * Camurati–Engelmann disease Ephrin * Craniofrontonasal dysplasia WNT * Tetra-amelia syndrome TGF * OFC 11 Fas ligand * Autoimmune lymphoproliferative syndrome 1B Endothelin * EDN3 * Waardenburg syndrome IVb * Hirschsprung's disease 4 Other * DHH (DHH XY gonadal dysgenesis) * BMP15 (Premature ovarian failure 4) * TSHB (Congenital hypothyroidism 4) See also intercellular signaling peptides and proteins [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Tetra-amelia syndrome	c2931218	28,672	wikipedia	https://en.wikipedia.org/wiki/Tetra-amelia_syndrome	2021-01-18T18:34:12	{"gard": ["5148"], "mesh": ["C536498", "C536500"], "umls": ["C2931218", "C2931216"], "orphanet": ["294971", "3301"], "wikidata": ["Q2406697"]}
Tracheal agenesis (TA) is a rare congenital malformation in which the trachea may be completely absent (agenesis), or partially in place but underdeveloped (atresia). In both cases, proximal-distal communication between the larynx and the alveoli of the lungs is lacking. ## Epidemiology The prevalence at birth is approximately 1 in 50 000. There is a male predominance and an association with prematurity and polyhydramnios. ## Clinical description Associated congenital malformations are present in 90% of cases, most frequently affecting the cardiovascular or gastro-intestinal systems and the genito-urinary tract, thus overlapping with the much commoner condition, VATER association. ## Etiology No risk factor for the occurrence of this malformation has ever been suggested. ## Diagnostic methods Tracheal agenesis should be suspected in any neonate with a history of hydramnios, respiratory distress, cyanosis and no audible cry, and in those in whom tracheal intubation proves impossible. The diagnosis of TA is confirmed by laryngoscopy and a helical computerized tomography (CT) scan of the airway. The diagnosis has been established antemortem in only a few cases. ## Management and treatment There is no long-term surgical solution because no suitable material for a tracheal prosthesis is available at present. Research into tissue engineering might lead to possibilities for definitive surgical repair of tracheal agenesis or atresia; however, until curative repair becomes possible, prolonged ventilation via the oesophageal tube does not seem to be worthwhile. ## Prognosis This malformation is usually fatal in newborns; however, one infant, who had tracheal agenesis with a bronchoesophageal fistula, was managed successfully. At 3 years of age, esophageal reconstruction was performed with a colonic interposition graft. The patient was thriving and developing normally at 4 years of 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 [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Tracheal agenesis	c1261567	28,673	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3346	2021-01-23T17:28:57	{"gard": ["5233"], "mesh": ["C536975"], "umls": ["C1261567"], "icd-10": ["Q32.1"]}
A number sign (#) is used with this entry because autosomal recessive nonsyndromic mental retardation-14 (MRT14) can be caused by homozygous mutation in the TECR gene (610057) on chromosome 19p13.12. Clinical Features Nolan et al. (2008) described a large consanguineous Hutterite family, originally identified by Ober et al. (2001), with autosomal recessive nonsyndromic mental retardation. The family included 2 sisters, aged 32 and 47 years, and 2 brothers, aged 40 and 49 years, with mild to moderate mental retardation. The remaining 9 sibs and their parents were intellectually normal. The 4 affected sibs had developmental delay since birth, communicated verbally but had speech delays, and could read and write their names but otherwise had minimal reading or writing skills. They were unable to live independently as adults, performed jobs requiring manual labor, but were unable to perform tasks requiring fine motor skills. Growth parameters, including head circumference, were normal. There were no dysmorphic features other than a narrow palate in the 3 individuals examined. Their neurologic exams were unremarkable except for an initiation tremor when asked to do finger-nose-finger exam or any other task requiring fine motor coordination. Mapping In a Hutterite family with autosomal recessive nonsyndromic mental retardation, Nolan et al. (2008) demonstrated linkage to chromosome 19p13 (lod score 1.2-3.5, depending on assumptions of allele frequencies). The pedigree that contained all of the common ancestors of the parents was too large and complex for linkage programs that use exact calculations. Fine mapping defined a critical region of 3.6 Mb, which overlapped a gene previously implicated in mental retardation (CC2D1A; 610055); however, no mutations in the coding region of CC2D1A were found. The authors suggested that another gene causing autosomal recessive nonsyndromic mental retardation was located within this genomic region. Molecular Genetics Caliskan et al. (2011) performed exome sequencing of the 4 affected individuals described by Nolan et al. (2008) as well as of another sib whose mild developmental delay had been attributed to birth trauma and infection and who had not been considered affected by Nolan et al. (2008). All 5 sibs were homozygous for a pro182-to-leu substitution in trans-2,3-enoyl-CoA reductase (610057.0001), a synaptic glycoprotein. Among 1,496 Schmiedeleut (S-leut) Hutterites from the United States, Chong et al. (2012) found 103 heterozygotes and 5 homozygotes for the P182L mutation in the TECR gene (rs199469705), for a frequency of 0.069, or 1 in 14.5. This is a private mutation in the Hutterite population. INHERITANCE \- Autosomal recessive HEAD & NECK Mouth \- Narrow palate NEUROLOGIC Central Nervous System \- Mental retardation, mild to moderate \- Developmental delay since birth \- Speech delay \- Minimal reading and writing skills \- Poor fine motor skills MISCELLANEOUS \- All known cases are caused by a Hutterite founder mutation in the TECR gene MOLECULAR BASIS \- Caused by mutation in the trans-2,3-enoyl-CoA reductase gene (TECR, 610057.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MENTAL RETARDATION, AUTOSOMAL RECESSIVE 14	c3151462	28,674	omim	https://www.omim.org/entry/614020	2019-09-22T15:56:46	{"doid": ["0060308"], "omim": ["614020"], "orphanet": ["88616"], "synonyms": ["AR-NSID", "NS-ARID"]}
A number sign (#) is used with this entry because hereditary sensory and autonomic neuropathy type IIA (HSAN2A) can be caused by mutation in the HSN2 isoform of the WNK1 gene (WNK1/HSN2; see 605232) on chromosome 12p13. HSAN2B (613115) is caused by mutation in the FAM134B gene (613114). For a discussion of genetic heterogeneity of HSAN, see HSAN1 (162400). Clinical Features Giaccai (1952) reported 'neurogenic acroosteolysis' in 4 children born of an Arab man who married 2 first cousins. By the first wife, 1 of the children was affected, and by the second wife, 3 of 5 children were affected. Since the spinal cord was normal at autopsy, Giaccai (1952) concluded that the abnormality resided in peripheral sensory nerves. Heller and Robb (1955) described a French Canadian family in which 5 members had the full form of hereditary sensory neuropathy and 3 had an incomplete form, suggesting autosomal dominant inheritance. No amyloid was found on dorsal root ganglion biopsy. Heller and Robb (1955) suggested that the disease was the same as Morvan disease. The patient reported by Ogden et al. (1959) as having progressive sensory radicular neuropathy of Denny-Brown (HSAN1) may have had neurogenic acroosteolysis because symptoms began as early as 1 year and the parents were first cousins. Biemond (1955) described 11-year-old fraternal twins (male and female) with loss of pain sensation, diminished touch and temperature sense, and absent tendon reflexes. Postmortem examination showed deficient development in the posterior root ganglia, gasserian ganglion, posterior roots, posterior horns of the spinal gray matter, and posterior columns. The spinothalamic tracts could not be demonstrated. In a child with sensory and autonomic dysfunction, Freytag and Lindenberg (1967) found decreased posterior ascending tracts, severe reduction in the number of neurons in peripheral sensory and autonomic ganglia, and hypoplasia of the pyramidal tracts. Johnson and Spalding (1964) described a slowly progressive sensory neuropathy in 2 unrelated boys, aged 10 and 15 years, each of whom had consanguineous parents. The disorder began in early childhood and involved all modalities of sensation with no disturbance of motor or autonomic function. Involvement was predominantly distal with late involvement of the trunk, and resulted in loss of digits and Charcot joints at the ankles. Johnson and Spalding (1964) differentiated the disorder from congenital indifference to pain (147430, 243000) by the involvement of all sensory modalities, preservation of proximal sensation, including pain, loss of tendon reflexes, gradual progression, and peripheral nerve degeneration, and from autosomal dominant HSN1 by the recessive mode of inheritance, early age of onset, and ultimate involvement of the trunk. Haddow et al. (1970) described a brother and sister, offspring of nonconsanguineous parents, with a nonprogressive sensory defect leading to extensive damage of the fingers. The patients had low spinal fluid protein and had suffered from unexplained chronic diarrhea in early life. The mother was Irish and the father was French Canadian. Haddow et al. (1970) suggested that the disorder in the French Canadian family described by Hould and Verret (1967) was the same, although onset in that family was not until the middle of the first decade. Ohta et al. (1973) reported further on the family described by Hould and Verret (1967). They suggested that the families of Schoene et al. (1970), Ogryzlo (1946), and Parks and Staples (1945) had the same condition. Ohta et al. (1973) suggested the designation 'hereditary sensory neuropathy type II,' giving the name of type I to the dominant disorder. Murray (1973) reported 2 daughters of first cousins with a recessive form of congenital sensory neuropathy. Impairment of pain, temperature, and touch sensations in varying degrees affected the limbs and trunk. The disorder was thought to be nonprogressive and perhaps caused by a failure of sensory nerve formation rather than by sensory nerve degeneration. Murray (1973) noted that those affected with the disorder often developed painless finger and toe ulcerations which consequently led to damage to the underlying bone. Some patients also developed neuropathic joint degeneration. Murray (1973) compiled 33 cases of congenital sensory neuropathy from the literature, 20 of whom were from 6 families. Jedrzejowska and Milczarek (1976) reported light and electron microscopic findings in the sural nerve from a patient with HSAN2. There was a marked reduction in the number of myelinated fibers due to Wallerian-like axonal degeneration, as well as segmental demyelination, most likely secondary to axonal changes. The authors suggested a progressive nature of the pathologic process. Sirinavin et al. (1982) reported a 12-year-old Cambodian girl with digital clubbing and joint and leg pain with swelling. Acroosteolysis of the distal phalanges was accompanied by profuse hyperhidrosis of the hands and feet and thickening of soft tissues around the knees and ankles, giving a cylindrical appearance to the legs; these associated features suggested pachydermoperiostosis (167100) to the authors. However, the periosteum showed no radiologic changes and the 'clubbing,' was more suggestive of foreshortening due to collapse of the distal phalanges, similar to that seen in chronic uremia. There was generalized osteoporosis and the bones of the calvaria were thin with a single small wormian bone in the lambdoidal suture; these features suggested Cheney syndrome (102500), but the fact that the parents were first cousins favored recessive inheritance for the disorder in this patient. Sugiura and Sengoku (1986) reported 2 kindreds with 4 affected persons. In the first family, the parents were consanguineous and had 2 affected children; in the second family, second cousins were affected. The authors suggested that the disorder referred to as the recessive form of hereditary sensory radicular neuropathy is the same as the Giaccai type of acroosteolysis. Bockers et al. (1989) observed 3 sibs in a Turkish family who developed progressive foot drop between ages 7 and 12 years and ulcers on the lateral edge of the feet. Hyperkeratotic plaques, erosions, and ulcers of the fingers developed in 1 patient at the age of 11 years. The fingers showed ainhum-like constriction bands and spontaneous amputations. Osteomyelitis and osteolysis led to amputations. A high urinary excretion of sphingomyelin and lecithin suggested that the pathogenetic mechanism might be a disorder of phospholipid metabolism. Two of the patients showed the rare blood group O (Bombay); see 211100. Lafreniere et al. (2004) reported 5 families with HSAN2, including the large family from Newfoundland originally reported by Ogryzlo (1946). Beginning in early childhood, affected individuals experienced numbness in the hands and feet, aggravated by cold, together with reduced sensation to pain. They experienced loss of touch, pain, and temperature, with touch most severely affected. The loss was predominantly distal, extending from the elbows to the fingertips and from just above the knees down to the toes, a pattern of distribution often described as 'glove and stocking.' The lower limbs were typically more severely affected than the upper limbs, and the trunk was involved in some patients. Ulceration and infections caused spontaneous amputation of digits and surgical amputation of lower limbs. There was no overt autonomic dysfunction; sweating and tearing were within normal range, and postural hypotension was not present. As in the other hereditary sensory neuropathies, there was absence of axon flare after intradermal histamine, indicating defective nociceptive fibers. Biopsy showed a severe loss of myelinated axons, some loss of nonmyelinated fibers in the sural nerve, and the absence of cutaneous sensory receptors and nerve fibers. Mapping By linkage analysis of 8 affected members from the consanguineous multigenerational Newfoundland pedigree reported by Ogryzlo (1946), and an additional family with 2 affected members, Lafreniere et al. (2004) mapped the HSAN2 disease locus to 12p13.33 (maximum lod score of 8.4). Molecular Genetics Among 5 families with HSAN2, including those from Newfoundland reported by Ogryzlo (1946) and patients from rural Quebec and Nova Scotia, Lafreniere et al. (2004) identified 3 different truncating mutations in the HSN2 isoform of the WNK1 gene (605232.0003-605232.0005) In 4 affected members of a large consanguineous Lebanese family with HSAN2, Riviere et al. (2004) identified a homozygous 1-bp deletion in the HSN2 isoform of the WNK1 gene (605232.0006). In 16 patients from 13 HSAN2 families originating from southern Quebec, Roddier et al. (2005) identified 2 HSN2 founder mutations: 56% of patients were homozygous for a nonsense mutation (Q315X; 605232.0005), 6% were homozygous for a 1-bp insertion (918insA; 605232.0004), and 38% were compound heterozygous for the 2 mutations. In a Korean man with HSAN2, Cho et al. (2006) identified compound heterozygosity for 2 mutations in the HSN2 isoform of the WNK1 gene (605232.0008 and 605232.0009). Coen et al. (2006) reported 3 unrelated patients with HSAN2 from Italy, Austria, and Belgium, respectively. All had compound heterozygous or homozygous truncating mutations in the HSAN2 gene resulting in complete loss of protein function. All patients had early onset of a severe sensory neuropathy with mutilating acropathy but without autonomic dysfunction. Muscle strength was preserved. In a girl with HSAN2, Shekarabi et al. (2008) identified compound heterozygosity for 2 mutations in the WNK1 gene: 1 in the WNK1/HSN2 isoform (605232.0010) and 1 in the WNK1 isoform (605232.0011). She did not have hypertension. The authors noted that all recessive mutations associated with the HSAN2 phenotype resulted in truncations of the WNK1/HSN2 nervous system-specific protein. Disease-causing mutations in WNK1 resulting in pseudohypoaldosteronism type 2 (PHA2C; 614492) were large, heterozygous intronic deletions that increase the gene expression. This impact on the expression level in PHA2C patients may explain the absence of hypertension in individuals affected with HSAN2, as the expression of the WNK1 isoform in which the HSN2 exon is not incorporated should not be affected. The findings in their patient suggested that 1 mutation in the HSN2 exon is sufficient to cause the HSAN2 phenotype when combined with a mutation in WNK1 on the other allele. Moreover, homozygous mutations disrupting WNK1 isoforms without HSN2 may be lethal, which would explain why all loss-of-function mutations reported to date have been located in the HSN2 exon. Population Genetics Clustering of cases of HSAN II in eastern Canada was reported by Murray (1973) and had first been noted in Newfoundland in the early 1900s. The original family members came from Dorset, United Kingdom, approximately 100 years earlier, as part of a mass migration of Protestant settlers from southwestern England and Roman Catholic settlers from southern Ireland (Lafreniere et al., 2004). Roddier et al. (2005) reported that 12 of 16 patients with HSAN2 originated from the Lanaudiere region of Quebec, along the Saint Lawrence River, that was first settled by the French during the second half of the 17th century. Several of the families were consanguineous, and several of the families were distantly related. The affected family reported by Heller and Robb (1955) also originated from the Lanaudiere region. The regional carrier frequency for the identified Q315X and 918insA mutations was estimated at 1 in 116 and 1 in 260, respectively. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Impaired corneal reflex Mouth \- Decreased taste sensation ABDOMEN Gastrointestinal \- Poor feeding \- Gastroesophageal reflux SKELETAL \- Painless fractures due to injury \- Neurogenic joint degeneration Hands \- Acroosteolysis \- Acral ulceration leading to autoamputation of digits Feet \- Acroosteolysis \- Acral ulceration leading to autoamputation of digits SKIN, NAILS, & HAIR Skin \- Hyperhidrosis, episodic \- Anhidrosis, patchy \- Ulcerations of distal extremities Nails \- Paronychia MUSCLE, SOFT TISSUES \- Muscle strength and bulk is preserved NEUROLOGIC Peripheral Nervous System \- Impaired sensation in distal extremities (pain, temperature, position, touch) \- Lower limbs more affected than upper limbs \- Trunk may be involved later \- Decreased taste sensation \- Impaired corneal reflex \- Impaired gag reflex \- Hyporeflexia \- Areflexia \- Hypotonia \- Decreased sensory nerve conduction velocities (NCV) \- Sural nerve biopsy shows severe loss of myelinated fibers \- Some loss of unmyelinated fibers \- Absence of cutaneous sensory receptors and fibers \- Autonomic involvement does not always occur LABORATORY ABNORMALITIES \- Decreased axonal flare response after intradermal histamine injection MISCELLANEOUS \- Onset in infancy or early childhood \- Slow progression \- High disease prevalence among French-Canadians MOLECULAR BASIS \- Caused by mutation in the HSN2 isoform of the protein kinase, lysine-deficient 1 gene (WNK1, 605232.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IIA	c0020072	28,675	omim	https://www.omim.org/entry/201300	2019-09-22T16:31:29	{"doid": ["0070155"], "mesh": ["D009477"], "omim": ["201300"], "orphanet": ["970"], "synonyms": ["Alternative titles", "HSAN IIA", "NEUROPATHY, HEREDITARY SENSORY, TYPE IIA", "HSN IIA", "ACROOSTEOLYSIS, NEUROGENIC", "ACROOSTEOLYSIS, GIACCAI TYPE", "NEUROPATHY, HEREDITARY SENSORY RADICULAR, AUTOSOMAL RECESSIVE", "MORVAN DISEASE", "NEUROPATHY, PROGRESSIVE SENSORY, OF CHILDREN", "NEUROPATHY, CONGENITAL SENSORY"], "genereviews": ["NBK49247"]}
Nevoid basal cell carcinoma syndrome (NBCCS) leads to the growth of non-cancerous and cancerous tumors. The symptoms include basal cell cancers, jaw cysts, skin pits on the hands and feet, and abnormal deposits of calcium in the brain. Other symptoms may include bone abnormalities of the spine, ribs, or skull, and a large head. Some of the signs and symptoms of NBCCS are present at birth. There is an increased risk for a type of brain tumor (medulloblastoma) in childhood. Jaw cysts and basal cell cancers typically appear by adulthood. NBCCS occurs when the PTCH1, PTCH2, or the SUFU gene is not working correctly. It is inherited in an autosomal dominant manner. NBCCS is diagnosed based on clinical examination for specific features and genetic testing. Treatment is aimed at addressing the symptoms and associated cancers. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Nevoid basal cell carcinoma syndrome	c0004779	28,676	gard	https://rarediseases.info.nih.gov/diseases/7166/nevoid-basal-cell-carcinoma-syndrome	2021-01-18T17:58:43	{"mesh": ["D001478"], "omim": ["109400"], "umls": ["C0004779"], "orphanet": ["377"], "synonyms": ["Gorlin-Goltz Syndrome", "Basal Cell Nevus Syndrome", "Multiple Basal Cell Nevi, Odontogenic Keratocysts, And Skeletal Anomalies", "Gorlin syndrome"]}
46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome is a rare, genetic, developmental defect during embryogenesis disorder characterized by partial (unilateral testis, persistence of Müllerian duct structures) or complete (streak gonads only) gonadal dysgenesis, usually manifesting with primary amenorrhea in individuals with female phenotype but 46,XY karyotype, and sensorimotor dysmyelinating minifascicular polyneuropathy, which presents with numbness, weakness, exercise-induced muscle cramps, sensory disturbances and reduced/absent deep tendon reflexes. Germ cell tumors (seminoma, dysgerminoma, gonadoblastoma) may develop from the gonadal tissue. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome	c2751325	28,677	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=168563	2021-01-23T19:08:12	{"mesh": ["C567773"], "omim": ["607080"], "umls": ["C2751325"], "icd-10": ["Q56.1"]}
Occult macular dystrophy SpecialtyOphthalmology Occult macular dystrophy (OMD) is a rare inherited degradation of the retina, characterized by progressive loss of function in the most sensitive part of the central retina (macula), the location of the highest concentration of light-sensitive cells (photoreceptors) but presenting no visible abnormality. "Occult" refers to the degradation in the fundus being difficult to discern.[1] The disorder is called "dystrophy" instead of "degradation" to distinguish its genetic origin from other causes, such as age. OMD was first reported by Y. Miyake et al. in 1989.[2][3] ## Contents * 1 Symptoms * 2 Etiology * 2.1 Physiology * 3 Diagnosis * 3.1 Differential diagnosis * 4 Prognosis * 5 Future research * 6 Prevalence * 7 References ## Symptoms[edit] An Amsler grid, as seen by a person with normal vision. Symptoms entail a loss of visual acuity in both eyes, including darkened vision, ring scotoma (ring of blindness close to the center of vision), color blindness, and difficulty with bright lights. The scotoma may cause text slightly away from the center of vision to disappear; the appearance would not be black (in early stages) but of the same color as the nearby background. Many lines of an Amsler grid would be faded or invisible to the patient. The area of invisibility on the Amsler grid spreads with time. Symptoms do not include headaches or eye pain. The loss of acuity tends to be symmetric between the eyes. ## Etiology[edit] OMD that is caused by mutations of the retinitis pigmentosa 1-like 1 (RP1L1)[4] gene (OMIM 608581) is called Miyake's disease.[1][5] While the mutation is dominant, OMD may manifest more strongly and earlier in children than in the parent (anticipation).[2][6] However, cases have presented with no mutation to RP1L1.[6][7] One study suggests that OMD arises because of two mutations arising simultaneously, one in RP1L1 and another in ABCA4.[8] OMD is generally believed to be autosomal dominant, meaning that if you get the abnormal gene from only one parent, you can get the disease. However, this does not always seem to be the case.[7] OMD differentiates from Stargardt macular dystrophy in which gene is mutated (RP1L1 instead of ABCA4), the process of OMD isn't a buildup of toxic lipofuscin,[9] and Stargardt is regressive.[10] [11] ### Physiology[edit] The connection between these mutations and OMD is unclear, but cone density is significantly lower in patients with OMD compared to the general population. Use of adaptive optics to obtain high-resolution retinal images reveal abnormal changes in patients with OMD, including thinning of the foveal thickness and the outer nuclear layer and disruption of the IS/OS line and COST line.[6] ## Diagnosis[edit] OMD returns negative results for a funduscopic inspection, fluorescein angiogram, and full-field electroretinogram (ERG),[4] for both rod and cone components. The key to diagnosing this disorder is the multifocal ERG (mfERG), providing a single procedure for diagnosis.[6] Onset is known to range from age 6 to 81, with about half of onsets occurring after age 65.[1] ### Differential diagnosis[edit] A visual field test can differentiate between whether the reduced visual acuity is centered on the optic nerve or the fundus. Once a neurological problem has, therefore, been ruled out, the disorder's reduced visual acuity without visible fundus abnormalities may be misdiagnosed as optic neuritis, dominant optic atrophy, amblyopia, or nonorganic visual disorder.[12] The combination of weak amplitudes in the mfERG with no visible fundus abnormalities then rules out other explanations. For example, OMD presents negative for a full-field ERG while retinitis pigmentosa presents abnormal.[13][14] ## Prognosis[edit] Since the abnormality is not in the eye lens, the disease is not correctable with eyeglasses. Vision becomes dimmer over the course of years as the macula loses function. Eventually the patient may become legally blind. The peripheral vision field is preserved. In other words, OMD does not cause total blindness, due to the concentration of the degradation at the cone-rich (color-sensitive) region of the retina. No treatment is known to slow the progression. The speed of progression varies by case — even between donor and recipient of the mutation[2] — and can last for 10 to 30 years.[5] ## Future research[edit] Because of the rarity of OMD, no clinical trials are in the pipeline as of January 2019.[15] However, mutations in RP1L1 might play a role in retinitis pigmentosa (RP),[16][17] raising hope for a spillover effect for OMD patients should an RP1L1-related treatment be developed for RP. Given the possible relation between ABCA4 and OMD,[8] progress with Stargardt disease via gene therapy might have a spillover effect for OMD patients as well. Adeno-associated viral (AAV) vectors have been particularly successful in gene therapy of eyes and muscles.[18] Unfortunately, their size is limited--too limited to hold the RP1L1 gene.[19] Therefore, a non-viral approach would need to be developed for gene therapy to treat OMD. Since RP1 has the same size problem, a gene therapy for RP could have a spillover effect for OMD. A stem-cell approach might entail taking stem cells from the patient, editing the mutation with CRISR, and inserting the stem cells in the eye. However, as of 2014, researchers did not yet know if retinal stem cell surgery would work.[20] ## Prevalence[edit] Prevalence is unknown,[21] but seems to be elevated in Asian populations, given that most OMD studies are of Japanese and Korean subjects.[22] Given that Stargardt's, the most common macular dystrophy, has a prevalence of 1 in 10,000 in the US,[10] [11] the prevalence of OMD is likely well below 1 in 100,000. ## References[edit] 1. ^ a b c Akahori, Masakazu; et al. (10 September 2010). "Dominant Mutations in RP1L1 Are Responsible for Occult Macular Dystrophy". Am J Hum Genet (paper). 87 (3): 424–429. doi:10.1016/j.ajhg.2010.08.009. PMC 2933341. PMID 20826268. 2. ^ a b c Miyake, Y.; Ichikawa, K.; Shiose, Y.; Kawase, Y. (15 September 1989). "Hereditary macular dystrophy without visible fundus abnormality". Am J Ophthalmol (paper). 108 (3): 292–299. doi:10.1016/0002-9394(89)90120-7. PMID 2774037. 3. ^ Miyake, Y.; et al. (November 1996). "Occult macular dystrophy". Am J Ophthalmol (paper). 122 (5): 644–653. doi:10.1016/S0002-9394(14)70482-9. PMID 8909203. 4. ^ a b "RP1L1 Gene(Protein Coding)". GeneCards Human Gene Database. Retrieved 24 August 2019. 5. ^ a b Tsunoda, K. (2018). "20". In Prakash, Gyan; Takeshi, Iwata (eds.). Advances in Vision Research, Volume II. Springer. ISBN 978-9811308840. 6. ^ a b c d Tojo, Naoki; et al. (8 May 2013). "Analysis of macular cone photoreceptors in a case of occult macular dystrophy". Clin Ophthalmol (paper). 7: 859–864. doi:10.2147/OPTH.S44446. PMC 3659265. PMID 23696695. 7. ^ a b Ahn, Seong Joon; et al. (July 2013). "Clinical and genetic characteristics of Korean occult macular dystrophy patients". Investigative Ophthalmology & Visual Science (paper). 54 (7): 4856–4863. doi:10.1167/iovs.13-11643. PMID 23745001. 8. ^ a b Qi, YH; et al. (25 August 2017). "Next-Generation Sequencing-Aided Rapid Molecular Diagnosis of Occult Macular Dystrophy in a Chinese Family". Front Genet (paper). 107 (8): 107. doi:10.3389/fgene.2017.00107. PMC 5574873. PMID 28890726. 9. ^ "Facts About Stargardt Disease". NEI. April 2015. Retrieved 17 January 2019. 10. ^ a b Bernstein, M.D., Ph.D., Paul S. (3 November 2017). "Retinal and Macular Dystrophies" (lecture). University of Utah Moran Eye Center. Retrieved 17 January 2019.CS1 maint: multiple names: authors list (link) 11. ^ a b Paul Bernstein (2017-11-03). "Moran CORE \| Retinal and Macular Dystrophies" (.mp4). morancore.utah.edu. Retrieved 2020-02-08. 12. ^ Wildberger, H.; Niemeyer, G.; Junghardt, A. (March 2003). "Multifocal electroretinogram (mfERG) in a family with occult macular dystrophy (OMD)". Klin Monbl Augenheilkd (paper). 220 (3): 111–115. doi:10.1055/s-2003-38161. PMID 12664360. 13. ^ "Facts About Retinitis Pigmentosa". National Eye Institute. December 2015. Retrieved 17 January 2019. 14. ^ Lim, M.D., Jennifer; et al. (23 May 2018). "Retinitis Pigmentosa". American Academy of Ophthalmology. Retrieved 17 January 2019. 15. ^ "ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world". ClinicalTrials.Gov. Retrieved 17 January 2019. 16. ^ Davidson, AE; et al. (March 2013). "RP1L1 variants are associated with a spectrum of inherited retinal diseases including retinitis pigmentosa and occult macular dystrophy". Hum Mutat (paper). 34 (3): 506–514. doi:10.1002/humu.22264. PMID 23281133. 17. ^ Yamashita, T; et al. (5 August 2009). "Essential and Synergistic Roles of RP1 and RP1L1 in Rod Photoreceptor Axoneme and Retinitis Pigmentosa". Journal of Neuroscience (paper). 31 (29): 9748–9760. doi:10.1523/JNEUROSCI.5854-08.2009. PMC 2748320. PMID 19657028. 18. ^ Nasso, M; et al. (1 July 2017). "Non‐viral retinal gene therapy: a review". BioDrugs (paper). 4 (31): 317–334. doi:10.1007/s40259-017-0234-5. PMC 5548848. PMID 28669112. 19. ^ Issa, P; et al. (11 July 2011). "Non‐viral retinal gene therapy: a review". Clinical & Experimental Ophthalmology (paper). 40 (1): 39–47. doi:10.1111/j.1442-9071.2011.02649.x. PMID 21745262. 20. ^ Weiss, Jeffrey (2014). "4". Patient's Guide to Retinal and Optic Nerve Stem Cell Surgery. Author. ISBN 978-1495336997. 21. ^ "Occult macular dystrophy". Orphanet. 19 January 2019. Retrieved 20 January 2019. 22. ^ Piermarocchi, Stefano; et al. (2016). "Occult macular dystrophy in an Italian family carrying a mutation in the RP1L1 gene". Molecular Medicine Reports (paper). 13 (3): 2308–2312. doi:10.3892/mmr.2016.4784. PMID 26782618. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Occult macular dystrophy	c3150833	28,678	wikipedia	https://en.wikipedia.org/wiki/Occult_macular_dystrophy	2021-01-18T18:41:55	{"umls": ["C3150833"], "icd-10": ["H35.5"], "orphanet": ["247834", "24783"], "wikidata": ["Q18553320"]}
Severe combined immunodeficiency due to complete RAG1/2 deficiency is a rare, genetic T-B- severe combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, normal NK counts and low or absent serum immunoglobulins; some patients may have eosinophilia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Severe combined immunodeficiency due to complete RAG1/2 deficiency	c1832322	28,679	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=331206	2021-01-23T17:22:11	{"gard": ["10339"], "mesh": ["C563311"], "omim": ["601457"], "umls": ["C1832322"], "icd-10": ["D81.1"], "synonyms": ["SCID due to complete RAG1/2 deficiency"]}
Family of orthopedic diseases of the joint Osteochondrosis SpecialtyRheumatology, orthopedic surgery Osteochondrosis is a family of orthopedic diseases of the joint that occur in children, adolescents and other rapidly growing animals, particularly pigs, horses, dogs, and broiler chickens. They are characterized by interruption of the blood supply of a bone, in particular to the epiphysis,[1] followed by localized bony necrosis,[2] and later, regrowth of the bone.[3] This disorder is defined as a focal disturbance of endochondral ossification and is regarded as having a multifactorial cause, so no one thing accounts for all aspects of this disease.[1] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 3.1 Classification * 4 Prognosis * 5 See also * 6 References * 7 External links ## Signs and symptoms[edit] These conditions nearly all present with an insidious onset of pain referred to the location of the bony damage. Some, notably Kienbock's disease of the wrist, may involve considerable swelling,[4] and Legg-Calvé-Perthes disease of the hip causes the victim to limp.[5] The spinal form, Scheuermann's disease, may cause bending, or kyphosis of the upper spine, giving a "hunch-back" appearance.[6] ## Cause[edit] The ultimate cause for these conditions is unknown, but the most commonly cited cause factors are rapid growth, heredity, trauma (or overuse), anatomic conformation, and dietary imbalances; however, only anatomic conformation and heredity are well supported by scientific literature. The way that the disease is initiated has been debated. Although failure of chondrocyte differentiation, formation of a fragile cartilage, failure of blood supply to the growth cartilage, and subchondral bone necrosis all have been proposed as the starting point in the pathogenesis, recent literature strongly supports failure of blood supply to growth cartilage as most likely.[1] ## Diagnosis[edit] ### Classification[edit] In humans, these conditions may be classified into three groups: 1. Spinal: Scheuermann's disease (of the interspinal joints) which is a curve in the thoracic spine.[6] 2. Articular: Legg-Calvé-Perthes disease (or, avascular necrosis of the femoral head in the hip), Köhler's disease (of the tarsal navicular bone of the foot), Panner's disease (of the capitulum of the elbow), and Freiberg's infraction (of the second or third metatarsal of the foot and less frequently the first or fourth; sometimes called Freiberg's Infraction or Freiberg's disease)[7] 3. Non-articular: This group includes Sever's disease (of the calcaneus, or heel), and Kienbock's disease of the hand, and other conditions not completely characteristic of the osteochondrosis, such as Osgood-Schlatter's disease (of the tibial tubercle) and Osteochondritis dissecans.[7] ## Prognosis[edit] The term osteochondrosis has been used to describe a wide range of lesions among different species. There are different types of the prognosis: latens, which is a lesion restricted to epiphyseal cartilage, manifesta, a lesion paired with a delay in endochondral ossification, and dissecans which is a cleft formation in the articular cartilage.[1] The prognosis for these conditions is very variable, and depends both on the anatomic site and on the time at which it is detected. In some cases of osteochondrosis, such as Sever's disease and Freiberg's infraction, the involved bone may heal in a relatively normal shape and leave the patient asymptomatic.[8] On the contrary, Legg-Calvé-Perthes disease frequently results in a deformed femoral head that leads to arthritis and the need for joint replacement.[5] ## See also[edit] * Osteochondritis * Osteochondritis dissecans * Osteochondropathy ## References[edit] 1. ^ a b c d Ytrehus B, Carlson CS, Ekman S (July 2007). "Etiology and pathogenesis of osteochondrosis". Vet. Pathol. 44 (4): 429–48. doi:10.1354/vp.44-4-429. PMID 17606505. Archived from the original on 2009-01-31. Retrieved 2008-10-03. 2. ^ "osteochondrosis" at Dorland's Medical Dictionary 3. ^ "Medical College of Wisconsin". Archived from the original on 2012-02-04. Retrieved 2005-12-10. 4. ^ "Bone Scintigraphy in Kienbock's Disease". Retrieved 2008-11-17. 5. ^ a b "Legg-Calvé-Perthes Disease". Retrieved 2008-11-17. 6. ^ a b "Scheuermann's Disease - Orthogate - Improving orthopedic care, education and research with Internet technologies". Retrieved 2008-11-17. 7. ^ a b McCoy, A. M.; Toth, F.; Dolvik, N. I.; Ekman, S.; Ellermann, J.; Olstad, K.; Ytrehus, B.; Carlson, C. S. (2013). "Articular osteochondrosis: A comparison of naturally-occurring human and animal disease". Osteoarthritis and Cartilage. 21 (11): 1638–47. doi:10.1016/j.joca.2013.08.011. PMC 3815567. PMID 23954774. 8. ^ "Sever's Disease - The Southern California Orthopedic Institute". Archived from the original on 2012-07-22. Retrieved 2008-11-17. ## External links[edit] Wikimedia Commons has media related to Osteochondrosis. Classification D * ICD-10: M42, M91-M93 * ICD-9-CM: 732 * MeSH: D010007 * DiseasesDB: 9320 External resources * Orphanet: 399319 * 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 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Osteochondrosis	c0029429	28,680	wikipedia	https://en.wikipedia.org/wiki/Osteochondrosis	2021-01-18T18:35:18	{"mesh": ["D055034"], "umls": ["C0029429", "C0158445"], "orphanet": ["399319"], "wikidata": ["Q1154055"]}
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: "Papilloma" – news · newspapers · books · scholar · JSTOR (May 2013) (Learn how and when to remove this template message) Papilloma Intraductal papilloma of breast, H&E, 10x SpecialtyOncology A papilloma (plural papillomas or papillomata) (papillo- \+ -oma) is a benign epithelial tumor[1] growing exophytically (outwardly projecting) in nipple-like and often finger-like fronds. In this context, papilla refers to the projection created by the tumor, not a tumor on an already existing papilla (such as the nipple). When used without context, it frequently refers to infections (squamous cell papilloma) caused by human papillomavirus (HPV), such as warts. Human papillomavirus infection is a major cause of cervical cancer, although most HPV infections do not cause cancer.[2] There are, however, a number of other conditions that cause papilloma, as well as many cases in which there is no known cause. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Prognosis * 4 Differential diagnosis * 5 Treatment * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] A benign papillomatous tumor is derived from epithelium, with cauliflower-like projections that arise from the mucosal surface. It may appear white or normal colored. It may be pedunculated or sessile. The average size is between 1–5 cm. Neither sex is significantly more likely to develop them. The most common site is the palate-uvula area followed by tongue and lips. Durations range from weeks to 10 years. ## Cause[edit] Immunoperoxidase stains have identified antigens of the human papillomavirus (HPV) types 6 and 11 in approximately 50% of cases of squamous cell papilloma. ## Prognosis[edit] There is no evidence that papillomas are premalignant. ## Differential diagnosis[edit] * Intraoral verruca vulgaris, * Condyloma acuminatum, and * Focal epithelial hyperplasia. Note: differentiation is done accurately by microscopic examination only. ## Treatment[edit] With conservative surgical excision, recurrence is rare. ## See also[edit] * Skin tag * Inverted papilloma * Squamous cell papilloma * Urothelial papilloma * Intraductal papilloma of breast * Wart * Genital wart * Plantar wart * Papillomavirus * Human papillomavirus ## References[edit] 1. ^ "papilloma" at Dorland's Medical Dictionary 2. ^ "Warts: Overview". U.S. National Library of Medicine. 30 July 2014. Archived from the original on 10 September 2017. Cite journal requires `\|journal=` (help) ## External links[edit] Classification D * ICD-O: 8050/0 * MeSH: D010212 * SNOMED CT: 711329002 Look up papilloma in Wiktionary, the free dictionary. * Choroid Plexus Papilloma \- Palmer, Cheryl Ann and Daniel Keith Harrison; EMedicine; Jun 5, 2008 * v * t * e Glandular and epithelial cancer Epithelium Papilloma/carcinoma * Small-cell carcinoma * Combined small-cell carcinoma * Verrucous carcinoma * Squamous cell carcinoma * Basal-cell carcinoma * Transitional cell carcinoma * Inverted papilloma Complex epithelial * Warthin's tumor * Thymoma * Bartholin gland carcinoma Glands Adenomas/ adenocarcinomas Gastrointestinal * tract: Linitis plastica * Familial adenomatous polyposis * pancreas * Insulinoma * Glucagonoma * Gastrinoma * VIPoma * Somatostatinoma * Cholangiocarcinoma * Klatskin tumor * Hepatocellular adenoma/Hepatocellular carcinoma Urogenital * Renal cell carcinoma * Endometrioid tumor * Renal oncocytoma Endocrine * Prolactinoma * Multiple endocrine neoplasia * Adrenocortical adenoma/Adrenocortical carcinoma * Hürthle cell Other/multiple * Neuroendocrine tumor * Carcinoid * Adenoid cystic carcinoma * Oncocytoma * Clear-cell adenocarcinoma * Apudoma * Cylindroma * Papillary hidradenoma Adnexal and skin appendage * sweat gland * Hidrocystoma * Syringoma * Syringocystadenoma papilliferum Cystic, mucinous, and serous Cystic general * Cystadenoma/Cystadenocarcinoma Mucinous * Signet ring cell carcinoma * Krukenberg tumor * Mucinous cystadenoma / Mucinous cystadenocarcinoma * Pseudomyxoma peritonei * Mucoepidermoid carcinoma Serous * Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma Ductal, lobular, and medullary Ductal carcinoma * Mammary ductal carcinoma * Pancreatic ductal carcinoma * Comedocarcinoma * Paget's disease of the breast / Extramammary Paget's disease Lobular carcinoma * Lobular carcinoma in situ * Invasive lobular carcinoma Medullary carcinoma * Medullary carcinoma of the breast * Medullary thyroid cancer Acinar cell * Acinic cell carcinoma * v * t * e Human papillomavirus Related diseases Cancers * Cervical cancer * cancers * Anal * Vaginal * Vulvar * Penile * Head and neck cancer (HPV-positive oropharyngeal cancer) Warts * * genital * plantar * flat * Laryngeal papillomatosis * Epidermodysplasia verruciformis * Focal epithelial hyperplasia * Papilloma Others Acrochordon (skin tags) Vaccine * HPV vaccines * Cervarix * Gardasil Screening * Pap test: * stain * Bethesda system * Cytopathology * Cytotechnology * Experimental techniques: * Speculoscopy * Cervicography Colposcopy Biopsy histology * Cervical intraepithelial neoplasia (CIN) * Koilocyte * Vaginal intraepithelial neoplasia (VAIN) * Vulvar intraepithelial neoplasia (VIN) Treatment * Cervical conization * Loop electrical excision procedure (LEEP) History * Georgios Papanikolaou * Harald zur Hausen [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Papilloma	c0030354	28,681	wikipedia	https://en.wikipedia.org/wiki/Papilloma	2021-01-18T18:49:36	{"mesh": ["D010212"], "umls": ["C0030354", "C0205875"], "wikidata": ["Q912796"]}
Type I hypersensitivity Other namesImmediate hypersensitivity SEM of miscellaneous plant pollens: Pollens are very common allergens. SpecialtyImmunology Type I hypersensitivity (or immediate hypersensitivity) is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen.[1] Type I is distinct from type II, type III and type IV hypersensitivities. Exposure may be by ingestion, inhalation, injection, or direct contact. ## Contents * 1 Pathophysiology * 2 Treatment and prognosis * 3 Examples * 4 See also * 5 References * 6 External links ## Pathophysiology[edit] In type 1 hypersensitivity, B-cells are stimulated (by CD4+TH2 cells) to produce IgE antibodies specific to an antigen. The difference between a normal infectious immune response and a type 1 hypersensitivity response is that in type 1 hypersensitivity, the antibody is IgE instead of IgA, IgG, or IgM. During sensitization, the IgE antibodies bind to FcεRI receptors on the surface of tissue mast cells and blood basophils.[2] Mast cells and basophils coated by IgE antibodies are "sensitized". Later exposure to the same allergen cross-links the bound IgE on sensitized cells, resulting in anaphylactic degranulation, which is the immediate and explosive release of pharmacologically active pre-formed mediators from storage granules and concurrent synthesis of inflammatory lipid mediators from arachidonic acid;[3] some of these mediators include histamine, leukotriene (LTC4 and LTD4 and LTB4), and prostaglandin, which act on proteins (e.g., G-protein coupled receptors) located on surrounding tissues.[3] The principal effects of these products are vasodilation and smooth-muscle contraction. Type 1 hypersensitivity can be further classified into immediate and late-phase reactions. The immediate hypersensitivity reaction occurs minutes after exposure and includes release of vasoactive amines and lipid mediators, whereas the late-phase reaction occurs 2–4 hours after exposure and includes the release of cytokines.[4] List of a few mediators released by mast cells in type 1 hypersensitivity and their actions Vasodilation and increased permeability * Histamine * PAF * Leukotriene C4, D4, and E4 * Prostaglandin D2 * Neutral proteases Smooth muscle spasm * Histamine * PAF * Leukotriene C4, D4, and E4 * Prostaglandin Leukocyte extravasation * Cytokines (e.g. chemokines and TNF) * Leukotriene B4 * Chemotactic factors for neutrophils and eosinophils Unless otherwise specified, the reference for this table is:[5] The reaction may be either local or systemic. Symptoms vary from mild irritation to sudden death from anaphylactic shock. ## Treatment and prognosis[edit] If the entire body is involved, then anaphylaxis can take place, which is an acute, systemic reaction that can prove fatal. Treatment usually involves adrenaline (epinephrine) because it counteracts anaphylaxis by increasing blood flow and relaxing bronchial muscles that block one’s airways.[6] Antihistamines and corticosteroids are also commonly used in less severe reactions.[7] ## Examples[edit] Some examples: * Allergic asthma * Allergic conjunctivitis * Allergic rhinitis ("hay fever") * Anaphylaxis * Angioedema * Urticaria (hives) * Eosinophilia * Penicillin allergy * Cephalosporin allergy * Food allergy * Sweet itch ## See also[edit] * Hypersensitivity ## References[edit] 1. ^ med/1101 at eMedicine 2. ^ "The Adaptive Immune System: Type I Immediate Hypersensitivity". Archived from the original on 2010-07-27. Retrieved 2008-09-22. 3. ^ a b Moon TC, Befus AD, Kulka M (2014). "Mast cell mediators: their differential release and the secretory pathways involved". Front Immunol. 5: 569. doi:10.3389/fimmu.2014.00569. PMC 4231949. PMID 25452755. "This release of pre-formed mediators enables not only rapid anaphylactic reactions and allergic responses but also initiates recruitment of leukocytes to sites of pathogen invasion, activation of innate immune processes, and inflammatory responses (1). ... Two types of degranulation have been described for MC: piecemeal degranulation (PMD) and anaphylactic degranulation (AND) (Figures 1 and 2). Both PMD and AND occur in vivo, ex vivo, and in vitro in MC in human (78–82), mouse (83), and rat (84). PMD is selective release of portions of the granule contents, without granule-to-granule and/or granule-to-plasma membrane fusions. ... In contrast to PMD, AND is the explosive release of granule contents or entire granules to the outside of cells after granule-to-granule and/or granule-to-plasma membrane fusions (Figures 1 and 2). Ultrastructural studies show that AND starts with granule swelling and matrix alteration after appropriate stimulation (e.g., FcεRI-crosslinking)." Figure 1: Mediator release from mast cells Figure 2: Model of genesis of mast cell secretory granules Figure 3: Lipid body biogenesis Table 2: Stimuli-selective mediator release from mast cells 4. ^ Shiv Pillai MD; Abul K. Abbas MBBS; Andrew Wilson (2011). Cellular and Molecular Immunology: with STUDENT CONSULT Online Access. Philadelphia: Saunders. ISBN 978-1-4377-1528-6. 5. ^ Table 5-2 in:Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 8th edition. 6. ^ Kemp, S. F., Lockey, R. F., Simons, F. E., & World Allergy Organization ad hoc Committee on Epinephrine in Anaphylaxis (2008). Epinephrine: the drug of choice for anaphylaxis-a statement of the world allergy organization. The World Allergy Organization journal, 1(7 Suppl), S18–S26. https://doi.org/10.1097/WOX.0b013e31817c9338. “The β-adrenergic properties of epinephrine cause bronchodilation… Epinephrine administration enhances coronary blood flow…” 7. ^ Recognizing and Treating Reaction Symptoms. (n.d.). Retrieved December 01, 2020, from https://www.foodallergy.org/resources/recognizing-and-treating-reaction-symptoms. “Although steroids do not work fast enough for emergency treatment, they may help prevent a severe reaction from coming back…antihistamines are prescribed to relieve mild allergy symptoms.” ## External links[edit] Classification D * MeSH: D006969 * v * t * e Hypersensitivity and autoimmune diseases Type I/allergy/atopy (IgE) Foreign * Atopic eczema * Allergic urticaria * Allergic rhinitis (Hay fever) * Allergic asthma * Anaphylaxis * Food allergy * common allergies include: Milk * Egg * Peanut * Tree nut * Seafood * Soy * Wheat * Penicillin allergy Autoimmune * Eosinophilic esophagitis Type II/ADCC * * IgM * IgG Foreign * Hemolytic disease of the newborn Autoimmune Cytotoxic * Autoimmune hemolytic anemia * Immune thrombocytopenic purpura * Bullous pemphigoid * Pemphigus vulgaris * Rheumatic fever * Goodpasture syndrome * Guillain–Barré syndrome "Type V"/receptor * Graves' disease * Myasthenia gravis * Pernicious anemia Type III (Immune complex) Foreign * Henoch–Schönlein purpura * Hypersensitivity vasculitis * Reactive arthritis * Farmer's lung * Post-streptococcal glomerulonephritis * Serum sickness * Arthus reaction Autoimmune * Systemic lupus erythematosus * Subacute bacterial endocarditis * Rheumatoid arthritis Type IV/cell-mediated (T cells) Foreign * Allergic contact dermatitis * Mantoux test Autoimmune * Diabetes mellitus type 1 * Hashimoto's thyroiditis * Multiple sclerosis * Coeliac disease * Giant-cell arteritis * Postorgasmic illness syndrome * Reactive arthritis GVHD * Transfusion-associated graft versus host disease Unknown/ multiple Foreign * Hypersensitivity pneumonitis * Allergic bronchopulmonary aspergillosis * Transplant rejection * Latex allergy (I+IV) Autoimmune * Sjögren syndrome * Autoimmune hepatitis * Autoimmune polyendocrine syndrome * APS1 * APS2 * Autoimmune adrenalitis * Systemic autoimmune disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Type I hypersensitivity	c0020523	28,682	wikipedia	https://en.wikipedia.org/wiki/Type_I_hypersensitivity	2021-01-18T18:46:54	{"mesh": ["D006969"], "wikidata": ["Q5941165"]}
A number sign (#) is used with this entry because of evidence that anterior segment dysgenesis-4 (ASGD4) is caused by heterozygous mutation in the PITX2 gene (601542) on chromosome 4q25. Description Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Patients with ASGD4 have been reported with iridogoniodysgenesis or Peters anomaly subtypes. Iridogoniodysgenesis, which is characterized by iris hypoplasia, goniodysgenesis, and juvenile glaucoma, is the result of aberrant migration or terminal induction of the neural crest cells involved in the formation of the anterior segment of the eye (summary by Mears et al., 1996). Peters anomaly consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea (Peters, 1906). Clinical Features Berg (1932) described 22 affected individuals in 6 generations. McCulloch (1950) described 18 affected in 5 generations. Weatherill and Hart (1969) observed glaucoma in many members of 5 generations. Not only is the stroma of the iris hypoplastic but the iris is also light in color, a feature that antedates development of glaucoma and permits recognition of affected persons at birth. Jerndal (1970, 1972) updated the Berg (1932) pedigree. Jerndal (1983) presented 3 pedigrees in which autosomal dominant glaucoma was shown to be the result of goniodysgenesis. The author suggested that it is improper to classify glaucoma on the basis of age of onset, which can be highly variable. In all 3 pedigrees, glaucoma was congenital in some and as late as age 34, 46, and 68 in others. The disorder reported by Weatherill and Hart (1969), Jerndal (1970), and Pearce et al. (1983) might be referred to as autosomal dominant iris hypoplasia associated with early-onset glaucoma. The term iridogoniodysgenesis has the virtue of correctly emphasizing the maldevelopment of the trabecular meshwork as well as the iris. The pathogenesis of the condition is thought to involve abnormal differentiation of neural crest cells. Heon et al. (1995) described an extensively affected family of Scandinavian descent in which iris hypoplasia was found in 15 members, 9 of whom had associated glaucoma. Almost all affected individuals had a peculiar eye color (slate gray or chocolate brown) that resulted from the pigmented iris epithelium showing through the markedly hypoplastic anterior iris stroma. The normal pupillary sphincter stood out as an elevated tan-colored ring against a rather featureless background. Glaucoma usually was detected in the second decade of life but might begin at any age; when it did develop, it tended to be resistant to medical therapy, and if left untreated, total blindness could result. Mapping In a Scandinavian family segregating iris hypoplasia, Heon et al. (1995) found linkage of the disorder to chromosome 4q25. Molecular Genetics In the family with autosomal dominant iris hypoplasia with early-onset glaucoma reported by Heon et al. (1995), Alward et al. (1998) identified heterozygosity for a mutation in the PITX2 gene (601542.0007). Kulak et al. (1998) demonstrated mutation in the PITX2 gene in a family with iridogoniodysgenesis (601542.0008). In a child with Peters anomaly, Doward et al. (1999) identified a heterozygous splice site mutation in the PITX2 gene (601542.0009). Eyes \- Glaucoma \- Hypoplastic iris stroma \- Light colored iris \- Goniodysgenesis Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ANTERIOR SEGMENT DYSGENESIS 4	c1842031	28,683	omim	https://www.omim.org/entry/137600	2019-09-22T16:40:44	{"doid": ["0050786"], "mesh": ["C535536"], "omim": ["137600"], "orphanet": ["91483"], "synonyms": ["IRIS HYPOPLASIA WITH EARLY-ONSET GLAUCOMA, AUTOSOMAL DOMINANT", "Alternative titles", "IRIDOGONIODYSGENESIS SYNDROME", "IRIDOGONIODYSGENESIS, TYPE 2"]}
Cole disease is a disorder that affects the skin. People with this disorder have areas of unusually light-colored skin (hypopigmentation), typically on the arms and legs, and spots of thickened skin on the palms of the hands and the soles of the feet (punctate palmoplantar keratoderma). These skin features are present at birth or develop in the first year of life. In some cases, individuals with Cole disease develop abnormal accumulations of the mineral calcium (calcifications) in the tendons, which can cause pain during movement. Calcifications may also occur in the skin or breast tissue. ## Frequency Cole disease is a rare disease; its prevalence is unknown. Only a few affected families have been described in the medical literature. ## Causes Cole disease is caused by mutations in the ENPP1 gene. This gene provides instructions for making a protein that helps to prevent minerals, including calcium, from being deposited in body tissues where they do not belong. It also plays a role in controlling cell signaling in response to the hormone insulin, through interaction between a part of the ENPP1 protein called the SMB2 domain and the insulin receptor. The insulin receptor is a protein that attaches (binds) to insulin and initiates cell signaling. Insulin plays many roles in the body, including regulating blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. Cell signaling in response to insulin is also important for the maintenance of the outer layer of skin (the epidermis). It helps control the transport of the pigment melanin from the cells in which it is produced (melanocytes) to epidermal cells called keratinocytes, and it is also involved in the development of keratinocytes. The mutations that cause Cole disease change the structure of the SMB2 domain, which alters its interaction with the insulin receptor and affects cell signaling. The resulting impairment of ENPP1's role in melanin transport and keratinocyte development leads to the hypopigmentation and keratoderma that occurs in Cole disease. The mutations may also impair ENPP1's control of calcification, which likely accounts for the abnormal calcium deposits that occur in some people with this disorder. For reasons that are unclear, the changes in insulin signaling resulting from these ENPP1 gene mutations do not seem to affect blood sugar control. ### Learn more about the gene associated with Cole disease * ENPP1 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases of this disorder, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Cole disease	c3809781	28,684	medlineplus	https://medlineplus.gov/genetics/condition/cole-disease/	2021-01-27T08:24:57	{"gard": ["12384"], "omim": ["615522"], "synonyms": []}
Trichilemmal carcinoma Other namesTricholemmal carcinoma SpecialtyOncology, dermatology Trichilemmal carcinoma is a cutaneous condition reported to arise on sun-exposed areas, most commonly the face and ears.[1]:674 ## See also[edit] * Trichilemmoma * Skin lesion A similar tumor, although in the nail bed, is called onycholemmal.[2][3] ## 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. 2. ^ http://dermatology.cdlib.org/1603/case_presentations/onycho_carcinoma/rashid.html 3. ^ Onycholemmal carcinoma. Rashid RM, Cutlan JE. Dermatol Online J. 2010 Mar 15;16(3):12. ## External links[edit] Classification D * ICD-10: C44 (ILDS C44.L47) * v * t * e Cancers of skin and associated structures Glands Sweat gland Eccrine * Papillary eccrine adenoma * Eccrine carcinoma * Eccrine nevus * Syringofibroadenoma * Spiradenoma Apocrine * Cylindroma * Dermal cylindroma * Syringocystadenoma papilliferum * Papillary hidradenoma * Hidrocystoma * Apocrine gland carcinoma * Apocrine nevus Eccrine/apocrine * Syringoma * Hidradenoma or Acrospiroma/Hidradenocarcinoma * Ceruminous adenoma Sebaceous gland * Nevus sebaceous * Muir–Torre syndrome * Sebaceous carcinoma * Sebaceous adenoma * Sebaceoma * Sebaceous nevus syndrome * Sebaceous hyperplasia * Mantleoma Hair * Pilomatricoma/Malignant pilomatricoma * Trichoepithelioma * Multiple familial trichoepithelioma * Solitary trichoepithelioma * Desmoplastic trichoepithelioma * Generalized trichoepithelioma * Trichodiscoma * Trichoblastoma * Fibrofolliculoma * Trichilemmoma * Trichilemmal carcinoma * Proliferating trichilemmal cyst * Giant solitary trichoepithelioma * Trichoadenoma * Trichofolliculoma * Dilated pore * Isthmicoma * Fibrofolliculoma * Perifollicular fibroma * Birt–Hogg–Dubé syndrome Hamartoma * Basaloid follicular hamartoma * Folliculosebaceous cystic hamartoma * Folliculosebaceous-apocrine hamartoma Nails * Neoplasms of the nailbed 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 [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Trichilemmal carcinoma	c1266009	28,685	wikipedia	https://en.wikipedia.org/wiki/Trichilemmal_carcinoma	2021-01-18T18:31:16	{"umls": ["C1266009"], "icd-10": ["C44"], "wikidata": ["Q7840657"]}
A rare primary immunodeficiency characterized by recurrent and/or invasive bacterial, viral, and fungal infections, associated with low to absent blood IgM levels, while IgG, IgG subclasses, and IgA levels, as well as IgG antibody response to vaccinations, are normal. Patients may also present allergic diatheses, and the prevalence of autoimmune diseases is increased. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Selective IgM deficiency	c0154275	28,686	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=331235	2021-01-23T17:15:08	{"gard": ["12547"], "icd-10": ["D80.4"], "synonyms": ["Selective immunoglobulin M deficiency"]}
A number sign (#) is used with this entry because of evidence that oncocytoma can be caused by mutation in the mtDNA MTND6 gene (516006). Description Oncocytomas are usually benign tumors that occur in various organs but particularly in the kidneys. Histologic evaluation of renal oncocytomas shows that they are composed entirely of peculiar epithelial cells with granular eosinophilic cytoplasm. Ultrastructural characterization exhibits densely packed cells with mitochondria, which show morphologic differences from those in normal cells. On the average they are larger than those in renal carcinoma cells and their shape is abnormal (summary by Welter et al., 1989). Clinical Features Weirich et al. (1998) described 5 families in which multiple members had multiple bilateral renal oncocytomas. On dermatologic examination by Toro et al. (1999), 13 members of 3 of these families were found to have cutaneous lesions of Birt-Hogg-Dube syndrome (135150). Mapping Using 5 restriction endonucleases, Welter et al. (1989) performed mitochondrial DNA analysis of 6 renal cell oncocytomas and adjacent renal tissue. In the HinfI restriction pattern, they found an additional 40-bp band in all oncocytomas but in none of the corresponding renal tissue or in renal carcinomas. By reisolating and hybridizing this band to the mitochondrial genome, they localized the sequence within the cytochrome c oxidase subunit I gene (516030). Welter et al. (1989) suggested that the alteration of mitochondrial DNA is specific for oncocytomas and that it represented the first mitochondrial change observed in a solid tumor. Brauch et al. (1990) showed that, unlike other forms of renal neoplasia, renal oncocytomas do not show loss of alleles at loci on 3p. Cytogenetics Neuhaus et al. (1997) reviewed the reported cytogenetic abnormalities that had been observed in renal oncocytoma. Loss of chromosomes 1 and Y appeared to represent at least 1 subset of oncocytomas. The frequent finding of rearrangements involving 11q13 appeared to characterize another subset. Neuhaus et al. (1997) reported the case of a 72-year-old woman with a translocation t(9;11) involving 11q13. They pointed out that the large, well-differentiated eosinophilic granular cells of renal oncocytomas express electron microscopic and immunohistochemical characteristics of the intercalated cell type A of the collecting duct. Molecular Genetics Bartoletti-Stella et al. (2011) stained an oncocytic tumor of the adnexal lacrimal glands of the conjunctiva with a specific antibody against complex V(6) and observed mitochondrial abundance in the neoplastic cells. Analysis of the entire mtDNA sequence revealed a frameshift mutation in MTND6 (516006.0009) in tumor cells. Ki67 staining revealed a low proliferation index of 1.8%, consistent with the benign nature of the case. Oncology \- Multifocal benign oncocytomas, esp. renal Lab \- Mitochondrial cytchrome c oxidase subunit I gene mutant Inheritance \- Mitochondrial ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ONCOCYTOMA	c1510502	28,687	omim	https://www.omim.org/entry/553000	2019-09-22T16:16:47	{"doid": ["6245"], "mesh": ["D018249"], "omim": ["553000"]}
A number sign (#) is used with this entry because of evidence that this form of cerebral cavernous malformations (CCM2) can be caused by mutation in the CCM2/malcavernin gene (607929). Evidence suggests that a 2-hit mechanism involving biallelic germline and somatic mutations is responsible for CCM2 pathogenesis, see PATHOGENESIS and MOLECULAR GENETICS sections. For a phenotypic description and discussion of genetic heterogeneity of cerebral cavernous malformations, see CCM1 (116860). Clinical Features Ahdab et al. (2008) reported 2 sibs with CCM2 confirmed by genetic analysis. The 57-year-old proband presented with generalized tonic-clonic seizures and status epilepticus. Brain MRI showed multiple rounded gradient echo hypointense signals mainly in the right frontotemporal region, consistent with CCM. He also had numerous small erythematous 2 to 3-mm macules that blanched on his palms. The pattern was consistent with capillary telangiectasia. His 60-year-old sister developed mild gait ataxia associated with multiple supra- and infratentorial CCMs on brain MRI. She also had palmar telangiectasia. Their mother reportedly had episodes of diplopia and vertigo and also had the same palmar lesions. Pathogenesis For each of the 3 CCM genes, Pagenstecher et al. (2009) showed complete localized loss of either KRIT1 (604214), CCM2/malcavernin, or PDCD10 (609118) protein expression depending on the respective inherited mutation. Cavernous but not adjacent normal or reactive endothelial cells of known germline mutation carriers displayed immunohistochemical negativity only for the corresponding CCM protein, but stained positively for the 2 other proteins. Immunohistochemical studies demonstrated endothelial cell mosaicism as neoangiogenic vessels within caverns from a CCM1 patient and normal brain endothelium from a CCM2 patient stained positively for KRIT1 and CCM2/malcavernin, respectively. Pagenstecher et al. (2009) suggested that complete lack of CCM protein in affected endothelial cells from CCM germline mutation carriers supports a 2-hit mechanism for CCM formation. Mapping Craig et al. (1998) reported analysis of linkage in 20 non-Hispanic Caucasian kindreds with familial CCM. Linkage to new loci, CCM2 at 7p15-p13 and CCM3 (603285) at 3q25.2-q27, was demonstrated. Multilocus analysis yielded a maximum lod score of 14.11, with 14% of kindreds linked to CCM1, 20% linked to CCM2, and 40% linked to CCM3, with highly significant evidence for linkage to 3 loci; linkage to 3 loci was supported with an odds ratio of 2.6 x 10(5):1 over linkage to 2 loci, and 1.6 x 10(9):1 over linkage to 1 locus. Multipoint analysis among families with high posterior probabilities of linkage to each of the 3 loci refined the locations of CCM2 and CCM3 to approximately 22 cM intervals. Linkage to these 3 loci can account for inheritance of CCM in all kindreds studied. Significant locus-specific differences in penetrance were identified. Molecular Genetics Liquori et al. (2003) sequenced positional candidate genes in the 7p region for mutations in CCM2. One of these genes, the CCM2 gene which they called MGC4607, was chosen because its translation product protein encodes a putative phosphotyrosine-binding (PTB) domain. The same domain is found in ICAP1-alpha (607153), a binding partner of the KRIT1 gene (604214). In a panel of 27 probands without a KRIT1 mutation, Liquori et al. (2003) detected 8 different mutations in the CCM2 gene (see, e.g., 607929.0001-607929.0004). In 2 (14%) of 14 unrelated patients with sporadic CCM and multiple lesions, Felbor et al. (2007) identified a respective deletion in the CCM2 gene using multiplex ligation-dependent probe amplification. One of the deletions involved the entire coding region of the CCM2 gene. In 8 (13%) of 63 U.S. families with CCM, Liquori et al. (2007) identified a 77.6-kb deletion encompassing exons 2 through 10 of the in the CCM2 gene (607929.0009). Liquori et al. (2008) reported 6 additional CCM families from the United States with the 77.6-kb CCM2 deletion. Haplotype analysis, which included the previously reported families with this deletion, indicated a founder effect. This deletion was not present in 24 Italian families with CCM, indicating that it is specific to a certain cohort of patients. Among the 24 Italian families with CCM, Liquori et al. (2008) identified 4 deletions and 1 duplication in the CCM2 gene. Through repeated cycles of amplification, subcloning, and sequencing of multiple clones per amplicon, Akers et al. (2009) identified somatic mutations that were otherwise invisible by direct sequencing of the bulk amplicon. Biallelic germline and somatic mutations were identified in CCM lesions from all 3 forms of inherited CCMs. The somatic mutations were found only in a subset of the endothelial cells lining the cavernous vessels and not in interstitial lesion cells. Although widely expressed in the different cell types of the brain, the authors also suggested a unique role for the CCM proteins in endothelial cell biology. Akers et al. (2009) suggested that CCM lesion genesis may require complete loss of function for 1 of the CCM genes. Gallione et al. (2011) identified a founder mutation in the Ashkenazi Jewish population that affects mRNA splicing of the CCM2 gene causing cerebral cavernous malformations (607929.0010). INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Palmar telangiectases (described in 1 family) NEUROLOGIC Central Nervous System \- Cerebral cavernous malformations \- Seizures \- Recurrent headaches \- Hemorrhagic stroke MISCELLANEOUS \- Genetic heterogeneity (see 116800 for summary) \- Sporadic cases often single lesions versus multiple lesions in familial cases MOLECULAR BASIS \- Caused by mutation in the CCM2 gene (CCM2, 607929.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CEREBRAL CAVERNOUS MALFORMATIONS 2	c2931263	28,688	omim	https://www.omim.org/entry/603284	2019-09-22T16:13:07	{"doid": ["0060670"], "mesh": ["C536610"], "omim": ["603284"], "orphanet": ["221061"], "genereviews": ["NBK1293"]}
A number sign (#) is used with this entry because of evidence that retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities (RDGCA) is caused by heterozygous mutation in the ITM2B gene (603904) on chromosome 13q14. One such family has been reported. Clinical Features Audo et al. (2014) examined 9 affected members of a large 3-generation family segregating an autosomal dominant form of inner retinal dystrophy with ganglion cell abnormalities. Onset of symptoms was between 25 and 40 years of age. Light sensitivity was the first sign, reported by all subjects, followed by progressive loss of central vision. Visual acuity varied from 20/25 to 20/400 (average, 20/50). Visual fields showed decreased central retinal sensitivity with preservation of peripheral visual field. There were macular changes, optic disc pallor, and hyperreflectivity of ganglion cell and nerve fiber layers, with loss of optic nerve fibers. Full-field electroretinography (ERG) showed inner retinal (postreceptor) dysfunction in all cases, with absent or very reduced b-waves but normal a-waves under scotopic conditions. Oscillatory potentials were reduced in amplitude with a simplified wave shape in younger patients and were undetectable in older patients, consistent with inner retinal dysfunction. Long-duration stimulation recordings suggested both ON and OFF pathway dysfunction, and pattern ERG revealed reduced amplitude for both P50 and N95 components, consistent with proximal macular dysfunction. None of the affected individuals had systemic disease, and there was no family history of dementia; specifically, all examined individuals were temporally and spatially oriented, and Mini-Mental State Examination was normal in the 50-year-old proband. Inheritance The transmission pattern of retinal dystrophy in the family reported by Audo et al. (2014) was consistent with autosomal dominant inheritance. Molecular Genetics In a large 3-generation family segregating autosomal dominant retinal dystrophy, in which analysis of all known genes implicated in retinal diseases did not reveal any pathogenic variants segregating with disease, Audo et al. (2014) performed whole-exome analysis and identified a missense mutation in the ITM2B gene (E261A; 603904.0003). The mutation, which segregated with disease in the family, was not found in 380 control alleles. Haplotype analysis of 19 family members identified a 24.6-Mb interval on chromosome 13q that included ITM2B and cosegregated in affected individuals; sequencing of 74 genes in that interval revealed no variants that cosegregated with disease except for E261A in ITM2B. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Photophobia, mild \- Progressive loss of central vision \- Night blindness (in some patients) \- Relative central scotoma \- Optic disc pallor \- Subtle foveal changes \- Hyperreflectivity of ganglion cell layer \- Hyperreflectivity of nerve cell layer \- Markedly reduced or absent b-wave on scotopic electroretinography \- Decreased to undetectable oscillatory potentials MISCELLANEOUS \- Onset of disease between 25 and 40 years of age \- Based on report of 1 3-generation family (last curated November 2014) MOLECULAR BASIS \- Caused by mutation in the integral membrane protein-2B gene (ITM2B, 603904.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	RETINAL DYSTROPHY WITH INNER RETINAL DYSFUNCTION AND GANGLION CELL ABNORMALITIES	c4015146	28,689	omim	https://www.omim.org/entry/616079	2019-09-22T15:50:00	{"omim": ["616079"], "orphanet": ["397758"], "synonyms": ["Retinal dystrophy with inner nuclear layer and ganglion cell anomalies"]}
3q27.3 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the long arm of chromosome 3, characterized by mild to severe intellectual disability, neuropsychiatric disorders of the psychotic and dysthymic spectrum, mild distinctive facial dysmorphism (incl. slender face, deep-set eyes, high nasal bridge with a hooked nose, small, low- set ears, short philtrum, small mouth with thin upper lip, prognathism) and a marfanoid habitus. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	3q27.3 microdeletion syndrome	None	28,690	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=397695	2021-01-23T19:09:12	{"icd-10": ["Q93.5"], "synonyms": ["Del(3)(q27.3)"]}
Saethre-Chotzen syndrome is a genetic condition characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. Most people with Saethre-Chotzen syndrome have prematurely fused skull bones along the coronal suture, the growth line that goes over the head from ear to ear. Other parts of the skull may be malformed as well. These changes can result in an abnormally shaped head, a high forehead, a low frontal hairline, droopy eyelids (ptosis), widely spaced eyes, and a broad nasal bridge. One side of the face may appear noticeably different from the other (facial asymmetry). Most people with Saethre-Chotzen syndrome also have small, rounded ears. The signs and symptoms of Saethre-Chotzen syndrome vary widely, even among affected individuals in the same family. This condition can cause mild changes in the hands and feet, such as partial fusion of the skin between the second and third fingers on each hand and a broad or duplicated first (big) toe. Delayed development and learning difficulties have been reported, although most people with this condition are of normal intelligence. Less common signs and symptoms of Saethre-Chotzen syndrome include short stature, abnormalities of the bones of the spine (the vertebra), hearing loss, and heart defects. Robinow-Sorauf syndrome is a condition with features similar to those of Saethre-Chotzen syndrome, including craniosynostosis and broad or duplicated great toes. It was once considered a separate disorder, but was found to result from mutations in the same gene and is now thought to be a variant of Saethre-Chotzen syndrome. ## Frequency Saethre-Chotzen syndrome has an estimated prevalence of 1 in 50,000 people. ## Causes Mutations in the TWIST1 gene cause Saethre-Chotzen syndrome. The TWIST1 gene provides instructions for making a protein that plays an important role in early development. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. The TWIST1 protein is active in cells that give rise to bones, muscles, and other tissues in the head and face. It is also involved in the development of the limbs. Mutations in the TWIST1 gene prevent one copy of the gene in each cell from making any functional protein. A shortage of the TWIST1 protein affects the development and maturation of cells in the skull, face, and limbs. These abnormalities underlie the signs and symptoms of Saethre-Chotzen syndrome, including the premature fusion of certain skull bones. In a small number of people with Saethre-Chotzen syndrome, the condition is caused by a structural chromosomal abnormality, such as a deletion or rearrangement of genetic material, in the region of chromosome 7 that contains the TWIST1 gene. When Saethre-Chotzen syndrome is caused by a chromosomal deletion instead of a mutation within the TWIST1 gene, affected children are much more likely to have intellectual disability, developmental delay, and learning difficulties. These features are typically not seen in classic cases of Saethre-Chotzen syndrome. Researchers believe that a loss of other genes on chromosome 7 may be responsible for these additional features. ### Learn more about the gene and chromosome associated with Saethre-Chotzen syndrome * TWIST1 * chromosome 7 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. Some people with a TWIST1 mutation do not have any of the obvious features of Saethre-Chotzen syndrome. These people are still at risk of passing on the gene mutation and may have a child with craniosynostosis and the other typical signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Saethre-Chotzen syndrome	c1867146	28,691	medlineplus	https://medlineplus.gov/genetics/condition/saethre-chotzen-syndrome/	2021-01-27T08:24:46	{"gard": ["7598"], "mesh": ["C537183"], "omim": ["180750", "101400"], "synonyms": []}
A rare benign peripheral nerve sheath tumor characterized by a usually encapsulated space-occupying lesion composed of differentiated neoplastic Schwann cells. It most commonly arises from peripheral nerves in the head and neck region and extensor aspects of the extremities, but also from spinal and cranial nerves, especially the vestibular nerve. The tumor may be asymptomatic or cause symptoms related to a mass effect. It grows slowly and only rarely undergoes malignant transformation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Benign schwannoma	c0854906	28,692	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=252164	2021-01-23T19:01:33	{"gard": ["4767"], "umls": ["C0027809", "C0854906"], "synonyms": ["Neurilemmoma", "Neurilemoma", "Peripheral fibroblastoma"]}
Trisomy 18 is a chromosomal abnormality associated with the presence of an extra chromosome 18 and characterized by growth delay, dolichocephaly, a characteristic facies, limb anomalies and visceral malformations. ## Epidemiology Incidence is estimated at between 1/6000 and 1/8000 births. In utero death occurs in more than 95% of fetuses with this chromosome anomaly. For unknown reasons, the rate of survival is higher in females than in males, leading to a female predominance among live-born trisomy 18 infants. ## Clinical description Hypotonia, hyporeactivity and feeding problems (poor suction) are present in the first weeks of life and are followed by a progression to hypertonia with infants showing an apparent lack of awareness of their surroundings. Common features are intrauterine and postnatal growth delay, an emaciated appearance with hypotrophy, microcephaly with a narrow skull and dolichocephaly, microretrognathia, hypertelorism, and poorly modeled and angular ears. Foot anomalies include pes equinovarus and/or rocker-bottom feet and the fingers overlap (the fifth and second fingers with the fourth and third). Malformations are common with involvement of the eyes (microphthalmia, coloboma), heart (over 90% of cases) digestive tract (esophageal atresia, anorectal malformations), kidneys and urinary tract (hydronephrosis, uni- or bilateral agenesis). Less frequently, cleft/lip palate, arthrogryposis, radial aplasia, spina bifida and anencephaly, holoprosencephaly and omphalocele are observed. ## Etiology The majority of cases are associated with free trisomy 18. Mosaic trisomy 18 has been detected in a few patients presenting with a clinical picture that varies from classical trisomy 18 to a normal phenotype depending on the number of trisomic cells present in the tissues. The trisomy 18 phenotype appears to be associated with the presence of three copies of the 18q11-q12 interval. ## Antenatal diagnosis Trisomy 18 may be suspected during pregnancy from ultrasound findings (growth retardation, malformations, multiple choroid plexus cysts) and can be confirmed by karyotype analysis of the fetus. Serum markers (used for the diagnosis of trisomy 21) may also be abnormal. ## Genetic counseling The risk of recurrence of trisomy (21, 13 or 18) in families of an index case with trisomy 18 is around 1%. However, in families in which trisomy 18 is caused by translocation, the recurrence risk is higher if one of the parents is a carrier of a balanced translocation. ## Management and treatment Management is supportive only. ## Prognosis Surgical treatment of the malformations does little to improve the poor prognosis associated with this syndrome: 90% of infants die within the first year of life from cardiac, renal or neurological complications, or from repeated infections. Prolonged survival (in some cases into adulthood) has been reported, mainly in cases involving mosaic or partial trisomy (resulting from translocation). The majority of non-mosaic patients develop only limited autonomy (absence of speech and ambulation). The growth retardation is significant. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Trisomy 18	c0152096	28,693	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3380	2021-01-23T18:54:02	{"gard": ["6321"], "mesh": ["D000073842"], "umls": ["C0152096"], "icd-10": ["Q91.0", "Q91.1", "Q91.2", "Q91.3"], "synonyms": ["Chromosome 18 duplication", "Edwards syndrome"]}
A rare congenital knee dislocation characterized by permanent knee flexion with limited extension. It can be unilateral or bilateral and may occur as an isolated malformation or be part of a syndrome (especially arthrogryposis multiplex congenita). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Congenital genu flexum	None	28,694	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=295232	2021-01-23T17:05:29	{"icd-10": ["Q68.2"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-104 (DFNB104) is caused by homozygous mutation in the FAM65B gene (611410) on chromosome 6p22. One such family has been reported. Clinical Features Diaz-Horta et al. (2014) reported a consanguineous Turkish family in which 6 individuals had congenital profound nonsyndromic sensorineural hearing loss. Available audiograms did not suggest progression of the hearing loss. Evoked otoacoustic emissions, acoustic reflexes, and auditory brainstem responses were absent in affected individuals. None had balance problems. Inheritance The transmission pattern of DFNB104 in the family reported by Diaz-Horta et al. (2014) was consistent with autosomal recessive inheritance. Molecular Genetics In 6 affected members of a consanguineous Turkish family with DFNB104, Diaz-Horta et al. (2014) identified a homozygous splice site mutation in the FAM65B gene (611410.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In vitro functional expression studies showed that the mutant protein accumulated abnormally in cytoplasmic inclusion bodies and did not reach the membrane. Mutations in the FAM65B gene were not found in 248 other families with autosomal recessive deafness or in 437 simplex cases with deafness. Diaz-Horta et al. (2014) concluded that FAM65B is a plasma membrane-associated protein of hair cell stereocilia that is essential for hearing. Animal Model Diaz-Horta et al. (2014) found that fam65b was expressed in the otic vesicle of zebrafish. Morpholino knockdown of the fam65b gene in zebrafish embryos resulted in a significant reduction in the number of saccular hair cells and neuromasts, and caused hearing loss. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Deafness, sensorineural, profound MISCELLANEOUS \- Prelingual onset \- One consanguineous Turkish family has been reported (last curated August 2015) MOLECULAR BASIS \- Caused by mutation in the family with sequence similarity 65, member B gene (FAM65B, 611410.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	DEAFNESS, AUTOSOMAL RECESSIVE 104	c4225298	28,695	omim	https://www.omim.org/entry/616515	2019-09-22T15:48:38	{"doid": ["0110465"], "omim": ["616515"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"]}
Daly et al. (1959) found 3 of 4 sibs affected. Neuro \- Photogenic seizures \- Spastic diplegia \- Mental retardation Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	EPILEPSY, PHOTOGENIC, WITH SPASTIC DIPLEGIA AND MENTAL RETARDATION	c1856931	28,696	omim	https://www.omim.org/entry/226800	2019-09-22T16:28:11	{"mesh": ["C565587"], "omim": ["226800"]}
A number sign (#) is used with this entry because of evidence that Brugada syndrome-6 (BRGDA6) is caused by heterozygous mutation in the KCNE3 gene (604433) on chromosome 11q13. Description Brugada syndrome is characterized by an ST segment elevation in the right precordial electrocardiogram leads (so-called type 1 ECG) and a high incidence of sudden death in patients with structurally normal hearts. The syndrome typically manifests during adulthood, with a mean age of sudden death of 41 +/- 15 years, but also occurs in infants and children (summary by Antzelevitch et al., 2005). For a general phenotypic description and discussion of genetic heterogeneity of Brugada syndrome, see BRGDA1 (601144). Clinical Features Delpon et al. (2008) studied a Danish pedigree in which the previously asymptomatic proband had cardiac arrest at age 36 years and was resuscitated. Electrocardiogram (ECG) showed a coved-type ST segment elevation (type 1) in leads V1 and V2 and a saddleback ST segment elevation (type 2) in V3, diagnostic of Brugada syndrome. A cardiac defibrillator was implanted (ICD) and over the next 7 years, a total of 70 appropriate ICD discharges occurred. The proband then underwent ablation of the right ventricular outflow tract and over the next 2 years, only 1 additional appropriate ICD shock was delivered. The proband's asymptomatic brother displayed a coved-type ST segment elevation in V1 and V2 on ECG and was also implanted with an ICD, which had not yet discharged at the time of the study. One of the proband's daughters and 1 of his brother's sons, who were both initially negative for signs of Brugada on examination at ages 8 and 14 years, respectively, had ST segment elevation on ECG after flecainide challenge at ages 18 and 23 years, respectively. The 23-year-old male had an ECG typical of Brugada syndrome, whereas the 18-year-old female showed a very prominent exaggeration of the R wave (J wave) in lead aVR. Molecular Genetics In the proband of a Danish pedigree with Brugada syndrome, who was negative for mutation in the SCN5A gene (600163), Delpon et al. (2008) identified heterozygosity for a missense mutation in the KCNE3 gene (604433.0002). The mutation was detected in 3 more affected family members, but was not found in 3 unaffected family members, in 200 Danish control alleles, or in an additional 206 alleles of Caucasian European controls. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BRUGADA SYNDROME 6	c1142166	28,697	omim	https://www.omim.org/entry/613119	2019-09-22T15:59:36	{"doid": ["0110223"], "mesh": ["D053840"], "omim": ["613119"], "orphanet": ["130"], "genereviews": ["NBK1517"]}
Diaphragmatic hernia This is a photo of a peritoneopericardial diaphragmatic hernia in a cat. The photo was taken during necropsy from the right side of the cat. To the left is the abdomen, where part of the liver and the gall bladder can be seen. The diaphragm is in the middle. To the right is the thorax. The largest object seen in the thorax is the rest of the liver. Just to the right of that is the heart. The liver was connected to itself through a small hole in the diaphragm (not seen). SpecialtyGastroenterology Diaphragmatic hernia is a defect or hole in the diaphragm that allows the abdominal contents to move into the chest cavity. Treatment is usually surgical. ## Contents * 1 Types * 2 Signs and symptoms * 3 Diagnosis * 4 Treatment * 5 Other animals * 6 References * 6.1 Bibliography * 7 External links ## Types[edit] * Congenital diaphragmatic hernia * Morgagni's hernia * Bochdalek hernia * Hiatal hernia * Iatrogenic diaphragmatic hernia * Traumatic diaphragmatic hernia ## Signs and symptoms[edit] A scaphoid abdomen (sucked inwards) may be the presenting symptom in a newborn.[1] ## Diagnosis[edit] A right sided diaphragmatic hernia with the stomach in the chest (left side of image marked by the arrow). Note the air fluid level in the stomach. Diagnosis can be made by either CT or X-ray.[citation needed] ## Treatment[edit] Treatment for a diaphragmatic hernia usually involves surgery, with acute injuries often repaired with monofilament permanent sutures.[2] ## Other animals[edit] Peritoneopericardial diaphragmatic hernia is a type of hernia more common in other mammals.[3] This is usually treated with surgery.[3] ## References[edit] 1. ^ Durward, Heather; Baston, Helen (2001). Examination of the newborn: a practical guide. New York: Routledge. p. 134. ISBN 0-415-19184-X. 2. ^ Turhan, Kutsal; Makay, Ozer; Cakan, Alpaslan; Samancilar, Ozgur; Firat, Ozgur; Icoz, Gokhan; Cagirici, Ufuk (June 2008). "Traumatic diaphragmatic rupture". European Journal of Cardio-Thoracic Surgery. 33 (6): 1082–1085. doi:10.1016/j.ejcts.2008.01.029. ISSN 1010-7940. PMID 18299201. 3. ^ a b Bonagura, John D. (2006-01-01), Birchard, Stephen J.; Sherding, Robert G. (eds.), "Chapter 151 - Pericardial Diseases", Saunders Manual of Small Animal Practice (Third Edition), Saint Louis: W.B. Saunders, pp. 1549–1560, ISBN 978-0-7216-0422-0, retrieved 2021-01-05 ### Bibliography[edit] * Eren S, Ciris F (2005). "Diaphragmatic hernia: diagnostic approaches with review of the literature". Eur J Radiol. 54 (3): 448–59. doi:10.1016/j.ejrad.2004.09.008. PMID 15899350. ## External links[edit] Classification D * ICD-10: K44.k * ICD-10-CM: K44 * ICD-9-CM: 553.3 * MeSH: D006548 * DiseasesDB: 31491 * SNOMED CT: 39839004 External resources * MedlinePlus: 001135 * eMedicine: med/3487 Wikimedia Commons has media related to Diaphragmatic hernia. * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum This article about a congenital malformation is a stub. You can help Wikipedia by expanding it. * v * t * e This article about a medical condition affecting the respiratory system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Diaphragmatic hernia	c0019284	28,698	wikipedia	https://en.wikipedia.org/wiki/Diaphragmatic_hernia	2021-01-18T18:36:38	{"mesh": ["D006548"], "icd-9": ["553.3"], "icd-10": ["K44"], "wikidata": ["Q2119430"]}
A number sign (#) is used with this entry because cerebrotendinous xanthomatosis is caused by homozygous or compound heterozygous mutation in the CYP27A1 gene (606530), which encodes sterol 27-hydroxylase, on chromosome 2q35. Description Cerebrotendinous xanthomatosis is a rare inherited lipid-storage disease characterized clinically by progressive neurologic dysfunction (cerebellar ataxia beginning after puberty, systemic spinal cord involvement and a pseudobulbar phase leading to death), premature atherosclerosis, and cataracts. Large deposits of cholesterol and cholestanol are found in virtually every tissue, particularly the Achilles tendons, brain, and lungs. Cholestanol, the 5-alpha-dihydro derivative of cholesterol, is enriched relative to cholesterol in all tissues. The diagnosis can be made by demonstrating cholestanol in abnormal amounts in the serum and tendon of persons suspected of being affected. Plasma cholesterol concentrations are low normal in CTX patients. Dotti et al. (2001) examined the ophthalmologic findings of 13 CTX patients. In addition to cataracts, which were found in all cases, optic disc pallor was identified in 6 of the patients. Premature retinal senescence was also observed. In a tabular presentation, Moghadasian et al. (2002) compared and contrasted CTX with 2 other lipid disorders with certain similarities and clinical course: familial hypercholesterolemia (143890) and sitosterolemia (210250). Clinical Features Van Bogaert et al. (1937) described affected cousins. Onset was at age 12 or 13 years. When examined in their 30s, the patients demonstrated cerebellopyramidal signs, myoclonus of the soft palate, mental debility, cataracts, xanthelasmata, and tendon xanthomata. At autopsy many deposits were found in the white matter of the cerebellum and the cerebral peduncles. Philippart and Van Bogaert (1969) gave follow-up on a member of the first family described by Van Bogaert et al. (1937). Menkes et al. (1968) described brother and sister, aged 60 and 57 years, respectively. The brother had slowly progressive ataxia in later years. Cataracts were removed in his 20s and he had enlarged Achilles tendons from childhood. Serum cholesterol was normal. He died of myocardial infarction. The cerebellar white matter was demyelinated and contained cholesterol deposits. The sister had had progressive enlargement of Achilles tendons, minimal mental retardation, and unsteadiness of gait. Bilateral cataracts were removed at age 24 years. Serum cholesterol was normal. Menkes et al. (1968) speculated that the defect concerns transport of cholesterol out of cells. Cholesterol can be synthesized in many tissues but oxidation is virtually limited to the liver. Whereas tendon xanthomata and cataracts may appear early, neurologic impairment may be a late development. Harlan and Still (1968) described black brother and sister with multiple tendinous and tuberous xanthomas despite plasma lipids that were quantitatively and qualitatively normal. Evidence of xanthomatous involvement of the lungs was found in the male. The authors suggested that normolipemic xanthomatosis is a distinct entity inherited as an autosomal recessive and that it should be classified as a reticuloendotheliosis. Swanson (1968) suggested that normolipemic xanthomatosis is the same entity as cerebrotendinous xanthomatosis. Although neurologic manifestations were not evident, these may be late in appearing. Cruysberg et al. (1991) suggested that bilateral juvenile cataract associated with chronic diarrhea may represent the earliest clinical manifestations of CTX. They described a 6-year-old girl, her 12-year-old brother, and another unrelated 12-year-old boy. Dotti et al. (1994) described the CT and MR findings in brain and spinal cord of 10 patients with cerebrotendinous xanthomatosis. All patients were aged 35 years or older and had cerebral and/or cerebellar atrophy. The majority had focal lesions distributed through the cerebrum, cerebellum, brainstem, or basal nuclei. Some of these lesions appeared to be xanthomata. Verrips et al. (1999) described 7 Dutch patients from 6 families with a slowly progressive, mainly spinal cord syndrome that existed for many years before the classic CTX symptomatology became manifest. The diagnoses were confirmed by biochemical and MRI findings and mutation assays of the CYP27A1 gene. The authors concluded that spinal xanthomatosis should be included in the differential diagnosis of chronic myelopathy. Early recognition of this myelopathy is important since effective therapy is available. Sugama et al. (2001) reported a 44-year-old woman with progressive frontal lobe dementia and spastic paraplegia. Examination revealed increased serum levels of cholestanol with abnormal cholesterol metabolism and a heterozygous mutation (arg441 to gln; 606530.0005) of the sterol 27-hydroxylase gene. While biochemical findings were compatible with the diagnosis of cerebrotendinous xanthomatosis, the clinical manifestations were very dissimilar. Clayton et al. (2002) reviewed the medical histories of a group of patients with CTX and found that prolonged neonatal cholestatic jaundice was common. The family histories also revealed fetal and neonatal deaths among sibs of CTX patients. Clayton et al. (2002) concluded that defective activity of cholesterol 27-hydroxylase can lead to neonatal cholestatic jaundice ('hepatitis of infancy'), which may be self-limiting. After a latent period, however, progressive accumulation of cholesterol and cholestanol can lead to the xanthomata, neurodegeneration, cataracts, and atherosclerosis that are typical of CTX. Guyant-Marechal et al. (2005) reported a 53-year-old man with an unusual CTX phenotype, involving xanthomas since adolescence but no mental retardation, and development of a progressive neuropsychiatric disorder beginning at age 44 that was suggestive of frontotemporal dementia. He had no cataract or ataxia. Despite combination cholesterol-lowering therapy over a 3-year period, his cognitive function continued to decline, although no other signs of neurologic deterioration appeared. Szlago et al. (2008) reported 2 Argentinian sibs with CTX confirmed by genetic analysis. Both had chronic diarrhea from birth, seizures, mild mental retardation, and developed cataracts in childhood. At 17 years of age, the boy showed palatal myoclonus, dystonic posture, distal tremor, uncoordinated gait, and hyperreflexia. The girl had distal tremor at age 14. Neither patient had tendon xanthomas. Both patients had high plasma levels of cholestanol. Szlago et al. (2008) noted the lack of tendon xanthomas but stated that xanthomas may manifest at a later date in these 2 young patients. Biochemical Features Setoguchi et al. (1974) found that bile acid production in CTX1 is subnormal, yet the activity of cholesterol 7-alpha-hydroxylase, the rate-determining enzyme of bile acid synthesis, is elevated. Oftebro et al. (1980) found that liver mitochondria in a CTX patient were completely devoid of 26-hydroxylase activity involved in oxidation of the side chain of 5-beta-cholestane-3 alpha,7 alpha,12 alpha-triol. The same mitochondrial fraction catalyzed 25-hydroxylation of vitamin D3. Thus, the major pathway in the biosynthesis of cholic acid in human liver involves a mitochondrial C27-steroid 26-hydroxylase. The substrate for 26-hydroxylation accumulated in the microsomal fraction to a level about 50 times normal. Shore et al. (1981) found that, in addition to the defect in bile acid synthesis (impaired oxidation of the cholesterol side chain in the formation of cholic acid), there is an abnormality of high density lipoproteins (HDL). Although morphologically normal by electron microscopy, HDL had a low cholesterol content. They postulated that HDL in CTX is deficient in the performance of its normal functions of modulating LDL-cholesterol uptake by cells and removing excess cholesterol from peripheral tissues. Bjorkhem et al. (1983) interpreted the results of in vivo studies as supporting their conclusion that CTX is due to lack of a hepatic mitochondrial C27-steroid 26-hydroxylase, involved in the normal biosynthesis of cholic acid and chenodeoxycholic acid (CDCA). Chenodeoxycholic acid is virtually absent from the bile in this disorder. In cultured skin fibroblasts, Skrede et al. (1986) demonstrated 26-hydroxylation of C27-steroids. The activities were normally about 5 to 10% of those found in liver homogenates. In fibroblasts from 3 patients with CTX, 26-hydroxylation proceeded at a rate only 0.2 to 2.5% that of healthy controls. Koopman et al. (1988) reported biochemical findings in 20 patients in the Netherlands. Diagnosis was best based on determination of urinary bile alcohols, in particular 5-beta-cholestane-3-alpha,7-alpha,12-alpha,23,25-pentol, by means of capillary gas chromatography. Koopman et al. (1986) developed a test for biochemically identifying heterozygotes from normals. By subjecting individuals to oral administration of cholestyramine, a marked decrease in the bile acid pool is observed. The production of newly synthesized bile acids is increased to compensate for that loss. During the provocation test, heterozygotes, like homozygotes, produce raised quantities of the pentol, which is excreted in the urine. In contrast, noncarriers do not produce the unusual bile acid. Koopman et al. (1985) found that cholic acid, which produces reduction in bile acid synthesis by a negative feedback mechanism, could be used in the treatment of this disorder. Population Genetics Berginer and Abeliovich (1981) observed 6 patients from 3 Moroccan Sephardic Jewish families. In this particular group they estimated the gene frequency to be 1 in 108. Clinical Management Because of the differences in expression of CTX, Berginer and Abeliovich (1981) recommended serum cholestanol studies in cases of undiagnosed cataract or tendinous xanthomas in childhood or early adolescence. Treatment with cholic acid and chenodeoxycholic acid was promising. Berginer et al. (1984) treated 17 patients with CDCA. All were symptomatic before treatment: Achilles tendon xanthomas (in 15 of 17), cataracts (in 12 of 17), dementia (in 13 of 17), pyramidal-tract signs (in all 17), cerebellar dysfunction (in 13 of 17), EEG changes (in 10 of 13), and abnormal cerebral CT scans (in 10 of 12). After at least 1 year of treatment, dementia cleared in 10; pyramidal and cerebellar signs disappeared in 5 and improved in 8 others; peripheral neuropathy disappeared in 6 and the EEG became normal in 5 and improved in 3 others. The CT scan improved in 7, including 1 patient in whom a cerebellar xanthoma disappeared. Mean plasma cholestanol levels declined 3-fold. The rationale of treatment with CDCA is to compensate for the pronounced deficiency of CDCA in the intrahepatic pool. The treatment produces a substantial reduction in cholestanol synthesis and lowers the cholestanol levels. Salen et al. (1987) found that treatment reduced high levels of cholesterol and cholestanol in the cerebrospinal fluid. Furthermore, untreated patients showed increased levels of apolipoprotein B and albumin. These results suggested that increased cerebrospinal fluid sterols were derived from plasma lipoproteins by means of a defective blood-brain barrier and that treatment with CDCA reestablished selective permeability of this barrier. Kuriyama et al. (1994) treated 7 patients with cerebrotendinous xanthomatosis either with CDCA alone, pravastatin (another inhibitor of HMG-CoA reductase), or the 2 agents in combination. CDCA treatment alone reduced serum cholestanol, but the sera of the patients on this treatment became more 'atherogenic' with an increase in total cholesterol, triglyceride, and low-density lipoprotein cholesterol, and a decrease in high-density lipoprotein cholesterol. In contrast, pravastatin made the sera markedly 'anti-atherogenic,' but only modestly reduced cholestanol and sitosterol levels. However, the combination of CDCA and pravastatin resulted in improvement of serum lipoprotein metabolism, suppression of cholesterol synthesis, and reduction of cholestanol and plant sterol levels. The progression of disease was arrested in all 7 patients, but no dramatic reversal of clinical manifestations was seen. Molecular Genetics The defect in cerebrotendinous xanthomatosis was shown by Cali et al. (1991) to reside in the CYP27A1 gene; see 606530.0001-606530.0002. In a 53-year-old man with an unusual CTX phenotype involving no mental retardation but a progressive neuropsychiatric disorder beginning at age 44, Guyant-Marechal et al. (2005) identified compound heterozygosity for mutations in the CYP27A1 gene (606530.0013-606530.0014). INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Juvenile cataracts CARDIOVASCULAR Heart \- Angina \- Myocardial infarction RESPIRATORY Lung \- Respiratory insufficiency SKELETAL \- Osteoporosis Limbs \- Tendon xanthomas (Achilles tendon, tibial tuberosity) \- MRI of Achilles tendon shows diffuse enlargement of the tendon, multiple hypersignal areas in T(1)- and T(2)-weighted images \- Fracture SKIN, NAILS, & HAIR Skin \- Tuberous xanthoma \- Xanthelasma NEUROLOGIC Central Nervous System \- Dementia \- Spinal cord paresis \- Cerebellar ataxia \- Mental retardation \- Spasticity \- Pseudobulbar paralysis \- Psychiatric symptoms (delusions, hallucinations) \- MRI - diffuse or focal cerebral and cerebellar white matter disease Peripheral Nervous System \- Peripheral neuropathy LABORATORY ABNORMALITIES \- Normal to slightly elevated plasma cholesterol \- Elevated plasma cholestanol \- Elevated urinary 7 alpha-hydroxylated bile alcohols \- Sterol 27-hydroxylase deficiency MOLECULAR BASIS \- Caused by mutations in the cytochrome P450, subfamily XXVIIA, polypeptide 1 gene (CYP27A1, 213700.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CEREBROTENDINOUS XANTHOMATOSIS	c0238052	28,699	omim	https://www.omim.org/entry/213700	2019-09-22T16:29:50	{"doid": ["4810"], "mesh": ["D019294"], "omim": ["213700"], "orphanet": ["909"], "synonyms": ["Alternative titles", "CEREBRAL CHOLESTERINOSIS"], "genereviews": ["NBK1409"]}

Subsets and Splits

No community queries yet

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